Dermal Tumors: The Basics
Dermal Tumors: The Basics
Bruce R. Smoller Department of Pathology University of Arkansas for Medical Sciences Little Rock, AR, USA and
Kim M. Hiatt Department of Pathology University of Arkansas for Medical Sciences Little Rock, AR, USA
Dr. Bruce R. Smoller Department of Pathology University of Arkansas for Medical Sciences Little Rock, AR 72205 USA
[email protected] Dr. Kim M. Hiatt Department of Pathology University of Arkansas for Medical Sciences Little Rock, AR 72205 USA
[email protected] ISBN 978-3-642-19084-1 e-ISBN 978-3-642-19085-8 DOI 10.1007/978-3-642-19085-8 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2011929931 © Springer-Verlag Berlin Heidelberg 2011 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: eStudioCalamar, Figueres/Berlin Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)
Preface
In this fourth, and final, volume of the series on dermatopathology we conclude our framework which students, at all levels of learning, can use to continue building from in the classification and diagnoses of cutaneous diseases. This volume is focused on lesions arising from dermal-based processes. The format is structured, like the previous volumes, as a bullet-point outline of the main clinical and histologic features with an atlas of quality images to demonstrate these points. This format provides a small-sized reference that is easily accessible to the sign out microscope and provides a foundation that is elaborated on in the already published excellent larger texts available to the student. Little Rock, Arkansas, USA Little Rock, Arkansas, USA
Bruce R. Smoller Kim M. Hiatt
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Acknowledgment
These volumes could not have been made possible without the dedication of the dermatopathology laboratory staff at the University of Arkansas for Medical Sciences. Their commitment to provide high quality histology allows us the opportunity to share the numerous images in these volumes. As always, Bruce Smoller wishes to acknowledge his wife, Laura, and two (now adult) children, Gabriel and Jason, for their constant enthusiastic support and love. He would also like to acknowledge the entire Department of Pathology at the University of Arkansas for Medical Sciences for the honor of having worked with them over the entire duration of this project. And, Dr. Hiatt would like to thank her husband, Jim, and her children Stephanie, Nicholas, Kaitlyn and Natalie for their support.
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Contents
1 An Overview of Cutaneous Lymphomas . . . . . . . . .
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2 Vascular Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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3 Histiocytic Proliferations. . . . . . . . . . . . . . . . . . . . . .
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4 “Fibrohistiocytic” Proliferations. . . . . . . . . . . . . . . .
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5 Tumors of Fat, Nerve, and Smooth Muscle . . . . . . .
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6 Cutaneous Metastases. . . . . . . . . . . . . . . . . . . . . . . . .
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Further Reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Chapter 1
An Overview of Cutaneous Lymphomas
• Classifications of cutaneous lymphomas –– Two recent systems both had problems °° Revised European-American Classification of Lym phomas (REAL) °° European Organization for Research and Treatment of Cancer (EORTC) –– REAL classification °° Uses classification of systemic lymphomas and applies them to cutaneous lymphomas °° Classification based upon pathologic, genetic, and clinical features and adds immunohistochemical criteria °° Cutaneous involvement accounted for in clinical features –– EORTC classification °° Recognized cutaneous lymphomas as a distinct entity °° Organ-based classification system °° Only system that has been clinically validated for this group of diseases; classified as indolent, intermediate or, aggressive –– WHO-EORTC classification °° Consensus conference in 2005 incorporated features of both systems to acknowledge particulars of cutaneous lymphomas B.R. Smoller, K.M. Hiatt, Dermal Tumors: The Basics, DOI: 10.1007/978-3-642-19085-8_1, © Springer-Verlag Berlin Heidelberg 2011
