Microneurosurgery, 4 Vols., Vol.4A, CNS Tumors: Clinical Considerations and Microsurgery of Intracranial Tumors: TEILBD IV, Tl A

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Microneurosurgery 1114Volumes

M.G.Ya~argil IVA CNS Tumors: Surgical Anatomy Neuropathology Neuroradiology Neurophysiology Clinical Considerations Operability Treatment Options

Thieme

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ProfessOrJosef Kliiigler (18-88-1963), Professor of Anatomy at the University of Basel, Switzerland, from whom 1 learned a unique process for the dissection of'the brain and particularly the white matter systems, and thereby gained an inimitabk neuroanatomical perspective óf these complex structures. Dissection of both Hippocampal formations, by Professor1.Klingler, who always maintained that the Hippocampus was the most complex structure in all of Nature, possessing qualities which are not immediately apparent from its confined anatomical structure.

Microneurosurgery in 4 Volumes

M. G. Y a~argil

1 Microsurgical Anatorny of the Basal Cisterns and Vessels of the Brain, Diagnostic Studies, General Operative Techniques and Pathological Considerations of the Intracranial Aneurysrns 11 Clinical Considerations, Surgery of the Intracranial Aneurysrns and Results 111 A A VM of the Brain, History, Ernbryology, Pathological Considerations, Hernodynarnics, Diagnostic Studies, Microsurgical Anatorny 111 B A VM of the Brain, Clinical Considerations, General and Special Operative Techniques, Surgical Results, Nonoperated Cases, Cavernous and Venous Angiornas, Neuroanesthesia

IV A CNS Turnors: Surgical Anatorny, Neuropathology, Neuroradiology, Neurophysiology, Clinical Considerations, Operability, Treatrnent Options

IVB Microsurgery of CNS Turnors

Georg Thieme Verlag Stuttgart . NewYork Thieme Medical Publishers,Inc. NewYork

IVA

CNS Turnors: Surgical Anatorny, N europathology, N euroradiology, N europhysiology, Clinical Considerations, Operability, Treatrnent Options

M. G.Ya§argil

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Collaborators: T.E. Adamson, G. F. Cravens, R. 1.Johnson, 1.D. Reeves, :P.1.Teddy, A.Valavanis, W.Wichmann, A. M. Wild and :P.H.Young Anatomical preparations by A. Lang, U.Türe Illustrated

by :P.Roth

1126 illustrations,

58 tables

1994 Georg Thieme Verlag Stuttgart . New York Thieme Medieal Publishers, lne. NewYork

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IV

Author's Address: M. G. Ya~argil, M. D. Professor and Chairman (emeritus) Dept. of Neurosurgery University Hospital Zurich, Switzerland

Collaborators of Volume IV A: T. E. Adamson, M. n Charlotte Neurosurgical Associates, P.A. 1010 Edgehill Road North, At East Morehead, Charlotte, North Carolina 28207-1830,USA G. F. Cravens, M. n, FACS Center for Neurological Disorders 1319 Summit Ave. Fort Worth, Texas 76102, USA R. 1.Johnson, M. n Department of Neurosurgery, Louisiana State University, School of Medicine, Medical Center, 1542Tulane Avenue, New Orleans, LA 70112-2822 A. Lang Anatomical Preparator for Biology and Medicine, Anatomical Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich 1.n Reeves, M. D. Neurosurgeon, 1801Fairfield Ave., Suite 200, Shreveport, LA 71101, USA

P. Roth Scientific Artist, Neurosurgical Department, University Hospital of Zurich, CH-8091 Zurich P. 1. Teddy, DPhil, FRCS Consultant Neurosurgeon, The Department of Neurological Surgery, Oxfordshire Health Authority, The RadcIiffe Infirmary, Oxford OX2 6HE, UK U. Türe, M. D. Neurosurgeon Neurosurgical Department, Sisli-Etfal Hospital, Istanbul, Turkey A. Valavanis, M. D. Professor, Director and Chairman, Institute of Neuroradiology, University Hospital, CH-8091 Zurich W. Wichmann, M. n Institute of Neuroradiology, University Hospital, CH-8091 Zurich A. M. Wild, FRCS Neurosurgeon, Coordinator Joint European Project on Minimally Invasive Neurosurgery and Neuroendoscopy Eaton Socon Huntingdon Cambridge PE19 3PU, GB P. H. Young, M. D. Microsurgery and Brain Research Institute, P. C. 6725 Chippewa Street, Sto Louis, Missouri 63109, USA



Retrosplenial,cingulate, and subcallosal areas (23, 25, 33)

Cingulate

} Proísorcortícal areas Perirhinal (35, ectorhinal (36) Agranular temporal pole (38) Dysgranular ínsula Dysgranular cortex (13 posterior, 14 posterior)

Paralimbiclobe

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors

Anatomy of the Sulci

19

concomitant variations in sulcal anatomy. Nevertheless, certain consistent patterns in sulcal anatomy can be observed and classified.

Surgically relevant descriptions of the sulcal anatomy and its associatedvascularityhave, until recently, been lacking. The Atlas o[IheCerebralSulci (Ono et al. 1990) details many of the anatomicvariations in the sulcal patterns, and is highly recommended.The key features of normal sulcal anatomy, which can be ofpracticalhelp in microsurgical transsulcal approaches, are outlinedhere. Thereis considerable individual variation between gyral patterns,as a result of the genetic and remodelling process (see the sectionon embryogenesis above). These gyral variations result in

The classifications shown here of the large (Fig. 1.13) and short main sulci (Fig. 1.14) are reproduced from Ono et al. 1990. Only four of the large named sulci consistently have a 100% uninterrupted rate: the Sylvian fissure, the collateral sulcus, the callosal sulcus, and the parieto-occipital sulcus. The central and calcarine sulci are found to be uninterrupted in 92% of cases. The rates of uninterruption for other sulci vary from 28% to 58%.

a

a

b

b

e

e

Flg.1.13 Percentage incidence rates of large median sulci (fram Ono, Kubik,andAbernathey,Atlas of the Cerebral Sulei, Stuttgart: Thieme, 1990,p. 14, Fig. 3.1). a Lateral surface, b basar surface, e mediar surface I Sulciwitha high eontinuous (uninterrupted) rate 4 Callosal sulcus, 100% 1 Centralsulcus,92% 2 Sylvianfissure, 100% 5 Calcarine sulcus, 92% 3 Collateralsulcus, 100% 6 Parieto-occipital sulcus, 100% /1 Sulciwitha lowcontinuous(uninterrupted)rate , Superiorfrontal sulcus, 36% 11 Superior temporal sulcus, 32% 8 Inferiorfrontal sulcus, 48% 12 Occipitotemporal sulcus, 36% 9 Postcentralsulcus, 46% 13 Cingulate sulcus, 58% 10 Intraparietalsulcus, 50% Iff Regularly interruptedsulei 14 Precentral sulcus, 100% 15 Inferiortemporal sulcus, 100%

Fig.1.14 Percentage incidence rates of short, branched, and supplementarysulci(fromOno,Kubik,and Abernathey,Atlasof theCerebral Sulci, Stuttgart: Thieme, 1990, p. 15, Fig.3.2). a Lateral surface, b basal surface, e medial surface

Classification of the Sulci

Short main sulci 1 Lateral occipital sulcus, 96% 2 Olfactory sulcus, 100% 3 Rhinal sulcus, 100% 4 Superior rastral sulcus, 100% 5 Inferior rostral sulcus, 98% 6 Anterior parolfactory sulcus, 88% Sulci eomposed of several branehes 7 Orbital sulci, 100% 8 Subparietal sulcus, 100% Supplementary (free) sulei 9 Intermediate precental sulcus, 14% 10 Marginal precentral sulcus, 30% 11 Intermediate frontal sulcus, 86% 12 Medial frontal sulcus, 68%

13 Lunate sulcus, 62%

20

1 Anatomy

Types of Sulci There are four types of sulci: axial, limiting, operculated, and complete. Axial sulci develop along the long axis of rapidly growing homogeneous are as. They are 10ngitudina11yinfolded (as seen in the posterior calcarine sulcus ofthe visual cortex). The invaginations or indentations made by axial sulci in any given gyrus lead to the formation of subgyri (as seen on coronal or horizontal brain sections). The subgyral white matter, limited by these sulcal invaginations, can be termed the subgyral sector of a named gyrus. Limiting sulci develop along planes separating cortical areas, which differ in the functiQns they predominantly subserve. Formed earlier in embryonic development than the axial sulci, they are more prominent in their appearance and greater in depth. (An example is the central suIcus). An operculated sulcus is similar to a limiting sulcus in that it separates structura11y and functiona11y different are as, but the transition occurs at the lip and not the floor. Often a third area of function is present in the floor and wa11sof the sulcus. An example is the lunate suIcus (separating the striate and peristriate areas at the surface), which contains the parastriate area within its wa11s. A suIcus that is deep enough to produce an elevation in the wa11of a ventricle is ca11eda complete suIcus. There is no obvious functional significance attached to the fact that some suIci are complete and others incomplete. (An example of a complete sulcus is the collateral suIcus). The suIci are not simply invaginations with accompanying vessels. A11sulci have complex anatomical shapes within their depths. A straight side-by-side relationship does not exist. Instead, interdigitating gyral ridges and promontories characterize the sulcal depths, resulting in serpentine CSF channels betweeen the gyri. A gyrus may have fingerlike projections within its depths. These projections at the bottom of sulci may indent upon extensions descending from other proximal or even distal gyri. The depth of the sulci may range from less than 1 cm in an axial suIcus to 2-3 cm or more in a complete suIcus. With crude

Gyral Cerebral Anatomy The large increase in cortical surface area, necessitated by the evolutionary development of the neocortex in man, occurred without a proportionate increase in cranial volume. This was made possible by the invagination of over two-thirds of the cortical surface into the depths of the sulci and fissures, resulting in the convoluted shape of the gyri of the human cerebral mantle. This gyral complexity has recently assumed greater clinical importance with the advent of MR imaging. Most neurosurgeons know the basic morphology of the cerebral gyri, and can fo11owand describe (on the surface, at least), their course, extent, and connections. It is genera11yaccepted that each hemisphere has the fo11owingbroad orientations of recognizable gyri: three horizontal frontal gyri, three horizontal temporal gyri, two slanting perpendicular gyri (precentral and postcentral), four to five diagonal insular gyri, and two to three semicircular parietal occipitallobules. This information is partia11ycorrect and of some descriptive value, but it is grossly inadequate for microneurosurgical applications.

lobectomy and lobulectomy techniques, injury to extensions of normal and pathologica11y uninvolved gyri at the base of a suIcus may occur, without recognizable injury at the convexity surface. The Importance of Sulcal Anatomy The study by Ono et al. (1990), based on twenty-five human brains clearly demonstrates the complexity and the extent of individual variation in the surface gyri. It is essential for neurosUfgeons to know the large and short main suIci, but it is unrealistic and unnecessary for them to know a11the variations in detail. Furthermore, an unfortunate problem exists. Many of the sulci described, observed in anatomical material, and visualized clearly in MR images of living brains, cannot be recognized on the surgica11yexplored brain surface. The MR images seem to overrepresent in-vivo sulcal widths and underestimate gyral surfaces (a pseudoshrinkage of gyri due to the electronic effect of the MRI technique). During microsurgical exploration of the living brain surface, it is therefore extremely difficult (or often impossible) to identify with certainty the same suIci that appear so obvious on the MR images. The gyri are tightly apposed to one another in the normal human brain in vivo, and often even more tightly apposed in the hemisphere of a brain containing a tumor. The lesion may cause a spectrum of swe11ing, distortion, and displacement. In such cases, even recognizing main sulci, like the central, precentral and postcentral, parieto-occipital, calcarine, and cingulate sulci, or even the Sylvian fissure, may be difficult and sometimes impossible during surgery. Nevertheless, a knowledge of suIcal anatomy, particularly the main large and short sulci (and their variations), is very important, as it provides the microsurgeon with the primary key to a systematic understanding of the anatomy of the gyri.

Though subtle anatomic variations of gyral convolutions exist from one patient to another, careful analysis reveals patterns that permit useful generalizations to be made. Neurosurgeons are presently confronted with a situation similar to that which occurred almost sixty years ago with the advent of cerebral angiography. The variations in the arterial and venous anatomy must have seemed overwhelming at that time. Eventua11y, however, analysis and experience demonstrated that the normal anatomy fo11owed basic rules and the cerebral vascular tree was systematized. This axiom also holds true for gyral and sulcal anatomy. The fascinating history of the discovery of gyral anatomy has taken centuries to unfold and wi11continue we11into the future. The Gyral Convolutions Any attempt to draw or depict individual gyral convolutions, even in two dimensions, is frustrated by the complexities of deciding where an individual gyrus begins and ends and which "extension

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors arm"connectionsbetween gyri belong to which gyrus. As a result, it is cIearthat this approach to the formulation of a systematic planofgyralanatomy (from the outside) is flawed. Even a meticulousexaminationof the surfaceof the brain giveslittle idea of the complexityof the extensive infolding and interconnecting structureof the gyrihidden within the sulcal depths. A study of the depthsof the sulcireveals an impressively intricate anatomy, composedof interdigitating gyral extensions, with a seemingly randomseriesof dovetailing ridges, dips, and promontories between adjacentgyri (see Fig. 1.16c, 1.17, 1.34e, 1.44b, 1.51b). In addilÍon,there are considerable variations in the gyral anatomy, not onlybetween individuals but also between hemispheres in the sameperson (see Fig. 1.37, p. 45). Ultimately, the single most constantlyidentifiablesurfacefeature is the narrow Sylvianfissure,a resultof the overlapping growth of the infolding opercula of the surroundinglobes onto the insula (Fig. 1.15). Nevertheless, certainconsistentgeneralizations can be made about gyral patterns. Al! gyriareirregularinshape,and are composedof small,undulatingsubgyri(somesubgyriare even curved in a semicircularmanner).The only apparent exception is the gyrus rectus, which does appearto be straighl. On the surface, each gyrus seems to be separated from the adjacentgyri by short or long furrows that extend down to the bottomoftheinterveningsulcus(1-3 cm in depth). ThisgyralsepFig.1.15 Gyralconvolutionsof the Jeft cerebralhemisphere 1 Superior 2 Middle 3 Inferior F Frontalgyrus O Occipitalgyrus Op Opercularpart of inferiorfrontalgyrus OrbOrbitalpartof inferiorfrontal gyrus P Parietalgyrus Pe Postcentralgyrus Pr Precentralgyrus T Temporalgyrus Tri Triangularpartof inferiorfrontal gyrus

21

aration is, however, very superficial. At a depth of 2-3 mm, we start to see multiple extension "arms" connecting the gyri. These are the short or long, small or voluminous gyri of the main gyri. These transverse gyri cross over at acute angles to the line of the sulcus (Fig. 1.16). When the depths of the sulci are examined, reciprocal transverse gyral interdigitations (like intertwined fingers) are seen, that add to the complexity of this puzzle. Due to the shorter and longer intrasulcal furrows, the inner surface of the gyri becomes undulating. The wavelike opposing surfaces of the gyri are interlocked like cogwheels. (Ono et al. 1990, Figs. 6.3a-f, 6.191,19.3). We have long been aware of the hidden gyri of the insula (within the Sylvian fissure). But within every sulcus, there are numerous short and long gyri that should be termed the transverse gyri of a main gyrus, e. g., the transverse gyri (Heschl) of the superior temporal gyrus (Fig. 1.17; see also Figs. 1.16a, e, 1.34e, 1.35, 1.42c, 1.43b, 1.44a, 1.45c, 1.46b, 1.48b, 1.49b, e, 1.51b). In fact, each gyrus has 5-10 well-shaped intrasulcal extensions (transverse gyri), hidden within the depths of the sulci. They make up over two-thirds of the cortical surface and have not, as yet, been mapped by physiological studies. Neither present-day triplanar nor even three-dimensional MR imaging can demonstrate the extensive nature of this gyral interface.

22

1 Anatomy

Fig.1.16 The left superior frontal gyrus. Note the multiple extension "arms" (arrows) connecting this gyrus to the surrounding gyri. The transverse gyri are not visible from the surface, and can only be appreciated when the surrounding sulci are fully opened

Fig. 1.17 a The left frontal lo be of a rubberized brain. The depths of the sulci and interdigitations of the gyri are well shown. Note the variations in the inferior frontal gyrus. There is a connective arm Iying superoanteriorly to the middle frontal gyrus (small arrow). Note the transverse gyri in the frontal sulci. Central sulcus (large arrow) F1 Superior frontal gyrus F2 Middle frontal gyrus Op Opercular part

Orb Orbital part Tn Tnangular part Pr Precentral gyrus

of inferiorfrontal gyrus

}

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors Fig.1.17b The right centrallobes of a rubberizedbrain with opened sulci. Note the intersulcal transversegyri and their connections 1 Precentralsulcus 2 Centralsulcus 3 Postcentralsulcus Pc Postcentralgyrus Pr Precentralgyrus

Fig.1.17e The left Sylvian fissure in a rubberizedbrain,viewed through the slightly opened sulci.The intersulcal structures can be well recognized.The middle temporal gyrus lies between thesuperiortemporal sulcus (sts) and the interruptedmiddle temporal sulcus (mts) 1 Insula 2 Opercular part of inferior frontal gyrus 3 Precentralgyrus 4 Postcentralgyrus 5 Inferiorparietallobule 6 Superiortemporal gyrus 7 Anteriorand posterior transverse gyri (Heschl) 8 Middletemporal gyrus mIs Middletemporal sulcus sts Superiortemporal sulcus

23

I 24

1 Anatomy

General Features of Hemispheric Gyri Another problem is that the gyri form a continuous convolution system. It is noteworthy that no sharp delineation exists between what may be deemed the "beginning" and what appears to be the "end" of a gyrus. Starting at a polar area (whether frontal, temporal, or occipital) and tracing the contour of any prominent gyrus, it is possible to follow that same gyrus without interruption along the whole length of the hemisphere. This gyral continuum concept (uninterrupted gyri throughout a hemisphere) is iIIustrated in Figure 1.18. This continuous gyral pattern is hemispheric in the cerebrum and bihemispheric in the cerebellum. The striking feature of the gyri on the lateral, medial, or basal surfaces of the hemispheres is the serpentine configuration of the gyral convolutions. They are fairly constant in number, size, and orientation, but vary in their connections, both on the surface and in the depths of the sulci and fissures. A consequence of this gyral variation are the irregular interruptions of suIci. The individual variations of gyri on MR images and during surgical exploration of the brain surface, have convinced us that all attempts to identify areas or structures of the brain by surface "Iandmarks" are, at best, limited.. For example, it is simply impossible to recognize and identify, with any precision, the suIci and gyri and distinguish them from each other during open surgery. Even using computer-assisted intraoperative location devices, the tight suIci significantIYalter accuracy.

As a result, we have found that, for cIinical examinations, the complexities of gyral anatomy are best conceptualized by examining the basic white-matter patterns underlying gyral developmento This results in a simplified scheme that allows for variations. It is used to enhance anatomical descriptions, so that all those involved in the care of brain tumor patients immediately recognize the are a alluded to. It should prove useful in comparative studies and treatment trials between tumor groups, surgeons' patient groups, and institutions. Most important of all, it is very useful in planning the correct approach for intrinsic neoplastic lesions of the CNS. As previously mentioned, however, the application of topographic gyral information to surgery is still problematic. Hopefully, the newly-developed frameless stereotactic localization system will provide much-needed improved accurary (Kikinis and Jolesz 1993). Conversely, the technical innovations will produce new anatomical concepts, such as the proposed scheme of gyral segment or white matter, which is based on the embryological, functional, pathological, topographic, and surgical characteristics of the white matter of the brain.

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Fig. 1.18 The gyral continuum concept, demonstrated in the left cerebral hemisphere. There is an uninterrupted connection, either on the surface or intrasulcally, between every gyrus within the hemisphere

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors

TheWhiteMatterof the Cerebrum Themassivemedullary center of each cerebral hemisphere consistsof myelinated connecting fibers, other subsystem pathways, andvessels(Fig. 1.19, 1.20). Myelin is a semifluid fatty substance, whosepresence gives the characteristic color to the white matter. ofthesefibersystemscan nowadaysbe clearlyidentified on Some triplanarMR images (optic tract, corticospinal tract, anterior commissure,etc.). Our ability to think in three dimensions can be

greatly improved by studying coronal, sagittal and axial MR sections. With practice, it becomes a straightforward matter to construct a three-dimensional image of the orientation and major connecting of fiber systems within the white matter, including the relations to the central nuclei and the ventricular system. When combined with the three-dimensional gyral anatomy, this greatIy aids the surgeon in gyral, su1cal, and CSF space identification during microsurgical dissection.

/ /

Fig.1.19 The organizationand course of the projecting fibers within the cerebral white matter (after Krieg, Neuroanatomy, 2nd ed. New York: McGraw-Hill,1953, p. 659, Fig. 106). Note the following projection bundles:frontal, precentral and postcentral (pyramidal fibers), occipital(opticradiation), temporal (acoustic radiation), and temporoinsulofrontal(uncinate fasciculus)

25

26

1 Anatomy

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J

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Fig. 1.20 Artistic perception 01 the organization and complexity 01the white-matter libers within the cerebrum Red Projection libers Blue Association libers Yellow Commissural libers Green Cingulate libers

Gross anatomical and pathological examination of the brain reveals a substructure beneath the lobar level which is immediately evident, but for which no common terminology exists. The suIci and fissures serve to divide the convolutions and underlying white matter into a "cauliflowerlike" substructural arrangement. (Fig. 1.21). This substructure (readily evident on MR images) can now be viewed in vivo with great cIarity. One great advantage of this scheme of cerebral anatomical organization is that individual gyri can be consistentIy and reliably identified, even when

expanded or displaced by tumors. This inside-out conceptual ization is the key to understanding the sectorial architectural organization of the cerebrum. In this section, a practical scheme is presented that emphasizes not the traditional lobar architecture of the cerebral hemispheres, but the gyral and subgyral white-matter patterns and relationships. These patterns are, in fact, a consequence of the underlying anatomical cascade, based on an organized sectorial framework. The word "cascade" may appear to be a surprising choice in

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors ananatomicalscheme, but is chosen to indicate that the structure ofthe brain is genetically programmed and repeatedly modified duringdevelopment at a variable, multidichotomic rateo Early topographicaldevelopment is especially dynamic and subject to manyintrinsic and extrinsic modifications (see the section on embryogenesis above). The ultimate gyral configuration is dependenton the sum of total developmental "events" (pro-

27

grammed embryological stages, maldevelopments, intrauterine or neonatal insults, etc.) and of "inputs" (programmed, acquired, and learned information, etc.). The basic sectorial (peduncular) organization of the brain reflects its true "inside-out" development by neuronal migration, myelination, selective neuronal death and synaptic development (see the section on neurogenesis above ).

b Fig.1.21 Sectoral (peduncular) architectural organization, as seen in nature. a structure

Contents01the White Matter In triplanar section, the white matter appears as a uniform structure.Its voluminous mass can usually be equated with only the fibersystemwithin it. The white matter, however, contains other structures,indicated in Table 1.4. The courses of blood vessels and connectivefiber systems within the white matter have been well studiedand described. Other sub-systems (5-6 in Table 1.4 and Fig.1.25),however, are still not entirely known. In the near future, morespecific information about these pathways will hopefully be available.

Surface view 01a caulillower, and b

its sectoral (peduncular) sub-

Table 1.4 Contents of the white matter (subsystems) cephalon

of the telen-

The embryological neuroglial migration network oriented in the ventriculocortical axis within individual gyral segments 2 The vascular pattern 01white matter withinthe gyral segments a Arterial pathways: The branches 01the leptomeningeal arteries pass centripetally and supply the external lour-lifth01the white matter, while branches 01the perlorating arteries course centrilugally and supply the internal lifth01the white matter b Venous pathways: In contrast to the arterial distribution, only the external lifth01the white matter drains centrilugally to the superlicial medullary veins. The internal lour-lifths 01the white matter drain centripetally to the deep medullary veins 3 The connective libers a Association libers (hemispheric pathways) b Commissural libers (hemispheric pathways) c Projection libers (hemispheric, but crossing) - Corticothalamic, corticostriatal, thalamocortical - Corticopontine, corticobulbar, corticospinal 4 Transcerebral pathways 01the CSF 5 Neurotransmitter pathways 6 Neuroimmune pathways

28

1 Anatomy

White Matter Sublevels The white matter substancecan be subdivided into two distinct zones,the peripheral zone (gyral) and the central zone (capsular). The large peripheral zone consists of white matter located between the cortex and the periventricular matrix of the lateral ventricles. The smaller central zone consists of the projection fibers surrounding the lateral border of the lentiform nucleus (external capsule) and the V-shaped projection fiber bundles, located lateral to the lentiform nucleus and lateral to the caudate nucleus and thalamus (intemal capsule). The peripheral zone contains all of the axonsthat travel to or from the hemispheric or bihemispheric cerebral cortex, while the central zone contains only axonsthat connect the cortex to structures outside of it (corticopontine, corticobulbar, cortico-spinal, corticothalamic, and corticostriatal). While all varieties of whitematter fibers (association, commissural, and projection fibers) are found in the peripheral zone, only projection fibers are located in the central zone.As a result of its make-up (to andfrom cortical axons), the peripheral zone is composed of groups oí fibers that are segmentally related to the adjacent, overlying cortex (gyrus). Morphologically, each gyral segment resembles a cone (or pyramid), whosebaseoccupies a segment of a gyrusand whose apex is directed perpendicularly towards the underlying periventricular matrix (Fig. 1.22). Thus, the entire peripheral zone can be subdivided into numerous gyral segments. The number of gyral segments per gyrus varies between individual gyri (i.e., the gyrus rectus only has one segment, while the superior frontal gyrus has more than ten). Each gyral segment can be subdivided into sectors (Fig. 1.23, Table 1.5). Sectors 1 to 4 comprise the peripheral white matter zone, while sector 5 alone constitutes the central zone. It is noteworthy that the telencephalic vascularization pattern (arterial and venous), the embryonic neuroglia migration pathways, and the perivascular CSF drainage routes all resemble (to a striking degree) the characteristic gyral segmental white-matter pattern which courses from the cortex (sector O)through the peripheral zone (sectors 1 to 4) towards the periventricular matrix. This pattern is clearly different from that of the projection white-matter fibers, which run a similar course through sectors 1 to 4, but then leave sector 4 to enter sector 5 (the capsular sector). The term "peduncular" better describes the projection fibers, as they cascade in peduncles from the corte x to the internal capsule. (Fig. 1.24). The hemispheric association fibers and bihemispheric commissural fibers also leave sector 4, but do not enter sector 5.

b

Table

/

of white matter within gyral segments

Description

Composition

o 1

Cortical sector Subcortical sector (peduncle) Subgyral sector (peduncle) Gyral sector (peduncle)

Gray matter

3

Fig. 1.22 The pyramidal (conical) structure of gyral segments a Lateralview b Coronal view, demonstrating the gyral segments of the individual lobes e A gyral segment in relation to the lateral ventricle

Sectors

Sector

2

e

1.5

4

Peripheral white matter

Lobar sector

(peduncle) 5

Capsular

sector

(peduncle)

Central white matter (external and internal capsule)

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors F:g.1.23a

29

Artistic diagram of the white matter sectors within a gyral

segment(coronal section) O Cortex (gray) . Subcortical (brown) 2 Subgyral (Iight brown) 3 Gyral (yellow) 4 Lobar (dark brown) 5 Capsular. pyramidal

~

I

Flg.1.23b The white matter sectors and connective fibers (coronal section)

Short association

fibers

Long association

fibers

Commissural fibers Sector of gyral segments

Head of caudate nucieus

Claustrum Putamen

Thalamus

Globus pallidus Subthalamic nucieus

Anterior commissure

Corticopontine, corticobulbar, and corticospinal fibers , Substantia nigra

30

1 Anatomy Fig, 1.24 The sectorial organization 01 the projection libers (coronal section), 0-1 e: Sectors or peduncles, respectively, in relation to the projection libers O Cortical sector

1a Subcortical sector 1b 1c 1d 1e

Subgyral sector Gyral sector Lobar sector Capsular sector

(or peduncles)

11 2 3a 3b 3c 4 5

Callosal radiation (red) Hippocampus Parahippocampus (Iight green) Insula (olive) Cingulum (dark green) Central nuclei (gray) Ventricular (blue)

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l) l'

White Matter Subsystems

), !(

\

The white matter is composed of six subsystems (Table 1.4). 1. The migration pathway of neuroglia follows their embryologic course from the periventricular matrix to the cortical areas (sector O) along the sectors of gyral segments 4, 3, 2, 1 (Figs. 1.8a, 1.2Se) (Kostovic and Rakic 1980, Hinrichsen 1990: 380-448). 2. The vaseularizatiou patteru of gyral segmeuts. Arterial (see M. Marin-Padilla, "Embryology," Vol. lIlA in Chapter 2 of the present work). The branches of the leptomeningeal arteries course through each gyral segment centripetally along sectors O, 1, 2, 3, down to sector 4 (and the periventricular area) (Fig. 1.23a). This results in a conical-shaped pattern of white-matter arterial supply (resembling the shape of the individual gyral segments). The branches of the perforating arteries centrifugally supply sectors 5 and 4. The external capsule receives its arterial blood supply from M2 branches, whereas the internal capsule receives blood supply from branches of the lenticulostriate arteries, from the anterior choroidal artery and from Heubner's artery (Table 1.12b, p. 103, Fig.1.2Sa). Venous. The white-matter venous drainage pattern is contrary to the pattern of the arterial supply. The venous drainage of sector 1 is outwards (centrifugal) into the superficial medullary veins, whereas sectors 2, 3, 4, and the internal capsule drain centripetally into deep medullary veins. The external capsule drains into both superficial and deep medullary veins (Fig. 1.2Sb).

3. The trauseerebral CSF- pathways. The subarachnoidal CSF circulates along the subpial-periarterial spaces centripetally from cortical sectors down to the ventricle (sectors O, 1,2,3,4). Along the subpial-perivenous spaces of transcerebral veins, CSF also circulates along gyral segments between the ventricular and subarachnoidal cisterns (Krisch et al. 1984, Weller et al. 1986, Cserr et al. 1992). Cserr et al. (1992) state: The main channel of interstitial fluid (ISF) flow appears to be the perivascular space, or Virchow-Robin space (Fig. 4.Sa), as first suggested by His (1965), over a century ago. This space extends along arteries and veins penetrating into the nervous tissue, down to the point at which arterioles and venules merge with capillaries. Recent studies (Krisch et al. 1984, Hutchings and Weller 1986) have shown that it also extends along vessels in the subarachnoid space, as first suggested by Foldi et al. (1968). Thus, perivascular spaces can be categorized according to their location as either intracerebral or subarachnoid. Because the outer sheath of the perivascular space is permeable (Zhang et al. 1990) and, further, since blood vessels penetrate to all portions of the brain, the vast network of perivascular spaces provides a pathway for bulk flow of extracellular fluid between CSF and the entire CNS, comparable in extent to the lymphatics. It is not known whether the perforating arteries and the deep medullary veins are also surrounded by a similar channel with such a subependymal CSF pathway (Figs. 1.2Sd); (see also Chapter 4).

, j "J

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors

b

31

e

e

Fig. 1.25 White-matter subsystem segmental patterns (coronal view) a Arterial blood supply from the leptomeningeal arteries centripetally, and from the perforators centrifugally b The superficial and deep venous drainage e Neuroglial migration pathways d Transcerebral CSF pathways e The association and commissural fibers f Corticopontine and corticospinal fibers 9 Thalamic-striatal radiation h Neurotransmitter pathways

32

1 Anatomy

4. The connective fibers (Table 1.6). a) Association fibers (Figs.1.25e, 1.26, 1.27). The short association fibers (arcuate or U-fibers) are located only in sector 1 (connecting parts of a single gyral segment). Fibers range into sectors 2 and 3, connecting the cortical are as within the same gyrus or neighboring gyri. The arterial supply of these fibers is from branches of leptomeningeal arteries, and the venous drainage is centrifugal to the superficial medullary veins. The long association fibers (fasciculi) course through sections O,1,3, and 4 of numerous gyral segments, and be come a well-circumscribed bundle in sector 4 that runs from one lobe to another (over long distances) to conI}ect ipsilateral gyri. These fiber bundles intersect the radiating prajection fibers at sector 4. These long fiber bundles receive arterial blood from branches of numerous leptomeningeal arteries (from the anterior, middle, and posterior cerebral arteries). The venous drainage is centripetal to the numerous deep medullary veins.

Table

1.6

Reciprocal

Connective

b) Commissural fibers. 1. Bihemispheric bundle s of anterior commissural fibers course in a semicircular fashion from sectors O, 1,2,3, and 4 of temporal gyral segments along the basal ganglia to the opposite temporal gyral sectors 4, 3, 2, 1 and O (Fig. 1.25e). The posterior (hippocampal) bundle connects the hippocampi from both sides. The anterior commissure in temporal areas receives its arterial blood supply fram the leptomeningeal arteries of A¡, MCA, and PCA, whereas the middle part receives its blood supply fram branches of the anterior communicating artery, Heubner's artery and Al branches. The hippocampal commissure receives its arterial blood supply from the posterior choroidal artery and P3 and P4branches and drains into the atrial veins. The anterior commissure venous drainage is to the superficial medullary vein in sector 1, and to the deep medullary veins in sectors 2, 3, and 4 (bilateral).

fibers of the telencephalon

associative

fibers (i"psilateral hemispheric)

Short arcuate fibers

Reciprocal connection between two ipsilateral gyri, interconnecting the primary, modality-specific areas of the 90rtex

(U-fibers)

Between the ipsilateral neighboring gyri: connective fibers between modalityspecific areas of the parasensory association cortex and multimodal sensory areas

Long arcuate fibers

Superior longitudinal fasciculus Inferior longitudinal fasciculus Superior fronto-occipital fasciculus Inferior fronto-occipital fasciculus Vertical occipital fasciculus

Connecting the ipsilateral modalityspecific parasensory association cortex and the multimodal areas of the neocerebrum in the occipital, temporal, and parietal lobes with the premotor and prefrontal cortex of the frontal lobe

Uncinate fasciculus (hook bundle)

Connection fibers between the frontal and temporallobes (neocortical, allocortical and mesocortical): fronto-orbital, anterior F2' F3and anterior T3' T2' T, and parahippocampus, and to the anterior part of the insula (under the limen insulae)

Arcuate fasciculus (Zenker 1985, p. 157)

Between middle F2' F3external capsule and middle T3-T2

Cingulum

Main medial connective fibers within the white matter of the cingulate gyrus, between the neocerebrur:1 (frontal, central, parietal, occipital, temporal) and the limbic lobe (allocerebrum)

Corpus callosum Rostrum, genu, body, splenium Forceps minor (frontal)

commissural

Anterior commissure Anterior crus Posterior crus

Allocortical connection of the contralateral parahippocampal areas via the splenium

Forceps major (occipital) Hippocampal commisure (fornical commissure) Posterior commissure

Allocortical connection to the crus fornicis (psalterium); fibers from the entorhinal and perirhinal cortices Not a real commissure. A fiber connection between the contralateral thalamic medullary stria and the pretectal nuclei

Projection fibers Partially reciprocal corticofugal and corticopetal connective fibers Ipsilateral thalamostriatal, thalamocortical and corticothalamic fibers crossing over within the brain base or brainstem Olfactory tract (traverse allocortical areas) Gustatory fibers Acoustic tract Optic tract Ipsilateral hemispheric fibers, a minor part crossing the midline along the commissural system Fornix Connective fibers between the hippocampus and the septal nuclei, the anterior nucleus of the thalamus, the head nucleus of the stria terminalis and the mamillary body Striatal Crossing over via the subcallosal system Ipsilateral telencephalic fibers, crossing over within the brainstem Neocortical

Reciprocal

Interconnecting the corresponding neocortical are as of the contralateral hemispheric lobes

fibers (contralateral

hemispheric)

Connection to the olfactory bulb Contralateral connective fibers between the allocortical areas; amygdala, parahippocampus

Allocortical and mesocortical

r

Corticodiencephalic

(thalamus,

hypothalamus) Corticomesencephalic (nucleus ruber, substantia nigra) Corticopontine (frontopontine, temporopontine, parietopontine, occipitopontine, insulopontine undiscovered) Corticobulbar (nuclear) Corticospinal Limbic lobe to diencephalon, mesencephalon and metencephalon

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors

33

b

Fig. 1.26 Coronal view of the white-matter connective fibers within the cerebrum Blue Projection fibers Green Association fibers Red Commissural fibers 1-5 Long association fibers 1 Cingulum 2 Superior fronto-occipital fasciculus 3 Superior longitudinal fasciculus 4 Inferior fronto-occipital fasciculus 5 Inferior longitudinal fasciculus a, b Commissural fibers a Anterior commissure b Callosal fibers c Corticobulbar, corticopontine, and corticospinal fibers u U-fibers, short association fibers

@)

4

b

Fig.1.27a,b

Lateralview of the left cerebral hemisphere: association

fibersdissected by Dr. J. Klingler, Institute of Anatomy, Basle (from Lud..IgandKlingler, Atlas Humani Cerebri, Basel: Karger, 1956, Tabula 8)

1 2 3 4 5 6 7 8 9 10

Inferior occipitofrontal fasciculus Uncinate fasciculus External capsule White matter of the middle and inferior temporal gyri Inferior occipitofrontal fasciculus Superior longitudinal fasciculus Superior longitudinal fasciculus Sagittal stratum Fibers of splenium Parieto-occipital sulcus

34

1 Anatomy

2. Cal/osal[ibers are bihemispheric between the corresponding cortical areas of the seven cerebral lobes. They traverse thraugh sectors O,1, 2, 3, and 4 of the gyral segments of one side, then cross the midline and traverse the opposite sectors 4, 3, 2, 1, and Oof the gyral segments of the opposite side. The course of the callosal fibers is shown in Fig. 1.28a-b. Comprehensive information on the anatomy and physiology is given in Innocenti (1986): "The adult corpus callosum consists of myelinated and unmyelinated axons. The former comprise 43-69% of the total. There is but scanty information regarding the number of callosal axons. In an electron-micrascopic study, we have recently counted an average of 23 million axons in the ~dult cat, i. e. nearly 5 times more than the previous light-micrascopic figure. Few studies have tried to correlate the topography of the corpus callosum with that of the hemispheres." Sunderland (1990) concluded his Marchi study on the Macaque by stating, "The localization in the corpus callosum is of a very general type. Not only are the commissural fibers fram some cortical areas diffusely spread over the corpus callosum, but there is also an overlap of fibers coming from difierent areas in the same lobe, and also, apparently, fram areas in difierent lobes." This statement is still appropriate. More precisely, though, in cats and monkeys the rostrocaudal axis of the corpus

callosum corresponds roughly to that of the hemisphere, while the dorsoventral callosal axis does not seem to correspond to a mediolateral trajectory of the hemisphere. The topography ofaxons in the corpus callosum is interesting for at least two, very difierent, reasons. Sidfis et al. (1~81) demonstrated that different parts of the corpus callosum transfer the sensory and semantic attributes of a visual stimulus. It would be important to know which area-to-area connections are responsible for these two actions. On the other hand, sex-related differences in the shape of the corpus callosum have been found in human brains (De Lacoste-Utamsing and Holloway 1982). "Women seem to have a more bulbous and larger splenium than men, which may indicate difierences in the connectivity of specific cortical areas in the occipital, temporal, or parietal lobe. Along the same lines, it is interesting that left-handers seem to have a larger corpus callosum (at equal brain weight) than right-handers" (Witelson 1983). More detailed information is available in Innocenti (1986) and from recent MRI-based morphometric studies by Weiss et al. (1993). The anatomical variation of the corpus callosum as well as of the splenium and fornix has been studied using MRI. These are shown in Fig. 1.29a-c.

-

I ,,

I

\'1

"

..

k

r

-

I

I

4

JtI-

'

vr

.... 11

1

,

t. l\'),\ ..

.1

l

b a Fig. 1.28a The commissural fibers of the telencephalon, viewed from the basal side of the brain (from Niewenhuys et al., 8, Berlin: Springer, 1988, p. 366, Fig. 214)

Fig. 1.28b An anatomical dissection of the corpus callosum, performed by Dr. U. Türe. The indusium griseum has not been removed in the anterior and posterior areas of the corpus

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors

35

Flg.1.29a-c Average measurements and variations in the callosal body,related to the analysis of 150 MR images on normal subjects over sixyearsof age, and 25 anatomical brain sections (from Iliev-Urbaniec, Kubik,and Valavanis, Corpus callosum 1988). See also Figures 1.6b,d, 1.7a-e, 1.34c,1.38a, b, 1.41a, b, 1.53a, 1.57a, b, 1.58a, b, 160d, 1.67a, b a Variationsin the corpus callosum b Variationsin the splenium e Variationsin the position of the fornix

e

b

Thecallosal arterial supply in sectors 1-3 is from branches of ¡hesegmentalleptomeningeal arteries, and in sector 4 from the perforating arteries. The arterial vascularization of the hemispheric callosal fibers involves the participation of all three cerebral arteries (ACA, MCA, and bilateral PCA), in addition to of the lCA along the anterior choroidal artery. branches

The outer layers of the anterior two-thirds of the callosal bodyreceivetheir arterial blood supply from Az branches, and the inferiorlayer of this area from perforators (even from the anteriorcommunicatingartery). The posterior third of the corpus callosum(splenium) receives its blood supply from P3 and P4 branches (and the inner layer of the same area from perforators of ¡heposterior choroidal arteries).

The venous drainage in sector one is outwards to the superficial medullary veins, and in sectors 2, 3 and 4 down to the deep medullary veins. The venous drainage of the anterior callosal body (externallayers) is outwards to the superficial veins, while the inner layers drain to the deep medullary veins (or to the septal and frontal atrial veins). There are collaterals between both venous drainage systems (which can be seen in cases of callosal AVMs). The venous drainage of the posterior part of the callosalbody is outwards (in the outer two-thirds layers) and inwards (in the internallayer) to the deep medullary vein (atrial). It is interesting that the callosal arterial branches of both hemispheres do not have collaterals along the callosal fibers that cross the callosal body, while the veins of the callosal body have multiple connections across the midline.

36

1 Anatomy

c. Projection fibers (afferent and efferent). These fibers connect the telencephalic cortex with the basal ganglia, central nudei, brainstem, and spinal cord. There are two main connective fiber systems. 1. The regional corticothalamic-thalamocortical fiber system (optic, acoustic, vestibular, somatosensory, gustatory, and olfactory), and the corticostrio-pallido-thalamocortical fiber systemoTheir fibers pass along the gyral segments 0,1,2,3, and 4, and enter into the striatum and thalamus through the internal capsule, the corticodausatral fiber through the external capsule. They return from the thalamus along the sectors 4, 3, 2,1, and the corte x (Fig. 1.25g, 1.30a, b). . 2. The corticopontine, corticobulbar, and corticospinal fibers pass through the sectors of gyral segments O, 1,2, 3, and 4, and merge in a peduncular fashion to form the external and internal capsules (sector 5, or the hemispheric pedunde). (see pages 66-68 and Fig. 1.25f, 1.31a, b.) The arterial supply of fibers in sectors 1, 2, 3 is from leptomeninge al branches, and in sector 4 from perforating branches of all the cerebral arteries (ACA, MCA, and PCA) and the anterior choroidal artery. The venous drainage is centrifugal in sector 1, centripetal in sectors 2, 3, 4.

It is dear that commissural and projection fibers course together with the vascular and other network systems (through sectors 1,2,3, and 4) within gyral segments. At the lobar level (the central zone of the white matter), the commissural and projection fibers merge into well-defined bundles that intersect each other in a semicircular fashion and leave the gyral segments. The anterior and hippocampal commissures and fornix are selectively small bundles in comparison to the enormous fiber system of the anterior, superior, and posterior parts of the callosal commissure. The supralenticular, retrolenticular, and sublenticular projection fibers of the seven lobes (frontal, central, parietal, occipital, temporal, insular, and limbic lobes) course within the radiate corona to converge into the anterior and posterior limbs and genu of the internal capsule, and then finally merge as the crus cerebri (Fig. 1.31). Within the internal capsule, crus cerebri, and cerebral pedunde, these projection fibers have a distinct topographic organization, corresponding to the telencephalic lobar and thalamic pedundes (pp. 65-68, Fig. 1.62, 1.63).

Gyri orbitales

Gyri occipitales

Fig. 1.30a Connections between the thalamic nuclei and the cerebral cortex, in horizontal section (from Niewenhuys et al., The human Central Nervous System, Berlin: Springer, 1988, p. 242, Fig. 167) 1 Gyrus cinguli 2 Corpus striatum 3 Globus pallidus 4 Nucleus anterior thalami 5 Nucleus medialis thalami 6 Nucleus ventralis anterior 7 Nucleus ventralis lateralis 8 Nucleus ventralis posterior 9 Nucleus ventralis posterior, pars parvocellularis 10 Nucleus lateralis posterior 11 Nucleus centromedianus 12 Nucleus parafascicularis 13 Pulvinar thalami, pars anterior 14 Pulvinar thalami, pars medialis 15 Pulvinar thalami, pars lateralis 16 Corpus geniculatum laterale 17 Corpus geniculatum mediale

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors

37

Superior thalamic peduncle to the premotor and motor cortex and the somatic.sensory cortex nterior

thalamic

lo the cortex

peduncle

Posterior thalamic

01

he frontallobe, nd cingulate

peduncle, to the cortex 01 the parietal, occipital and temporallobes

gyrus

!nlerior thalamic peduncle, to the ital cortex 01the entallobe, the temporal ele and the amygdaloid

nucleus

Fig. 1.30b The thalamic peduncles (radiations projected onto the brain surface), lateral view (alter England and Wakely, A color atlas 01 the brain and spinal cord, London: Wolle, 1991) Diagram to show the thalamic peduncles (radiations) projected onto the brain surlace, lateral view

b

. .1.31a, b

A dissection 01 the projection and commissural

libers,

rlormedby Dr.J. Klingler,Institute 01Anatomy, Basle (Irom Ludwig AtlasHumaniCerebri,Basel:Karger,1956) d Klingler,

1 2 3 4 5 6 7 8 9 10 11 12

8

7

Corona radiata Internal capsule Decussation of the callosal body fibers and corona radiata Impression 01the lentilorm nucleus Ollactory tract Cortex 01the parahippocampal gyrus within the amygdala Lateral cerebral lossa Anterior perlorator substance Anterior commissure Temporopontine tract alter partial removal of the optic tract Temporopontine tract The optic radiation in sagiUal projection

38

1 Anatomy

The semicircular and semispiral courses of connective fibers are indeed difficult to imagine, even though numerous publications have presented brilliant two-dimensional and three-dimensional illustrations. There are also models, three-dimensional slides in stereoscopic atlases, and three-dimensional videotapes available. Still, an inborn artistic ability is necessary to develop an instantaneous yet understandable imaginative representation of these pathways from a specific perspective. This mental image can be stimulated by repeated exercises in drawing, and particularly by hand-crafting different pathways using colored wires and plastic (Fig. 1.32).

5. The neurotransmitter pathways are currently being investigated; current knowledge is presented in related publications of neuroscientists in the field of neurochemistry (Niewenhuys et al. 1985). Basically, their course is along the associate, commissural, and projectingiiber pathways. (Fig. 1.25h). (See Chapter 4, Neurophysiology. ) 6. The pathway of the neuroimmune system follows the vascular and neuroglial pattern (gyral segmental fashion), but may enter the basal ganglia, central nuclei, and brainstem (see Chapter 4). (See Fig. 1.25c.)

Fig. 1.32 The sectorial five-tiercascading organization of the white matter Orange Commissural fibers Yellow Frontopontine fibers Red Corticospinal fibers Beige Parietopontine and temporopontine fibers Green Occipitopontine fibers

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors

WhiteMatterSublevelsand Clinicallmplications 8asedon MR coronal views of the brain, five sublevels in white matter,according to major sectorial divisions, can be identified (Fig.1.23a-b, 1.24). Starting from the outside they are subcorticallyand proceeding inwards: subcortical, subgyral, gyral, lobar, and capsular. This subdivision of the white matter into sectors has madeour interpretation

of CT and MR images more methodical,

hascIarifiedthe way we interpret surgical pathology, and has modifiedour approach to surgery for intrinsic CNS tumors. It has been evidentto us that gliomas may begin in what we have termed the subcorticalsectors of a gyrus (see Figs. 2.2-2.4). They then grow by expandingfirst the subgyral, and then the gyral sectors, and

39

only finalIy the lobar sector. The adoption of this system has allowed us to identify the precise sublevel of white matter that is involved by any lesion. Somewhat surprisingly, it has even forced us to revise our thoughts on the growth and spread of glial tumors in their initial and intermediate phases, as these lesions do not follow the connective fiber bundles, as generally believed, but rather grow in the direction of the gyral segmental vascular supply and in the reverse direction to that of the embryological neuroglial migration (see p. 12). Accordingly, a new perspective on the topographical anatomy of each of the cerebral lobes and their gyri, based on a sectorial five-tier hierarchical organization of the white matter, is presented here.

Topographical Anatomy01the Lobes and Gyri 01 theBrain

Boundaries. The frontallobe extends on the dorsolateral surface fromthe frontal pole to the superior and inferior precentral sulcUS. withoutclear separation from the precentral gyrus. It is separatedframthetemporallobe by the Sylvianfissure,and from the insulaby the superoanterior part of the cingular sulcus. On the medial surface,itisseparatedfrom the gyruscinguli(but not from the paracentral gyrus) by the sulcus cinguli. Mediobasally, the frontallobeis separated by the superior rostral sulcus from the subcallosal part of the gyrus cinguli. Basally, the entire orbital surfacebelongsto the frontallobe (For variations of the frontal gyri andsulci,seealsoFig.8.10-8.23,11.5-11.7in Ono et al. 1990). Surfaces. The frontallobe has, in practical terms, four main surfaces (inferomedial and superomedial, superolateral, operculoinsular,and fronto-orbital) and several sulcal surfaces. Figure 1.33showsthe surfacesof the frontal lobe. The frontallobe is separatedconvenientlyin its sagittal, fronto-occipital extension, into threeparts:anterior (level of the temporal pole), middle (level of the striatum), and posterior (level of the foramen of Monro). In coronal section five pedunculi can be identified; an anterior part of the cingulate gyrus, together with superior, middle, inferior,and orbital frontal gyri (Fig. 1.69A. a-e, p. 78). The cingulate gyrus, with its supracallosal and subcallosal parts, is topographicallyincorporated into the medial part of the frontal lobe. Thecingulategyrus will be discussed later as part of the limbic lobe.

Fig. 1.33 The surface of the frontal lobe (coronal section through the striatum) a, Superomedial (interhemispheric) surface a2 Inferomedial(interhemispheric) surface b Superolateral surface c Opercular-insular (Sylvian)surface d Fronto-orbitalsurface

40

1 Anatomy Sulciof the frontallobe. The followingsulci can be identified: Medial

Superolateral

Operculoinsular Fronto-orbit

Anterior part of the callosal sulcus Anterior part of the cingular sulcus Superorostral sulcus Inferorostral sulcus Parolfactory sulcus Superior sulcus Middle sulcus Inferior sulcus U nnamed (opercular) sulcus 5- 7 sulci Olfactory sulcus H -shaped orbital sulci (cruciform Rolando)

sulcus of

The (intermediate) middle frontal sulcus, occasionally single, and often interrupted, several times separates the gyrus into two or more subdivisions (secondary gyri). Classification of frontal gyri. 1 Superior frontal gyrus a Medial part b Superolateral part 2 Middle frontal gyrus 3 Inferior frontal gyrus a Orbital part b Triangular part c Opercular part 4 Gyrus rectus 5 Orbital gyri

Fig. 1.34 Frontal lo be gyri a MRI 01the lrontallobe (horizontal section). Note the superior frontal gyri (right and left), both with numerous symmetrical gyral interdigitations b Left cerebral hemisphere (superior view). An intermediate sulcus separates the superior Irontal gyrus (F1) into two longitudinal parts. Note the undulating course 01F2, and the connection 01F1 and F2 to the precentral gyrus (Pr, arrows) F1 Superior lrontal gyrus F2 Middle lrontal gyrus Pc Postcentral gyrus Pr Precentral gyrus e Left cerebral hemisphere (medial view). Note the semicircular medial lrontal gyrus around the anterior hall 01 the cingulate gyrus (between the two white arrows). The black arrow indicates the connection between the cingulate gyrus and the medial Irontal gyrus 1 Paracentral gyrus

There are three longitudinally oriented gyri (with a serpentine cours.e) that constitute the convex surface of the frontal lobe. 1. The superior frontal gyrus (F¡ with anterior, middle, posterior segments, Brodmann areas 6, 8 and 9) is one of the principal gyri of the voluminous frontal lobe. It is made up of a substantial parasagittal part, measuring approximately 1-2 cm in width and 11 cm in length (from the superior precentral gyrus to the frontal pole). Posteriorly, it has connections to the superior part of the precentral gyrus, and anteriorly it merges (within the frontal pole area) with the middle frontal, orbital, and rectus gyri. It has two parts, one supero lateral and one media!. Approximately 10 transverse gyri form an intertwining interface with the adjacent transverse gyri of the middle frontal gyrus. The subgyral anatomy is highly variable, as demonstrated by the 12-15 small extension arms of cortex merging with neighboring gyri (Fig. 1.34a-c). The superolateral part is often divided by one long, or numerous small, sulci in two longitudinal areas.

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors Themedial surface of the superior frontal gyrus is often given aseparatename-the medial frontal gyrus. (Brodmann area 6, 8, 9.10,11,12, and 32). It commences immediately anterior to the paraolfactorysulcus, and curves upwards, anteriorly between the and inferiorrostral sulci, towards the frontal pole (see superior Fig.1.53p. 57). It then turns posteriorly around the cingulate gyrus.11lecingulate sulcus separates this gyrus from the cingulate gyrus, butthere are individualvariations with one or more small orlargeconnective arms between the medial part of the superior frontalgyrus and the anterior part of the cingulate gyrus (see Figures1.57,1.58 and 1.59). Along the cingulate sulcus, several gyrifrom the medial, frontal gyrus and the cingulate transverse gyrusinterdigitatewith each other (Fig. 1.58). Many subgyri, dividedby axial sulci, mark the medial surface of this gyrus (Fig.1.34c).The frontopolar artery courses anteriorly within the superiorrostral sulcus. 2. The middle frontal gyrus (F2 with anterior, middle, and posteriorsegments), (Brodmann are as 6, 8, 9, and 10) is a more serpentine,longitudinal convolution. The secondary sulci (middle frontalsulcus) divide the gyrus into two or more sections. The middlefrontal sulcus can be regularly recognized on coronal MRl.The F2gyrus has connective arms to F¡ and F3 on the surface.Its removal results in the appearance of a "valley ringed by The interlockingpaUern of the juxtaposed gyri is tallmountains." evident.It is separated from the inferior frontal gyrus by the inferiorfrontalsulcus,whichcontainsportions of the prefrontal arteriesthatdipinto the sulcusas they ascend over the lateral surface ofthehemisphere.This sulcus sometimes appears as an anteriorlydirected branchofthe precentralsulcus(Fig.1.34d, e). It has regularlyone,andoccasionallytwo,connectivearms to the precentral gyrus,which cause the interruption of the precentral gyrus into t\Voor three sections. Along the superior and inferior frontal sulci,the middle frontal gyrus extends several transverse gyri (see Fig.1.34e). 3. The inferior frontal gyrus (F3 with anterior, middle, and posteriorsegments, Brodmann areas 44, 45, and 47), located betweenthe inferior Sylvian fissure and the antero-superior lip of theSylvianfissure, forming the frontal operculum, overlying the anteriorhalf of the insula. The frontal operculum is divided into three parts between theanteriorandascendingrami of the Sylvianfissureand the inferior precentralsulcus: a. The orbital part (Brodmann are a 47) merges anteriorly \Viththe lateral orbital gyri, superiorly with the anterior parts of F2'andposteriorly with the triangular part. b. The triangular part (Brodmann area 45) lies between the anteriorand ascending rami of the Sylvian fissure, and merges anteriorlywith the orbital part, posteriorly with the opercular part,and also has connective arms to the middle parts of F2. The triangularpart is easy to recognize on anatomical section and on MRIpictures(Naidich 1991). c. The opercular part (Brodmann 44) lies between the ramiof the Sylvianfissure and the inferior precentral ascending andinferiorfrontal sulci, and merges anteriorly with the triangularpartand posteroinferiorly with the inferior part of the precentralgyrus.The opercular part of F3coincides with Brodmann area 44.but some authors also inc1ude area 45. In anatomical and functionalpublications, the location and extension of the Broca areais veryapproximate;the encirc1edareas on drawingsare irregular,usuallyextending into the adjacent F2and inferior part of precentral gyrus.

41

Fig. 1.34 d The left superior (F1), middle (F2), and inferior (F3) frontal gyri (anterolateral view). Note the connection between the voluminous middle frontal gyrus and the precentral gyrus (arrow) F1 Superior frontal gyrus Pc Postcentral gyrus F2 Middle frontal gyrus Pr Precentral gyrus F3 Inferior frontal gyrus

Fig.1.34e The transverse gyri of the superior frontal gyrus (F1) and inferiorfrontalgyrus (F3) are wellvisualized after removalof the middle frontal gyrus (arrows)

Broca's are a (well-known since 1861) fascinates neuroscientists as a reliable functional center. Interestingly, the individual anatomical variations of this area have not been thoroughly investigated; this part may consists of one voluminous convolution with a superficial short sulcus on the surface, or it may comprise two or even three gyri displayed parallel to the inferior part of the precentral gyrus (Fig. 1.34f-i). The variations of the inferior frontal and inferior precentral sulci, and of the anterior and ascending rami of the Sylvian fissure, are described in ano et al. (1990). As the sulcal variations result from gyral developments, the individual variability of the frontal operculum is obvious. In addition to these variations (which can be easily recognized on the surface of the gyral configuration), there are also more hidden variations within the sulcal depth, with interdigitations (transverse gyri) into the inferior frontal sulcus, into the inferior precentral gyrus, and especially into the Sylvian fissure, where five or six short or long transverse interdigitations (3-4 cm) extend lateromedially from

42

1 Anatomy

Fig.1.341 The left inferior frontal gyrus (F3). Note the gyral eontinuity betweenthe opereular part of F3 and the middle frontal gyrus (F2) and preeentralgyrus (Pr,arrows) F2 Middle frontal gyrus F3 Inferiorfrontal gyrus Op Opereular gyrus Orb Orbital gyrus Pe Posteentralgyrus Pr Preeentralgyrus Tri Triangularpart of the inferior frontal gyrus

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Fig. 1.349 A variation of the inferior frontal gyrus (F3). The preeentral gyrus is not interrupted F1 Superior frontal gyrus F2 Middle frontal gyrus F3 Inferior frontal gyrus Pe Posteentral gyrus Pr Preeentral gyrus

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ij central artery branches (cent) withinthe central sulcus (fromSziklaet al., Angiography of the Human Brain Cortex, Berlin: Springer, 1977, p. 9, Fig.13)

Two basic patterns of vasculature exist. One characteristic pattern is for the vessel to dip into a sulcus, give off several branches, and then regain the surface en route to its next destination. The other common pattern is for a cortical vessel to traverse the external surface of a gyrus, enter into a sulcus to supply the gyri on either side of that sulcus, and then continue within the depth of that sulcus en route to another without reappearing 00 the free surface. This particular phenomenon is not unusual at the level of the precentral sulcus, which freely communicates with the frontal sulcus. Thus, wide exposure of a sulcus is important to differentiate between end vessels, transit vessels, and tumor-supplying vessels, and to eliminate only those vessels which directly supply blood to the tumor.

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors

BloodSupplyof Cerebraland Cerebellar Tumors

Table 1.10 Intrinsic cerebral tumors and their vascularization in relation to their location

Thevascularityof the neocerebrum and neocerebellum has been describedin many publications, and will not be repeated here. Thereaderisalsoreferredto Vol.1,p. 54-143-intracranial arteries;pp. 144-64-perforating arteries; pp. 165-7-cerebral veins; and Vol. III A, pp. 327-32-venous system, pp. 338-44-blood vesselsof the cerebral cortex; pp. 345-9-blood vessels of the cerebellar cortex. Thearterialandvenoussupplyof each individualsegment of thecerebrum(and cerebellum) is distinctive, in terms of the proportionsderived from leptomeningeal versus perforating arteries (Table 1.10). The vascularization of tumors arising in an individualsegment assumes this same arrangement. Figures 1.87-1.91summarizethe common patterns of leptomeningeal versus perforator supply for cerebral and cerebellar tumors. Table 1.11on p. 102outlines the vascular supply to individual cerebral

99

Arterial supply

Neocerebral and cerebellar Paleo- and archicerebral, cerebellar Paralimbic Limbic Central Nuclei Intraventricular

Venous drainage

Leptomeningeal

Perlorator

+++

(+)

+++

(+)

+++ (+)

+ ++ +++ +++

++ ++

+ + +++ +++

Superlicial

Deep

lobes and gyri.

b

Fig.1.87a The vascularization 01 a neocerebral tumor The majar blood supply is via leptomeningeal arteries, supply Irom the deep perlorating vessels. This pattern throughoutal! neocerebral areas (see also Fig. 1.84 b, p.

(Irontallobe). with a small is the same 97)

Fig. 1.87b Diagrammatic representation 01the vascular supply to a neocerebral tumor. In the case 01a hypervascularized tumor,the deep perlorating vessels can be enormously dilated

100

1 Anatomy

a

b

Fig. 1.88 The vascularization of a mediobasal limbic lobe tumor. The vascularization of tumors in this location is via branches from the anterior choroidal, uncal, and posterior cerebral branches

a b

a

Fig. 1.89 The vascularization of a central nucleus tumor a A right thalamic tumor (medial view). Note the major arterial supply, via branches from the deep perforating vessels (PCOA, P1, P2, P3, A1).

Coronal view Superior view

b

The leptomeningeal supply, if present, is scanty, but the vessels may become dilated in vascularized gliomas b A schematic representation of a

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors

101

b Fig. 1.90. The vascularization of a tumor in the pineal area a A right pineal tumor (medial view). The vascularization pattern of tumorsinthis area is via direct branches from the medial or lateral poste-

rior choroidal, collicular, posterior callosal, posterior cerebral, and pericallosal arteries b A schematic representation of a

CerebellarBlood Supply

vasculature (see Vols. I and III A, B). Figures 1.81 and 1.82 on p. 94 and Fig. 1.91 are given in this volume to illustrate the common pattern of the arterial supply of a cerebellar tumor (Fig. 1.91).

Themicrosurgicalremoval of cerebellar tumors (as in the cerebrum) requires a knowledge of the cerebellar and brainstem

~Flg.1.91 The vascularization of a paramedian cerebellar tumor a A left posterior quadrangular lobule tumor (superior view). Note the extensiveleptomeningeal artery supply (via superior, anterior inferior,

and posterior inferior arteries), and the small supply from the deep perforating vessels (paramedian pontine vessels) b A schematic representation of a (see Fig. 1.84 b, p. 97)

--

102

1 Anatomy

Table 1.11 Vascular supply of cerebrallobes and gyri Lobe

Frontal Superior frontal gyrus Middle frontal gyrus Inferior frontal gyrus Central lobe Precentral gyrus

Postcentral gyrus Paracentral gyrus

Temporal Superior temporal gyrus

Feeders

Cortical drainage

Terminal drainage

A3

Frontal ascending veins Frontal ascending and Sylvian veins Frontal ascending and Sylvian veins

SSS

A 3 and M 3

M3

M 3>A 3

M 3>A 3 A3

ICA, M 1, M 2 and M 3

Central Ascending and descending veins Central descending veins Frontal ascending and descending veins Sylvian, ascending, descending, and laterobasal veins

Middle temporal gyrus

M 3>P 3

Sylvian, ascending, descending and lateralobasal veins

Inferior temporal gyrus

P 3>M 3

Sylvian, ascending, descending and lateralobasal veins

Temporal occipital lateral gyrus Temporal occipital medial gyrus

P 3-anterior choroidal artery P3

Laterobasal vein Mediobasal vein

SSS and sphenoparietal sinus SSS and sphenoparietal sinus SSS, Sylvian veins to sphenoparietal sinus

Lobe

Feeders

Cortical drainage

Terminal drainage

Parietal Superior parietallobule Inferior parietal lobule

A 3, M 3 and P3 M 3 and A 3

SSS

Precuneus

A 3 and P 3

Ascending parietal vein Ascending and descending parietal veins Ascending parietal vein

Occipital Cuneus

P3

Basal gyri

P3

Dorsal gyri

P3

Ascending and descending veins

Insular lobe Insular gyri

M 2 and M 3

Ascending and descending veins

Ascending and descending veins Medial and lateral veins

SSS

Sphenoparietal Sinus, Sylvian vein and vein of Labbe, superior petrosal, sinus Sphenoparietal sinus, Sylvian vein and vein of Labbe, superior petrosal, sinus Sphenoparietal sinus, Sylvian vein and vein of Labbe, superior petrosal, sinus Superior petrosal and tentorial veins Basal vein

Arterial Supply of Central Nuclei and the Internal Capsule Basal ganglia. The basal ganglia can be divided into the caudate nucleus, putamen, globus pa11idus,subthalamic nucleus, and substantia nigra. The majority of the blood supply to a11basal ganglia structures comes from only two sources (Table 1.12a). The caudate nucleus is divided into head, body, and tail. The ventromedial head is supplied by Heubner's artery, which originates from the Al segment of the anterior cerebral artery (ACA) (Perlmutter and Rhoton 1976). The dorsolateral head is fed by the lateral striate perforators of the middle cerebral artery (MCA), which also supply the body. In some cases, one of these two vessels may dominate and supply the whole head of the cau-

SSS, Sylvian vein, or vein of Labbe SSS

SSS & vein of Galen Vein of Galen, sigmoid and transverse Sinus and SSS Temporooccipital vein and Sigmoid Sinus Sylvian Vein Frontal ascend. Temporal vein

SSS: Superior sagittal sinus

date (Marinkovic et al. 1986). The dual perfusion of the tail arises from branches of the anterior choroidal artery (AChoA) and lateral posterior choroidal artery. The major blood flow to the putamen comes from lateral striate branches of the MCA. The ventromedial part and the caudal part are nourished from the recurrent artery of Heubner and branches of the AChoA respectively (GilIilan 1968, Dunker and Harris 1976). The globus pa11iduscan be divided into a lateral and medial region. The medial area receives blood flow via many perforators from the internal carotid (lCA), ACA and AChoA. While the majority of the lateral area is perfused by lateral striate branches of the MCA, contribution also arises from medial striate branches of the ACA and occasiona11yAChoA perforators.

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors The subthalamic nucIeus has three sources: peduncular branchesof the AChoA, the posterior cerebral artery (PCA), and the premamillarybranches of the posterior communicating artery (PCoA) (Haymaker 1976). Similarly,the rostral substantia nigra receives blood from the peduncularbranches of the AChoA and premamillary branch of the PCoA (Duvernoy 1978, Rhoton et al. 1979). The caudal area obtains supply from peduncular branches of PCA, collicular, medial posterior choroidal, and superior cerebellar arteries (SCA). Internalcapsule.Perfusion of the internal capsule is anatomically subdivided.The anterior limb receives a dual supply: the ventromedialportion is supplied by branches of Heubner's artery, whileperforators of the middle cerebral artery irrigate the dorsolateral portion (Dunker and Harris 1976, Rosner et al. 1984, Marinkovicet al. 1987) (Table l.Ub). The dorsal portion of the genu receives blood from the lateralstriate branches of the MCA, and the ventromedial aspect fromperforators of the ACA, ICA, and AChoA. The lateral striate branches of the MCA perfuse the dorsal aspectof the posterior limb (Marinkovic et al. 1987). Perforators of the ICA and ACA supply the part closest to the genu (the rostral part of the ventral portion). The caudal aspect is supplied by branchesof the AChoA. The thalamogeniculate branches of the PCAmayalso feed the posterior limb (Schlesinger 1976). The retrolenticular part is irrigated by capsular branches of the AChoA(Herman et al. 1966, Rhoton et al. 1979).