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–– WHO 2008 classification °° Integrated the WHO-EORTC classification of cutaneous lymphomas in the general classification °° Only minor changes in terminology, except blastic plasmacytoid dendritic cell neoplasm, previously CD4+/ CD56+ hematodermic neoplasm, previously blastic NK cell lymphoma • Overview –– 3% per year increase in incidence of cutaneous lymphomas every year since 1970 –– Cutaneous lymphomas represent a very heterogeneous group of diseases with very different clinical presentations, courses, treatment programs, and prognoses –– Second most common (after GI tract) site of extra-nodal non-Hodgkin’s lymphomas –– Large groupings include T cell lymphomas, B cell lymphomas, and Hodgkin’s lymphoma –– Overall incidence estimate of 1:100,000 –– 75% of cutaneous lymphomas are T cell lymphomas, 25% B cell lymphomas –– Hodgkin’s lymphoma is exceedingly rare in skin –– 5–10% of T cell lymphomas are not mycosis fungoides • T cell lymphomas (Table 1.1) • Mycosis fungoides (MF)/Sezary syndrome –– Epidemiologic features °° 0.42 cases/100,000 population °° Overall, more than 50% of all cutaneous lymphomas °° Incidence rapidly increased in 1970s–1980s, but now stabilized Table 1.1 T cell lymphomas Mycosis fungoides/Sezary syndrome Primary cutaneous CD30+ lymphoproliferative disorders Subcutaneous panniculitis-like T cell lymphoma Extranodal NK/T cell lymphoma, nasal type Blastic plasmacytoid dendritic cell neoplasm (Peripheral T cell lymphoma)
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°° Twice as common in African Americans as in Caucasian Americans °° Twice as common in men as in women °° Associated with 3.3X relative risk for second, non- cutaneous malignancy –– Clinical features °° Usual onset in middle age (mean 55–60), but can appear at any age °° Starts most commonly as erythematous, slightly scaly patches on flank and buttocks °° Progress to plaques and ultimately tumors (in a minority of patients) °° Poikilodermatous variant – uncommon °° Involvement of lymph nodes, spleen, liver only late in course –– Histologic features (Figs. 1.1–1.4) °° Epidermotropic proliferation of hyerconvoluted, hyperchromatic lymphocytes in clusters (Pautrier’s microabscesses) and as single cells within epidermis
Fig. 1.1 Early lesions of mycosis fungoides show an epidermotropic lymphocytic infiltrate. Single atypical lymphocytes are seen lining up along the basilar epidermis
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Fig. 1.2 In more evolved lesions of mycosis fungoides, small clusters of atypical lymphocytes and increased single lymphocytes are present in the epidermis which also shows only minimal spongiosis and no dyskeratosis
Fig. 1.3 This case of mycosis fungoides shows only a mild dermal infiltrate but numerous Pautrier’s microabscesses
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Fig. 1.4 Variable number of eosinophils and some plasma cells are often present in the dermal infiltrate of mycosis fungoides
°° Difficult diagnosis to make in early lesions °° Later lesions with less epidermotropism and more cytologic atypia °° Variable number of eosinophils and some plasma cells –– Immunologic features (Figs. 1.5 and 1.6) °° Mycosis fungoides is defined as a neoplastic proliferation of CD3+, CD4+ T helper lymphocytes °° CD8+ tumors are rare but are now classified as MF °° Loss of CD2, CD3, and CD5 often seen °° Clonal rearrangements of T cell receptor is ultimately detected in most cases, but only 50% of early lesions. –– Molecular features °° T-cell gene rearrangements seen in 50–80% of patchstage lesions, nearly 100% of tumor stage and Sezary cases °° When same clone is present in two separate locations, worse prognosis is reported
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Fig. 1.5 The epidermotropic lymphocytes in mycosis fungoides most commonly express CD4
Fig. 1.6 Loss of normal T-cell markers such as CD5 is common as in this case of mycosis fungoides
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–– Treatment protocols °° °° °° °° °° °°
Topical steroids Topical nitrogen mustard Electron beam irradiation Interferon Chemotherapy Photopheresis