Table 1.12 a

103

The arterial blood supply of Basal Ganglia (central nuclei)

Caudate Ventral medial head by Heubner artery Dorsal lateral head and body by MCA Entire head can be irrigated by MCA perforators or Heubner artery (in some cases) Tail by AChA, lateral posterior choroidal artery

Putamen supplied

by several groups of perforators Rostral ventromedial part from Heubner artery Most of putamen by lateral striate of MCA Occasionally, caudal putamen-AChA Globus pallidus lateral segment - Rostroventrallateral-medial striate of ACA - Large remainder. later striate of MCA, perforators AChA Medial-internal carotid, ACA, AChA

Subthalamic nucleus -

Peduncular branches of ACha PCA Premamillary of PCoA

Substantia nigra Rostral

-

Peduncular

-

Premamillary of PCoA

branches

of AChA

caudal peduncular branchesof PCA COllicular,medial postchoroidal Superiorcerebellararteries

Table 1.12 b The arterial blood supply of the internal capsule Anterior limb

ArterialSupply of the Thalamus

-

Dorsolateral:perforatorsof MCA

-

Dorsal portion: laterial striates of MCA Ventromedial: perforators of ACA, ICA, AChA

Genu Thethalamusreceives its blood supply from anterolateral, lateral posterolateral,medial, and dorsal arteries. The premamillary branchof the PCoA givesrise to the anterolateral arteries. In additionto irrigatingthe anterior ventral (AV), reticular, ventral anterior(VA),and ventral medial dorsal (VMD) thalamic nuclei, they supplytelencephalic and mesencephalicstructures.These include thecrus,substantianigra, optic tract, posterior caudal and lateral hypothalamus, and the subthalamus (Haymaker 1976, Schlesinger1976).The AChoA provides the lateral arteries to the thalamus.They supply the ventral anterior (VA) thalamic reticular nucleus,the ventral lateral (VL), and occasionally the ventroposterolateral(VPL) and the pulvinar. Outside the thalamus, they supply the crus, substantia nigra, red nucleus, and subthalamicnuclei (Schlesinger 1976). The thalamogeniculate arter¡esserveastheposterolateralarteries and perfuse the VPL, ventroposteromedial(VPM), VL, LP and part of the centromedian nuclei(Graff-Radfordet al. 1985, Caplan et al. 1988). Also, they irrigatethe crus cerebri, the brachium of the superior colliculus, and the medial geniculate body (MGB) prior to supplying the thalamicnuclei(Table l.12c on p. 104). The diencephalic interpeduncular (thalamoperforating) branchescomprise the medial thalamic arterial supply. Prior to reachingthe thalamus,they provide blood fIow to the red and subthalamicnuclei. The thalamic supply goes to the VPM, VPL, medialdorsal,centromedian,parafascicular, AV, VL, LD, and LPM(Schlesinger,1976,Graff-Radford et al. 1985). The dorsal branches arise from P2 as branches from the medialandlateralposteriorchoroidalarteries. Mainlythe geniculate bodies,pulvinar,lateral dorsal, medial dorsal, posterior

Ventromedial: Heubner artery

-

Posterior limb Dorsal aspect: lateral striates of MCA Rostral part of ventral portion. close to gen u - Perf. of ICA - ACA Caudal dorsal and caudal ventral branches of AChA

Retrolenticular part: capsular

branches of AChA

nuclei, anterior and midline thalamic nuclei are supplied (Schlesinger 1976, Zeal and Rhoton 1979). The habenula, pineal body, and midbrain receive branches of the medial posterior choroidal artery.

104

1 Anatomy

Table 1.12e The arterial blood supply of the thalamus Anterolateral artery 1. From premamillary branches 01PCoA a. Premamillary branch belore reaching thalamus (1) Supplies crus, optic tract, substantia nigra (2) Part 01posterior hypothalamus, caudal lateral part (3) Subthalamic area b. Once in thalamus may irrigate (1) Anterior ventral (2) Part 01ventral lateral and medial dorsal nuclei 2. Some authors say rostral thalamus receives Irom a. Perlorators 01internal carotid b. Perlorators 01ACA Lateral arteries 01the thalamus-originating Irom AChA 1. At rostral crus, also supplies: nigra, subthalamic and red nuclei 2. Ventral anterior, reticular, and ventrolateral thalamic nuclei 3. Occasionally irrigate VPL and Pulvinar Posterolateral (thalamogeniculate) arteries supply: 1. Crus, brachium 01superior colliculus, MGB 2. Terminal branches supply: VPL, VPM, part 01centromedian nuclei, ventral lateral, posterior lateral nuclei, some cases paralascicular and medial dorsal nuclei Medial (diencephalic) group 01interpeduncular (thalamoperlorators) 1. Irrigate ventral to thalamus: subthalamic, red nuclei 2. Thalamic: medial dorsal, centromedian, paralascic, VPM, VPL, anterior ventral, ventral lateral, lateral dorsal, lateral posterior 3. These perlorators can perluse part 01the mamillary body, posterior hypothalamic area, third nerve, crus 4. Occasional diencephalic perforators 01thalamoperlorator give off mesencephalic perlorators Dorsal: Irom medial and lateral posterior choroidal arteries 1. Supply geniculate bodies and pulvinar 2. Medial dorsal nuclei, lateral dorsal posterior nuclei, anterior and midline nuclei 01thalamus 3. Medial posterior choroidal: branches to habenula, pineal, midbrain

Arterial Supply of the Hypothalamus The specific blood supply of the hypothalamus and pituitary gland has been studied in detail (Haymaker 1976). The hypothalamic vasculature is dense and has many anastomoses and the richest blood supply of any brain area. The hypothalamus is supplied by arteries derived from the proximal branches of the circle of Willis. The hypothalamic blood supply can be divided into rostral, middle, and caudal divisions. The rostral hypothalamic vessels derive from the ACA, ACoA, and ICA, and form a dense network. The ACA gives rise to the preoptic, commissural, suprachiasmatic and supraoptic arteries (Duvernoy et al. 1969, Haymaker 1976, Marinkovic et al. 1989, 1990). The ACoA may give off branches to the median preoptic and anterior median commissural areas. The supraoptic, paraventricular, and superior hypophyseal arteries may stem from the ICA. The middle hypothalamic arterial division comes from the ICA or PCoA. These give off tuberoinfundibular branches. The ICA also gives off the superior hypophyseal artery (Haymaker 1976). The PCoA and PCA provide branches to the caudal hypothalamic area. Both supply the mamillary region, with the PCA also providing thalamic peforators (Table l.12d).

Table 1.12 d The arterial blood supply of the hypothalamus and the pituitary gland Hypothalamic vasculature (all Irom circle 01Willis) 1. Rostral a. ACA (1) Medial and lateral preoptic artery (2) Right and left commissural artery (3) Suprachiasmatic (4) Supraoptic artery (5) Supply medial and lateral preoptic nuclei, suprachiasmatic nuclei, organum vasculosum, lamina terminalis, supraoptic nuclei b. AChoA (1) Median preoptic (2) Anterior median commissural artery (a) Vascular network in organum vasculosum (b)and lamina terminalis (3) Supply part 01preoptic area, median part 01anterior commissure, portion 01lornix column, septal region c.ICA (1) Supraoptic artery to supraoptic nuclei (2) Paraventricular artery, tuberoinlundibular branches-paraventricular nuclei (3) Superior hypophyseal artery, posterior median commissural artery (a) Runs ventorostral to optic chiasm (b)Anastomoses with other commissural arteries 2. Middle hypothalamic arteries (Irom ICA, PCoA) a. ICA gives tuberoinlundibular artery, superior hypophyseal artery (1) Supply intermediate portion 01 hypothalamus b. PCoA gives off several tuberoinlundibular vessels (1) Supply lateral hypothalamus, later tubo nuclei (2) Arcuate nuclei, ventromedial dorsomedial nuclei (3) Posterior part 01hypothalamic area 3. Caudal hypothalamic arteries (PCoA, PCA) a. PCoA (1) Mamillary branches (2) Premamillary artery (3) Supplies mamillary body and caudal lateral and posterior hypothalamus b. PCA (1) Mamillary branches (2) Thalamic perlorators (3) Interpeduncular perlorators 4. Hypothalamus gets supply lrom many vessels and with rich anastomoses, is well protected Pituitary gland vasculature 1. Inlerior hypophyseal artery a. From C 3-intracavernous portion b. At sella, divides into ascending and descending C. Anastomose around posterior lobe d. Supply posterior lobe 01neurohypophysis e. Connect to superior hypophyseal artery by right and lel! middle artery 2. Superior hypophyseal artery lrom C 4 opthalmic segment a. Collateral branches (1) Optic nerve (2) Chiasmatic branches: ventral, rostral, dorsal chiasm (3) Tuberoinlundibular vessels

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors

ArterialSupplyof the Midbrain

lar, medial posterior choroidal, PCA, SCA, PCoA, and AChoA (Duvernoy 1978, Rhoton et al. 1979 Zeal and Rhoton 1979). These branches supply the crus, substantia nigra, and mediallemmscus. The SCA, medial posterior choroidal, collicular, and accessory collicular comprise the lateral arteries. After entering the midbrain at the lateral mesencephalic su1cus, these vessels supply the lateral tegmentum. The laterallemniscus, the central tegmental tract, and the reticular formation are served by these vessels. The posterior arteries are formed by branches of the SCA and collicular artery, and form a plexus overlying the collicular plate (Duvernoy 1978). They enter the dorsal midbrain via the tectum and supply the superior and inferior colliculi as well as the periaqueductal grey.

(Fig. 1.92 a).

The circumference of the midbrain is penetrated by mesencephalicperforators. They can be separated into anteromedial (paramedian),anterolateral (short circumflex), lateral, and posteriorbranches(Duvernoy 1978) (Table 1.13a). Theanteromedial arteries divide into lateral and median subgroups.The medial branches supply the red nudeus and the periaqueductal gray, trochlear, and oculomotor nudei (Duvernoy 1978).The mediallemniscus, substantia nigra, and decussation of ¡hesuperiorcerebellar pedunde are perfused by the lateral group. Theanterolateral arteries to the midbrain are called peduncular branches.They arise from many vessels, induding the collicu-

654

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Fig.1.92 The vaseularizationof the brainstem (G. Tondury et al. In: Leonhardt,et al, eds. Rauber/Kopsch: Anatomie des Menschen, Stuttgart:Thieme, 1987,vol.3, pp. 213-15, Figs. 8.35-8.37) a Thearterialbloodsupply of the meseneephalon 1

2 3 4 5 6 7 8 9 10 11 12 13 14

Aqueduet Centralgray matter Superioreollieulus Perlianueleus Dorsaltrigeminallemniseus Centralsegmental faseicle Laterallemniseus Medialgenieulate body Spinothalamietraet Substantia nigra temporopontine fibers Trigeminallemniseus mediallemniseus Cortieospinalfibers

105

15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

Nucleus ruber Frontopontinefibers Mediallongitudinal fascicle Nucleus of Westphal-Edinger Nucleus of the oculomotor nerve Basilar artery Interpeduncular perforating arteries Superior cerebellar artery Posterior cerebellar artery (P2 segment) Short circumferentialarteries Thalamogeniculate arteries Quadrigeminal arteries Posteromedial choroidal artery Geniculate body Posterolateral choroidal artery Pulvinar Quadrigeminal plate

32 Pineal body

--

106

1 Anatomy

Arterial Supply of the Pons

Arterial Supply of the Medulla

(Fig. 1.92 b).

(Fig. 1.92 e, d).

The pontine blood supply is separated into three groups: anteromedial (paramedian), lateral, and dorsal (Table 1.13b). The anteromedial arteries are derived fram the terminal vertebral artery and basilar artery, and can be further subdivided into middle, rastral and caudal vessels. These arteries supply the paramedian tegmentum, including the fascicles of the pyramidal tract, mediallemniscus, mediallongitudinal fasciculus, reticular formation, and the raphe, para median pontine, and abducens nuclei. The lateral perforators aris~ from SCA, AICA, and long pontine arteries (Duvernoy 1978). They supply the lateral pons including the superior cerebellar peduncle, central tegmental tract, lateral lemniscus, locus coeruleus, motor and principal sensory nuclei of V, abducens nucleus, facial nucleus, superior olivary nucleus, oral pontine reticular nucleus, laterallemniscus, and pyramidal tract. Terminal branches of the SCA constitute the posterior arterial supply to the pons (Duvernoy 1978). They perfuse the superior cerebellar peduncle, the mesencephalic nucleus of the trigeminal nerve, and the locus coeruleus.

Like other are as of the brain stem, the medulla receives circulation from anteromedial (paramedian), anterolateral, lateral, and dorsal arteries (Duvernoy 1978) (Table 1.13c). The vertebral and anterior spinal arteries give rise to the paramedian medullary branches, which supply the pyramidal tract, mediallemniscus, central reticular formation, medial accessory olivary nucleus, reticular formation, and inferior olivary nucleus. The antera lateral arteries perfuse the pyramidal tract and inferior olivary nucleus. The lateral arteries arise fram branches of the PICA, AICA, vertebral, and basilar arteries (Duvernoy 1978) and supply the lateral dorsal medulla, including the inferior cerebellar peduncle, inferior olivary nucleus, spinothalamic and spinocerebellar tracts, spinal trigeminal nucleus, central reticular formation, dorsal motor nucleus of the vagus, nucleus and tractus solitarius, and the hypoglossal, vestibular, cochlear, cuneate, and ambiguous nuclei. The PICA gives rise to the posterior arteries supplying the dorsal medulla (Marinkovic and Milisavljevic 1990). The gracile and cuneate nuclei, area postrema, and vagal, solitary, and medial vestibular nucleus are supplied by these branches.

5 4 3 2 1

28 27 26

,1 6 25

7

8 9 10 11 12

13 14 15 16 17 18 19 20 21 22 Fig. 1 2 3 4 5 6 7 8 9 10 11 12 13 14

1.92 b The arterial blood supply of the pon s Teetospinal traet Mediallongitudinal faseiele Retieular formation Central segmental faseiele Loeus eoeruleus Superior eerebellar faseiele Ventral spinoeerebellar traet Rubrospinal traet Middle eerebellar pedunele Trigeminal nueleus Motor trigeminal nueleus Spinal traet of the trigeminal nerve Laterallemniseus Spinothalamie traet

15 16 17 18 19 20 21 22 23 24 25 26 27 28

23 Trigeminal lemniseus Medial lemniseus Cortieospinal fibers Pontine nueleus Pontine raphe Basilar artery Median pontine branehes Short pontine branehes Anteroinferior eerebellar artery Long pontine branehes Superior eerebellar artery Branehes to the fourth ventriele Fourth ventriele Anterior medullary velum

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors

2a

1a

13 37

36

107

30

31 3 4 8 5 6 7 32 12 11 14

17 33 18 19 20 21

22 23 24

25 e

30 29

1a 2 2a 3 4 5 6 7 8 9 10 11 12 13 14 15 16

28

27 26

17 18 19 20 21

22

23 24

25 d

Fig. 1.92c, d The arterial blood supply of the e Rostral,d caudal 13 1 Funieulusgraeilis 14 1a Nueleusgraeilis 2 Funieuluseuneatus 15 2a Nueleuseuneatus 16 17 3 Spinaltraet 01the trigeminal nerve 18 4 Spinal nueleus of the trigeminal nerve 19 5 Solitarynueleus 6 Dorsalnueleus of the vagal nerve 20 7 Nueleusambiguus 21 8 Dorsalspinoeerebellar traet 22 23 9 Rubrospinaltraet 24 10 Trigeminallemniseus 11 Spinothalamietraet 25 12 Ventralspinoeerebellar traet 26

medulla

oblongata.

Mediallongitudinal faseiele Caudal olivary nueleus Medial aeeessory olivary nueleus Olivospinal traet Nueleus of the hypoglossal nerve Mediallemniseus Cortieopontine traet Median medullary branehes Ventromedian fissural artery (from the basilar artery) Anterior spinal artery Inferior pyramidal arteries Anterolateral suleal artery Vertebral artery Olivary artery

27 Posterolateral suleal artery 28 Posteroinferior eerebellar artery 29 Posterior arteries of the medulla oblongata 30 Posterior spinal artery 31 Inferior vestibular nueleus 32 Olivoeerebellar traet 33 Retieular formation 34 Superior olivary artery 35 Posterior olivary artery 36 Ventrieular branehes 37 Teetospinal traet

--

108 Table 1.13a

1 Anatomy The arterial blood supply of the midbrain

Mesencephalic perforators 1. Anteromedial (paramedian) a. Median subgroup (1) Median mesencephalic branches 01thalamoperlorating arteries (2) Enter PPS, go through tegmentum, close to raphe (a)short-medial red nuclei supply (b)Long-toward periaqueductal gray supply: i) Trochlear nuclei ii) III nuclei iii) Ventral part 01periaqueductal gray b. Lateral subgroup-small mesencephalic perlorators (1)Enter midbrain at entry zone 01 III (2) Supply: medial substantia nigra, lateral red nuclei part 01 mediallemniscus, and decussation 01the superior cerebellar peduncle in caudal midbrain 2. Anterolateral (short circumflex) peduncular branches originating Irom collicular, acessory collicular, and medial posterior choroidal arteries, and PCA, SCA, PCoA, AChA a. Supply and penetrate crus, substantia nigra, and mediallemniscus 3. Lateral branches-small numerous perforating vessels Irom: a. Collicular b. Accessory collicular c. Medial posterior choroidal d. Superior cerebellar e. Enter midbrain at level 01mesencephalic sulcus and lemniscal trigone l. Supply lateral tegmentum, laterallemniscus, central tegmental tract, and adjacent reticular lormation 4. Posterior branches-small perlorators lrom plexus over colliculi a. From colliculi, and superior cerebellar artery b. Enter tectum, supply: superior and inlerior colliculi, dorsal periaqeductal gray Major structures supplied 1. Red nucleus a. Mesencephalic paramedian perlorators lrom P1 b. Diencephalic paramedian perforators 2. Substantia nigra a. Rostral (1)peduncular branches 01AChA (2) Premamillary 01PCoA b. Caudal (1) Peduncular branches 01PCA (2) Collicular, medial postchoroidal (3) Superior cerebellar arteries

Table 1.13 e

Table 1.13 b

Arterial blood supply of the pons

Anteromedial (paramedian) 1. Middle: short and long pontine arteries a. Short, to the medial lascicles 01the pyramidal tract b. Long, to the medial part 01the mediallemniscus, MLF, paramedian pontine nuclei 2. Rostral, irrigate a. Paramedian tegmentum b. MLF c. Reticular lormation 3. Caudal: irrigate paramedian tegmentum a. MLF b. Caudal reticular lormation c. Abducens nuclei

Anterolateral arteries lrom paramedian arteries supply 1. Ventral lateral pyramidal tract 2. Pontine nuclei 3. Mediallemniscus

Lateral (many perlorators lrom long pontine artery) 1. SCA perlorators: supply rostrolateral pon s a. Peduncle b. Central tegmental tract c. Oral pontine reticular nuclei d. Laterallemniscus e. Part 01locus coeruleus 2. AICA perlorators irrigate the caudalateral pons, supply a. VII Nucleus b. Superior olivary nucleus c. Laterallemniscus d. Middle cerebellar peduncle e. Portion 01VI nucleus l. Principal sensory nucleus 01V g. Central tegmental tract 3. Lateral pons also supplied by long pontine arteries a. Supply lateral lascicle 01pyramidal tract b. Pontine nuclei c. Laterallemniscus d. Central tegmental tract (motor and principal trigeminal nuclei)

Posterior (dorsal) branches 01the terminal stem 01the SCA 1. Superior cerebellar peduncle 2. Mesencephalic trigeminal nucleus 3. Locus coeruleus

Arterial blood supply of the medulla oblongata

Anteromedial (paramedian) 1. From vertebral or anterior spinal artery 2. Enter medulla at anteromedian sulcus a. Short-supply (1)Mediallemniscus and pyramidal tract (2) Central reticular lormation and medial accessory olivary nuclei, medial inlerior olivary nuclei b. Long-between raphe and mediallemniscus to Iloor 01lourth ventricle (1)Mediallemniscus, dorsal accessory olivary nuclei (2) Central reticular lormation, XII nuclei Anterolateral-supply

pyramidal tract and inlerior olivary nuclei

Lateral lrom vertebral, AICA, PICA, BA 1. Penetrate olive and lateral medullary lossa, ICP a. Supply lateral and lateral dorsal inlerior olivary nuclei b. Spinothalamic and spinocerebellar tracts c. Spinal trigeminal nuclei central reticular lormation d. Dorsal nuclei 01X e. Solitary nuclei and lasciculus l. Part 01XII nuclei vestibular and cochlear nuclei g. Cuneate nuclei, ambiguus, ICP in caudal medulla Posterior-lrom PICA and posterior spinal artery 1. Supply gracile and cuneate 2. Area postrema 3. Caudal parts 01vagal nucleus and solitary nucleus 4. Occasionally medial vestibular nucleus

Topographic Anatomy for Microsurgical Approaches to Intrinsic Brain Tumors

Veins

109

Table1.14 Venous drainage o, the brain

Comprehensivedescriptions of the dural sinuses and superficial anddeepvenoussystems of the brain can be found in Vol 1 and 11 and in the publications of Huang 1964, 1965, 1974, Duvernoy andMatsushimaet al. 1983.For present purposes, we 1975,1978, wJl limit our considerations to the parenchymal white-matter venoussystem,as this relates directly to the location of intrinsic braintumors.

The DeepWhite-Matter Veins of the Brain

1. Corticalareas ~ corticalveins~ superficialmedullary veins~ leptomeningeal veins ~

'

2 . Whlema t tter

Subcorticalareas (1-2 mmdeep) ~ superficialpialveins ....---Deep white matter and central nuclel Ventricular wall Choroid plexus

}

Deep medullary veins~lnternal

}

. Subdependymal velns

I

cerebral

vein . Basilar veln Veinof Galen

3. Transcerebral vein (Kaplan) Transanastomotic vein (Schlesinger 1939, Hassler 1966)

Thewhite-mattervenous drainage can be divided into three main typesof small veins: The short superficial medullary veins, the longerdeepmedullaryveins, and the larger transcereberal anastomoticveins.The superficialmedullaryveins begin 1-2 cm below thecortex and run a straight course through the cortex to the pia, to join the superficial cortical draining veins (Tables 1.14, 1.15) (seealsoVol.III A, 7.1, 7.2, pp. 327-8). Table1.15 Synopsis o, the cerebral veins (from Krayenbühl and Ya9argil 1972; see also Vol. 111 A of the present work Tables 7.1, 7.2, pp. 327, 328)

" Internalcerebral vein

I External(cortical) cerebral veins (drainage) (1)Ascending(superior) cerebral and cerebellar veins

Septalvein

Frontal veins

Precentralveins Parietalveins Occipitalveins Superiorcerebral veins Fluccular

veins

Petrasalsinus

}

Superior longitudinal sinus

{ }

Great cerebral vein Straight sinus Inferior petrosal sinus

Temporo-occipital veins (veinof Labbé) Inferiorcerebellarveins

} { }

)

Insular vein Hippocampal Olfactorial vein Anterior cerebral vein Peduncular vein

'"temal oembat

,el"

Basilar vein

j

:> Great cerebral vein

Ponlinevein

(2)Descendingcerebral and cerebellar veins Superficialmiddle cerebralveins (Sylvian)

Thalamostriate vein Caudate vein Choroidal vein

Internaloccipitalveins Cavernous sinus Sphenoparietal sinus Transverse

sinus

Transverse

sinus

Sigmoid

sinus

Dorsal callosal vein

Superiorcerebellarvein Precentralcerebellarvein Medialfrontoparietalveins Callosal

dorsal veins

j ]

}

Straight sinus Inferior longitudinal

sinus

i

(3)Inferiorcerebralveins Medialand lateral frontobasal veins

Superior longitudinal sinus

Temporobasalveins

Superficial petrosal sinus

Occipitobasalveins

Transverse sinus Great cerebral vein

{

The deep medullary veins similarly begin 1-2 cm below the cortex,but run a long, deep course along the white-matter fiber tracts toreachthe ventricular surface

and join the deep venous sys-

tem (through the subependymal veins). These veins are of very smallcaliber(although larger than the superficial medullary), and unlikesystemic veins, they do not in crease in caliber as tributaries join (at rightangles) along their course (Fig. 1.93). These vessels are not randomly positioned, but are grouped in fan-shaped bundles that converge on the ventricular surface (Fig. 1.94). Theseare the vesselsthat can be identified angiographically as a groupof cIoselypacked, dilated veins adjacent to glioblastomas.

It is noteworthy that in this instance these vessels do not deviate (as a result of tumor mass effect) but have a spray-like appearance, and can be traced to dilated, tortuous subependymal veins. Similar changes in these veins are no! seen in less malignant tumors, metastatic lesions, or meningiomas. With such lesions, the deep medullary veins surrounding the tumor are instead displaced and dilated in an arcuate fashion around the periphery of the tumor. This certainly suggests that highly malignant gliomas produce dilatation without compression, perhaps on the basis of a vascular reactive substance.

110

1 Anatomy

a

Fig. 1.93 The white-matter venous system of the brain. The venous circulation in the white matter,and the connections between the superficial cortical and ventricular veins through the intracerebral and extracerebral anastomotic veins (from Ya$argil, Microneurosurgery, Vol. 111 B, Stuttgart: Thieme, 1988, p. 209, Fig. 4.90) 1 Pialartery 2 Pialvein 3 Basal artery 4 Basal vein 5 Cortical artery 6 Cortical vein 7 Cortical and long subcortical vein 8 Subventricularartery 9 Subventricularvein 10 Intracerebralanatomic vein 11 Extracerebralanatomic vein 12 Great vein of Galen 13 Intravenousanastomosis 14 Junction of the cortex and the white matter

b

Fig. 1.94 Angioarchitecture of the deep cerebral venous system(from Hassler, Neurology 1966;16:507, Figs. 2a, b) a A coronal section through the anterior part of the caudate nucleus. The arrow indicates an anastomotic vein T Terminal vein b A similar venogram from a coronal section at the level of the thalamus, which is drained by direct branches from the internal cerebral vein B Basal vein I Internal cerebral vein T Terminal vein

Topographic Anatomy tor Microsurgical Approaches to Intrinsic Brain Tumors The transcerebral anastomotic veins connect the superficial (cortical)and the deep (ventricular) venous systems. These veins are larger than the medullary veins, but fewer in number (Fig.1.95).Both the deep medullary veins and the anastomotic veinsfollowthe path of developmental migration of the cortical neurons andsupportingastroglialcells (from the ventricular SUffact to the cortex), perhaps deriving their position from this embryologicaldevelopment. It is interesting to note that glial tumors.whichcornrnonlyoriginate in the subcortical region, eventuallyexpandin the direction of the deep white matter veins,

2

111

toward the ventricular surface. Hassler has noted that internal medullary veins from a particular regio n of white matter empty into subependymal veins in a defined anatomical pattern (Fig. 1.96). As a result, one can devise a white-matter topographical schema related to these subependymal venous drainage patterns (Fig. 1.97). It is interesting to note the similarity between the morphology of these white-matter venous drainage zones and the morphology of peritumoral edema on neuroimaging changes that frequently occur with tumors and other diseases of the white-matter. Perhaps the pathogenesis of these changes will be found to

3

4

2 5

6

10

9

8

7

Flg 1.95 The anastomotic veins between the internal and external cerebralvenous systems (coronal view) (from Leonhardt, Tbndury and Zllles,Rauber/ Kopsch: Anatomie des Menschen, Stuttgart: Thieme, 1987 vol.3, p. 222,Fig.8.43) 1 Superiormarginalsinus 2 Externalcerebral vein 3 Medullary anastomotic vein 4 Central semioval vein 5 Medullary vein 6 Superficial middle cerebral vein 7.

8

9 10 11 12 13 14 15

Centralnucleusvein Perforatingvein Deep middle cerebral vein Thalamostriate vein Internal cerebral vein Choroidal vein Central nuclei veins

Fig. 1.96 The drainage area of the deep central venous system (coronal sections). The brain siices were were at 2, 4, 6, 8, 11.5, and 13 cm posterior to the frontal pole. The choroid vein drained a small portion of the white matter adjacent to the choroid plexus, but it was too narrow to be indicated on the diagrams. Note the similarity between the whiter-matter patterns of venous drainage and the shape and location of peritumoral white-matter changes (from Hassler, Neurology 1966;16:507, Fig. 2a, b) B Basal vein I Internal cerebral vein P Vein of the posterior horn S Septal vein T Terminal vein

112

1 Anatomy

relate to abnormalities of these venous networks (Chapter 3, Cases 3.52-3.59 on pp. 243-5). The prolific and exquisite nature of the cerebral venous system was recognized by William Harvey centuries ago, but only now are we beginning to appreciate its real significance (Fig. 1.98a-b).

Fig. 1.97 The centripetal drainage 01 the white matter (horizontal view). Four-lifths 01 the white matter and the central nuclei drain via deep medullary veins to the internal cerebral vein, basilar vein, and vein 01 Galen

Topographic Anatomy for Microsurgical Approaches to IntrinsicBrain Tumors

113

Fig.1.98a The architecture of the anastomoticwhite-mattervenous system. A latexinjectedspecimen (lateral view) (preparation by Mr.A. Lang, Dept. of Anatomy, University of Zurich) b Closedview. Note the fine structure, size, andcourse of the anastomotic white-matter veln2joining the superficial and deep venous systems

b

114

1 Anatomy

Conclusions The combination of improved surgical anatomical knowledge with modern neuroimaging would seem to have solved many, if not all, of the localization problems that traditionally have been uppermost in neurosurgeons' minds when dealing with CNS tumors. This is certainly true to a degree for many extrinsic lesions. In addition, the general localization of intrinsic lesions does not normally pose any difficulty. For this we are most gratefuI to the impressive neuroradiological achievements of the last decade. . At the same time, however, our traditional neuroanatomical views of the cerebrum must be redefined so that we can better understand the three-dimensional teality of micro-surgical anatomy and pathology and make full use of the information displayed on MR and PET images.The direct triplanar capabilities and high resolution quality of modern MR imaging has truly made possible an in vivo evaluation of neuroanatomy with a precision scarcely thought possible eight years ago. Attention to the additional neuroanatomical information that MR imaging can routinely provide is of paramount importance in the optimum microsurgical remo val of tumors. The problem so far has be en how to make useful sense of all the available in vivo anatomical data. At present, much of this available topographical information is, at best, simply not seen, and is at worst grossly misinterpreted, leading to erroneous surgical approaches for many intrinsic tumors. The traditional lobar concept of the cerebrum continues to dominate the diagnostic reporting of neuroradiologists and neuropathologists, when describing gross specimens, as well as neurosurgical planning. Yet triplanar MR images display the anatomy of the hemispheres in more detail. Not only are the grossly discernible features of the brain, such as lobes, gyri, fissures, sulci, and cisterns easily identified, but it is also now possible to identify their substructures, such as the architectural substructure within the white matter, the main pathways of the associative, commissural, and projection systems (Schnitzlein and Murtagh, 1990) of cortical are as, the individual central nudei, and the distinctly different ventricular spaces (and associated choroidal plexuses). In addition, the pathomorphological effects of pathophysiological changes can be recognized in similar detail on MR images. These effects are attributed to anisotropically restricted diffusion with the white matter. The technique may have application in a wide range of neurological diseases and result in better localization of lesions and improved detection of disease (Doran et al. 1990). As a result, our traditionallobar descriptive terms (with reference to frontal, temporal, parietal, occipital), though carrect, are no longer adequate. The resolution capabilities of modern neuroimaging have facilitated the diagnosis and location of lesions within the CNS to the extent that an updated scheme is necessary to undestand the topographic anatomy and its relationship with the underlying white matter. Such a scheme must correspond directly with the anatomical detail that neuroimaging currently displays. In addition, this scheme must overcome the difficulties associated with the tremendous variability in the gyral and sulcal surface anatomy of the cerebrum. A precise correlation between the gyral antomy and the white-matter substructures requires a detailed knowledge of the surface gyral topography. Widely employed functional maps

(Brodmann) in ~urrent use are excellent for electrophysiological studies. For neurosurgical purposes, however, the topographical gyral pattern presented by von Economo and Koskinas almost 70 years ago is recommended (Fig. 1.65a-c, pp. 70-71). We must reassert our knowledge of the gyri and sulci in precise anatomical terms, as we correlate them with ever-improving neuroimaging studies. The anatomical scheme presented in this Chapter is based on the sectoral and peduncular white-matter architecture of the cerebrum and cerebellum. This methodological approach has enhanced our understanding of the surgical anatomy of the white and gray matter, and is the foundation of our approach to intrinsic CNS tumors. It permits exact localization of these tumors based on MR images. It allows more exact determination of operability, and subsequently more precise microsurgical removal. As a result, this anatomical strategy has significantly improved our ability to care for brain tumor patients. This anatomical design may in the future lead to a better understanding of the pathophysiology of CNS tumors. It is interesting to note that each distinct part of the brain (neocerebral, archi- and paleocerebral, central nudei, and ventricular) is not only anatomically and physiologically distinct, but also each has special pathophysiological characteristics. These characteristics probably determine to a large degree the frequency of tumor occurrence in specific locations, the biological activity of tumor growth, especially in its early and intermediate phases (perhaps related to vascular supply or embryological astroglial migration, or both), and location of peritumoral edema. The answers to these questions await future neurophysiological and neuropathological studies based on a solid neuroanatomical foundation.

2

RichardPau!Lohse Thirtyverticalsystematic colourseries""ithred diagonals,1943/1970. x 165cm,Oil on canvas. @RichardPaulLohse Foundation,Zürich

Neuropathology

I

116

2 Neuropathology

Introduction

Historical Perspective Attempts to classify cerebral tumors centered on gross pathological characteristics until Virchow (1847), the founder of cell pathology, identified the glial constituents of nervous tissue and coined the term Nervenkitt or neuroglia.Previously, the concept of epigenesis as a central theory of embryology had been established by von Baer (1828 to 1837), and the cell theory had been introduced by Schwann (1837). Improvements in the microscope at that time enabled Remak (1854), von Koelliker (1859), and Virchow (1858) to confirm that nerve cells and neuroglial cells are the basic units of organization in the nervous system. Subsequently, Virchow gave the name "glioma" (1864) to tumors arising from intrinsic brain tissue, and he developed a histological tumor classification system that was accepted for decades. Better staining techniques and improved microscope resolution around the turo of the century provided the means for revolutionary discoveries in histology. Golgi (1894), von Koelliker (1896), Ramón y Cajal (1908), and Rio-Hortega (1933), were at the forefront in developing an understanding of the cellular components of the nervous system. With this new knowledge, several classification systems aros e, notable among them being those of Tooth (1912) and Ribbert (1918). In 1926, Bailey and Cushing published their landmark monograph A Classification ofTumors ofthe Glioma Group. Their categorization consisted of 14 main groups, and correlated clinical features, histology, and outcome. Based on the identification of 20 cell types, it reflected similarities between the cellular morphology of the tumors studied and the cellular appearance of developing (primitive) cells seen in normal embryogenesis. However, the notion that tumors arise from aberrations in the normal development of the various components of the central nervous system remained controversial. Roussy and Oberling (1932) arrived at a similar classification scheme in their atlas, but were careful to point out that cell resemblances should not be regarded as proof of origin in the etiology of tumors. Other notable contributors to neuropathology during this period were Ostertag (1932), and, again, Rio-Hortega (1934), who focused on cell morphology, and gave comprehensive combination names to tumors. The complexity of Rio-Hortega's classification and its lack of clinical correlation made his scheme impractical. Scherer (1940) advocated complete examinations of brain tumors in serial section after fixation. Willis (1960) summarized contemporary knowledge in an excellent review. The realization that the degree of anaplasia seemed to correlate with malignant behavior was emphasized by Kernohan et al. (1949). Following Broders (1926), who conceived a grading system for epithelial tumors, a classification scheme subsequently proposed by Keroohan and Sayre (1952) did away with all but five groups in the categorization of gliomas (an unwarranted reduction), but, more usefully, also suggested a grading system (with grades 1-4, in ascending order of malignany). The simplicity of this scheme and the universal practicality of the grading system assured its ready adoption. However, with widespread usage, drawbacks have become evident. As with any grading system, the classification is limited by sampling errors to such an extent that

there is little assurance that a single sample is agrade 2 (and not a grade 3). This scheme, with usage, has demonstrated better prognostic correlation in purely astrocytic tumors than in oligodendrocytic lesions. The elimination of other major groups that account for rare (but real) glioma types (mainly of an embryonal character) appears, in retrospect, to have been a mistake. The classification debate has continued over the last forty years, with significant differences aired by Ringuertz (1950), Henschen (1955), Zülch (1949, 1951, 1956, 1971, 1980, 1986), Rubinstein (1970, 1972, 1982, 1985), Russell and Rubinstein (1977. 1989), Burger and Vogel (1982), Voth et al. (1982), Jellinger (1978. 1987), Burger, Scheithauer and Vogel (1991) and conceroing the intratumoral heterogeneity of gliomas (Daumas-Duport et al. (1979). Nevertheless, considerable consensus has been achieved through the efforts of a panel established under the auspices of the World Health Organization. This resulted in the monograph Histological Typing of Tumors of the Central Nervous System (Zülch 1979), which was recently updated following the WHOpanel meeting in Zurich, in Apri11990, and published by P. Kleihues, P. C. Burger, and B. W. Scheithauer, 1993.

The Scope of Modern Neuropathology The pioneering contributions of the German, French, and Spanish histopathologists of the nineteenth century were essential in defining the morphological aspects (both macroscopic and microscopic)of neuropathology. The twentieth century has seen phenomenal growth in the expertise provided by other scientific disciplines, particularly the basic sciences. A greater fundamental understanding of the nature of CNS tumors requires multidisciplinary cooperation on a large scale. Funding for these projectsis enormous. Important clues as to the most beneficial allocation of research efforts continue to come from studies of epidemiology (incidence and prevalence studies, genetic and familial studies, endogenous and exogenous environmental studies, etc.) and biology (molecular neurobiology, neurohistochemistry, tumorcell kinetics, immunocytochemistry, tumor immunology,etc.) (Table 2.1).

Introduction

Table 2.1

The range of neurapathological

features

encountered

in CNS tumors

Epidemiology

Age, Sex Hereditary factors (germ cell mutations) Familial incidence (tumour clustering within lamilies) Genetic lactars (somatic mutations) Prenatal environmental factars, postnatal factars Trauma Radiation Progressive multifocalleukoencephalopathy Multiple sclerosis

Morphology

Location (supratentorial, infratentarial, spinal, or combinations)

Macroscopicmorphology

Supratentorial and inlratentarial

Spinal

Number Size

Microscopicmorphology

Shape Extension Tissue pattern Tissue consistency Translarmation (instant or gradual)

Changed cell marphology Changed ultrastructure Mitosis Proliferation Tumor cell culture

Biology Etiologyand pathogenesis (notknown)

Initiallocus (unicentric, multicentric,or global

Molecular biology signals the imp.artance 01mutations in proto-oncogenes that may result in oncogenes with subsequent neoplastic change. Loss 01narmal tumar supressar gene lunction may be equally importan!. Extrinsic

Intrinsic

Number

Unicentric Multicentric Global

Growthdynamics

Growth pattern Growth kinetics

117

Single multicentric, or global Small5 cm Circumscribed ar diffuse Expansive ar inliltrative Homogeneous, heterogeneous, or mixed Soft, hard, or mixed From normal cell to tumor cell (WHO Grade 1) From normal cell to anaplastic cell (WHO Grade IV), rapid changes From tumor cell Grade 1to 11,to 111, ar to IV

Parenchymal Vascular Cell kinetics Proliferation Dormant pool

Sone, cartilage, connective tissue, sinus mucosa, vascular tissue, Iymphatic tissue, paraganglial tissue, dural, ar arachnoid Cortical, subcartical, central nuclei, subependymal plate, ependyma, choroid plexus, ar intraventricular Unilateral, ar bilateral (midline lesions) Unilateral, bilateral, cerebrocerebellar, ar cerebrospinal Gliomatosis, meningiomatosis, neurofibromatosis, or Iymphomatosis Diffuse (local, hemispheric, ar global) Demarcated (circumscribed) Preoperative Inactive (dormant) Active Progressive (slow or last rate of growth) Alternating (active-inactive) Regressive

Extrinsic (epidural, intradural ar subdural; epiarachnoidal ar subarachnoidal) Intrinsic (neocerebral, transitional, central nuclei, or intraventricular regions) Mixed: extrinsic ar intrinsic Extrinsic (epidural, intradural ar subdural; epiarachnoidal ar subarachnoidal) Intrinsic (juxtamedullary, intramedullary, or central canal)

118 Table 2.1

2 Neuropathology The range of neurapathological features encountered in CNS tumors (Continuation)

Growth tactics

Spread (migration)

Postoperative Regrowth (recurrent) or growth of residual tumor Local Perifocal Global Expansive Displacement or destruction Infiltrative Insinuation between fiber tracts wTiiiout destruction or transgression of fiber tracts and penetration with destruction Extrinsic Intrinsic

1

"1

Interactions between tumor and surrounding tissue

Interface between tumor and normal tissue Types of membrane or pseudomembrane formation

Cleavage No cleavage (different degrees of adherence) Dural

Arachnoidal

Arachnoidal-pial Glial Ependymal

Alteration

of tumor tissue

Alteration

of vasculature

(vasogenic

factors)

Alterations of normal tissue

Metabolic changes (increased glucose utilization, etc.) Necrosis Cyst formation Lipomatosis Embryonal tissue differentiation Changed arterioles, capillaries and veins (hypervascularization or hypovascu larization) Thrombosis of arterioles Thrombosis of intratumoral veins (typical of glioblastomas) Changes in flow rate (slow flow, or high flow) Changes in direction of flow Angioneogenesis Erosion, destruction, or hyperostosis of bone Changes in dura and arachnoidea Compression, stenosis or occlusion of veins, dural sinuses, or arteries Alterations in CSF dynamics Compression of neural parenchyma

Calcification, ossification

thickening or thinning

obstructive hydrocephalus Edema, displacement, or herniation

Epidural, intradural, or subarachnoid (cisternal) Along parenchymal vascular system Along CSF pathways (intraventricular or subarachnoid) Along: 1) White matter association fibers (short distance fibers e. g., uncinate tract, or long-distance- fi bers-unknown) 2) Projection systems (cerebralunknown, or brainstem-bulbopontomesencephalic system) 3) Commissural systems (callosal system or anterior and posterior commisure-unknown)

Pituitary adenoma, epi-, intradural meningioma, chordoma, chondroma, paraganglioma, dermoid and epidermoid Craniopharyngioma, pinealoma, teratoma, germinoma, neurinoma, dermoid, epidermoid and arachnoid cyst Meningioma, craniopharyngioma, and optic glioma Cavernoma, hemangioblastoma, and glioma Ependymoma, subependymoma, neurocytoma, and choroid plexus papilloma

Introduction

119

Table2.1 The range 01 neurapathological leatures encountered in CNS tumors (Continuation) Biochemicaland pharmacologicaleffects (endocrine or exocrinesecretion, exudation) Changesin immunological activity(humoralor cellular immunity) Combination01different tumortypes (see Table 2.4 onp. 125)

Combination with other diseases

On neural parenchyma On CSF constituents

Focal Global Reabsorption impairment (increased protein)

Within the CNS Systemic Meningioma and neurinoma Meningioma and glioma Meningioma and cavernous Meningioma and choroid plexus papilloma Pituitary adenoma and glioma Optic glioma Aneurism Angioma Occlusive vessel disease Inlectious disease Degenerative disease

Intraventricular subependymal

Epidemiology and Pathogenesis

Biological Activity

Theepidemiologyand pathogenesis of brain tumors is reviewed ina reviewarticle by P. M. Black (1991), from which the following passagesare quoted by permission:

The propensity of the central nervous system to grow neoplasms is unrivaled by any other organ system. The variable expression and wide spectrum of biological behavior observed in these tumors provide constant amazement and unending challenges to those involved in the clinical and research neurosciences.

..New brain tumors develop in approximately 35000 adult Americanseach year ~alker et al. 1985, Mahaley et al. 1989). In children,astrocytomas and medulloblastomas are the most commontumors; in adults, the most common are metastatic tumors, astroglial neoplasms (including glioblastoma multiforme),meningiomas, and pituitary adenomas. There is recent evidence that the incidence of primary tumors among the elderlyis increasing (Greig et al. 1990). More adults die each year of primary brain tumors than of Hodgkin's disease or multiple sclerosis. Malignant gliomas alone account for 2.5% of deaths due to cancer and are the third leading cause of death from cancer in persons 15 to 34 yearsof age (Levin et al. 1989, Salcman, 1990). Thereis little information about the relation of environmental factorsto primary brain tumors. Tobacco, alcohol, or dietary patterns have not been associated with them. Cranial irradiationand exposure to some chemicals may lead to an increased incidenceof both astrocytomas and meningiomas (Schoenberg 1991,Nicholson et al. 1982). Head injury may possibly potentiate meningiomas,but does not appear to cause astrocytomas (Schoenberg1991). Sixteenpercent of patients with primary brain tumors have a familyhistory of cancer (Mahaley et al. 1989). Specific predisposinggenetic disorders include neurofibromatosis, with associated acoustic neuromas, meningiomas, and childhood gliomas;tuberous sclerosis with astrocytomas; von Hippel- Lindau disease with hemangioblastomas; Turcot's syndrome with glioblastomas, medulloblastomas, and colon carcinoma (Schoenberg1991); and Li-Fraumeni syndrome with multiple malignantfamilial tumors, including glioblastoma (Malkin et al. 1990)."

Growth Kinetics Every benign or malignant tumor type retains the ability to change. This may be intrinsic to the cell type of origin (genetically stable or unstable and mutational) or extrinsic (hormonal, local environmental such as growth factor, distant environmental such as radiation, chemical carcinogenic, or viral, or unknown stimuli). The unpredictability of individual tumor behavior makes any estimation of the prognosis in CNS tumors particularly difficult. Frequently, there is significant growth variation over time, with periods of tumor hyperactivity, inactivity, or even regression. The classical morphological changes used to distinguish benign from malignant tumors do not hold quite the same significance in the current appreciation of CNS neoplasms. These histological hallmarks are the presence or absence of nuclear atypia, mitoses, endothelial vessel proliferation, and necrosis. Mitoses and proliferation of vessels are seen in glioblastomas and anaplastic astrocytomas, but also in many "benign" meningiomas. The tendency of meningiomas, subtotally removed, to regrow is far from a "benign" characteristic. Hyperactive behavior without mitoses is observed in some meningiomas, as well as in some pituitary adenomas, dermoids, epidermoids, and low-grade astrocytomas, e. g., pilocytic astrocytoma. There are examples of meningiomas, pituitary adenomas, epidermoids, and craniopharyngiomas penetrating the arachnoid and dura into the epidural space, and even penetrating the pia into the brain parenchyma. Yet, histologically, there is no difference between these more locally invasive lesions and similar noninvasive tumors of identical pathological type found in the same locations. Conversely, some intrinsic tumors, including the classic infiltrative glioblastoma, on occasion remain confined to their area of

--

120

2 Neuropathology

origin for a prolonged period of time, becoming behaviorally malignant and functionally aggressive only in their final phase of exponential growth. Thus, even when the pathology is known, the unpredictability of tumor behavior still creates notorious difficulties and uncertainties in patient management. Future attempts to improve the prognostic yield through an examination of cell kinetics and genetic expression may prove promising in this regard. Cell Kinetics The reader is referred to recent work regarding the reliability of the various methods used to evaluate the proliferative rate of tumors (Schiffer 1991, Black 1991). The monoclonal antibody Ki-67 labeling index has been shown to corre late with the mitotic index of cerebral tumors. It appears useful in differential diagnosis between astrocytomas, anaplastic astrocytomas, and glioblastomas, especially in small biopsy specimens. It corre late s inversely with the duration of preoperative symptoms, but not with survival (Raghavan et al. 1990). Another reliable method of assessing the proliferation rate of a tumor is the in-vitro bromodeoxyuridine (BUDR) labeling index, which seems to correlate both with the clinical course of disease as well as with patient survival (Nishizaki et al. 1990). Other approaches to evaluating cell turnover are techniques that measure increased RNA and DNA activity. Using a silver staining method, the mean number of nucleolar organizer regions (NORs) per nucleus is estimated. NORs are the sites of genes transcribing to ribosomal RNA. An increased number and reduced size are considered signs of malignancy. The mean number of Ag-NORs per cell has been found to parallel the degree of histological malignancy in gliomas, and corre late s well with Ki-67 immunoreactivity (Plate et al. 1990, 1991, 1992) and with survival (Kajiwara et al. 1992). Finally, an analysis of DNA content by flow cytometry has also been shown to be a reliable method of assessing malignancy. A higher proliferative index correlates with poorer survival and increasing malignancy in gliomas, as do higher nuclear antigen p 105 measurements (Appley et al. 1990). Nuclear antigen p 105 increases throughout the cell cycle and distinguishes cycling from noncycling cells. Genetic Expression An intensive study of the genetics of certain individual tumors has provided important insights into possible mechanisms leading to the development of CNS neoplasms. Neuroblastoma is one of the most common malignant tumors in children, exceeded only by leukemia and lymphoma and brain neoplasms. It is derived from neural crest celllines, and undergoes spontaneous differentiation probably more frequently and to a greater extent than any other human cancer (Bolande 1985, Bove 1981). Schwab (1990) provides an exciting review of the clinical debut of oncogene research in an article on the amplification of the myc-n oncogene and deletion of the putative tumor suppressor gene in human neuroblastoma. Human neuroblastoma cells often carry nonrandom chromosomal abnormalities signalling regular alterations. Quite frequent are "double minutes" (DMS), homogeneously staining regions (HSRS) both cytogenetic manifestations of amplified DNA and chromosome 1 p deletions (indicating a loss of genetic informa-

tion). DMS have been shown to be a chromosomal manifestation of amplified DNA, and in neuroblastoma cells, this amplified DNA has always been found to encompass the cellular oncogene myc-n (Schwab 1985). The deletions seen in chromosome Ip appear to overlap at 1p36.1-2 (Weith 1989), indicating a loss of specific genetic material from the tumor cell that may well tum out to be identified as a tumor-suppressor gene. It seems likely that both the amplification of cellular oncogenes and the loss of tumor-suppressor genes play important roles in neuroblastoma. The amplification of myc-n is an indicator of a poor prognosis, even when classical morphological criteria would suggest a better outcome. More aggressive therapy can be offered early to patients with this fatal mark of biological destiny. Of further interest is the existence of a special subgroup (stage IV) characterized by frequent spontaneous regressions. In this group, only 7% showed myc-n amplification, and all underwent tumor regressions. Thus, in neuroblastoma, two abnormalities are consistently found that suggest rapid tumor growth: an excess of amplified DNA (encompassing the cellular oncogene myc-n), and deletions in chromosome 1p (corresponding to a likely tumorsuppressor gene). Along the same lines, it is known that an alteration or deletion of the likely tumor-suppressor gene in the RB1 gene (resident in chromosome 13, band q 14) predisposes not only to retinoblastoma but also to osteosarcoma, small-cell carcinoma of the lung, and breast cancer (Gennett and Cavenee 1990). Chromosome abnormalities are common in neural tumors. Cytogenetic analyses of glioma cultures have demonstrated structural abnormalities on cromosomes 1, 6, 4, 8, 9, 10, 17 and 22 (Bigner et al. 1984, 1986, 1988). Loss of part or all of chromosome 10 has been reported consistently in glioblastoma, with nonrandom alterations in other chromosomes in other glioma grades. Questions continue to be raised as to whether these genotypic changes are secondary to tumor initiation, or whether they are related to tumor progression. Allelic deletions of chromosome 17 p may contribute to the oncogenesis of all malignant grades of astrocytic tumors (lames et al. 1989). Alterations of 17pare also found in many other cancers. Other abnormalities in malignant glial tumors are amplified erb-b oncogene expression with trisomy 7 (chromosome 7 in excess) (80%), monosomy of chromosome 10 (60%), monosomy involving chromosomes 6, 14, or 22, loss of chromosome Y, or gain of chromosomes 19, 20, or X. The commonest deletion (40% gliomas) is on chromosome 9p. In oligodendrogliomas, a loss of chromosome Y, deletions of 1 p, and abnormalities of chromosome 6 (in the 6q band) and of chromosome 11 (in the 11q band) have been found. Many meningiomas show a loss of chromosome 22 (monosomy 22); others have, in addition, coexistent monosomy 8 and 14 and loss of chromosome Y, with deletions of 1p and 11 p. Based on cytogenetic analysis, James (1988) has concluded that, irrespective of the pathologic heterogeneity noted in glioblastoma, this tumor is donal in nature. These findings increasingly support the concept that the loss of a tumor-suppressor gene is important in the pathogenesis of brain tumors, and raise the possibility of ultimately treating the disease by replacing the defective gene (Weissmann et al. 1987). The full significance of oncogene amplification as a predictor for poor prognosis has become clearer with the identification of amplified erb-b 2 in aggressively growing breast cancers (Slamon 1989).

Introduction Other elements are also potentially important in the pathophysiologic development of brain tumors (Black 1991). Many malignant tumors induce the formation of new blood vesseis,increasingtheir own nutrient supply and possibly enhancing their growth (Folkman et al. 1987). Factors that stimulate angiogenesis include acidic fibroblast growth factor, also called endothelial-cell growth factor; transforming growth factors exand ~; angiogenin; tumor necrosis factor ex; and basic fibroblast growth factor (Folkman et al, 1987). Malignant astrocytomas wereimportant stimulators of angiogenesis in a physiologic assay (Brem 1976),and angiogenesis may be an important component in the progression of astroglial tumors. Benign tumors are also dependenton their blood supply; Takamiya et al. (193) could prove the inhibition of angiogenesis and the growth of human nervesheathtumors with AGM-1470 in 348 nude mice (nu/nu). Both benign and malignant tumors may cause edema in the surrounding brain; some appear to secrete factors that in crease vascularpermeability (Bruce et al. 1987). The extracellular matrix producedby malignant astrocytomas may promote the growth andinfiltration of tumor cells; the precise differences between normal cells and neoplastic cells require elaboration (Rutka et al. 1987).Finally, the host immune response to an astrocytoma is indequate(Bullard et al. 1986), partly as a result of the secretion of immunosuppressivesubstances, including prostaglandins and a glioblastoma-derived T-cell suppressive factor now identified as

transforming growthfactor 132 (Fontana et al. 1984).

.

Clearly the biology of tumor growth is multifactorial and highlyredundant (Table 2.2). One can only hope that future treatmentproceduresfor brain-tumor patients will involve the identification of amplified cellular oncogenes that better identify those patients who have a poor prognosis (and who may subsequently require more specific or aggressive therapeutic management.) More recent evidence suggests that mutations of the p53 tumor suppressor gene, also located on chromosome 17, are common in glioblastoma multiforme and represent an escape from the normal cell cycle control (Newcomb et al. 1993).

Table2.2 The regulatory factors involved in tumor growth, with positive or negative effects (C. MolI, Institute 01 Neuropathology, University 01Zurich)

+

Oncogenes

+/-

Chromosomal alterations Tumorsuppressorgenes

Al! levels

Growth lactors

Vascular endotheliar growth

Extracellular matrix

Chemical mutagens

Immunosuppression

121

The Neurosurgeon's Viewpoint Neurosurgeons and neuropathologists view CNS tumors from different perspectives. At a daily, practical level, neurosurgeons deal with tumors as active lesions in symptomatic patients who need solutions. Neuropathologists, on the other hand, are called upon to make decisions on the nature of tumors by processing fixed or cultured tumor material in isolation (albeit with an increasing array of cell-specific diagnostic techniques). It is important to realize that tumors have not only macroscopic and microscopic aspects (which are well known to neuropathologists), but in addition mesoscopic aspects, which come from long-term clinical follow-up, from three-dimensional neuroimaging, from position emission tomography (PET) and from the stereoscopic views most vividly witnessed during surgery. Mesoscopic means the intermediate (or interreacting) three-dimensional characteristics as seen "in situ" through the operating microscope. Neurosurgeons, through their close clinical contacts with patients, have the best opportunity to observe the natural history of tumors in their initial, intermediate, and final stages. During surgery, neurosurgeons are struck by the spectrum of dramatic consequences brought about by the biological nature of tumors. These include: Perilesional changes causing local distortion of the brain. Displacement and herniation of brain tissue. Elongation and distortion of cranial nerves and vessels, which are not usually visualized on even the most modern MR images. Changes in the vascularity or neovascularization of the adjacent brain. Variation in the type and quality of tumor vascularity, with capillary and venous changes. Mention is also not made of the local or general changes seen within the arachnoidal and ependymallayers. Wide variability in the adherence or adhesiveness at the interface between tumor and brain layers (dura, arachnoid, pia, ependyma, choroid plexus). Displacement, invasion into, or adherence or adhesiveness to major arteries, veins, venous sinuses, or cranial nerves. Changes of biological nature from grades I-III to III-IV within a short period of time (2-3 months) or over longer periods (3-4 years). In some cases a recurrence of malignant tumors occurs at increasingly shorter periods but in other cases is seen over longer periods (9-15 months). There is a surprising survival rate in 1% of glioblastoma multiforme grade IV cases. The reason for the regular venous thrombosis seen in glioblastomas and other malignant tumors. The histological diagnosis is not always clear in some cases. Extracranial metastases from malignant gliomas are extremely rare, in the absence of previous surgical intervention. Leifer et al. (1989) collected only two previously reported cases from the literature, in which the glial nature of the metastasis had been confirmed histologically. One of these patients had a multicentric glioblastoma and liver metastases. In Zürich extracranial metastases have not been observed prior to surgery but have been seen in a single case following surgery. Neurosurgeons continue to seek answers to the fundamental questions regarding the altered pathophysiology found around tumors. With the presence of high-resolution MRI scanners, neu-

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2 Neuropathology

ropathologists have become more interested in the pathological behavior of tumor cells, as they attempt to understand and better interpret what can now be imaged. As a result, the thrust of current neuropathological research is directed at the biological origins of tumors, rather than the physiological events that occur both around them and remote from them. Nevertheless, neurosurgery has cause to be grateful for the pivotal role played by modern neuropathologists in the development of our present understanding of the origin, nature, and growth characteristics of brain tumors. Indeed, in some respects, neuropathology has outpaced neurosurgery in the adaptation and incorporation of basic scientific knowledge into practice (e. g., molecular biology techniques). Neuropathologists made the conceptual leap to electron-microscopic studies twenty-five years ago, and to molecular, biological, and genetic investigations fifteen years ago. The results of the latter have been the establishment of neuropathology as a vital meeting-point between molecular biology, biochemistry, and physiology on the one hand, and the clinical neurosciences on the other. Our experiences in the management and treatment of over 3400 tumor patients has provided us with what we believe are important new insights into the ways tumors progress. Some of these views may appear, at first sight, to conflict with conventional neuropathological teaching, or to contradict the conclusions drawn from well-thought-out projects by experienced neurooncology researchers, neurosurgeons, and neuropathologists. We make no apology for presenting our hypotheses. It is our belief that the adaptation of microsurgical techniques for the removal of extrinsic as well as intrinsic, and malignant as well as benign, CNS tumors will results in a significant improvement in the quality of life for tumor patients. Of course, no claim can be advanced that the inexorable biological destiny of anaplastic meningiomas, neurinomas, astrocytomas, or glioblastoma multiforme tumors can be altered, but some patients survive for a longer time (see Case 2.36 and Vol. IV B). It is our belief, though, that the quality of survival for patients with high-grade malignant tumors, and the quality and duration of survival for a significant number of patients with low and intermediate-grade primary brain tumors, is significantly enhanced by the application of microsurgicql principies and techniques to these tumors.

Our microneurosurgical perspective stimulated our interest in carefully oberserving tumors with respect to their site of origin, initial growth, location, local behavior, extension, and vascularization. This made it evident that many of the traditional tumor concepts still currently in use in brain-tumor surgery and management have outlived their usefulness. It is fascinating to review the classical atlases of brain-tumor neuropathology with our anatomical architectural schema in mind. The white-matter sectorial (peduncular) cascade (as identified on neuroimaging) permits precise gyrallocalization of cerebral tumors. In reviewing the photographs from these works, one is thrilled at the accuracy of topographical identification using this scheme, and amazed at the inaccuracy resulting when the older methods of lobar anatomy where applied (Zülch 1971, Burger et al. 1982, 1991, Russel-Rubinstein 1983, Treip 1978, Janish et al. 1976). At first sight, the topography, micromorphology, and biological diversity of tumors may seem overwhelming. Fortunately, a closer study of CNS tumors reveals distinct structural and behavioral consistencies. Within defined limits, many tumors, regardless of their location, have predictable characteristics (e. g.. topography, lesion consistency, brain interaction, vascularity, pattern of spread, mode of presentation, etc.). Exceptional or unusual tumor behavior is not common. In fact, a recurrent surprise is the consistent absence of specific neurological deficits with large-sized, critically located tumors. In reviewing our series, we have drawn special attention to the surgical-pathological characteristics of tumors in an attempt to correlate preoperative radiological imaging. Our general observations are described in the conceptual synopsis of CNS tumor pathology that follows. More space is givento a speculative discussion on the nature of intrinsic tumors and how they grow, as these tumors continue to present formidable neurosurgical management problems. Indeed, there is a wide spectrum of operative management strategy in neurosurgical practice that stems from a disparity in the interpretation of the fundamental growth characteristics of many intrinsic tumors. Facts supporting our views on how tumors progress are discussed in detail in the following sections. The application of these concepts to the management of individual tumors is reinforced by many examplesgiven in the cases presented at the end of this chapter.

General Considerations: Categorization 01 CNS Tumors The following conceptualization is based on in vivo anatomicalpathological observations of tumors operated on during the past three decades. These ideas have served as a useful guide for the precise localization and removal of these tumors. CNS tumors are generally classified as follows. Extrinsic tumors. These tumors are derived from tissues that encase and support the brain (bone, dura, arachnoid), or from tissues that are strictly outside the brain (pineal and pituitary glands and their associated tissues, vascular structures, cell-residuetissue, craniofacial structures, and the mucosa of sinuses). Extrinsic tumors are extrapial (i. e., outside the pia) in origin and loca-

tion (or, at least, they start out that way). These tumors have special relationships with the bone, dura and arachnoid layers. with the subarachnoid cisterns and intracisternal structures (such as the cranial nerves and basal vessels), and with the gyral surfaces and sulci of the brain. Definition: extrinsic tumors are extrapial or epipial in origino Intrinsic tumors. These tumors are derived from nerve cells and their processes, from nonneuronal specialized support cells (which are collectively called the glia), or from cells of mesenchymal origino Neuronal tumors include gangliocytomas, gangliogliomas, central neurocytomas, and dysembroplastic neu-

Specific Considerations roepithelial tumors.The glialtumors are identifiedby their cellof origin,such as astrocytes, oligodendrocytes, ependymal cells, or microglialcells.The microglial cells are specialized macrophages, andarethe main type of derived CNS immune cell. These cells are associatedwith the uncommon (but increasingly frequent) CNS lymphomas.

Choroid plexus papillomas and intraventricular ependymomasand meningiomas are topographically regarded as intrinsic tumors. Primitive neuroectodermal tumors (PNETS), the groupof tumors that appear to arise from cells resembling the primitive embryonic cells of the developing brain, are also included.Secondary tumors that metastasize into cerebral parenchymavia the blood stream are also intrinsic, by definition. lntrinsictumors originate beneath the piallayer and beneath the "glia limitans"-the basement membrane (formed by a specialgroupof astrocytes) that completely invests the CNS. Consequently,during surgery both the pia and the glia limitans must be crossedin order to remove intrinsic tumors. Definition:intrinsic tumors originate beneath both the pia andthe glia limitans.

123

Some may question the usefulness of another classification scheme that amplifies parts of traditionally useful schemes. Inspection of the tables and outlines that follow will reveal few major differences from the accepted World Health Organization schema (WHO 1990) or with the consideration of tumors as "extra-axial" or "intra-axial." Still, the terms extrinsic and intrinsic, as defined above, are preferred here. The topographical distribution of neuraxis tumors into supratentorial, infratentorial, spinal, and mixed remains valido Thus, while our classification of extrinsic tumors is similar to that in standard texts, we find it useful to further subdivide the conventional classification systems for intrinsic tumors into more precise and surgically relevant neuroanatomical regions. This has enhanced our surgical conceptualization of the presice demarcation of tumor origin, of the tumor's three-dimensionallocation, of its likely pathology, and of the best routes for exploring and removing it.

SpecificConsiderations ExtrinsicCranialTumors ExtrinsicCNS tumors are defined as lesions that originate from outsidethe pia. They are thus extrapial (or epipial), and arise fromtissuesthat are neither neuronal nor glial. They include all tissuesthat encase or support the brain substance, and the pituitary,pineal, cranial nerve sheaths, dysembryogenic tissues, and extrinsicmetastases.We prefer the precise term "extrinsic" to the traditional term "extra-axial." The designation "extraraxial" denotesthat the tumor s located outside the neuraxis, but does not preciselydefine the relationship of the tumor to the brain linings or to the brain parenchyma. The one exception to these guidelines is optic glioma, which arisesfrom subpial glial cells in the optic nerve or anterior tract (i.e.,anterior to the lateral geniculate ganglion). Because it arises fromsubpialglialcells,it should strictly be classified as "intrinsic." However,because its expansion is mainly extrapial, into the arachnoidmembranes and cisternal spaces, it is categorized as "extrinsic."The affinity of certain epidural, extrinsic tumors for particularareas of the skull is well known. Examples from this seriesof casesare presented in Vol. IV B of the present work in detail.

GrowthPattern Extrinsictumors display two basic growth patterns, well circumscribedor diffuse.The biological and genetic factors that govern thegrowthpatterns of particular extrinsic tumors (e. g., meningiomas),haveattracted special interest with the advent of techniquesforproteinsequencing,gene analysis,and the cloning of

cells in culture, and with the development of assays for hormonereceptor status (see the section on biological activity above). Most extrinsic tumors (90%) are well demarcated, noninfiltrative, and surgically completely resectable using microtechniques. They almost always display readily dissectable leptomeningeal planes, which act as a barrier between the tumor and the brain surface. As a result, there is little or no adherence to neurovascular structures in the epidural, subdural, or subarachnoid spaces. Tumors with these characteristics include most meningiomas, neurinomas, chordomas, chondromas, glomus tumors, cranipharyngiomas, epidermoids, adenomas, and optic gliomas. Approximately 10% of "benign" extrinsic tumors, however, exhibit a tendency to grow diffusely and aggressively. This unfavorable tendency is most notable in meningiomas, adenomas, craniopharyngiomas, chordomas, glomus jugulare tumors, epidermoids, dermoids, and optic gliomas (Table 2.11, p. 149). The majority of tumors that exhibit this diffuse, expansive, and destructive growth pattern are located on the ventral side of the brain or spinal cord and their encasements. These tumors may initially grow expansively outwards, but under some unknown biological influence, they often proceed to insinuate themselves into every space available (be it crevice, fissure, cistern, sinus, canal, foramena, etc.). Instead of possessing easily dissectable arachnoid planes, these tumors become densely adherent to nerves, vessels, leptomeninges, and other surrounding structures, almost as if glue had been poured into the area and was in the process of setting. Many extrinsic tumors also have peculiar growth kinetics. Periodic neuroimaging follow-up of nonoperated tumors allows accurate documentation of growth patterns, and provides insight into their highly variable natural history. Some tumors remain inactive for years, causing no symptoms, or producing only minor

--

124

2 Neuropathology

symptoms that rema in stable. Some grow slowly but steadily. Stil! others, however, grow suddenly and aggressively after years of inactivity, penetrating barriers such as the skul!, scalp, sinuses, dura, and arachnoid. In this situation, it is common to find no histological evidence of mitoses and no other changes suggestive of abnormal proliferation. The trigger for this sudden alteration in behavior is unknown. Conversely, spontaneous regression of other tumors is also documented. Thrombosis of veins within a tumor or in the parenchyma immediately adjacent to a tumor is a sign of malignancy. This phenomenon, though common with highly malignant intrinsic tumors, is also seen with maligI).ant meningioma and neurinoma. The thrombosis cannot be explained by the external compression of the veins, as it is found both within and adjacent to the tumor.