–– MF – Prognosis °° Excellent, overall °° Patients presenting with stage I disease have the exact same 30-year survival as age and sex-matched controls without MF (97–98% 10-year survival) °° Generalized (>10% of skin surface) disease – 83% 10 year survival °° Tumor stage disease 42% 10-year survival °° Nodal involvement usually with less than 1-year survival –– MF variants (Figs. 1.7 and 1.8) °° Folliculotropic – characteristic morphology; 70–80% 5-year survival – less responsive to therapies –– Myxoid degeneration may be seen –– Folliculotropic MF replaces MF-associated follicular mucinosis °° Pagetoid reticulosis – localized patches, very epidermotropic; excellent prognosis °° Granulomatous slack skin/granulomatous mycosis fungoides – rare; responds to radiation, but with rapid recurrences °° Sézary syndrome –– Triad: erythroderma, generalized lymphadenopathy and neoplastic T cells in skin, lymph nodes, and peripheral blood: 3 (>1,000 cells/mm , CD4/CD8 ratio >10, loss of CD2, CD3, CD4, and/or CD4) Clonality of cells in blood
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Fig. 1.7 Folliculotropic mycosis (A) shows an atypical CD4+ (B) lymphocytic infiltrate with a predilection of the follicular epithelium. Myxoid degeneration may be seen
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–– Mean survival 2–4 years –– Treat with photopheresis • Primary cutaneous CD30+ lymphoproliferative disorders –– Primary cutaneous anaplastic large cell lymphoma –– Lymphomatoid papulosis • Anaplastic large cell lymphoma (ALCL) –– Epidemiologic features °° Primary cutaneous ALCL occurs primarily in adults (non-cutaneous in children) °° Most patients with solitary or localized skin lesions at time of presentation –– Clinical features °° One to several nodules or small tumors °° Ulceration may be present
Fig. 1.8 Granulomatous mycosis fungoides shows sarcoidal granulomas in the dermis and typically lacks an epidermotrophic lymphocytic component
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°° 75% of cells expressing CD30 in skin biopsy °° Lymphoma cells also express CD3 and CD4 in most cases
Fig. 1.9 Anaplastic large cell lymphoma shows a dense dermal infiltrate of large lymphocytes
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Fig. 1.10 The nuclei in anaplastic large cell lymphoma are round with one or multiple nucleoli and marked pleomorphism. Scattered reactive lymphocytes are also present
°° CD2, CD3, and CD5 may be absent °° CD15 negative (unlike Hodgkin’s disease) °° B cell variants of CD30+ lymphoma have been described °° t(2;5) translocation common in children but not seen in adults with ALCL °° Clonal rearrangements seen in most cases –– Treatment protocols °° Radiation is preferred mode of therapy for limited cutaneous disease °° Chemotherapy reserved for patients with generalized cutaneous disease or systemic involvement –– Prognosis °° Excellent for patients with primary cutaneous ALCL °° 10-year survival >90% °° Much worse prognosis for patients with nodal disease
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Fig. 1.11 The large cells in anaplastic large cell lymphoma express CD3 (A) and CD30 (B)
• Lymphomatoid papulosis –– Clinical features °° Chronic, recurrent, self-healing papulonecrotic process °° Mostly in adults (median age 45) °° Lesions at different stages simultaneously
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°° Process may last from weeks up to 40 years °° 20% of patients with LyP have associated lymphoma (MF, Hodgkin’s or ALCL) –– Histologic, immunologic, molecular features (Figs. 1.12–1.14) °° Large, atypical CD30+ cells interspersed with a brisk reactive inflammatory infiltrate (type B variant looks like MF and cells do not express CD30)
Fig. 1.12 Lymphomatoid papulosis shows a dense dermal infiltrate (A) with scattered atypical large cells (B)
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Fig. 1.13 This case of lymphomatoid papulosis shows an exuberant dermal infiltrate attenuating the overlying epidermis (A) and showing numerous large atypical cells (B)
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Fig. 1.14 The extent of large CD30+ cells in the dermal infiltrate of lymphomatoid papulosis varies from scattered (A) to numerous (B). Diagnosis hinges on clinical presentation