Extrinsic tumors are assigned to categories based on their primary area of growth (Table 2.3). These categories subdivide al! tumors orginating outside the CNS parenchyma into four types based on their relationship to the meninges. The relationships of expanding extrinsic masses to the leptomeningeal membranes are important from a surgical viewpoint. It is crucial for the surgeon to visualize the tumor compartment as a separa te space containing the growing mass, so that the dissection planes likely to be encountered at surgery can be recognized. For example, osteomas, chordomas, glomus tumors, and most paranasal sinus tumor extensions into the anterior and middle cranial fossae grow in the epidural space. The dura is invaginated into the brain and surrounding neurovascular structures as they grow.Pituitary adenomas, on the other hand, grow in an

Table 2.3 Extrinsic tumors Epidural Tumors(after Dr. J. Vignaud, Department of Radiology, Rothschild Hospital, Paris) Tumors originating in the skull, spine, or their linings

Cartilage

Chondroma, chondrosarcoma

Embryonal remnants

Chordoma, craniopharyngioma, dermoid, epidermoid Osteoma, osteosarcoma, osteoblastoma, aneurysmal bone cyst, giant-cell tumor, Paget's disease Fibrous dysplasia, fibrosarcoma, ossifying fibroma Multiple myeloma, leukemia, Iymphoma, eosinophilic granuloma Hemangiomas, cavernomas Glomus jugulare tumor Mucoceles, granuloma, cholesteatoma, malignancy Teratoma, angiofibroma, squamous-cell carcinoma, adenocarcinoma, cylindroma, rhabdomyosarcoma, Iymphoma Mucocele, osteoma, nasal glioma, inverting papilloma, esthesioneurobastoma, malignancy of epithelial, neurogenic, or mesenchymal origin Metastatic

Bone

Fibrous tissue Hematologic and reticuloendothelial Blood vessels Paraganglionic tissue Pneumatic cavities Extracranial tumors invading the skull base

Oronasopharynx

Nose and paranasal sinuses

Mixed-invading tumors arising in the intradural, subdural, or subarachnoid areas

Intradural (sella turcica,

sinus cavernosa)

Subdural (intrathecal)

Subarachnoid (cisternal)

Neoplasms invading all tour areas and also extending into the brain or vice versa

Meningioma . Meningiomsarcoma Neurinoma Chemodectoma Encephaloceles Pituitary adenoma Pituitary adenomas, meningioma, epidermoid, dermoid, cavernomas Metastasis Meningioma, angioblastic meningioma, hemangiopericytoma, chondroma, osteochondroma, osteoma of falx, fibrosarcoma, meningeal sarcomatosis, mesenchymal chondrosarcoma Metastasis, Leukemia (chloroma), Iymphoma Craniopharyngioma, neurinoma, epidermoid, dermoid, optic glioma, pineal tumors, lipoma, meningeal carcinomatosis, subarachnoid cysts, Sarcoidosis, melanoma Metastasis Meningioma Neurinoma Chemodectoma Arachnoid cysts Pituitary adenoma Craniopharyngioma Glioma Metastasis

Specific Considerations intraduralcompartment formed by the splitting of the dura into a sellarleaf and diaphragm. Thediaphragma sellae often acts as a restraint on the growth of giant pituitary adenomas, as they expand into the supratentorial compartment. The diaphragm must be transgressed (along withthe arachnoid of the parasellar cisterns) when removal is attemptedsupratentorially. Conversely, a patulous diaphragm can beseen herniating down into the sella after transsphenoidal removal of suchtumors. Similarly, tentorial and cavernous sinus meningiomasarise and grow between the dural sheets. Still other tumors arise in the subdural compartment (such as meningiomas, hemangiopericytomas, osteochondromas, etc.). These tumors pushawayand are invested by the arachnoid layers as they expand,and are thus "epiarachnoidal." Meningiomasof the planum or jugum sphenoidale may presenttheoppositesituation to that discussed above for pituitary adenomas.These tumors can invaginate the chiasmatic cistern and diaphragma sella into the sella turcica, causing the radiagraphic appearance of a giant pituitary adenoma. They can be difficult to differentiate radiographically, but one clue is that supratentorial tumorsherniating into the sella usually do not "fill up" or expand the sella on plain skull films, whereas most giant pituitary adenomas do. Craniopharyngiomas, meningiomas, optic and hypothalamic gliomas, pineal tumors, and epidermoids grow within the subarachnoidspace. Depending on their size, they are confined to one or more cisterns, meaning that one or more arachnoid layers mustbe transgressed prior to removal. Sometumor types appear on the list in multiple categories, indicatingthe diversity of their presentation and the unpredictability of their clinical behavior.

Table2.4 Sites of Predilection

Intrinsic Tumors Predilection The predilection of intracranial and spinal extrinsic tumors to originate from specific anatomical sites is well known (Table 2.4). Intrinsic tumors also demonstrate a specific anatomic and functional territories within the CNS. We have noted the tendency of gliomasto arise in white matter beneath homotypicalisocortex, in the limbic and paralimbic systems, and in the caudate nucleus, thalamus, hypothalamus, and brainstem. The theory that glial tumors have a predilection for specific areas of the brain has been the object of intensive studies. Schwartz (1932, 1936) reported, in 400 cases of gliomas, a predilection for these tumors to arise in the frontal, temporal, and parietal lobes. Ostertag (1932, 1936, 1941, 1949, 1950, 1952) described an ontogenetic tendency of tumors at certain locations. Zülch (1949, 1951, 1956, 1975) studied the relationships between his pathological classification and the frequency of site of origin in over 9000 brain-tumor cases,and was able to confirmthe concept of "preferential sites of origin of brain tumors, in the vast majority of cases," especially for glioblastomas. Interestingly, he concluded that this intrinsic tumor characteristic was of diminished importance, because the technical capability to image these regions had not yet been developed. These observations have been recognized and confirmed in many different parts of the world, but, surprisingly, little additional research has been carried out along the way. Contemporary neurosurgical practice has continued to focus primarily on the histology of the tumor with regard to prognosis, and on whether a

for CNS Tumor Intrinsic

Extrinsic Supratentaríal

Infratentaríal

Spín.al

Chordoma, chondroma Craníopharyng ioma

Adenoma Fíbroma Epídermoid Opticglíoma Pínealoma Glomus tumor Plexus

papilloma

Glíoblastoma Astrocytoma

Olígodendroglíoma Ependymoma

Ganglioglíoma Medulloblastoma Hemangíoblastoma

Cavernoma Lymphoma +++ Verycommon ++ Common + Occurs

+++ (+) ++ +++ +++ ++ ++ +++ +++

-

++ +++ ++ (+)

++ ++ + -

+ ++

(+) (+)

Infratentorial

Supratentoríal Subpallíal

Meningioma Neurínoma

125

-

í. v.

Subpallial

Spinal. íntramedullary í. v.

+

(+) (+) -

-

-

+

+++

-

-

-

-

+++

-

+++

-

-

-

+++ ++ +++ ++ ++

++ ++ ++ -

+

(+) ++

+

++ ++ + +

++ 7

(+)7 ++

(+) ++ (+) ++ ++ ++ +++ ++

++

-

+

+

+

-

-

-

(+)

-

í. v.

Rare Not seen intraventrícular

+ +

126

2 Neuropathology

generous lobar removal (on occasion in functionally important eloquent areas or in so-called "noneloquent" areas) can be accomplished. Unfortunately, this "lobar" concept of tumor location is far too broad to allow any consideration of the cytoarchitecture, myeloarchitecture, and angioarchitecture of the single cerebral or cerebellar gyrus. As pointed out by Russell and Rubinstein (1989), the initial genetic event or "hit" that transforms a cell into a malignancy may be far remo te in time from the eventual phenotypic expression of the tumor. In order for a cell or population of cells to be vulnerable, there must be active replication or the cell must be capable of returning to that state. Therefore, it is reasonable to suppose that a genetic event, occurring during the fetal or early postnatal period, might not be phenotypically expressed until adult life, after subsequent gene tic or epigenetic events have occurred. Knudson (1971), formulating a two-hit concept of cancer in his study of retinoblastoma, provides strong evidence for an initial genetic event resulting in a predisposed cell or cell line, which later, following a further genetic event, progresses to form a tumor. Other types of tumor may also require several genetic mutations before initiation. Russel and Rubinstein (1989) favored the idea of predilection with regard to intrinsic tumors such as the astroblastoma (predilection for paraventricular location), ganglioglioma (predilection for hippocampal regions), desmoplastic infantile ganglioglioma (frontal and parietal predilection), and desmoplastic (cerebellar hemisphere predilection) and vermal (midline predilection) medulloblastomas. The concept of predilection (based on Rubinstein's idea of a neoplastic "window of vulnerability") would stand on firmer scientific ground if the sites and periods of CNS myelinogenesis and prolonged gliocytogenesis (both known to occur well into postnatallife, possibly up to seven years) were precisely known, especially in relation to the individual gyri and subgyri. Precise studies using high-resolution MRI to map the timing of myelination in the fetal and infantile brain, and comparing these results to similarly studied early childhood tumors, would lend support to the concept of a predilection of tumors to originate at the sites of most active cellular turnover during development. Another possible explanation for the predilection of tumors to develop at specific sites is that oncogene initiation promotion, or both, are more likely to occur in phylogenetically more recently developed regions of the brain (e. g., the association cortex), or in older regions of the brain that are constantly active, creating new information (e. g., the memory and limbic system). In his concept of the "triune brain", McLean (1952) traced the evolutionary development of the human forebrain. Each evolutionary brain are a has unique connectivity, chemistry, and function. The "reptilian" brain is composed of a striatal complex of basal ganglia, and is rich in dopaminergic and cholinergic systems. The "paleomammalian" brain is represented by the development of the limbic system, which is rich in opiate receptors. Finally, the "neomammalian" brain emerges as the neocortex increases in volume and complexity (with an associated ascent of the mammalian species up the evolutionary ladder). Although the interconnectivity of regions has increased with evolution from lower animals to the human, each area maintains its identity, and is capable of functioning more or less independently of the other. Within the neocortex, there is also evidence of phylogenetic differences between regions. While they are familiar with the cerebral maps of Brodmann (1908) and others who focused on the unique architectonic fea-

tures of individual brain regions, some neurosurgeons, neuropathologists, and neuroradiologists may be unfamiliar with the work of brain theoreticians interested in the functional organization of the brain as related to regions sharing common architectonic characteristics (Fig. 2.1). Mesulam (1985) used these architectonic differences in the regional cortical layering pattern and divided the entire cortical mantle into five subtypes, which display a gradual increase in structural complexity and differentiation from phylogenetically primitive areas (limbic or allocorticaI), through transitional cortical regions (paralimbic or mesocortical), to neocortical regions (homotypical and idiotypical). Studies of this type that examine regional differences in the neuronallayering patterns do not suggest any associated regional difference in the architecture and biology of glial cells. But there is increasing evidence to show that glial cells have regional differences in their biology, and are not a homogeneous family of cells spread throughout the nervous system. Applying these concepts to intrinsic tumors, we note that certain patterns emerge. Neocerebral gliomas arise most frequently in the white matter subjacent to the heteromodal association areas (homotypical isocortex), less commonly in the unimodal areas, and only rarely beneath idiotypical cortex (primary sensorimotor cortex). Gliomas arising in the transitional zones are also common. more often in paleocerebral than archicerebral zones. Basal ganglia and central nuclei gliomas also have a predilection to arise within the white matter of the nuclei. Thus, pulvinar thalamic, caudate (head), and hypothalamic tumors are seen in decreasing order of frequency. We ha ve observed no instances in which a central glioma arose within the putamen, pallidum, caudate tail, substantia nigra, red nucleus, or dentate nucleus. Cerebellar tumors arise within the anterior, middle, and posterior lobes and the vermis, whereas gliomas of the flocculonodular lobes (archipallium) are not observed. Real intraventricular gliomas most commonly arise fram the septum pellucidum of the third ventricle and from the floor of the fourth. Less commonly, they originate in the lateral ventricular trigone, but no cases have been noted of these tumors beginning in the frontal, temporal, or occipital horns, which are often the sites of extension of periventricular tumors. Those tumors arising from the septum pellucidum may extend into the body of lateral ventricle (see Fig. 2.18 b). Upon initiation, these tumors also demonstrate a predilection to remain within the white matter. We have not witnessed the spread of these tumors by white-matter connecting fibers, but we have seen spread along the CSF in benign gliomas (Case 2.40). Spread along the uncinate and callosal systems can be observed, but not along the projection fibers (optic or auditive radiations), pyramidal radiations, thalamocortical, or corticothalamic, pathways and even not along the optic tracts. This restriction on migration may be related to the vascularization pattern, or to as yet unidentified immunological borderlines. In some situations, surgical intervention or radiation may playa role in the loss of these defense borderlines, leading to diffuse local and perifocal growth. This occurs uncommonly (5%), and it is certainly possible that this change in growth pattern would have occurred naturally in the late phase anyway (and may be not related to surgery). These observations have stimulated many questions about the origin of glial-cell tumors. Why do oligodendrogliomas not occur in the cerebellum or spinal cord and only rarely in the cenI ! jJ

.

Specific Considerations Extrapersonal space

Perhaps our ability to diagnose and remove tumors at an earlier course in their evolution, the future emergence of tumor growth factor suppressor, and the eventual creation of tumorspecific chemotherapeutic agents, will revitalize a wider interest in the topic of predilection.

Primary sensory and motor areas Idiotypic cortex Modality-specific

(unimodal) association

127

areas

Homotypical isocortex High-order (heteromodal) association areas

Initial Growth Pattern

Temporal poi e-caudal orbitofrontal anterior insula Cingulate-parahippocampal Paralimbic areas Septum-s.innominata amygdala-piriform

c. hippocampus

Limbic areas (corticoid and allocortex)

Hypothalamus Internal milieu Flg.2.1 Thecortical zones ot the human brain (from Mesulam, PrincipIesof Behavioral Neurology, Philadelphia: Paris, 1985)

tral nuclei?Is this difference in predilection for glial-cell tumors to arisein certain cortical zones related to the glial-cell density of that

zone?

Is the

embryological

glial-neuronal

matrix

responsible for the predilection of these tumors to remain associated with the neurons they "grew up" with? And where, along this primitive glial network, do the bias tic astroglial cells firstbecome neoplastic?

There is general agreement that astrocytic tumors arise in white matter. In the initial and intermediate growth phases, the tumor nidus grows by expansion, the most actively dividing cells being predominately those at the periphery. Clusters of these tumor cells extend into and separate local surrounding axons, neurons, and glia, splitting the fiber tracts (Fig. 2.2). Low-grade gliomas (generally), anaplastic gliomas (frequently), and even some glioblastomas (occasionally) remain confined within their site of origin for a long time. Littie is definitely known about the factors that limit tumor growth in these early stages. Convincing evidence exists for the presence of both a humoral and a cell-mediated immune response to astrocytic tumors. A specific humoral immune response to their tumors is produced by a majority of patients with astrocytic tumors (Gately et al. 1982). In addition, patients with clinically significant tumor masses, and those with more malignant gliomas, show evidence of impairment of cellmediated immune response (Roszman and Brooks 1982). Prominent perivascular cuffing of lymphocytic T-cells is found in the blood vessels within and around up to 60% of poorly differentiated gliomas.The majority of these appear to be T suppressorcytotoxic cells (von Hanewehr et al. 1984). The significance of these immune-response changes continues to be a matter of intense research activity, as well as a controversial debate. Nonetheless, it appears that early in the developmental growth of astrocytic tumors, there are biological factors that limit growth (tumor-suppressor proteins and an active local immune reaction). At some point, however, two other phases occur, either

b Fig. 2.2 The initial growth pattern of a subcortical glioma a A subcortical glioma nidus expanding between the surrounding white matter fiber bundles. Projection fibers: pink, association fibers: blue, commissural fibers: yellow. Note the separation of fibers by the growing tumor. They are not interrupted b Expansile subgyral tumor growth, with separation of surrounding fiber pathways

128

a

2 Neuropathology

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sequentially or concomitantly. First, the tumor changes its behavior (by further mutation) into a more malignant, less differentiated formo Second, the effectiveness of both the local and systemic immune responses becomes progressively impaired. It may be that the more malignant tumors secrete suppressor factors that prevent or limit any further effective host immune response. It is at this very advanced stage that we envision the unrestricted spread of tumor cells away from the main original nidus. Comparisons of serial stereotactic biopsies have suggested a wide area of tumor-field change at this late stage (Kelly 1987). However, just how many of the abnormal cells away from the main tumor mass are migrated tumor cells, as opposed to newly mutated tumor cells or re active astrocytic cells, remains open to speculation. It may also be that interval areas devoid of tumor cells are indicative of some continued efficacy of the local immune response. Another possible explanation for the restricted localization of early astrocytic tumors may be a dependence on the local subgyral or segmental blood supply. We have strong suspicions that tumors not yet capable of secreting angiogenic factors are forced to confine themselves to the areas of their segmental blood supply. With expansive growth in the subgyral region, the' astrocytic tumor may reach a size large enough for severe compression and displacement of adjacent gyri (with effacement of normal sulci) and impairment of venous drainage to occur. This results in distortion, but not distruction, of these gyri (see Fig. 2.8). With contrastenhanced MRI imaging, it can be very difficult, or even impossible, to distinguish a gyrus containing a low-grade tumor from adjacent distorted and perhaps edematous gyri. As a result, a false impression of extensive "lo bar" involvement may be produced when, in fact, the tumor is confined to only one subgyral sector.

I

Tumor growth tends to be directed centrally, down through the sectors of the involved gyrus towards the periventricular matrix (Fig. 2.3). Commonly, with astrocytic tumors, the anatomical integrity of the basal ganglia and thalamus is well respected. Tumor mass effect often compresses and distorts these structures, which then indent and deviate the ventricular walls. Similarly,the central nuclei may be compres sed and significantly displaced, without invasion or functional effect (until very late) (Cases 2.2, 2.30). Our observations favor the concept that astrocytic tumors grow initially from a focus of abnormal cells in white matter, in b

I r

I ..L ~

specific

architectonic

are as that

are

phylogenetically

more

recently evolved. In the early and intermediate phase of their biologicallife, these tumors grow expansively, but remain primarily restricted to their sectors of origino Only later, at an advanced stage, do they extend into other white-matter sectors, usually following either changes in the bioloy of the tumor (more malignant) or impairment of the immune response (against the tumor).

e

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n

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<JFig.2.3 The common growth pattern of a subcortical glioma a A subcortical glioma expanding into the gyral sector (along the segmental vascular and embryological glial pathway) towards the ventricular matrix b Overview of a, illustrating the most frequent pattern of growth towards the ventricular wall (coronal view, right side). Note that the pyramidal shape of this tumor growth is similarto that seen withsegmental infarction (perhaps suggesting that the direction of tumor expansion is somehow related to the local segmental vascularity). (See Vol.1I1B, pp. 43-4) e The pattern of growth into neighboring gyri (and across sulci) This occurs only later in tumor expansion, and is not seen initally

.

Specific Considerations

Localization 'These tumors are considered here under four main headings: 1 neocerebral(subpallial); 2 limbic and paralimbic (paleocerebral andarchicerebral);3 central nuclei; and 4 intraventricular. Neocerebral and Neocerebellar Tumors (Fig. 2.4a, b).

Thevastmajority of glial tumors arise from the subpallial regions ofthebrain in either the supratentorial or infratentorial compartments.Thesetumors arise predominantly in areas of white matter madeup of numerousbundles

of myelinated nerve fibers that

leadeithertowardsor awayfrom, the corticalneurons of the gray matter (Fig.2.2). Only the rarely occurring protoplasmatic astrocytomaarises from the cerebral corticallayer itself (namely ¡hetruepalliumor mantle layer). The thickness of the cerebral cortexvariesfrom nearly 6 mm in the precentral gyrus to 1.5 mm inthedepthsof the calcarine sulcus. It is estimated that the corte x containsover 14 billion neurons, made possible by the gross expansion of the total area of the cortex to 1800 cm2 through the infoldedfissures and gyri.

Neuroglial cells include &strocyte, oligodendrocyte, ependyma, and microglia cells. The neuroglial cells constitute support cells for the neurons, and outnumber neurons by a ratio of ten to one. It is from one or (some times more) of these types of support cells that most subpallial tumors arise. Thus, it is from the fibrillary astrocyte, oligodendroglia, or microgtia of the white matter of the cerebral and cerebellar hemispheres that the more common intrinsic brain tumors originate (astrocytic tumors, oligodendrogliomas, and lymphomas, respectively). Tumors arise much less commonly from neurons (neurocytoma, ganglioglioma), or from the protoplasmic type of astrocyte (which is more prevalent in the gray matter of the brain). Regardless of the initiating factors in the genesis of a tumorcell line, a particular subpallial cell type undergoes transformation and gives rise to a group of cells that grow abnormally. This group of cells most commonly originates within a sector of a gyrus, predominantly in the regio n of the subcortical white matter. As this group of cells replica tes into a recognizable tumor, is maintains a close-knit relationship within the white matter of its gyrus of origin (Fig. 2.4). This special, confined relationship is then preserved throughout its initial and intermediate growth phases. In

Flg2.4 Theinitialsites of glioma formation in the cerebrum. a coronal view,b horizontalview Lightblue Subcortical (most frequent) Oarkblue Subgyral (common) Red/blue Lobar (rare), (or MRI made in the late phase)

129

. t)

Red

Callosal (very rare)

Green

Limbic / paralimbic (frequent)

--

130

2 Neuropathology

our estimation, the gyrallocation of each individual tumor has a considerable bearing on treatment planning, and must be defined as accurately as possible, especia11yif one is to be able to sensibly compare different treatment modalities. (This is clearly important now that so many different treatment options are being tried). Consequently, subpallial tumors should be defined not just in terms of lobes (e. g., frontal lobe, parietal lobe, temporal lobe, Table 2.5 Intrinsic tumors 1. Neocerebral tumors (subcortical, subgyral, gyral, lobar peduncles) a. Frontallobe Superior frontal gyrus Middlefrontal gyrus Anterior,- middle, and posterior parts } Inferiorfrontal gyrus b. Centrallobe Precentral gyrus Postcentral gyrus Superior, - middle, and inferiorparts } Paracentrallobule c. Parietallobe Superior parietallobule Middle parietallobule (angular gyrus) Inferiorparietallobule (supramarginal gyrus) Precuneus d. Occipitallobe Cuneus Superior occipital gyrus Inferioroccipital gyrus Medialtemporo-occipital gyrus Lateral temporo-occipital gyrus (posterior part) e. Temporallobe .. . Superior temporal gyrus Middletemporal gyrus } Antenor, - mlddle, and postenor parts Inferiortemporal gyrus Lateral occipital-temporal gyrus (anterior two-thirds) 2. Paleocerebral and archicerebral tumors (transitional area) a. Limbic(allocortex) Amygdala, hippocampus, subcallosal gyrus, substantia innominata, septal areas b. Paralimbic (temporal pole, fronto-orbital, anterior insular, cingulate, parahippocampus [see also table 1.3c, p. 18]) 3. Central Gray Matter a. Basal ganglia (caudate, putamen, pallidum) b. Central nuclei (thalamus, meta-, epi-, subo, and hypothalamus) c. Brainstem (mesen-, meten-, myel-encephalon) 4. Intraventricular Infratentorial tumors 1. Neocerebellar (subfolial, lobular, lobar, medial peduncle) Posterior quadrangular lobe Superior semilunar lobe Inferiorsemilunar lobe Declive Folium Vermis } Tuber 2. Paleocerebellar (subcortical, sublobular, lobular, lobar peduncles) Lingula,centrallobe Anteriorquadrangular lobe Biventerlobe . Pyramis } Vermls Tonsil 3. Archicerebellar Flocculonodular lobe

etc.), but also in terms of the specific sector of the particular gyrus involved (Table 2.5). The anatomical origin of every tumor (wherever possible) should be precisely defined, on a named gyral basis. Although this presents an apparent cha11enge at first sight, our surgical experience from the pre-MRI era, and a careful study of MRI scans over the last ten years (especia11ycoronal sections) demonstrate that it is routinely possible to define the most likely gyrus oí origin in the vast majority of intrinsic tumors. The range of presentations and patterns of behavior of subpa11ialtumors are characteristic. The site of origin of these tumors within the white matter demonstrates a site "preference" that has be come more evident with the advent of high-resolution CT and MRI. Recalling the division of white matter into subcortical, gyral, subgyral, lobar, and capsular sectors as presented in Chapter 1, we may once again note that most gliomas arise in the subcortical or subgyral sectors of the cerebrum and cerebe11um. The second most frequent site is within the center of gyrus itself. Tumors that originate at deeper levels (e. g., within the lobar sector) are rare (see Fig. 2.9 on p. 134), and tumors that begin at the level oí the hemispheric peduncle (capsular sector) are very rare (see Cases 2.20, 2.21 on pp. 171-2). Initial growth phase. After beginning as a focus of abnormal cellsa tumor nidus-the subpa11ialtumor grows by spherical extension in a11directions. The multiplying ce11sform groups or columns that grow between the fiber tracts in a manner analogous to tha! of a cauda equina tumor spreading between the nerve roots, separating them as it grows. In fact, the initial expansive growth of subpa11ial tumors is analogous to that of a cerebral abscess, so that, as the tumor enlarges, it conforms to the shape of the gyrus within which it originates. Up to about 2 cm in diameter, the tumor mass is commonly somewhat spherical (Fig. 2.2 on p. 127). During this early phase oí growth, invasion and destruction of white-matter fibers (association, commissural, and projection myelinated nerve fibers) do no! usua11yoccur. Presumably at this stage, host tumor-suppressor factors and tumor factors promoting growth are in a steady state. This state of equilibrium, coupled with the plasticity and overlap of functional capabilities inherent within the central nervous system, sheds light on the frequent paucity of signs and symptoms in many patients with subpa11ial tumors. Only when such tumors reach a larger size do they exert direct destructive effects on the fiber bundles, due to invasion and transection. In the earlyphases of growth within some gyri, more often than not it is the geometric shape of the gyrus (rather than any biological constraint) that causes the physical contour of many gliomas to appear bizarre. Until this phenomenon is recognized, the true location of these tumors is easily misinterpreted. The radiological interpretation of these complex three-dimensional structures can be difficult, frequently leading to a misleading impression of more extensive involvement (i. e., lobar rather than gyral see the example cases at the end of this Chapter and the classic neuropathologic atlases). Tumors originating within the gyral sector expand in a somewhat e11iptical shape either centrifugally toward the subcortical sector or centripeta11y toward the lobar sector, or in both directions (Fig. 2.5). However, the prodominant direction of growth is towards the ventricle. With growth, these tumors assume a more pyramidal shape, related perhaps to the white-matter segmental vascular distribution pattern (see Chapter 1, Fig. 1.25a-b, p. 31),

Specific Considerations

131

or to the embryological migration of glial cells (from the periventricular region), or to lobar neurochemical properties (Fig. 2.5). Tumors arising in the lobar sector also grow in direction of the ventricle to resulting in an impressive indentation of the ventricular walls. The ependyma and modified internal glia limitans layers of the ventricle constitute a powerful biological and physical boundary to tumor penetration. Only very rarely do intrinsic tumors penetrate through the ependymal lining of the ventricular wall. The mode of expansion demonstrated by lobar tumors once the subgyral regio n is reached is the same as that for tumors originating there (Figs. 2.5, 2.6).

Fig.2.5 Advancingpatterns01subgyral tumor growth (coronal views) a Thetumorexpandsalong its own axis to the neighboring gyral segment b Expansionto neighboring subgyral white matter libers (advanced stage) e Theprelerentialdirection 01growth is towards the ventricular cavity (earlyandintermediatestages) d Expansion alongthe callosal radiation (advanced stage)

Intermediate growth phase. From its favored origin in the subcortical-subgyral sector, the typical glioma expands centripetally, growing mainly downwards and inwards through the white matter in the direction of the sectors of its own gyrus. Once through and deep to the originating gyrus, growth then proceeds in a predominantly inward and deep direction towards the ventricle (Fig. 2.3). The direction of this growth (though initially in a similar direction to the gyral white-matter sectorial cascade) is most intimately related to the direction and pattern of white-matter segmental vascular supply, neuroglial embryological migration, or chemical and immunological factors within a special functional area, such as the limbic lobe (see Cases 2.9-2.19, 4.1, 4.3, 4.24, 5.16-5.19, and Fig. 1.25). The architecture of the white matter was discussedon pages 27-39 above. The course of projection fibers passing proximally through sections 1,2,3, and 4 (though initially towards the ventricular cavity) is altered medially as they enter the hemispheric peduncle (sector 5) and are distributed to the internal capsule. The course of short associationfibers is through sectors0,1, and 2, and that of long association fibers through 3 and 4 and then along the fasciculi. Commissural fibers pass through all four sectors, but leave sector 4 to enter the corpus callosum. It is apparent that the cascading white matter fiber system is not aligned with the ventricle wall.

Fig.2.6a, b A glioma has expanded towards the ventricle and indented into the ventricularcavity

132

2 Neuropathology

The vascularization of the white-matter sectors (both arterial and venous), the embryological astroglial network (directing neuronal migration) and hitherto unknown biochemical and immunological entities are, however, oriented in this cortical-periventricular axis. (Case 2.1 on p. 154). The embryological astroglial network (that directs neuronal migration during development) may retain the capacity to direct traffic back towards the ventricle, or perhaps the ventricular-matrix astroglial cells retain their mitotic capacity and are somehow responsible for tumor genesis. The answers to these questions await further neuropathological work, but the fact remains that one or both of these entities seem to best explain the patterns of growth most commonly observed in subpal. lial gliomas (Fig. 2.7). Growth in an anterior-posterior or medial-lateral direction can also occur, but these are not the predominant vectors of growth. When significant growth occurs in these directions, a progressive stage of tumor involvement is seen es it sweeps around

the subgyral region of the affected gyrus and into the subgyral regions of adjacent gyri (Fig. 2.5 b). Once two gyri are involved, the intervening sulcus is compressed, and its associated subarachnoid space is obliterated. Further increase in tumor size preferentially expands the subgyral region, altering the pattern of venous drainage and causing obliteration of adjacent sulci. In the final stages of growth, the tumor tends to evert and turn out one or more of these compressed sulci, at which point the tumor can be considered truly "lobar" (Fig. 2.8). There is a predilection area in the frontallobar sector (prelenticular) at the confluence of lobar areas from the temporal and parietal lobes (retrolenticular) (Fig. 2.9 on p. 134). The term "lobar" implies that a tumor involves sector 4 with involvement of more than one gyrus (out of five that normally make up a lobe). Tumors can, in their advanced phases of growth, grow still deeper into the capsular sector (Case 2.25, p. 175), but this is a very late phenomenon.

~,' l.

¡~,:. I

e

_'c:

Fig.2.7 The lollowing cases are Irom the collection 01Prolessor P. Kleihues, Institue 01 Neuropathology, University 01 Zurich, and show the tumor in an intermediate growth phase a A well-circumscribed left medial F 1 (posterior part) glioblastoma. Note the precise delineation 01 the tumor margins

b An oligodendroglioma involvingthe left superior parietal lobules, with compression 01the procuneus medially and displacement 01the middle parietallobules laterally.Note the absence 01inliltrationintothe precuneus

e A well-circumscribed left Irontal lobar type oligodendroglioma, Grade 11.Notethat the surrounding cingulate gyrus and superior Irontal gyriare not involved.The tumor has inliltratedintothe corpus callosum, and there isassociated compression 01the caudate and lateralventricularsystem

d A left lrontal glioblastoma originating in the lobar sector and expanding into the F 1, F 2, and cingulate gyri without inliltration

Specific Considerations

133

Fig.2.7e A well-delineated astrocytoma, Grade 11,within the right Insula.Thetumor appears to be infiltrating within the insula, but there is a well-defined medial border with displacement of the putamen and caudatemedially. Extension of the tumor into the sylvian fissure

f A large, subcortical, right superior temporal gyrus glioblastoma, extending along the arcuate fiber system to the insula. There is associated displacement of the external capsule, claustrum, putamen and pallidum. T 2, T 3, LTOand the parahippocampal gyri are not infiltrated

9 A large glioblastoma of the left fronto-orbital, insular, and T 1 gyri in thelatephase. It extends and infiltrates medially into the putamen and caudate. The sylvian fissure is entirely blocked by the tlimor. The operculararea of F 3 is displaced, but not infiltrated

h A huge, left middle temporal gyral glioblastoma, herniating in a mushroom-fashionthrough the pia membrane. There is tremendousdisplacement of the sylvian fissure and insula upwards, and of the striatum medially

i A circumscribed oligodendroglioma of the left anterior F 1 gyrus, compressing the F 2 gyrus laterally, and the cingulate gyrus medially, without infiltration. However, the lobar sector of the frontal lobe is infiltrated, as well as the callosal body

134

2 Neuropathology

Fig. 2.8 A glioblastoma in the late phase, with its origin in the lobar sector and expansion into the frontal gyri and callosal radiation

Late growth phase. At the late stage, the tumor may become more aggressive (dedifferentiating into a more malignant, hybrid form) and escape the inhibiting host immune response. When this happens, destruction of the white matter surrounding the tumor may occur as a consequence of several processes (invasion, toxic metabolites, infarction, etc.). It is common for the original shape of the tumor to change from a spherical one to a more complex form at this point. The original center of the tumor may become ischemic, leading to cystic changes. The more malignant peripheral areas of the tumor may grow faster in one direction, as a result of a dependency on adequate blood supply, of a need for high concentrations of growth factors,or as a consequence of the density of white-matter connecting fibers. At this advanced stage of tumor growth, invasion along whitematter fiber pathways do es occur. Growth along short and long association fibers may promote true lobar involvement (Fig. 2.5a). Extension along commissural fibers may demonstrate spread into the corpus callosum (frequently at the forceps major and minor) (Fig.2.5d). Extension along the projecting fibers is extremely rare (Case 2.25 on p. 175).

Unusual patternsof spread.Only about one percent of tumors arising in a subcortical sector in the cerebrum or cerebellum present as an exophytic growth on the surface of the hemisphere. This pattern of tumor growth, through the corticallayers, and expanding in a mushroom-like fashion over the neocortical surface, is most commonly encountered in tumors originating from astrocytes and in the late phase of glioblastomas (see Fig. 2.7h). The external glia limitans membrane and pia mater remain intact in this situation, preventing tumor passage into the subarachnoid space. As a result, these tumors very rarely cross the sulci (Fig. 2.10). An exception to this role are insular tumors (anaplastic gliomas) that have a tendency to extend through the piallayer and extrude into the fissural space. In addition, certain benign tumors (piloid astrocytoma) (see Case 2.40) and malignant (glio-

Fig.2.9 Frequent sites of tumors in lobar sector 4: 1 prelenticular, 2 retrolenticular

Fig.2.10 An unusual pattern of subgyral glioma growth (coronal views) Mushroom-like gyral expansion, with compression of the surrounding gyri and overlying gyrus, creating an exophytic mass (but still retained in the pial membrane) that compresses and conceals the surrounding gyri. Note the scanty growth towards the ventricular cavity in this instance

Specific Considerations blastoma)tumors may emerge at presentation in multicentric, disseminated locations; this phenomenon is not well understood. lntrinsic cerebellar tumors have also predilection sites: median (vermian) and hemispheric (paramedian and lateral). Depending on the organization of the cerebellar white matter, theyexpand within one lobule and along the segment of the anterior. middle, 01' posterior lobule. They usually are directed towardsthe periventricular matrix, but occasionally they may also growoutwardslike a mushroom (Fig. 2.10; Cases 3.2, 3.33). Unique characteristics of cerebellar glial tumors. Hemispheric lesionsexpand locally and may extend medially towards the vermis. but rarely infi!trate across to the opposite side. Thus, hemispheric tumors are usually not bihemispheric. Lesions which arisein the vermis (superior, middle or inferior part) may expand bilaterally and give the impression of a bilateral hemispheric lesion. Tumors of the anterior quadrangular lobule do not extend alongthe superior cerebellar peduncle to the mesencephalon. Gliomas arising in the tonsillouvular region do not extend down alongthe inferior cerebellar peduncle. In contrast, lesions of the middlepart of the hemisphere may extend into and along the middlecerebral peduncle to infiltrate the pons, and vice versa (Tomita1986). Summaryof subpallial tumor growth. The physical development of neocerebral and neocerebellar subpallial tumors may be summarizedas follows: 1. Initiation occurs in white matter (as a nidus of abnormal

cells),in either: a) the subcortical subgyral sectors, 01'b) the gyral sectors;less commonly, in c) the lobar sector, and d) the capsular sector. 2. Early growth is expansive, in three dimensions, conformingto the shape of the gyrus. 3. Thereafter, the main direction of growth is centripetal, towardsthe ventricle. 4. Upon reaching the lobar sector, deformity and swelling of adjacentgyri may occur, but still without invasion of these gyri. Localinterstitial edema due to venous outflow obstruction may be marked. 5. Additional growth occurs in an anterior-posterior or verticaldirection,in the subgyral sector, in the gyral sector, 01'later in thelobar sector. This results in compression and, later, obliterationof suIci. 6. There is no invasion by neocerebral gliomas into the al/ocorticaland mesocortical areas (or vice versa), the central Ill/clei,or the ventrieles, until the end stages of growth (see the examplesat the end of this Chapter).

Thephylogeneticrestriction of intrinsic tumors. When tumors are followedup over the long term in patients who refuse surgery, 01' aredeniedit (for whatever reason), another consistent feature is noted.Thereis a tendency of these tumors to stay within their phylogenetic01'architectonic zone of origin and not to invade adjacentterritories with a different phylogeny and with different architectonicand functional features (such as the central, frontal, parietal,occipital,01'temporallobes, or the transitional areas, centralnuclei,01'intraventricular areas). This phenomenon has been observedin many patients who were later proved (often years later)to be suffering from astrocytomas, anaplastic astrocytomas, oligodendrogliomas, 01'other "infiltrative" glial types of tumor. Tumorsin the transitional areas show the same phenomenon.

135

These tumors originate in the white matter beneath allocortex and mesocortex, and their growth and spread remains almost entirely within the limbic 01'paralimbic system (as if there were a "barrier" prohibiting their spread into the central nuclei 01'into the neocortical zones). These interesting tumors are discussed in further detaillater in this Chapter. Peculiarities of the site of origin of intrinsic tumors. It is rare for gliomas of the cerebral pallium to originate in the white matter beneath highly specialized cortical areas such as the primary motor area, the primary sensory strip, the primary auditory area, or Brodmann areas 1,2,3,4,22, and 44. Gliomas in these areas present diffuse growth tendency (Cases 2.25-2.26 on p. 175). We have seen only one case in which the tumor apparently arose from the primary visual area (area 17), but autopsy revealed the origin to be area 19. There is a striking prevalence of glial tumors arising in the unimodal or heteromodal association areas of the cerebral pallium. In the cerebellum, they arise most commonly in the anterior, middle and posterior lobes and vermis. In our series, there are none that arise from the flocculonodular lobes (archicerebellum). It is tempting to explain this phenomenon on the basis of volume (i. e., association areas >primary sensorimotor areas 01' frontal >temporal >parietal >occipital). This volume theory is commonly put forward, yet it seems far too simplistic. Perhaps the explanation is based on the fact that those are as phylogenetically more recent are more susceptible to soma tic mutations than the more primitively envolved areas. We await further neuropathological information for definitive answers to this intriguing observation. Final observations. Our observations concern the initial site of origin of tumors, and the pattern of their expansion, development, and progression. As stated above, low-grade gliomas, anaplastic gliomas, and sometimes even glioblastomas demonstrate a propensity to remain localized within their initial sector of origin (subcortical, gyral, subgyral), confined there by little-known factors for a long time. Clear infiltration from subpallial and pallial areas into transitional 01' central nuclear areas 01' vice versa does not occur. In addition, early, intermedia te, and even late growth phase gliomas never extend along the long association and projection pathways, such as the superior or inferior longitudinal, the frontooccipital, occipitotemporal, or cingulate fasciculi, the optic 01' auditory radiations, 01' the sensorimotor pathway systems. Similarly, the short and long commissural pathways, such as the anterior and the hippocompal commissures, only very exceptionally transmit tumor to the opposite side. Only about one per cent of malignant tumors extend through the corpus callosum (forceps major and minor), these having arisen either in the lobar peduncles of the frontal or parietal lobes 01' within the genu 01' splenium of the corpus callosum, and having expanded bilaterally. Infiltration across the middle portion of the corpus callosum is extremely rare (Case 2.38 on p. 184). These observations are even true for most recurrent tumors, the vast majority of which are primarily located at their site of origin, regardless of time interval 01' prior adjuvant treatment therapies. We continue to ask ourselves why these limitations occur, what the factors are that, regulate the growth (at least for a while) of most glial tumors so well, why the general belief that these tumors are infiltrative at any early stage is not borne out by our observations, and why indeed the vast majority of gliomas do not metastasize outside the CNS.

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2 Neuropathology

Tumors in Limbic and Paralimbic Areas lntrinsic tumors arising in the transitional paBial regions are unique, and deserve special recognition for their unusual range of presentation and behavior. These tumors arise in white matter adjacent to the allocortex or mesocortex, areas that are more commonly known as the limbic and paralimbic cortex. The phylogenetic, embryological, and architectonic features of these regions differ from the remainder of the cerebral hemispheres. The allocortical structures are phylogenetically primitive, and appear early in the evolution of mammals. The number of cortical layers ranges from none to two. I.nman, the allocortical structures include the septum, subcallosal gyrus, substantia innominata, amygdala, and hippocampus. The mesocortical structures have three to five layers, and include the temporal pole, caudal orbitofrontal cortex, insula, and cingulate and parahippocampal gyri. In addition, the operculae of the frontal, frontoparietal, and temporallobes that abut the Sylvian fissure also demonstrate a transitional five-Iayered cortex (Figs. 2.11, 1.54, Table 1.3c on p. 18). The vascular anatomy of the limbic areas differs from the other transitional areas. lnstead of receiving blood exclusively either from the leptomeningeal vessels or from the perforating vessels, allocortical limbic areas receive a dual arterial supply from both (though more from the perforators). The arterial supply to the paralimbic are as is principally from the leptomeningeal arteries. The limbic areas drain into the deep cerebral venous system, whereas the paralimbic territories drain into both the deep and superficial system (Table 1.10 on p. 99).

Intrinsic transitional tumors originate and grow in a fashion similar to glial tumors in neocortical are as. Initial growth begins as a tumor nidus, gradually expanding in a spherical fashion. Later, this shape often expands to appear oval. As previously described, the predominant tendency is for these tumors progressively to take the form of a cone, with the base representing the initial spherical site of origin and the apex representing growth towards the ventricular system. However, with large tumors, the C-shape of the limbic system makes the identification of the nidus of origin difficult. Still, it is clear that these tumors remain confined within this system, and the vast majority respect the more recently developed regions of the cortex (neocortex), central nuclei, and ventricles. The reasons for this striking location remain open to speculation. It is worth repeating that these transitional glial tumors have a remarkable tendency during initial and intermediate growth, and expansion, to be confined to the white-matter beneath allocortical and mesocortical zones. It seems as if this group of tumors has an "affinity" for these phylogenetically primitive areas, an idea which was introduced by Filiminoff (1947) and later developed by Yakovlev (1959). Spread to adjacent neocortical (six-Iayeredisocortex) white matter is unusual, and tends to occur late (it at all) in the course of the disease. The pattern of growth within the allocortical/ mesocortical zones shows some very interesting sequences (Table 2.6, Fig. 2.12).

a

b

Fig.2.11 The divisionof the telencephalon (after Leonhardt, Tóndurg and Zilles, Rauber/Kopsch: Anatomíe des Menschen, Stuttgart: Thieme,1987,vol.3, p. 44, Fig. 13.28) Red Neocorticalareas Yellow Paleocortical areas Oarkblue Archicorticalareas Lightblue Periarchicorticalareas

a

Coronal view through the striatum

b Coronalview through the mid-thirdventricle

Specific Considerations Table2.6 Patterns of growth in limbic and paralimbic tumors 1a b e

d e f 9 2a b e 3 4 5

Temporalpole (mediobasal) Amygdala Hippocampus Uncus Ammon'shorn Dentate Parahippocampus Indusiumgriseum Fornix Mamillarybody Septalarea Cingulum,- anterior part Cingulum,- middle part Cingulum,- posterior part Insula Subcallosaland Ironto-orbital (in combination with types 1-3 above) Global(includes all 01the above types)

Patternsof growth. Type 1 tumors: region of the mediobasal temporalarea. A tumor arising in of one these areas (1a, 1b, or 1e) remainsrestrietedto this one area for a long time (initial and intermediategrowthphases). It remains reeognizably distinet and discrete,whilegradually expanding. Rarely, a fusiform tumor expan-

sion involving all three regions (1 a, 1 b, and 1e) may rapidly oceur on sequential seanning. In exeeptional cases, a tumor may spread up along the isthmus into the eingular gyrus (Cases 2.12, 4.1, 4.3, 4.24,5.17,5.18). Tumor growth does not proeeed along the fimbria to the fornix (1 e) or along the indusium griseum (1 d) to the eallosum. True fornieal tumors (as distinet from third ventrieular tumors obstrueting the foramina of Momo), seem to arise bilaterally (two observations of our own. Tumors in the 1f region, arising in the mamillary body, remain loeally eonfined and show no propensity of extend along the mammillary-thalamie fibers. Similarly, tumors that arise outside the limbie and paralimbie regions-for example, from the lateral temporo-oeeipital or medial temporo-oeeipital gyri, or from the superior, middle, or inferior temporal gyri-do not invade the limbie or paralimbie systems, or this only oeeurs in the late phase of tumor growth (Fig. 2.7h on p. 133). Type 2 tumors: cingular tumors. These arise in the posterior, middle, or anterior seetions of the eingulum. 1. Posterior eingular tumors (2e) arise at the base of the preeuneal regio n (often ealled the parasplenial region), and may extend up to the preeuneus. They do not extend bilaterally, as true splenial tumors frequently do. If there appears to be bilateral extension, it is due to herniation of exophytie parts of the tumor aeross the midline (Case 2.19).

/

Flg.2.12 Corticaland nuclear connections01the limbic-paralimbic system(sagittalview) 1a Temporalpole 1b Amygdala with the stria terminalis 1e Uncus/hippocampus parahippocampus 1d Indusiumgriseum 1e Fornix 1f Mamillary body 19 Septalregion 2a Anteriorcingulum 2b Middle cingulum 2c Posteriorcingulum 3 Insula 4 Fronto-orbital area Is Isthmuscinguli MTO Medial temporo-occipital gyrus

137

138

2 Neuropathology

2. Middle cingular tumors arising along the midsection of the cingulum (2 b) may expand into the paracentral areas (Case 2.18 on p. 169). 3. Anterior cingular tumors (2a) either stay well isolated within the cingulum, or expand downwards around the genu of the corpus callosum into the subcallosal and paraterminal areas, and later into the fronto-orbital areas (Case 2.16 and 2.17 on pp. 167-8). Type 3 tumors: insular tumors. These are also seen to arise from three sections, the anterior (a), middle (b), and posterior (c). 1) A tumor may arise in, and remain well confined to, one section a (anterior), b (middle), or c (posterior).

2) It may expand to occupy combinations of sections: a/b, b/c, or a/b/c. 3) Other tumors may expand into the opercular are as, so that: a) 3 a or 3 b types expand more in the frontal opercular region; b) 3 c types expand more in the temporal opercular areas (the gyrus transversus and gyrus circumflexus); and c) 3 a types may also present as a combined frontoinsulotemporal type (see Cases 2.13, 2.14, and other cases in Vol. IV B, chapter on insular tumors). Type 4 tumors: fronto-orbital, parolfactory, and septal types.The tumor expands within the fronto-orbital, parolfactorial gyrus, innominate substance, and basal parts of the pallidum (Fig. 2.13, Case 2.17, p. 168).

Fig.2.13 In our clinical experience, some limbic tumors were found exactly within the fronto-orbital areas shown here (adapted, with permission, from Alheid et al. in Paxinos, Human Nervous $ystem, Basal ganglia, 1990, pp. 491, Fig. 19.7) a A direct print of an acetylcholinesterase-stained coronal section from the Macaque brain. Note the continuation of the striatum to the base of the brain in the region of the accumbens (Acb) and olfactory tubercle (Tu), which together form the ventral striatum. Numerous cell bridges across the internal capsule indicate the continuity between the caudate and putamen. Internal variations in the intensity of the acetylcholinesterase staining within the striatum apparently represent a compartmentalization of this latter structure that is thought to result from a mosaic of afferents that end in terminal clusters

Fig. 2.13 b The relationships between the basal ganglia, extended amygdala, and magnocellular corticopetal forebrain cell groups (including the diagonal band complex and the basal nucleus of Meynert). Observe that caudomedial portions of the nucleus accumbens may represent a mixed territory of striatal and extended amygdaloid elements. Acb, nucleus accumbens; B, basal nucleus of Meynert; BL, baso lateral amygdala; B8T, bed nucleus of the stria terminalis; CeMe, centromedial amygdala; OB, nucleus of the diagonal band; GP, globus pallidus; VP, ventral pallidum; \ \ \ \ \, caudate, putamen, and ventral striatum; / / / I 1, extended amydala, stippled areas represent corridors occupied by neurons of the magnocellular corticopetal cell complex.

a

----

Specific Considerations Type5 tumors,involvingcombinations of the above three regions andthefronto-orbitalarea, are relativelycommon.These are: 1) 4a Fronto-orbital, anterior insula, and temporomediobasal(temporal pole + amygdala + uncus). 2) 4b Frontoorbital, anterior insula, and parahippocampus. 3) 4c Frontoorbital, mediobasal temporal, amygdala, uncus, hippocampus,and parahippocampus (Case 2.15 on p. 166). 4) 4d Bilateral extension: temporal pole, insula, fronto-orbital.septalareas, anterior commissure to opposite fronto-orbital, insula,and temporal poleo(Case 5.19). Tumorsinvolving the totality of the transitional system are seen.Al! of the above types (1-4) are involved. These patients mayhavea certain degree of intellectual impairment and memory butwedidnot observethe Klüver-Bucy syndrome in any deficits, case.The tumors arising in transitional areas in their initial and intermediatephases do not spread to adjacent neocerebral areas, suchasthe superior,middle,or inferior temporal gyri, the superior.middle or inferior frontal gyri, or the central or occipital regions.In addition, these lesions do not grow into the basal ganglia.central nuclei, or into the ventricles (Cases 2.13, 2.14, 2.15; morecaseswillbe presentedin Vol.IV B). Furtherobservations. 1. Tumors arising in the amygdala (corticoidorzero-Iayeredcortex) usually remain within the amygdala anddo not expand or infiltrate into architectonically or phylogenetical!ymore advanced are as (such as the neighboring hippocampus).Amygdala tumors do not infiltrate through the anterior commissureto the other side. 2. Tumors arising in the hippocampus usually do not infiltrateintothefornix,cingulum,or parahippocampalgyri.Thispat-

ing feature of transitional system tumors, even though some of these tumors are among the largest encountered. Transitional tumors, as a result of this propensity to expand within the confines of the allocortical or mesocortical zones, respect the adjacent neocerebral are as, basal ganglia, and central nuclei (such as the claustrum, putamen, pallidum, nucleus caudatus, thalamus, hypothalamus), and internal capsule. The spread of these tumors within the transitional zones tends to be toward phylogenetically or architectonically more primitive areas, and not in the opposite direction, toward more advanced or complex zones. The biological factors responsible for these phenomena are open to speculation, but may involve containment by the segmental vascular system, or inhibition by neurotansmitter concentrations distinctive to these areas, or both.

Tumors of the Basal Ganglia and Central Nuclei The basal ganglia and central nuclei represent the gray matter of the central telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon. Though the term "basal ganglia and central nuclei" is used, we perceive these tumors as arising from the glial cells supporting white-matter fibers that run between and through these nuclei. The tumors of the central nuclei are divided into supratentorial and infratentorial groups, as outlined in Table 2.7. Primary tumors of the basal ganglia and central nuclei are rare. In our series, there are no cases of tumors originated in the putamen, pallidum, or claustrum. Those that occur in this region arise from the head of the caudate, the thalamus, and the hypothalamus.

ternholdstrue for a majorityof limbicand paralimbic tumors.

3. Unlike tumors in the neocerebral subpallium, tumors of the caudal orbitofrontal lobe or anterior insula-temporal pole readilytraverse one of the association bundles (the uncinate fasciculus)to infiltrate rapidly from one are a to another. 4. The limbic and paralimbic areas can be divided into four primaryregions. A variety of tumor growth patterns are observed,but early tumors tend to remain confined to a single sub(suchas1a, 1b,or 1c, temporal pole, amygdala,uncus hipregion pocampus,parahippocampus). 5. Insular tumors may remain isolated (region 3), spread withintheinsularregion,or spread to neighboringregions (such asthefrontaland temporal opercular regions, along the uncinate fasciculus ).

6. Tumorsof the cingulum occur in subregions 2 a, 2 b, and 2c.Solitarytumors of the fornix (1 e) and mamillary body (lf) alsooccur. 7. Many intraventricular tumors (paraforaminal) may originatefromtheseptal region (1g). 8. Extensionalong the connective fibers of the limbic lobe to themesencephalonhas been seen only in one case, which will be presentedin Vol. IV B. 9. Involvement of the en tire limbic and paralimbic system canbeseen unilaterally or bilaterally. Conclusions. Transitional tumors remain well localized at their siteoforiginfor a considerable period of time, and even up to the finalstagesofgrowththey remain confined within their architectonic(andthus,phylogenetic)system of originoIn the initial and intermedia te phases of tumor growth, this confinement is a strik-

139

Table 2.7

Tumors of the basal ganglia and central nuclei

Supratentorial Telencephalic Caudate Claustrum Putamen Globus pallidus Diencephalon Epithalamus Metathalamus Thalamus Subthalamus Hypothalamus

basal ganglia

}

Lentiformnucleus }

Infratentorial Mesencephalic Dorsal (tectum: colliculi, brachii) Tegmentum Base of Peduncles (crus cerebrii) Metencephalic Pons Pedunculi cerebelli Superior (cranial, rastral, brachium conjunctivum) Middle (brachium pontis) Inferior (caudal), corpus restiforme Cerebellar nuclei Dentate, fastigial, globiform, emboliform Myelencephalic

--

140

2 Neuropathology Much like a glioma in the subpallial region, a glioma arising in one of the supratentorial central nuclei begins as a small, discrete nidus that expands centrifugally in all directions (Figs. 2.14-2.16). With enlargement, it distorts and displaces the surrounding structures, such as the internal and external capsules

and adjacent nuclei. Nonetheless, with growth it continues to

a

b

e Fig.2.14 Growth patterns for central nuclei tumors (coronal views) a Glioma originating in the left thalamus and expanding locally b Expansion beyond the thalamus into surrounding white matter. Note that the affected fiber bundles are separated, as are the neighboring vascular structures e Right thalamic glioma expanding (without ependymal penetration)

into the lateral ventricular

cavity

"respect" their anatomical fiber tract borders. In most cases, supratentorial central nuclear gliomas are unilateral and mesoscopically well-demarcated from the surrounding structures. Medially, these gliomas may indent and distort the ventricular wall, but violation of the ependyma and internal glial membrane (with intraventricular penetration and CSF dissemination) is rare. Laterally and superiorly, these tumors may expand into the subpallial white-matter of an adjacent lobe or gyrus, but not into the transitional are as. It is also characteristic for a tumor arising in a central nucleus to remain in the segment of the nucIeus from which it originated (i. e., the dorsal or caudal thalamus, pulvinar, head of the caudate nucleus, etc.). Infiltration into long projection, association, or commissural fiber systems does not occur. The most common areas of whitematter involvement are the connections between the caudate and lentiform nuclei anteriorly in the retrolenticular regio n posteriorly. Most thalamic and hypothalamic lesions remained unilateral. However, occasionally bilaterallesions occur (see IVB). Extension through the internal capsule into the lentiform nuclei occurs only in the final phase (Fig. 2.14 b). Similarly, tumors of the lentiform nuclei infiltrate through the internal capsule to reach the claustrum and thalamus only at a late stage. Gliomas of the caudate nucleus occur only in the head of the caudate, and never extend into the tail; in one case, bilateral occurrence was observed by the neuropathologist. This contrast with tumors of the fornix, which can display extension along the body of the fornix bilaterally to reach the trigonum, without extensions or penetration into the thalamus, hippocampus, or parahippocampus. Unlike their counterparts in the supratentorial compartment, infratentorial central nuclei gliomas (brainstem) demonstrate a dichotomy in their behavior that depends upon their location (Fig. 2.17). Dorsal, lateral, and ventral mesencephalic tumors are frequently well circumscribed. Basal and tegmental mesencephalic tumors, on the other hand, tend to be diffuse. Only a minority of pontine tumors (10%) are well demarcated and unilateral. The remaining 90% are primarily diffuse and bilateral, remaining within the pons or extending cranially to the mesencephalon and diencephalon, or caudally to the myelencephalon. Pontine gliomas commonly infiltrate along the middle cerebellar peduncle into the cerebellar hemispheres. Pontine lesions expand caudally along the corpus restiforme, but do not infiltrate the inferior cerebellar peduncle and vice versa. No explanation exists for the propensity of central brainstem gliomas to grow in such a diffuse fashion within the pons. However, they frequently present an exophytic growth tendency dorsolaterally or ventrolaterally. Perhaps an explanation for this growth of pontine gliomas may be found in the complex weaving of the horizontal and vertical white-matter tracts that characterize the basis pontis. Alternatively, the vascularizationpattern of this area may be relevant. In any case,even in those patients with a pontine glioma who survive for two or more years, infiltration into the spinal cord is not seen, and only rarely is there spread rostrally into the peduncles of the telencephalon. This lack of infiltration into these areas does not appear to be related to the patients' relatively short survival periodo Perhaps tumors in this location

Specific Considerations arelessaggressivebiologically, or the tumor-suppressor environmentrnaybe more effective. Might it be that a "borderline" exists between the brainstem (embryological metencephalon and mesencephalon)and the other anatomical subdivisions of the nervous system (myelencephalon, diencephalon, and teleneephalon)?Such a "borderline" (based on as yet unrecognized biologicalor vascular factors) might constitute a functional "line resistance"to tumor growth, perhaps related to higher concentrations of tumor-growth inhibitors, or better blood supply and immuneresponse in some are as. Answers to these speculative questionsremain elusive. A final observation noted in brainstem tumors is the relatively common occurrence of astrocytomas, gangliogliomas, ependyrnomas,and cavernomas, while glioblastomas are rare, and oligodendrogliomas are extremely rare (see Cases 3.32, 4.32-4.37,5.28-5.30,5.33-5.38). lt is surprising that patients with brainstem tumors and presentingwith minor symptoms, do not have involvement of long traetsignsin the initial phase. (One frequently sees patients with diplopia,who are able to walk and can even be active in some sports.)Thisis because the fiber tracts are not destroyed but just displaeedby the intervening tumor growth.

141

Internal rnedullary lamina

Fig.2.15 Predilection sites 01thalamic tumors 1 Anterior nucleus 2 Ventral nucleus 3 Not observed 4 Pulvinar 5 Centrallocalized gliomas, originating Irom the internal medullary lamina, with diffuse growth A Anterior nucleus LO Lateral dorsal nucleus LP Lateral posterior nucleus MO Medial dorsal nucleus VA Ventral anterior nucleus VL Ventral lateral nucleus VPL Ventral posterior nucleus VPM Ventral posterior nucleus

b

ir I

LJ Fig.2.16 Growth paUern 01 gliomas arising in the caudate nucleus head a Sphericalinitial intermediate growth within the capsule 01 the head 01the left caudate nucleus with compression and deviation (but no penetration)01the surrounding structures

(coronal view) b Late-stage growth across the striatal liber cOllnections (into the lentilorm nucleus), with destruction 01 this pathway but preservation 01 other surrounding projection libers and nuclear structures

--

142

2 Neuropathology Fig.2.17 Artistic diagram 01 predilection sites 01 gliomas within the brainstem C Central, mostly dilluse DI Oorsolateral

L V a b e, d

Lateral mostlycircumscribed } Ventral Mesencephalon Pons Medullaoblongata

The circumscribed type of brainstem tumors have a tendency to grow in a paraaxial fashion to adjacent cisterns, or with centrally periventricular placed lesions, to the fourth ventricle. The diffusely growing lesions generally remain within an anatomic area (e. g. within the pons), but occasionally transgress these anatomical borderlines to extend rostral into the encephalon (see Case 5.36, page 357 and also chapter Brainstem Tumors in Vol. IVB).

d

Intraventricular Tumors The intraventricular designation includes tumors of the lateral, third, and fourth ventricles, tumors of the aqueduct, tumors arising from the walls of the ventricles and from the septal areas, and tumors of the choroid plexus (Table 2.8 a, b). Intraventricular tumors are divided into: 1) those that arise primarily within the ventricle, and 2) those that secondarily invade the ventricle from beyond its walls. As stated in the section on subpallial tumors, the vast majority of tumors that appear on imaging studies to invade the ventricle secondarily do not actually do so, as they are in fact contained by the internal glia limitans and the ependyma. Compared to the subpallial and central lesions, a wider variety of tumors arise in and around the ventricles (Table 2.8a, b). This is not surprising, considering the developmental migration of many neurons and glia from the subependymal plate layer.

Frequently encountered lesions in this group are meningioma, choroid plexus papilloma, colloid cyst, neurocytoma, astrocytoma, subependymal giant-cell astrocytomas, teratoma, and ependymoma. A large majority of tumors in this region are well demarcated and removable. At surgery, it is clear that most do not transgress the ventricular ependymallining (an exception is the ependymoblastoma, which extends and invades in both intraventricular and periventricular directions) (Fig. 2.18 a-e). Curiously, meningiomas of the third ventricle are distinctly rare (see Case 5.19, p. 345), while those arising in the trigone are not uncommon. Choroid plexus papillomas of the third ventricle and meningiomas of the fourth ventricles are rarely seen. Some of the lateral ventricular tumors that appear to originate within the ventricular system actually arise from the septum pellucidum and be long to the transitional tumors types.

Specific Considerations Table 2.8a

Intraventricular

Lateralventricle

Thirdventricle

Aqueduct Fourthventricle

tumors: anatomical

sites of origin

Frontal horn Body (celia media) Septum peliucidum Trigone Posterior horn Temporal horn Anteroinferior (infundibular part) Anterosuperior (foramen of Momo) Posterior

Table 2.8b

Intraventricular tumors: origins of common tumors

Site of origin

Tumor type

From the ventricular wali

Ependymoma, subependymoma Astrocytic tumors Neurocytoma Oligodendroglioma Tuberous sclerosis (giant celi) Craniopharyngioma Optic glioma Ectopic pituitary adenoma Pinealoma Germinoma Teratoma Thalamic glioma Medulioblastoma Acoustic neurinoma Choroid plexus papilioma

From the periventricular region, expanding into the ventricle

Superior Lateral (foramina of Luschka) Inferior (foramen of Magendie)

From within the ventricle, especially the trigone and fourth ventricle From within the ventricle, especially the trigone (and occasionally from the third ventricle)

Fig.2.18 Predilection sites of intraventricular and periventricular tumor s a Lateralventricle 1 Frontobasal medial-origin mostly from septal area 2 Frontobasallateral-originmostly from caudate head 3 Gliomasfromthe septum peliucidum 4 Dorsaliyextendingthalamic gliomas 5 Precunealgliomas in the precuneus, isthmus area, and lingual gyrus 6 Cunealgliomasfrom the cuneus 7 Gliomasfromthe fusiform gyrus, 02, and 03 8 Gliomasfromthe parahippocampus and lateral temporo-occipital gyrus GliomasIromthe parahippocampus and inlerior temporal gyrus Temporalmediobasalgliomas lrom the amygdala, uncus, and hippocampus Retrolenticular gliomas Intraventriculartumors, such as oligodendrogliomas ependymomas,plexuspapiliomas,and meningiomas

143

Meningioma Craniopharyngioma (in the third ventricle)

b Intraventricular and periventricular tumors 01 the third ventricle, and periventricular tumors extending into the ventricles mimicking an intraventricular les ion Hy Proper third ventricle tumors: glioma, neurocytoma, meningioma, cavernoma, and metastasis 1 Gliomas 01 the amygdala and parahippocampal areas 2 Adenomas, Rathke's cyst 3 Craniopharyngeomas, epidermoids 4 Optic gliomas 5 Subcallosal-septal gliomas 6 Gliomas 01 the caudate head 7 Gliomas 01the septum pellucidum and lateral ventricle 8 Gliomas 01 the lornix 9 Colloid cyst in the loramen 01 Momo 10 Plexus papilloma 11 Gliomas 01 the thalamus 12 Hamartoma 01the mamillary body 13 Gliomas 01 the ventral mesencephalon 14 Gliomas 01 the dorsal mesencephalon 15 Pineal and parapineal tumors 16 Gliomas 01 the isthmus area

144

2 Neuropathology Fig.2.18c Tumorin the fourth ventricle 1a Superior median and paramedian 1b Inferiormedian and paramedian 2 Posterior (fastigial) 3 Lateral

Tumors of the fourth ventricle may arise primarily whithin the confines of the ventricle (subependymoma, ependymoma, plexus papilloma) or extend secondarily into the cavity (astrocytoma, ganglioma, cavernoma, medulloblastoma, dermoid and epidermoids). Although the fourth ventricle is a very small space, there are four main predilection sites (Fig. 2.18c), which can be differentiated.

Tumor Infiltration Burger (1990) considered the great affinity of neoplastic cells for fiber pathways (Maxwell1946, Matsukado et al. 1961, Burger et al. 1988, Burger 1990). He describes the corpus callosum as the best known of these routes, especially for glioblastomas that arise from the lobar peduncle of the frontal and parietallobes. A proposed second conduit is via the fornix (Burger 1990), reached either in the superior-medial temporal lobe orsubjacent to the

corpus callosum. Another alleged route of spread is via the anterior commissure, through which frontal and temporal lesions cross the midline to reach the contralateral side. Burger states that the optic radiations, cerebral peduncles, and multiple association pathways that link functional regions also serve as cornmon routes of spread (Fig. 2.19).