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°° CD3+, CD4+, CD8− °° T cell clonality seen in 60–70% of cases –– Prognosis excellent • Subcutaneous panniculitis-like T cell lymphoma (SPTCL) –– Epidemiologic features °° Previously known as histiocytic cytophagic panniculitis (at least some cases) °° Occurs primarily in adults (median age 37–56 years), but reported in children °° Rare neoplasm –– Clinical features °° Multiple red to violaceous cutaneous nodules °° No overlying epidermal changes except tendency to ulcerate °° Not painful °° Legs and arms most common sites, followed by the trunk °° Systemic symptoms present at time of presentation in most patients, but nodal involvement usually only late in course –– Histologic features (Figs. 1.15 and 1.16) °° Dense, diffuse infiltrate of small to medium-sized lymphocytes in deep dermis and subcutaneous fat °° Fat necrosis with extensive lobular involvement °° Rimming of adipocytes by neoplastic T cells helpful, but not specific °° Hemophagocytosis usually prominent, as are necrosis and karyorrhexis –– Immunologic and molecular features °° °° °° °° °°
All cases represent T cell lymphomas a/b+, CD3+, CD4−, CD8+, CD30− Clonal T cell gene rearrangement EBV not seen in these cases CD56+, l/d+ lymphomas are similar, but much more aggressive clinical course (different classification now in new system)
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Fig. 1.15 Subcutaneous panniculitis-like T-cell lymphoma shows a dense, diffuse infiltrate of small to medium-sized lymphocytes in deep dermis and subcutaneous fat
Fig. 1.16 Rimming of adipocytes by neoplastic T-cells is seen in subcutaneous panniculitis-like T-cell lymphoma. Karyorrhexis, shown here, is also common
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–– Treatment protocols °° Systemic chemotherapy °° Corticosteroids (systemic) – often control disease for long periods of time °° Radiation therapy –– Prognosis °° Generally favorable – 5 year survival of 80% with frequent recurrences but rare systemic involvement • Extranodal NK/T cell lymphoma, nasal type –– Epidemiologic features °° In this case, primary vs. secondary not important for prognosis or treatment °° Skin second only to nasal cavity in terms of frequency of involvement °° Neoplastic proliferations of NK cells or less commonly, cytotoxic T cells have been implicated °° Most common in Asia, Central and South America °° Male predominance –– Clinical features °° CD56+ lymphomas have a predilection for nasopharyngeal region (used to be called “lethal midline granuloma”) °° Multiple skin lesions may be present on trunk and extremities – subcutaneous nodules with ulceration commonly °° Systemic features including fever, weight loss, lymphadenopathy, splenomegaly and anemia may be present °° Hematophagocytic syndrome also common –– Histologic features (Figs. 1.17 and 1.18) °° Superficial and deep dermal infiltrates of atypical lymphocytes °° Epidermotropism is present but not extensive °° Angiocentric and angiodestructive infiltrates are the characteristic finding with secondary necrosis °° Panniculitis-like infiltrate also present in most cases
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Fig. 1.17 Extranodal NK/T-cell lymphoma has a superficial and deep dermal infiltrate of atypical lymphocytes
°° Neoplastic cells often accompanied by heavy mixed inflammatory infiltrate –– Immunologic features °° Neoplastic cells express CD2, CD56, and cytotoxic proteins such as TIA-1, granzyme B, and perforin and are CD3 negative °° Almost all are EBV+ °° CD56 negative-type very rare, with much less association with EBV infection
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Fig. 1.18 Angiocentric infiltrate with complete necrosis of the vessel is seen in this extranodal NK/T-cell lymphoma
–– Molecular features °° Gene rearrangements usually not seen –– Treatment protocols °° Aggressive chemotherapy (cytoxan, vincristine, adriamycin, and prednisone in one series) °° Radiation –– Prognosis °° CD56+ lymphomas have less than 12 month median survival °° If presenting with only skin lesions, survival is 27 months, compared with 5 months if they also have extracutaneous disease °° Most patients develop systemic disease and bone marrow involvement • Hematodermic neoplasm (NK blastic lymphoma) (Fig. 1.19) –– Newly described