Fig.2.19 Proposed common pathways of glioma spread (fromBurger et al. 1982, 1990, 1991).Our observations suggest that routes 1,4, and 5 may occur, but only in the late phases of glioma growth. Routes2 and 3 have not been observed 1 Corpus callosum 2 Fornix 3 Optic radiations 4 Association fibers 5 Anterior commissure

Tumor Infiltration The view that glial tumors frequently demonstrate widespreadearly dissemination, and the belief that peritumoral density(intensity) changes on imaging tests represent infiltration, are refutedby the followingobservations. (1) Recurrent tumors, even thosethat recur months or years after removal, tend to be found at thesamesite (Fig.2,20a, b). This is a well known phenomenon Ihat is widelydocumented

in the literature. (2) The incidence of

multicentric tumors is low, averaging 5-6% in most large series (4% macroscopic and 6% microscopic in Russell and Rubinstein's series). In most of these cases, the tumors prove to be glioMultiple gliomas of other cell types are rare. (3) Glioblastomas. matosiscerebri is an extremely rare condition (0.05%). (4) A higherincidenceof gliomatosis cerebri has not been reported in fue MRI era. Our observations concerning the initial site of gliomasand the pattern of expansion do not confirm the descriptionsof Burger. As asserted in the section on subpallial tumors, low-gradeglioma,anaplastic glioma, and even glioblastoma show apropensityto remain confined within their initiallocation (subcortical,segmental,gyral, and lobar sectors). The routes of spread are restricted for a long time by the local vascular system and otherunknown factors. We have discussed and confirmed this obvious discrepancy withBurger,who concedes that most neuropathological observationsaremadeon the brains of patients who survived until the terminalphasesof the disease and who have undergone surgery and radiationtherapy. We also have observed dissemination along the CSFpathwaysin the terminal phase of glioma patients who have undergonesurgery and radiotherapy. This mode of spread, however,isnot seen in these tumors during the initial and intermediatephases. Certain gliomasoriginating within the subcortical, gyral, and lobarsectors,however, may show extension (expansion with and without infiltration) along the short associative fibers to reach neighboringsubgyri, through the uncinate fasciculus (transitional tumors)or acrossthe corpus callosum (rare tumors of the frontal or parietallobar pedunde). This mode of infiltrative spread may

Fig.2.20 Recurrentgliomas: commonsites(horizontalviews) a Recurrent rightIrontallobe glioma.Recurrentgliomasmost frequently ariseat the site 01initial presentation. Thechronology may be:glioblastoma alter one year, anaplasticgliomaalter 3-5 years, benign(Grade11)astrocytomaalter 8-10years b Thepatterns01spread lor recurren!gliomas.Alter initialrecurrence attheprimarysite(in the walis 01the prevlous tumorcavity),recurrent tumorsIrequentlyspread via surgical pathways (throughthe pia into the subarachnoid space,or through the ependyma intothe CSF),contralateralspreadacrossthe lorceps major(orminor)mayalso occur (arrow)

145

relate to the special arterial and venous patterns in these territories (Case 2.38). Primary su1cisuch as the sylvian, parieto-occipital, ca1carine, transverse, and interhemispheric fissures are not traversed by intrinsic tumors. Gliomas respect the double layer of pia, which must be traversed in crossing a su1cus to invade adjacent gyri. AIso, these tumors usually respect the layers of the membrana limitans gliae (external and internaI) and pia. Occasionally, they are seen to distend these layers and expand, mushroom-like, over the neighboring gyri. It is extremely rare for gliomas to penetrate the pia or arachnoid and spread along the cranial-spinal axis via the subarachnoid space with the exception of insular anaplastic gliomas) (see Case 2.40 on p. 186). This is only observed in the postoperative terminal phase. The belief that gliomas diffusely invade brain parenchyma, and that they have spread beyond the confines of the gross and radiological boundaries of the tumor by the time of their discovery, is one that pervades not only the literature, but daily neurosurgical practice. We do not dispute that malignant gliomas spread in this way, but we add the proviso that this does not occur until the terminal phases of tumor growth. The infiltration of gliomas into neighboring gyri, into the ependymallayer, or into the pia, is a late occurence, the tumor having been present at its initial locus for some time. Several examples of these observations are presented at the end fo this chapter. Intrinsic tumors frequently lie in one place for a long time with no infiltration into surrounding tissues. On the other hand, there are examples (see Case 2.31 on p. 179) of these same tumors (5-10%) that behave aggressively, respecting no margins, and infiltrating deeply into surrounding structures. In these cases, there is severe adhesion to surrounding tissues, with destruction of all bordering layers. The reason for this sudden change in tumor characteristics is not well understood, but may reflect the same aggressive change of behavior observed in some intrinsic lesions.

146

2 Neuropathology

Peritumoral Changes The peritumoral intensity changes dramatically displayed on CT and MRI studies have received a great deal of attention as to their significance. The issue is, which imaging changes are due to tumor per se, and which are related to nontumoral changes (i. e., are reactive). Much has been written correlating peritumoral tissue changes evident on neuroimaging studies with postmortem examinations. It has been proposed that the changes are secondary to compression of normal brain, to edema, to vasoactive substances acting on the blood-brain barrie¡;, to infiltrating cells, or to metabolic tissue changes. Perhaps the answer is a combination of some or all of the above. Although the pattern of peritumoral change is often identical in a wide variety of pathologic situations, many believe that the peritumoral changes have different causation in different processes. Still, the question always comes down to what the changes mean in an individual case. In the face of considerable peritumoral edema, some tumors (especially meningiomas, anaplastic gliomas, hypernephromas, and melanomas) can be expected to exhibit significant adherence or infiltration into surrounding brain, or both, while others (metastatic cancers, lymphomas, and. plexus papillomas) demonstrate no such behavior. Conversely, some tumors (acoustic neuroma, epidermoid, dermoid, craniopharyngioma, adenoma, oligodendroglioma, chordoma, etc.) may manifest striking adherence, infiltration, or both, without any evidence of peritumoral edema (see Table 3.7, p. 204, and pp. 203-207). Overall, marked hyperintensity from peritumoral focal or holohemispheric changes is observed in glioblastoma (90%), anaplastic astrocytoma (75%), metastatic tumor (75%), meningioma (70%), abscess (95%), parasite infestation (25%), radionecrosis (90%), and neurinoma (5%). There are suggestions that these findings depend on lesion location, as both benign and malignant tumors situated in regions of rich venous drainage often have no peritumoral changes. We have observed that the pattern of these changes closely resembles the venous drainage patterns of the cerebral white matter, as outlined by Hassler (1964) (Figs. 1.94, 1.96, pp. 110,111, Cases 3.52-3.56, Table 3.7, p. 204). The presence of these changes around a meningioma signals an increased adherence of the tumor to the arachnoid and pia (as discussed on p. 147). It has also been shown that these peri-

tumoral findings may relate to (1) estrogen or progesterone activo ity by the tumor; (2) malignant change; (3) compression ofnormal brain, with alterations in cerebral blood flow, the cerebral metabolic rate of oxygen, glucose utilization, and oxygen excretion (compressiveischemia with compromise of the blood-brain barrier); (4) venous mechanical obstructions; and (5) elevated hydrostatic pressure within the tumor (secondary to hemorrhageor rich vascularization). In glioblastoma, it is postulated that the peritumoral hyperintensity changes may represent (1) edema secondary to the release of vaso active peptides by the tumor with damaged parenchyma and consequent blood-brain barrier breakdown; (2) tumor cells infiltrating along the white-matter tracts; (3) metabolic changes in the white-matter, such as alterations in cerebral blood flow, the cerebral metabolic rate of oxygen, glucose utilization, and oxygen excretion; or (4) compression or thrombosis of the deep medullary venous system. Although (1) and (2) maybe present in some cases, they are not constant factors. Burger and Vogel (1988) studied eleven cases to determine the microscopic extensions of gliomas in relation to the contrast-enhanced rimon CT, and concluded that "the distribution of tumor cells cannot be inferred from CT images, since peritumoral changes may over-or underestimate the tumor's extent." Metastatic tumors often ha ve the most peritumoral changes, but no studies have shown that these changes reflect tumor invasion. Usually the contrary is found at operation. It is erroneous to always equate the presence of a tense and swollen brain with edema formation. After the removal of a lesion with marked peritumoral changes, the brain is usually very relaxed, even though the white-matter changes may persist for months or years after removal. This is particularly true in meningiomas (Case 3.59, p. 245). The white-matter changes in malignant gliomas usually disappear after complete removal, clearly refuting the argument that these changes reflect tumor invasion. It is quite clear that the presence of peritumoral changes,per se, should not deter the neurosurgeon from planning a complete tumor removal. At the present time, there are no definitive answers as to the significance of these changes in any individual case (Cases 3.52-3.58, pp. 243-245).

Tumor Demarcation The concept of demarcation (i. e., clear separability, or a distinguishable border) between different biological tissues is easily appreciated with regard to most extrinsic tumors. In addition though, many intrinsic tumors are also well-demarcated when observed under operating conditions. This point stands in contradiction to the statement of Greig (1989): "An important aspect of primary brain tumors is the diffuse border that exists between the tumor tissue and the surrounding brain, which cannot be demarcated macroscopically... it is difficult for a neuropathologist to determine where exactly brain begins that is completely free from neoplastic invasion." This is correct for the gliomas in their final stage.

Under the mesoscopic view of the surgical microscope, a discernible plane of demarcation can be found in most intrinsic tumors in the early phase (Fig.2.21). Of course, microscopic tumor extension beyond this apparent demarcation is outside the resolution of the operating scope (5-10 x), so the smallest extensions of infiltrating astrocytic tumor cells (detectable histologically) cannot be appreciated during surgery. No reliable method of detecting tumor extension at the time of surgery exists. It is clear that recurrent glial tumors nearly always return at the site of previous occurence (Fig. 2.20). Those factors (vascular or fiber topography, inhibitory proteins) responsible for the circumscription of the initial tumor continue to restrict the spread of

Brain-Tumor Interface: Adherence and Adhesiveness

147

b Flg.2.21 Glialtumor demarcation a Coronalsection.A left lrontallobe glioma which is well demarcated by glioticchanges in the surrounding white matter. This peritumoral 'capsule"maybe produced by either hardening or softening 01the surrounding whitematter

b The "encapsulation" 01 a similar glioma, resembling that 01 an

therecurrence.In addition, any tumor cells remaining after initial

sis can be totally deceiving.A note of warning must be given. It has occasionally been our experience to have easily removed a discrete and nicely circumscribed meningioma-like lesion, only to have the histopathological diagnosis return as glioblastoma and, conversely, to have removed a diffuse, poorly marginated gliomalike mass, only to have the final pathology return as meningioma.

surgicalremoval must reside in the immediate vicinity of the originaltumor.The only other possible explanation is that those factors(genetic,molecular, viral) responsible for inducing the initial tumorarestillpresent, resulting in another new tumor in the same location.

abscess

Thetendency of surgeons to equate the presence or absence ofacleardemarcation plane with a presumed histological diagno-

Brain-TumorInterface:Adherence and Adhesiveness Benignand malignant tumors in both the intrinsic and extrinsic categories haveunpredictable reactions with local surrounding tissues. As a consequence, a pseudocapsular formation arises aroundsomeextrinsic and intrinsic tumors (Table 3.8, p. 205). The interfacebetween the tumor mass and the surrounding tissues is a \'itallyimportant zone for the neurosurgeon, for it is at this site thatthefinal determination of resectability is made. The existence anddegreeof adherence of a particular tumor to the pia and arachnoid,blood vessels, dura, sinuses, and glial surfaces often cannotbe reliably predicted preoperatively by angiogram, CT, or MRI. Usually, it is familiarity with tumor adherence characteristicsframpast experience that provides the best guide as to what to expectwith future tumors. However, unwelcome surprises involvingunbelievableadhesive difficulties are more common than we wouldlike (Fig.3.47, p. 239). Our experience has demonstrated that the degree of adherenceisnot particularly related to the tumor type or classification. Meningioma,craniopharyngioma, glioma, papilloma, teratoma, some neurinomas, and metastatic tumors may have partial, subtotal,or total adherence to the surrounding tissue. The explanation for this tremendous variability defies current analysis and meritsfuture study.The physiology and reactive properties oi the

arachnoid system are poorly understood. Perhaps the extreme degrees of adherence reflect exaggerated (and abnormal) biochemical, inflammatory or autoimmune reactions between the arachnoid and the tumor surface. A better understanding oi the mechanisms of this process may lead to preoperative or intraoperative targeted agents that soften or reduce tissue adhesiveness (see Table 2.9). MRI has shown some promise in characterizing tumor consistency (e. g., differentiating Antoni A from Antoni B types of acoustic schwannoma). More studies correlating tumor texture, composition, and adherence characteristics (as demonstrated at surgery) with MRI would be beneficial in operative recommendations, especially as regards the timing of surgery and the assessment of morbidity risks. Specific points relating to the adhesion characteristics of tumors are: (1) Small and large meningiomas with imaging evidence of increased peritumoral intensity of MRI or decreased density on CT usually exhibit marked arachnoid-pia adherence, with atrophic glial changes on the underlying cortex (see Cases 3.43, 3.45 on pp. 236-7). Meningiomas, with minimal or no peritumoral reaction on imaging, are usually dissected from the adjacent tissue

148

2 Neuropathology

with little difficulty (see Cases 3.42, 3.44, 3.46, and 3.51 on pp. 235-242). (2) Neurinomas rarely have peritumoral hypodensity, and rarely demonstrate adhesion with the pia layer of the cerebellar lobulus, pons, and medulla, but do adhere with nerves seven and eight. (3) Craniopharyngiomas demonstrate surprisingly little peritumoral edema and tissue reaction on imaging (even in large, cystic lesions). Yet despite the paucity of peritumoral imaging changes, these tumors are notoriously very adherent (see Case 3.47 on p. 239). (4) Glioblastomas can be very adherent to the arachnoid and dura; this feature appears tó be independent of the degree of perilesional changes. (5) Lymphomas do not seem to produce perilesional changes. (6) Metastases often produce a high degree of peritumoral change, but are rarely adherent (see Table 3.7, p. 204).

(7) In some cases, piloid astrocytomas, gangliogliomas, and especially oligodendrogliomas, there is a tendency to escape through the piallayer and to infiltrate into the arterial adventitia. Table 2.9 Surgically observed variables between peritumoral socalled edema and changed interface (adherence and adhesiveness) Edema

++ / Adherence

++

Edema Edema

++ /Adherence / Adherence

++

Edema

-

/ Adherence -

Meningioma. metastasis (hypernephroma). acoustic neurinoma. glioma Metastasis (Ca). Iymphoma. abscess Craniopharyngioma. adenoma. chordoma. dermoid. oligodendroglioma. plexus papilloma Cavernoma. hemangioblastoma. chondroma. optic glioma. adenom. craniopharyngioma. meningioma, neurinoma

++ Severe - None

Tumor Vascularization A quantitative and qualitative determination of the peritumoral vascular state with contrast CT scan and MRI, together with angiography and a presumptive diagnosis of the tumor type, typically provides the neurosurgeon with some assurance that the patient can be offered safe surgery. Nevertheless, our surgical experience indicates that many features of tumor vascularity are unmeasurable and unpredictable. The angiographic features of both extrinsic and intrinsic tumors were studied extensively between 1930 and 1970. The patterns of vessel shift tumor blush, venous stasis, and neovascularity, and the changes and qua lity of the cerebral blood flow in and around the tumor are described thoroughly in numerous publications and monographs. For the performance of tumor surgery, this information concerning vascularity and cerebral blood flQw (in and around the lesion) is of great value. The vascularity of a tumor is estimated on CT and MRI by noting the intensity of contrast enhancement. MRI "flow voids", which may penetrate or encircle a tumor, can also been seen. Magnetic resonance angiography (MRA) can be very helpful in the precise indentification of peritumoral and intratumoral vascular structures. Other vascular changes in and around tumors may be angiographically undetectable, including the development of increased local collaterals, fistulas, microaneurysms, and sinusoids. Huang et al. (1964) noted that this increased vascularity in the normal white-matter surrounding glioblastomas may correspond to "remarkable dilatation of the adjacent normal medullary vessels." The relationship of these changes to peritumoral edema seems clear. On histological examination, pathological vessels are often found to be deficient in the normal anatomicallayers. These vesseIs demonstrate marked fragility on manipulation and an inability to constrict reflexly when cut. Along these lines, about 5% of tumors in our experience show a marked and unpredictable fragility of their vascularity, which occurs independently of tumor type (benign and malignant). Due to these abnormalities, difficulties

with proper hemostasis can occur in the resection of some adenomas, gliomas, ependymomas, plexus papillomas, medulloblastomas, and angioblastomas. Normally vascularized or hypovascularized tumors do not present problems with blood loss or hemostasis, provided they are devascularized properly and in sequential steps. Even many hypervascularized lesions can be controlled easily with stepwise devascularization using standard microsurgical techniques. A highly vascular tumor with high flow characteristics should be approached with special attention directed towards reducing the input of the arterial feeders before any attempt is made to remove the tumor. Draining veins are preserved until later, when the tumor is well isolated from its arterial blood supply. Embolization of larger feeders in meningiomas, neurinomas, and glomus tumors does not guarantee a relatively bloodless field, and even the experienced surgeon may have almost insurmountable difficulties when encountering very vascular tumors of these types. Historically, neuropathology has provided valuable descriptions of the idiosyncracies of tumor vasculature, primarily from a histopathologic perspective. Tumor capillary endothelial abnormalities, such as failed tight junctions and endothelial fenestrations, explain, at least in part, tumor vascular "leakiness" and peritumor al edema formation. The identification of a series of tumorsecreted angiogenic factors has opened up a promising field oí research, with possible therapeutic applications. Continued investigation into the dependence of tumor growth upon the coincident development of its vasculature is needed. Venous thrombosis. Thrombosis of arteries around and within intrinsic tumors occasionally occurs (meningiomas, craniopharyngiomas). However, the thrombosis of small, modera te, and large veins within a intrinsic tumor is a pathognomonic sign of malignancy. While this is very frequent in glioblastoma, it is also seen other gliomas (including the anaplastic variety), with angioblastic meningiomas, with neurinomas PNET, and with lymphomas.

The Numbers and Types of Tumors Unfortunately,this firm indicator of malignancy cannot be visualizedon imaging studies, including MRI, MRA, or selective angiography.This tendency for venous thrombosis cannot be

The

149

explained by mechanical and hemodynamic factors alone, as it never occurs with benign extrinsic and intrinsic tumors. It certainly appears to be a biologically induced phenomenon.

Numbersand Types 01 Tumors

Although some pathological entities are most commonly seen as

processes (i. e., demyelinating or infectious), neoplastic diseaseof the CNS is most frequently solitary (95%), with multidiffuse

centricity less common (0.3%) (Cases 2.41, 2.42), (Case 2.24). This pattern orderssuchas aneurysma

(4.5%), multihistological types rare and diffuse varieties very rare (0.1 %) is similar to that seen in vascular dis-

and AVMs (Table 2.10).

Definitions.A. A unicentric tumor is a solitary, singular, separateoindividualprocess that

nonetheless may be bilateral if

encounteredin the midline. B. Mu/ticentric tumors grow simultaneously or consequently,but are topographically remote from each other, withoutevidenceof disseminationby seeding or direct extension andwithout demonstrablemicroscopiccontinuity (Reichenthal 1983).In simple terms, multicentric tumors develop totally independently. Accordingto Russel and Rubinstein (1989) most cases of assumed multicentricity take the form of one or more small inconspicuous foci, situated on the periphery of the main tumor

Table 2.10

CNS disease processes:

patterns

Disease of the CNS

Pattern of morphological changes

Neoplasms

Unicentric > Multicentric > Multihisto- > Globallogical type type "-matosis" Unicentric > Multicentric > Diffuse

Vascular disease Infectious disease

Unicentric < Multicentric < Global (Abscess) (Meningitis) (Parasites)

Demyelina-

(Encephali-

tis) Unicentric < Multicentric < Global

tion

mass. True multicentricity, in which the tumors are widely separated is exceptional. The pattern of growth for common CNS tumors are shown in Table 2.11. The occurence of multicentric

Table2.11 Patterns of occurrence in CNS tumors Tumor

Unilateral Unicentric

Extrinsic Meningioma Neurinoma Chordoma Chondroma

Craniopharyngioma Adenoma Fibroma Glomustumor Pineal tumor

Teratoma

Epidermoid Dermoid Intrinsic Glioblastoma Astrocytoma

Xanthoastrocytoma Oligodendroglioma Ependymoma Ganglioglioma Medulloblastoma Hemangioblastoma Lymphoma Plexuspapilloma Metastasis

Multicentric

Bilateral

Diffuse

Global

+++ +++ +++

++ + -

+ +

(+) (+)

+ +++ +++

+

-

-

+++ +++ +++ +++ +++

-

+ + +

-

+

-

+ -

-

-

-

-

-

-

-

-

Unicentric

+ -

+ + + + + + + +

Metastasis

Aggressive growth

Multicentric

+ +

-

-

-

+ -

-

-

+ (+)

+ + + +

-

+ +

+ + +

+

-

+

-

-

+

+ + ...:.

+ -

+ + -

+ + -

+ -

+ +

-

-

-

-

-

+++ +++ ++

(+) -

+++ +++ +++ +++ +++ +++ +++ +

-

-

-

++ + ++

+ -

-

-

-

+ -

+

-

-

-

-

+ + + -

+ + +

+

-

?

-

+

+ + + + + (+) ? + +

150

2 Neuropathology

gliomas has been reported by many authors (Solitare 1962, Batzdorf et al. 1963, Solomon et al. 1969, Borovich et al. 1976, Bussone et al. 1979, Chadduk et al. 1983, Reichenthal et al. 1983, and Barnard et al. 1987). Kato et al. (1990) recently reviewed these cases. There is a considerable variation in the reported incidence of multicentric tumors (0.9%-10.0%) (Batzdorf et al.), but it average s 2-3%. For meningiomas, however, the introduction of modern neuroimaging has increased this rate to 5-10% (Domenicucci et al. 1989), with more than 90% of these in women. The pathogenesis of multicentric tumors remains elusive. Storch (1899) suggested that gliomas have the ability to induce neoplastic change in adjacent ~lial tissue. Ostertag (1936, 1941) postulated that these tumors arise from primitive cells (with a blastomatous potential) displaced during development. Later the concept was developed that these lesions arise from multiple embryonal rests scattered at different sites. This dysoncogenetic theory, however, do es no! explain the chronological delay between brain maturation and tumor appearance. Perhaps this is what led Zülch (1957) to suggest that the only difference between multiple and multicentric lesions is that the latter disseminate by as yet unrecognized pathways. Other theories were presented by Willis (1960), who suggested that multifocallesions develop as a result of a staged neoplastic transformation occurring over diffuse areas and progressive proliferations at specific sites simultaneously, as a result of biochemical, hormonal, and mechanical factors. The possibility of such a premalignant state prior to the development of frank anaplasia was also suggested by Moertel et al. (1961), who proposed that it might be brought about by specific intrinsic or extrinsic carcinogenic influences acting on susceptible tissue over a sufficient period of time.

A familial occurence of glial tumors was noted by Heuch el al. (1986), who reported on glioblastomas in three family members, with one case being multicentric. Similar associations were made by Baughman et al. (1969) and linked to Turcot's syndrome. Kato (1989) suggested that underlying diseases such as neurofibromatosis, tuberous sclerosis, or multiple sclerosis are often responsible for promoting multicentric neoplastic changes. The etiology of multicentric meningiomas is probably the presence of multicentric dural foci, as multiple minute foci are frequently found around solitary meningiomas (Borovich and Doron 1986). Final answers on the genesis of multicentric glial tumors clearly await a better explanation of unicentric tumor formation. From a histological perspective, a solitary tumor characteristically has one cellular type (unitype), though on very are occasions (0.1%), more than one histological cell type (multitype) can be seen in the same neoplasm. Multitype tumors are observed more frequently in multicentric lesions, though even in this instance it is rare (0.3%) (Table 2.12). The majority of unicentric and unitype CNS tumors are unilateral (two-thirds), but bilateral tumors (both intrinsic and extrinsic) are common (one-third). These are all midline tumors, in the parase llar, callosal, brainstem, vermian, and paraspinal regions. Unicentric and multitype tumors are extremely rare (0.01%), with only two cases in the present series (one case of meningioma + glioblastoma, one case of optic glioma + dermoid). Multicentric and unitype tumors are frequenl (5-10%), and may be found in a variety of combinations of CNS divisions (Table 2.12, Cases 2.38-2.42). Unitype or multitype tumors can be uni- or multicentric (unilateral, bilateral, supratentorial and infratentorial, cranial and spinal).

Table 2.12 Unicentricity and multicentricity, histological unitypes and multitypes in tumors and vascular diseases in own series Glo Glomus tumor Meningioma Neurinoma Adenoma Craniopharyngioma Chordoma, Chondroma Dermoid Optic glioma Glioblastoma Astrocytoma Oligodendroglioma Ependymoma

Plexuspapilloma Ganglioglioma Medulloblastoma Germinoma Lymphoma Sarcoma Melanoma Hemangioblastoma Cavernoma AVM Venous angioma Aneurysm

+ + -

+ + +

M

+ + -

N + + + -

Ad

Cr

-

-

+ -

+ + -

+

+ -

-

-

-

-

-

-

+ + + +

-

O -

+ -

+

-

O Always unicentric and histological unitype (+) Multicentric, unitype + Multicentric and combined type

De

-

-

-

-

Op

Gli

As

-

+ + -

+ + -

+ + -

+ + +

+ +

-

-

-

-

-

-

-

-

-

+

01

Ep PIPa G.GI Med Ger

-

Ly

Sar Mel Hbl

-

-

-

-

-

-

-

-

-

-

-

-

-

+ -

-

-

-

+ + +

+ + +

-

-

-

-

-

-

-

O -

O -

-

-

-

-

-

-

O

Ca AVM V.A A

-

+

+ +

+ +

-

-

-

+

-

+ +

-

-

-

+

+

+

+ + -

+ + +

-

-

-

+

(+) ? +

? (+) + +

+ +

+

O -

+

-

Ch

+

-

-

-

+ + +

+ +

+ +

-

+ -

-

(+) +

-

-

-

-

-

-

-

-

-

+

O -

(+) -

O -

(+) -

(+) -

? + (+) + ? (+)

Conclusions Locationof Multicentric Tumors Within the CNS Cerebralor cerebellar (unilateral or bilateral)

Cerebellar and spinal: Cerebral, cerebellar and spinal:

meningioma, neurinoma, glioblastoma, astrocytoma, cavernoma, hemangioblastoma, medulloblastoma, metastasis. hemangioblastoma. gliomatosis, neuromatosis.

meningiomatosis

Multicentric-multitypelesions are quite rare (0.3%), with only onecasein the present series (see Case 2.41 on p. 187). Some com-

151

binations, such as oligodendroglioma and ependymoma, hemangioblastoma and glioblastoma, medulloblastoma and glioblastoma, cavernoma and glioblastoma, etc., ha ve not been reported. It is c1ear that the spectrum of CNS tumors encompasses a diverse group of lesions. This led Courville (1936) to conc1ude that practically every combination of tumors can be found within the cranial cavity from the standpoint of location, tissue of origin, degree of malignancy, etc. Modern neuroimaging for CNS neoplasms has enhanced our ability to study their patterns of growth. With careful scrutiny by many observers over long periods of time, we will eventually come to a better understanding of the biological pathogenetic features (as related to location, cell type, and multiplicity) of CNS tumors.

Conclusions

Predilectivesites. For extrinsic tumors, predilective sites at the skullbase and along the calvarium are well known. For intrinsic tumors, predilectivesitesare welldocumented (see atlasesof neuropathologyand MRI neuroradiology) but not well systematized (Table2.13).Tumorsoriginatingin a particular area remain in thatareaeitherdueto the segmentalvascularpattern the anatomi-

calborderline,the embryonic glial-neuronal migration network, the sectional CSF transcerebral pathway, or the host immune defensesystem.

Tumorbiology.Forall CNStumors (both benign and malignant), growthoccursin initial, intermediate, and final phases. The duration ofeachphaseis generally predictable for

a group of similar

tumors,but in an individual case it can be quite unpredictable. Therate of growth for a majority of tumors is more or less linear, butina minorityof neoplasms, unpredictable growth is seen (suddenwildgrowth, slow growth and rapid growth alternating, no growth,regression, etc.). Edema (perilesional hyperintensity), interfacialadherence, penetration and infiltration (with destructionofborderlines),and migration(dissemination)occur in both benignand malignant tumors. Fortunately, a majority of neoplasms(bothbenign and malignant) demonstrate respect for their borderlines,and usually they remain circumscribed and demarcated. Histologicalinvestigations have reached their limits. Future understandingof tumor activities depends on molecular and cellular biology(i. e., what substances are produced by the tumor parenchymato inactivate the macrophages, to paralyze the defensiveactivityof the neuroglia, and to increase the local supply for their own needs).

Extrinsictumors. (1) While respecting dural and arachnoid planes,these may grow to a very large size. (2) Some initially well demarcated tumors (e. g., meningiadenomas,chordomas,and craniopharyngiomas)suddenly amas, changetheir growth characteristics and behave aggressively, with infiltrationinto surrounding structures. (3) Someextrinsic tumors are associated with extraordinary degreesof adherence and adhesiveness, making total removal impossiblewithout morbidity (e. g., hypothalamic damage with somecraniopharyngiomas, cranial-nerve injury with cavernous sinusmeningiomas, chordomas,and chondromas).

/ntrinsic tumors. (1) These tumors show a precise predilection to arise from certain localized areas of the brain. The reasons for this remain unc1ear, but it may be related to cytoarchitectonic structure, phylogenetic development, or vascularization patterns. (2) Descriptions of tumor location based on "lobar" terminology are no longer tenable. Instead, the tumor location must be defined in terms of precise topographic anatomy. This approach aids the neurosurgeon in preoperative planning, and optimizes the precise removal of tumor without injury or removal of uninvolved brain. It also allows a more valid comparison between specialists and between institutions comparing treatment protocols. (3) Multicentric, diffuse, and global forms of astrocytic tumors are rare, comprising about 1-5% of the total tumor incidence. They do occur, but late in the biological course. During the early and intermediate growth phases, 90-95% of intrinsic tumors are unicentric and mesoscopically well demarcated from the surrounding tissues. (4) Demarcations formed by pial, arachnoidal, and durallayers are readily respected. The biological nature of the well-demarcated surgical plane at the interface between intrinsic tumor and nontumorous glial white-matter is poorly understood. Many tumor demarcation borders are well defined and easily identified, while some are indeterminate. Still other groups are characterized by adherence and adhesion, so that it is more difficult to dissect at the borderline. The demarcation characteristics of tumors are, at present, inadequately predicted with neuroimaging, and can only be accurately assessed at surgery. (5) Most intrinsic tumors have a predilection to originate at certain sites. This is especially true for subpallial (neocortical and allocortical) tumors. Tumors arising in the highly specialized are as of the visual, auditory, and sensorimotor areas (inc1uding language areas) are very rare and more of a diffuse type. Further research, incorporating modern data on phylogenetic and architectonic concepts may provide relevant information on tumor origin and spread. (Diffuse intrinsic tumors occur in the limbic lobe, central lobe, brainstem, and spinal cord.) (Cases 2.23-2.28.)

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2 Neuropathology

Table 2.13

Location 01 CNS tumors by pre1erred site 01 origin Infratentorial

Supratentorial

Extrinsic Epidural Intradural Subdural Interarachnoidal

++ ++ +++ +++

Intrinsic 1. Neocortical areas a. Primary sensorimotor isotypical cortical areas (1,2,3,4,17,41,42, 43, 4~) b. Unimodal association, homotypical cortical areas (5,7,8,18,19,20,21,37) c. Heteromodal association, hOlÍlotypical cortical areas (9, 10, 11, 12,39,45,46,47) 2. Allocortical and mesocortical areas (Limbic lobe) a. Paleocortical b. Archicortical c. Periarchicortical d. Transitional septal, amygdala 3. Central nuclei

" /

a. Putamen-Pallidum

basal dorsal

b. Head 01caudate Tail 01caudate c. Thalamus Pulvinar Medial Lateral 4. Ventricular Frontal Temporal Occipital Trigonum Third ventricle +++ ++ + (+) ?

Frequent, Moderate, Rare, Very rare, Unknown

Extrinsic Epidural Intradural Subdural Interarachnoidal

(+)

+ +++

++ (+) +++ ++ (+) ? + ? + (circumscribed)

}

+ (Diffuse)

Horn

++ ++ +++ +++

Intrinsic 1. Cerebellar a. Neocerebellar (LOP, LSS, LSI) (Declive, lolium) b. Paleocerebellar LOA, centrallobule, c. Archicerebellar Flocculonodular 2. Central nuclei

(+)

Extrinsic Epidural Intradural Subdural Interarachnoidal

+ + ++ ++

Intrinsic Juxtamedullary Intramedullary Central canal

++ ++ +

++ ++ culmen

++ ? ?

3. Ventricular

++

Brainstem Mesencephalon Tectum Tegmentum

Ruber Substantia nigra

}

Spinal

Base Pons Base

++ (+) Diffuse ? ? +

Tegmentum

+ (circumscribed) + (Diffuse)

Medullaoblongata

+

+ + LOA LOP LSI LSS

Anterior quadrangular lobule Posterior quadrangular lobule Inlerior semilunar lobule Superior semilunar lobule

(6) Our experience indicates that the majority of intrinsic tumors grow by spherical expansion. The proliferating cells of intrinsic tumors enlarge by insinuating themselves between the myelinated neuronal tracts. Concentric expansions split the whitematter tracts apart as the tumor grows. Neuronal axons appear remarkably resistant to actual destruction. Functional abnormalities, even with large tumors, are compensated for by the capacity of the central nervous system for parallel processing. (7) Astrocytic tumors arise most commonly in the subcortical white-matter and maintain a localized relationship with the subgyral, gyral, or lobar sector of origino Similarly, tumors arising in the central nuclei (although growing to a large size) rema in confined to their central origina. Intraventricular tumors stay within the ependymallining, even when causing huge distortions within the brain parenchyma. The biologic factors underlying these relative or absolute containments are poorly understood. (8) Most recurrent tumors arise at the previous original site

of the tumor, lending further support to the concepts of unicentricity and containment. (9) The spread of intrinsic tumors to a separate site within the CNS is rare (1 %) within two years of initial operation. The spread of astrocytic tumors outside the CNS is extremely rare (Leifer et al. 1989). (10) Our observations on the spread of astrocytic tumors conflict with commonly reported pathological series. These reports are based on less common examples of end-stage tumors following multiple therapies, and should nOt be regarded as representing the "normal" natural history. During the early and intermediate growth phases, most astrocytic tumors do not infiltrate along the large association, commissural, or projection white-matter bundles, with two exceptions: (a) the uncinate fasciculus and (b) the corpus callosum. Only poor-grade tumors in their endstages of growth have been pathologically proved to have diffusely infiltrated the brain.

Conclusions (11)Thrombosis of veins within intrinsic, and also extrinsic, tumorsisusuallya hallmark of malignancy that can be recognized intraoperatively.It is a biologically induced feature of the tumor, ratherthan being due to mechanical venous compression.

TheFuture (1) Moleculargenetics and cytogenetic studies have proved very usefui in identifying abnormal chromosomes in various tumors. Manyhumangeneticdiseasesare caused by genetic deletions. If thedeletionsinvolve important tumor-suppressor functions, then thepatient may be predisposed to develop one or more tumors ",hena further genetic event ("hit") occurs. Alternatively, or in addition,if a patient inherits an oncogene with a predisposition towardstumor expression, or if a mutation develops in a normal oncogene.that patient has the possibility of tumor development. inneuroblastomaand retinoblastomahave provided modStudies elsofthe likelygenetic mechanisms of tumor initiation. Why they developin any one individual is still unknown. Similar studies in glialtumorssuggesta cascadeof gene abnormalities,particularly involvingchromosomes 17, 9 and 10, which upset the balance the actionsof oncogenesand tumor-suppressor genes. between Lossofa tumor-supressorgene on chromosome22 appears relevantinmeningiomas. Further geneticresearch maylead to an abil-

itytodetectthose patients at risk for CNS neoplasms, and perhaps tothediscoveryof methods of repairing abnormal oncogenes. In thenearfuture, the optimal approach to brain tumors will involve thedeterminationof the cytogenetic profile of every tumor and a precisedefinition of its prognostic features. Only then can completeand specific therapy be properly planned. (2) Immunohistochemistry has proved very useful in identifyingcell types within tumors. Research on functional tumor pathophysiologymay identify more of the factors elaborated by tumorsthat relate to why certain tumors are soft or hard, why somearehighlyvascularbut others not, and why some are very adherentto surrounding structures while others have clear and easilydissectedsurgicalplanes. More has to be known about these featuresif further reductions in microsurgical morbidity are to be achieved. (3) Our observations have not provided a breakthrough in the development of adjunctive therapy. However, in this regard, we know that 95% of these tumors retain a unicentric, unitype appearance during their initial and intermediate phase of growth (in many cases). This implies that if effective adjunctive therapy can be developed, there is a "window" during which it can be applied. Thus, the outlook in this regard is not hopeless. Hopefully,the future treatment of these tumors will resemble that witnessedwith CNS abscesses, so that adjuvant therapy will be curativewithoutsurgery.

153

The Present (1) Our experience favors more precisely defined approaches, and surgical removal of all CNS tumors. The indications for reoperative surgery for intrinsic lesions are greater than previously supposed. (2) The goal of surgery in extrinsic tumors is complete removal using microsurgical techniques, but not at the expense of neurological morbidity. The indications for early reoperation are less clear now that more precise follow-up is possible with MRI. (3) Adjuvant therapies must be specifically adapted to the biological characteristics of each tumor. Mesoscopic insights into tumor behavioral characteristics, in combination with advances in neuropathological knowledge have resulted in a better conceptualization of how operability must be defined. In addition, this permits a better assessment as to a genuine cure, as opposed to a macroscopic "surgical cure." Neurosurgeons must move forwards into the twenty-first century and apply microsurgical philosophy to the full spectrum of CNS tumors in routine practice. It seems very likely that effective biological and chemotherapeutic therapies will be come standard in the management of many intrinsic tumors within the next five years. Precise microsurgical tumor resection to less than log 1 remaining tumor cells will be vital for both the quality and length of survival. Stereotactic methods, though having tremendous patient appeal, are unlikely to achieve this. The goals to be achieved are ancient: to relieve symptoms, to achieve complete tumor removal so far as the nature of the pathology allows, and to accomplish this without injury to normal structures. Within the following section, 45 cases are presented to illustrate the various pathological problems that we have discussed in this chapter. The cases include Case 2.1-2.20 2.1-2.9 2.10-2.19 2.20-2.21 2.22 2.23-2.26 2.27 2.28 2.29 2.30 2.31 2.32 2.33-2.37 2.38-2.40 2.41-2.42 2.43-2.45

Well circumscribed tumors Neocerebral cases Limbic and para-limbic system Rare internal capsular tumors Retrolenticular area Diffuse tumors Slow growing tumor within a highly eloquent area Fast growing recurrence (within 4 weeks). Natural history of a glioma Fast growing unicentric recurring tumor Recurrence occurring outside anatomic borderlines Recurrence at an unexpected site Unpredictable behavior of multicentric tumors Multicentric, multitype tumors Problematical histological diagnosis

Additional relevant cases can be found at the end of chapters 3, 4, and 5 of this volume and within volume IVB.

r i

154

,

2 Neuropathology

I

Cases

Gyral Localization 01 Neocerebral Tumors

a

e

b

---.

Case 2.1 A 28-year-old male who had grandmal epilepsy for 1 year, without any neurological deficits. MRI views: a sagittal (T1), b coronal (T,). There is a well-delineated gyrallesion in the posterior part of the left superior frontal gyrus (F 1). Note the displacement of the middle frontal gyrus (F 2) laterally, and the conical extension in

d the direction of the ventricle. Postoperative views (T1) (two years postoperatively): e sagittal (paramedian), d corona!. The exact position of the tumor (anaplastic astrocytoma) within a segment 01F 1 is now well seen.

Cases

a

b

e

d

Case 2.2 A 41-year-old female who had had two Jacksonian seizures (with postictal aphasia) over 1 year. Neuroimaging views: a MRI(T1),coronal, b MRI (spin-echo), horizontal. e MRI (T1), sagittal. There is a well-delineated lesion in the opercular part of the left inferior frontal gyrus (F 3), with displacement of the inferior part of the precentral gyrus posteriorly. Herniation into the sylvian fissure. The neurological examination revealed a moderate receptive dysphasia. d Postoperative CT(contrast, one week postoperatively, horizontal view). The exact position of the tumor (oligodendrog/ioma, Grade 11)is now well seen. The tumor was approached through F 2 superior and anterior to Broca's area, and the patient's language difficulty resolved postoperatively.

e

155

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2 Neuropathology

a

b

e

d

Case 2.3 A 25-year-old female suffering increasing focal seizures

lesion lies within the postcentral gyrus, where some hyperintensily

(dysesthesia in the right leg) over 1 year. MRI views: a Horizontal (T2),b sagittal (T1).There is a well-delineated lesion in the supf3rior parietal lobule, adjacent to the postcentral gyrus (superior part). Note that the sagittal view gives the mistaken impression that the

can be seen. Postoperative

MRI (T1, 3 weeks postoperatively):

e hor-

izontal, d sagittal. The exact position of the tumor (astrocytoma, Grade 11)is now clear. The patient remains neurologically normal.

Cases

157

Case2.4 A 66-year-old lemale withacute left leg weaknessand incontinence.MRIviews(T1): a sagittal,b coronal. Thereis a welldelineatedlesion in the rightparacentralgyrus. Notethe miId displacement01the surrounding gyri.Theright cingulate sulcusis occluded. Postoperativeviews(two weekspostoperatively): e sagittal,d coronal. Onlya small-intensity changeidentiliesthe site 01thiscavernomaafter removal.

b

e

d Case2.5 A 12-year-old male who had suffered parietal complete selzuresover 2 years. MRI view (T1): a sagittal. There is a welldelineatedlesion in the right precuneus, herniating into the lower partof the parietooccipital sulcus. Postoperative view: (31/2years

postoperatively): b sagittal. The exact position of the tumor (pilocytic astrocytoma, Grade 1)is now clear. The child remains seizurefree.

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2 Neuropathology

a

b

e

d

Case 2.6 A 25-year-old woman with progressively severe leftsided frontal seizures over 10 years. MRI views: a horizoQtal(T1), b coronal (T2).There was a well-encapsulated lesion in the right middle parietal lobule. Its behavior was followed up with regular MRIexaminations over 6 years. Note that the lesion extended to the

surface. Postoperativeviews (1 year postoperatively):e horizontal (T2),d coronal (T1).A transsulcal approach was necessary, as this partially calcified oligodendroglioma (Grade 1/)was covered by a displaced thin layer of cortex. The patient remains seizure-free. Preoperatively and postoperatively, there were no neurological deficits.

Cases

159

b

d

Case2.7 A 40-year-old female suffering from right-sided epilepsy (aver10 years), progressing to mental slowing. MRI views (T1): a sagittal, b coronal,e horizontal. There is a well-delineated lesion in the left inferior lobule. Note the displacement of the deep structures herniation. The patient had no dysphasia, sensomotoric or visual field deficits. Postoperative views (one week postoperatively) d caronal, e sagittal. The exact position of the tumor (anaplastic astrocytoma) is now well seen. The patient's language function and parietallobe deficit improved, and she was able to return to work (untilthe tumor recurred 21/2 years later).

e

160

2 Neuropathology

a

e Case 2.8 A 35-year-old female suffering migraines (associated with scintillating scotomas in the right visual field). MRI views (T1): a horizontal, b sagittal. There is a well-delineated lesion in the right cuneus, both superior and inferior to the calcarine sulcus. This cystic lesion caused no visual-field deficit. Postoperative views

d (2 weeks postoperatively): e horizontal, d sagittal. This cystic ganglioglioma (Grade 1)was removed from a small incision in the occipital pole through a "yellowish"-Iooking transparent part of gyrus. The patient's visual fields remain normal.

Cases

161

Tumors of the Limbic Lobe Case2.9 A 16-yearoldfemalewith multipiepartialcomplex seizures(Iip smacking,generalized weakness,dizziness).MRIviews (T1)a coronal, b sagittal.A welldelineatedlesion in theleftamygdala. Postoperativeviews (14weekspostoperatively):e coronal,d sagittal. A parietalhippocampectomy(anterior two-thirds)revealed thisganglioglioma, Grade1.The patient remainsseizure-free.

a

b

e Case2.10 A29-year-oldman withgrandmal epilepsy.MRIview: acoronal.A welldelineatedlesion seemsto be spreadingtheentiretemporallobe.Postoperativeview(1 month postoperatively): b coronal.The positionof the tumor in theparahippocampusandamygdala (displacingthe temporalgyriIaterally, andnotinfiltrating)is wellseen.This anaplasticastrocytoma (GradeJ//)was removedvia a pterional-transsylvian approach.The patientremainssymptom-free 3yearsaftersurgery.

a

b

162

2 Neuropathology

a

e Case 2.11 A 39-year-old male with intermittent petitmal seizures, progressing to focal (right side) and then generalized seizures over 3 years. Despite radiation therapy, language deficits then arase. MRI views (T1):a horizontal, b sagittal, e corona!. There is a welldelineated medial-basal temporal lobe lesion, extending fram the temporal pole into the parahippocampus gyrus and fillingthe paramesencephalic cisterns. Note the displacement of the cerebral peduncle (a) by the herniating mass (but producing no clinical

signs). Postoperative view (1 week postoperatively):d corona!. A vascularized, very adherent pleomorphic xanthoastrocytoma (Grade 11I)was removed fram CN 111, and the anterior choroidal and posterior communicating arteries (and branches) in the paramesencephalic cisterns. The position of the tumor in the parahippocampus gyrus is well seen. Twoyears after surgery, the patient remains asymptomatic.

Cases

a

b

e

d

Case2.12 A 39-year-old female with partial complex seizures and progressivemental deterioration. MRI views (T1): a horizontal, b sagittal.A well-delineated right hippocampal and parahippocampallesion.Note its extension into the lateral temporo-occipital gyri andisthmuscinguli, with herniation into the trigonum and paramesencephaliccistern. There is also displacement of the cerebral

163

peduncle, without clinical signs. Postoperative views (1 year postoperatively): e horizontal d sagittal. The exact position of this tumor (anapIas tic astrocytoma) within the transitional zone (parahippocampus gyrus and hippocampus) is clear. This patient continues to do well 2 years postoperatively, with only an upper-Ieft quadrantanopsia, as a residual effect.

164

2 Neuropathology Case 2.13 A 54-year-old woman who had been suffering seizures for 2 years (with an aura), and a CT scan that suggested left temporal infarction. Over four years, she developed miId language deficits and right-sided apraxia. MRI views: a sagittal (T2), b horizontal (T1). e coronal (T1).There is a well-delineated lesion within the left insula, filling the sylvian fissure. Note the sharp medial border, with displacement and compression (but no infiltration) of the putamen and pallidum. Pastaperative views (3'/2years postoperatively): d sagittal (T1),e horizontal (T1),f coronal (T1).The precise location of the tumor (mixed gliama, Grade 1/)is evident. This patient remains asymptomatic 4 years following surgery.

e

Cases Case 2.131

1>

a

Case2.14 A 33-year-old female with focalseizures(Ieft hand) progressingto generalized seizures over1year.MRI views: a horizontal (T2),b coronal(T1),e sagittal (T1). A well-delineatedlesion in the right insula,withcompressionof the corpusstriatumand herniation into the sylvianfissure.Postoperative views (6 monthspostoperatively): d coronal(T1),e sagittal (T1).The exactpositionof the tumor (fibrillary astrocytoma,Grade 11)is well seen. Thepatientremainsseizure-free 4 yearspostoperatively,with no neurologicaldeficits. She is fully rehabilitated.

d

e

165

166

2 Neuropathology

b

a

e

Case 2.15 A 34-year-old male, initially with focal

e

seizures (right-sided dysesthesia, dysacusis, and loss of speech) and then a grandmal seizure. MRI views (T1): a horizontal, b coronal e sagittal. A large left limbic lobe lesion in the part of the insula with extension into the fronto-orbital, temporal pole, and amygdala. Note the sharp delineation against the striatum. Postoperative views (6 weeks postoperatively): d sagittal, e horizontal. The exact position of the tumor (anaplastic astrocytoma) is better seen. The patient remains seizure-free 5 years postoperatively, with no neurological deficits.

Cases Case2.16 A 50-yearoldmalewith a history 01headaches,mental slowingdiplopia, and rightlegweakness, over2 months.MRI views:a horizontal(T2), b coronal(T1),e sag¡ttal(T1).A welldelineatedlesion in the leltIronto-orbital region,involvingthe septaland paraollactoryareas.Note the displacementsurroundingthewhitematter, withoutinliltration.Postoperativeviews (7monthspostoperatively):d sagittal, e horizontal, f coronal.The position 01thetumor(glioblastomaGradeIV) in the paraolfactoryarea is clear.Thepatient remainsneurologically intact11/2years postoperatively.

167

a

b

e

d

e

168

2 Neuropathology

a

e

d

Case 2.17 A 63-year-old female with focal seizures

e

(speech arrest over 6 months, with pragressive headaches, mental slowing, loss of balance, and bilateral dysdiadochokinesia. MRI views: a horizontal (T2). b sagittal (T1, e coronal (T1). There is a lesíon in the paraolfactorial, septal areas and anterior cingulate gyrus. Note the severe herniation into the ventricular system. without penetration or infiltration. Occiusive hydrocephalus. Postoperative views (1 month postoperatively): d sagittal (T1), e horizontal (T1). The position of the tumor (anaplastic astrocytoma, Grade 111) is clear. The patient remains seizure-free more than 2 years postoperatively, with no neuralogical deficits. The psycho-organic syndrame has partially improved.

Cases

a

Case2.18 A 16-year-old female who had been suffering headaches,diplopia, and apathy for 3 months. MRI views: a horizontal (T2),b coronal (T1),e sagittal (T1). A well-delineated lesion in the middlepartof the cingulate gyrus, with severe ventricular compressionand subfalcial herniation,but no infiltration into the opposite side.Thereismarked perilesional hyperintensity within the right fron-

169

b

tal white matter, extending peripherally to sector 1. Postoperatively view (10 days postoperatively): d sagittal (T1). The location of the tumor a giant-cell glioblastoma, Grade IV), in the middle portion of the cingulate gyrus with small extension into the corpus callosum, is now well seen. Postoperative radiation therapy. The patient has been doing well for 2 years, with no seizures.

170

2 Neuropathology

a

e ~

b

d

J.

Case 2.19 A 39-year-old male with petitmal seizures over 2 years. MRI(TI) views:a sagittal,b corona!.A well-delineatedlesioninthe posterior portion of the cingulate gyrus, extending into the precuneus. Postoperative views (1 year postoperatively): e sagHtal,

d corona!. The histology indicated a mixed oligoastrocytoma, 11. Note that the posterior body of the corpus callosum has

Grade

also been partially removed. The patient remains symptom-free.

I I

I

~

Cases

171

RareLocalizations TumorsArising from the Internal Capsule

a

b

Case2.20 A 12-yearoldlemale,right handed,with a history 01 dizziness,latigue, diplopiaand right-sided weaknessover 3 months. MRIviews:a horizontal (T1),b coronal(T1), e sagittal(TJ A well-circumscribed,partially cysticlesion compressingthe lentilorm nucleuslaterally,the head01the caudate anterosuperiorly, and the thalamusmedially.Note thesevereventricular displacement.Postoperativeviews(8 monthspostoperatively): d sagittal(T,), e horizontal(T2),f coronal (T1).A vasculartumor (pilocyticastrocytoma) wasremovedusing an interhemispheric, transcallosalapproach. Entrancewas gained throughthe anterior thalamus,and the tumor originseemedto be in theregion01the internal capsulenearthe genu. Surprisingly, the patient remainsneurologically intact,withno speech difficulties. e

f

172

2 Neuropathology Case 2.21 A 4-year-old female, right handed, with progressive right-sided weakness (Ieg more than arm) and dysarthria over 2 years. MRI views (T1): a horizontal, b horizontal, e sagittal, d coronal. A large, well-circumscribed les ion in the area of the thalamus had been assumed preoperatively. The origin of this tumor is unclear. Note the tremendous displacement of the surrounding structures and the herniation of the tumor across the midline and into the left frontal horno Postoperative views: e sagittal, f coronal, 9 horizontal. A left-sided interhemispheric transcallosal approach was used to remove this tumor (a pilocytic astrocytoma, Grade 1), between the b thalamus and the head of the caudate. The tumor originated from the area of the posterior limb of the internal capsule. The medial internal capsule and lenticular nucleus are intact from its origino There was improvement of the dysphasia, and weakness of the right distalleg. Follow-up 4 years.

a

d

e

e

f

9

Cases

173

Rentrolenticular Tumors

a

b

e

d

e

f

Case2.22 A 9-year-old female with papilledema, left dysdiadochokinesia,dysmetria, loss of balance, and a left lower quandrantanopsia.MRIviews:a horizontal(T1),b coronal(T1),e sagittal(T1). Awell-circumscribedcystic lesion in the posterior part of the insula, beneaththe long insular gyrus. Postoperative views (9 months post-

operatively): d sagittal (T1), e horizontal (spin-echo), f coronal (T,). The exact origin of the tumor (pilocytic astrocytoma) was in the retrolenticular region. Postoperatively, the child had a moderate hemiparesis, which improved to permit fine motor skills after one year.

174

2 Neuropathology

Diffusely Growing Gliomas

a

b

Case 2.23 A 63-yearold female with occasional partial complex seizures and no neurological deficits. MRI views (T2): a coronal, b horizontal. A diffuse lesion in the left frontal, temporal, parietal, and occipitallobes, with displacement of the deep structures. Four years later, the patient remains without any neurological deficits and professionally active. Where is the tumor origin? Note that the anterior commissure can be well visualized, and that the putamen, pallidum, thalamus, and caudate all remain intact.

Case 2.24 A 62-yearold male with progressive headaches and seizures. MRI views: a coronal (T1), b horizontal (T,). A diffuse brainstem and cerebellar lesion, with multiple other supratentorial and bilateral mediobasal temporallesions. After a biopsy, this proved to be

a glioblastoma.

a

Cases

a

175

b

Case2.25 A 37-year-old female, right-handed, with focal sensory seizuresover 10 years. MRI views (T1): a horizontal, b sagittal, ecorona!.A diffuse lesion throughout the central and parietallobes, with extension into the pyramidal system. The patient refused surgery,and remained normal for 8 years (very vital). Her only troublefaryearswas occasional seizures, despite optimal and regularpharmacotherapy.She then developed a right hemiparesis and diedwithin 3 months (of paraneoplastic effects). An autopsy was refusedby the family. The assumed diagnosis was astrocytoma,

Grade11-11I.

e

a Case2.26 A 24-year-old male who had suffered several focal sensory seizures (Ieft side) and then two grandmal seizures. MRI v¡ewsa coronal (T2)' A diffuse les ion in the right superior and medial parietallobulus, with displacement of the ventricle. Postoperatively view(2 weeks postoperatively): b coronal (T1). An oligoastrocytoma

(Grade 11) was partially removed,

and the patient

remains

completely neurologically normal, but the seizures could not be controlled with pharmacotherapy. A thalamic stereotactic lesion was performed 1 year later to further treat the seizure disorder, and this was very effective in repressing the seizures. Thereafter, the patient regained full working capacity 2 years ago.

176

2 Neuropathology

Case 2.27 A 12-year-old male with epileptic seizures. MRIviews (T1). a horizontal, b coronal. There is a large, circumscribed les ion in the left thalamus, with elevation of the caudate. A stereotactic biopsy was performed, revealing an astrocytoma, and the child continues to do well (after 4 years), with no deficits, and attends school.

a Case 2.28 A 4-year-old girl with 10 days of headache and vomiting, but no neurological deficits. a MRI (T1), horizontal. A large, insular primitive neuroectodermal tumor (Grade IV) was totally removed, reducing the mass effect. The patient enjoyed an immediate recovery. b Follow-up view (4 weeks postoperatively). The arrows indicate residual or recurrent tumor. e MRI (T1, 8 weeks postoperatively). A large recurrent tumor at the same site. Clinically, there was headache and vomiting, but no neurological deficits. d Contrast CT, horizontal (1 week after the second operation). A subtotal removal, with reduction in mass effect, was carried out, and the patient enjoyed a recovery. However, 4 weeks later, the same symptoms arase again. No further therapy was applicable, and the child died 6 weeks later radiotherapy

was rejected.

a

b

Cases

b

a

d

e

Case 2.29 A 35-year-old male who had had a epileptic seizure 14 years previously and recent focal seizures, later progressing to another grandmal seizure. MRI views (T1):a horizontal, b sagittal. No clear lesion is identified. Possible intensity changes in the left mesiobasal temporal region were suggested. The patient remained asymptomatic tor 21/2 years, but then developed papilledema and a right homonymous hemianopsia. e sagittal. A definitive, well-delineated lesion is seen in the inferior temporal gyrus (T 3) of the temporal lobe. The patient wanted to discuss other options tor treatment. Subacute impairment occured 6 months later, and the MRI showed a large temporal lesion. Postoperative views (3 weeks postoperatively): d sagittal, e coronal. The lesion (glioblastoma, Grade IV) was removed. Postoperative radiotherapy and chemotherapy were provided. The patient died 3 months later.

177

r 178

2 Neuropathology

a

b

e

d

e Case 2.30 A 32-year-old male, right-handed, suffering generalized seizures, dysphasia, and weakness of the right side for only a few hours. MRI view: a A left insular tumor with hematoma in the center. A glioblastoma, Grade IV, was removed. b Postoperative CT. The patient refused radiotherapy, and consulted with a molecular biologist and immunologist. He continued to work as a surgeon. e First recurrence of the tumor, 5 months later. Postoperatively MRI views after the second operation: d Recurrent tumor at the same

site. The patient underwent further two operations within 6 months for recurrence at exactly the same site as the original tumor. He remaind neurologicaliy and mentaliy intact until the very end, and had no speech difficulties in three languages. In April 1992, there was acute deterioration. MRI view: e There was a local recurren! tumor, and he died. Particularly in the case of this young colieague, the absence of effective and adjuvant therapy was intolerable.

Cases

a b Case2.31 A 43-year-old male suffering epileptic seizures and speechdifficulties for a few hours. a MRI view: A small, circumscribedlesion in the left frontal operculum, part F 1. Extensive perilesional hyperintensitywithin the white maUer of the left'hemisphere. Befareand during surgery, a metastatic lesion was assumed. The

179

e tumor was sharply delineated. b Postoperatively CT:The histology, however, revealed a glioblastoma, Grade IV: Postoperative radiotherapy was applied. There was positive follow-up for only 4 months without neurological deficit. Therafter, there was acute deterioration with hemiparesis and aphasia. e MRI view: A huge recurrent tumor.

Case 2.32 A 31-yearold male, with headaches, papilledema, cerebellar signs, apathy, and a left lateral field cut MRI views: a horizontal (T2), b sagitlal (T). There is a diffuse leslon in the dorsal mesencephalon

and

adjacent thalamus, extending into the paraplneal region. This anaplastic astroeytama (Grade 111)was completely removed from its origin in the right pulvinar thalamic Postoperative

area.

a

b

radiother-

apy was provided,

and

the patient had a full recovery, working

as a

carpenter far 14 months, before developing

a pro-

gresslve psycho-organic syndrome. Note the second tumor in the frontal basal area. e sagitlal (T.) Surprisingly, was no evidence

there of

tumor recurrence

in the

mesencephalic region, but there was a second tumor In the right medial frontal area, which was removed by a second operation. d sagitlal

(T1,

2 weeks postoperatively).

d

180

2 Neuropathology

Unpredictable Behavior 01 Tumors

Case 2.33 A 40-yearold woman with occasional Jacksonian seizures manifested by right-sided weakness. Previously she had undergone removal of a left posterosuperior frontal (F 1) gyrus tumor (astrocytoma, Grade 1), with full recovery. Eighl years later, she began lo have headaches, increased seizures, and right leg weakness. MRI views (T1): a coronal, b sagittal. A recurrent tumor in the anterior parl of the previous tumor cavity was removed. Postoperative MRI views (4 months postoperatively): e coronal, d sagiltal. Histology: anaplastic astrocytoma, Grade 111. Radiotherapy was recommended. The patient is symptom-free 2 years after 2nd operation.

a

d

Cases

a

181

b

e Case2.34 A 26-year-old male suffering subacute headaches followedby a grandmal seizure. No neurological deficits. a Contrast Cl horizontal.There is a lesion in the left posterior temporal inferior gyrus(T3). The tumor (fibrillary astrocytoma Grade 11)has been removed.b Postoperativeview (1 month postoperatively). Preoperativelyand postoperatively, there were no visual field defects. Four yearslater,another seizure occured. e MRI (T1), horizontal view:

Tumor recurrence at the site of the original tumor, with perilesional diffuse edema. The location of the recurrent tumor is clear. Note the displaced position of the left optic radiations in this patient, whose visual fields remained intact. d Postoperative MRI view (2 weeks postoperatively). The patient continues to do well (2 years after 2nd operation), but has homonymous hemianopsia.

182

2 Neuropathology

d

Case 2.35 A 20-year-old woman with increasingly frequent migraines, diplopia, papilledema, hydrocephalus, and ataxia. a Horizontal contrast CT. A large, delineated septallesion with occlusive hydrocephalus. The tumor (neurocytoma) has been completely removed, and the hydrocephalus relieved. Recovery was good. Postoperative views (3 weeks postoperatively): b horizontal con-

trast CT.The same symptoms recurred six years later.e Horizontal MRI (T1): A large recurrence in the area of the original tumor,with occlusive hydrocephalus. Postoperative view (2 weeks postoperatively): d MRI (T1), horizontal view. Complete removal of the tumor. Note that the septum pellucidum has been removed. The patient continues to do well.

Cases

183

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Case2.36 A 58-year-old lemale with progressive conlusion, fatigue,loss 01 concentration, left hemiparesis, and lelt homonymaushemianopsia.a Horizontal (contrast) CT (1978). There is a dil¡uselesionin the right pulvinar thalami, with a large extension into thetrigonum.b Contrast CT, 10 years later. This tumor (glioblastoma,Grade IV) was removed radically. Postoperatively, conventianalradiotherapy was applied. The patient recovered lully and workedwithoutany disability lor 5 years until her retirement at the

age 0165. She died 01urinary carcinoma with metastases 14 years postoperatively. e, d The histology 01her tumor, which was lound to be glioblastoma also by Prol. Zülch and Prol. Rubinstein. Histology: A highly cellular, anaplastic tumor with increased polymorphism, multinuclear tumor cells, atypical mitotic ligures, and local necrosis with pseudopaíisading 01 tumor cells. In some areas vascular endothelial prolileration has also been observed. The diagnosis 01 glioblastoma multilorme (WHO Grade IV) was made.

184

2 Neuropathology Case 2.37 A 34-year-old man with epilepsy. a Contrast Cl A lesion in the left fronto-orbital area, with calcification. The tumor (anap/astic astrocytoma) was radically removed. Postoperative radiotherapy was given. The patient remains seizure-free, with no mental or neurologic defiQits. Postoperative views (9 years postoperatively): b MRI (T1),horizontal, e MRI (T1) coronal. No recurren! tumor.

a

b

Multiple Tumors

b

a

Case 2.38 A 58-year-old male, suffering headache, psychoorganic syndrome, and rapid deterioration. MR/ (T1): a horizontal, b sagittal. An unusual tumor within the entire callosum, septum pellucidum, anterior and posterior cingulate gyrus. There is a butterflytype bilateral extension along the forceps minor. No surgery was performed. The patient died before any treatment. Histology: G/iob/astoma.

Cases

185

Case2.39 A 68-year-old womansufferingrapidly progressivedeterioration. a-d MRIviews(T1).Multiple lesionsare identified bilaterally inthecerebraland cerebellar hemispheresand cisterns. The autopsyrevealed glioblastoma.

a

e

b

186

a

e

2 Neuropathology Case 2.40 A 10-year-old male with partial complex seizures and progressive forgetfulness, fatigue, and headaches. MRIviews(T1): a horizontal, b sagittal. Multiple lesions, particularly in the right mediobasal temporal region, with extension into the cisterns (right sylvian, interhemispheric, bilateral ambient, and left collateral). Postoperative view (6 weeks postoperatively):e horizontal. The large compact tumor (pilocytic astrocytoma) in the right amygdala and hippocampus was removed. The cisternal parts of the tumor (adhesive to arteries) could not be resected. No additional tumor growth was seen within 4 years, but tumor remains in the cisternal and su leal regions. The patient is symptom-free, with no neurological deficits, and attends school after 4 years. Follow-up views: d coronal, e sagittal.

Cases

Multicentricand Multitype Tumors Case2.41 A 59-year-old lemalewith subacute headaches,papilledema, homonymOJShemianopsia,and ataxia.CTcontrast views: a horizontal,b horizontal. Two lesionsare identified in the righttrigone(with surrounding perilesionalchanges) and alongthe falx. 80th tumors, a lalx meningiomaand oligoastrocytoma,Grade 11with adjacentcavernomawhich bled,werecompletely removedin one session. The patientremainedsymptomfreelor 7 years. Postoperativeviews (1 month postoperatively): e horizontal,d horizontal.

187

188

2 Neuropathology

b

Case 2.42 A 43-yearold female who had suffered a grandmal seizure and sudden coma. MRI views (T1): a coronal, b horizontal, e sagittal. Three lesions are identified. The right sphenoidal meningioma is associated with a significant shift in the underIying deep structure, while the left-sided thalamic lesion appears with a hematoma, and there is a third lesion in the third ventricle. Postoperative view (1 week postoperatively): d coronal. A left thalamic and third ventricular tumor (cavernoma) has been removed. At a second session, the sphenoid meningioma was removed 3 months later. The patient persisted with significant disability in a convalescent home.

d

e

Problematic Histological Diagnosis

Case 2.43a, b.

a

b

Cases

189

d

e

9 Case2.43 A 31-year-old female with progressive headaches and dizziness.No neurological deficits. MRI views (T1): a horizontal, b sagittal,a large lesion is identified in the right parietallobe. This strangetumorwas subcortical, with no relation to the dura and to the ventriclewall. The patient's visual fields remained intact. The histologyremainedunclear as to whether it was an atypical meningiamaoran anaplasticoligodendroglioma. MRI views (4 months postoperatively):e horizontal (T2).d coronal (Postero-anterior view). No residualtumor seen. Fourteen months later horizontal MRI view e withrecurrenttumor present, which was removed. Again the histoiogyremainedunclear. f horizontal MRI view. One year following the secondoperation. there is no evidence of tumor recurrence,

9 deeper horizontal view (T1). The optic radiations are preserved and the visual fields are normal and the patient remains asymptomatic. h Histology: A highly cellular tumor with mitotic activity consisting of small cell strands and nests, sometimes resembling whorls. A mucoid intercellular substance and PAS-positivity of tumor cells was noted. Immunohistochemically Pancytokeratin antibody, Epithelial Membrane Antigen (EMA) and Glial Fibrillary Acidic Protein (GFAP) were completely negative. Positive expression has been shown with anti-Vimentin and focally also with anti-S100 antibodies. In summary, histology and immunohistochemistry were compatible with anaplastic meningioma of a chordomatoid subtype (WHO Grade 111).It may be an atypical meningioma.

190

2 Neuropathology

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Case 2.44 A31-year-old male suffering grandmal seizures. Neurologicallyand mentally,there were no deficits. MRI views (T1):a sagittal, b sagittal, e corona!. Multiplelesions are identified in the left F 3, leftanterior cingulate gyrus, and right paraolfactorial gyrus. ThBhistology from the tumor biopsy was not definitive, suggesting either low grade tumor or infection. The patient has remained asymptomatic for2 years, withentirely unchanged MRIviews. d, e Histology;

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A lesion with reactive gliosis and inflammatory (Iymphoid) cell infiltration was observed histologically. There was no sign of a neoplastic tissue, monoclonality of infiltrating Iymphocytes, or necrosis. In special stains (Ziehl-Neelsen, toxoplasmosis-antibodies, fungal stainings) no germs or parasites could be identified. Thus, the definitive nature of the lesion could not be diagnosed histologically.

Cases

a

e Case2.45 A 26-year-old male suffering headaches, diminished balance, and right-sided dysmetria. MRI views (T1): a coronal (posteroanteriorview), b horizontal, e coronal, d sagittal. Multiple lesions are identilied. Open biopsy revealed a medulloblastoma, Grade IV. Radiotherapywas applied. Clinically the cerebellar lesion within the rightAOL concurs with the diagnosis 01 medulloblastoma, but what is unique is the preoperative dissemination 01 this lesion to both cavernous sinuses as well as into the sellar and parasellar areas. Histology:A malignant, highly cellular, and mitotic tumor wifh typical

191

b

d carot-shaped nuclei. Focal neuronal differentiation could be detected histologically and demonstrated with positive synaptophysin immunohistochemistry. Glial fibrillary acidic protein stained locally positive in trapped astrocytes. According to its morphology the tumor was graded WHO IV and termed Primitive Neuroectodermal Tumor (PNET). II its primary site would have been the cerebellum, medulloblastoma would be the name for the otherwise histologically identical neoplasia. Meningial seeding is a well-known leature 01these highly malignant tumors.