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–– Similar cells morphologically to NK/T cell lymphoma, nasal type –– Express CD4, CD43, CD56, and CD123, but not CD3 or CD20 –– EBV always absent –– Not angiocentric or angiodestructive –– May be derived from plasmacytoid dendritic cells • B cell lymphomas (Table 1.2) • Primary cutaneous marginal zone lymphoma (MZL) –– Epidemiologic features °° Slightly more common in men (1.5:1) °° Mean age 50 years – >50% are in fifth and sixth decades °° May represent 15–20% of all cutaneous lymphomas °° Cases previously called immunocytoma included in this category °° Part of MALT lymphomas – mucosa associated lymphoid tissue –– Clinical features °° Single or clusters of red-brown papules or nodules that usually do not ulcerate °° Upper extremities, back and lower extremities are most common sites °° Face involvement uncommon °° More than one region involved in 25% of cases °° Systemic symptoms are very uncommon but cutaneous recurrences common –– Histologic features (Figs. 1.20 and 1.21) Nodular dermal infiltrates involving dermis and subcutis No epidermotropism Reactive germinal centers with mantle zones present Lymphoplasmacytoid cells present in all cases but may represent the minority population °° Often with monotypic plasma cells at periphery of lesions °° °° °° °°
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Fig. 1.19 CD4+/CD56+ hematodermic neoplasms show a diffuse, non- epidermotropic dermal infiltrate (A) atypical and mitotically active cells (B) that co-express CD4 (C) and CD56 (D)
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Fig. 1.19 (continued)
Table 1.2 B cell lymphomas Marginal zone lymphoma (MALToma) Primary follicular center cell lymphoma Primary cutaneous large B-cell lymphoma of the leg Intravascular B cell lymphoma
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Fig. 1.20 Marginal zone lymphoma shows a nodular dermal infiltrate, without epidermotropism
–– Immunologic features (Fig. 1.22) °° Neoplastic cells express CD20, CD79a, and bcl-2 °° CD5, CD10, bcl-6, and CD43 negative °° Monoclonal immunoglobulin distribution in 75% of cases; these plasma cells also express CD138 and CD 79a °° Many CD3+ T cells present in infiltrate –– Molecular features °° Trisomy 3 is seen in 70% of cases °° Trisomy 18 and rearrangement of chromosome 1 also seen
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Fig. 1.21 Reactive germinal centers with mantle zones may be present in marginal zone lymphoma
°° t(14;18)(q32;q21) involving IgH gene on chromosome 14 and the MLT gene on chromosome 18 –– Treatment protocols °° Local excision and radiation are therapies of choice for primary lesions and local recurrences °° European studies emphasize antibiotic therapy and stress relationship with Borrelia burgdorferi infection (not seen in USA) – in these cases, antibiotics should be tried first °° Chemotherapy only for recurrent and widespread disease –– Prognosis °° Recurrences common °° 100% survival in one study with 5-year follow-up (median 24 months)
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Fig. 1.22 Neoplastic cells in marginal zone lymphoma express CD79a (A) and bcl2 (B)
• Primary cutaneous follicular center cell lymphoma (FCCL) –– Epidemiologic features °° Occurs in middle-aged to elderly patients (mean age 58.5) °° 1.6:1 male predominance
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Fig. 1.23 This case of follicle center lymphoma shows a dense nodular dermal infiltrate
°° When on back, previously known as “reticulohistiocytoma of the dorsum” or “Crosti lymphoma” –– Clinical features °° Usually presents as one (or several) grouped, erythematous to violaceous papules or nodules without surface changes in a localized distribution °° Head and neck are most common locations, then trunk °° Will gradually increase in size over years without disseminating if left untreated –– Histologic features (Figs. 1.23–1.25) °° Dense, deep dermal infiltrate of lymphocytes with no epidermal involvement and a frequent grenz zone °° May be nodular (more common on scalp) or diffuse °° Neoplastic follicles of lymphocytes may be difficult to find °° Eosinophils and plasma cells are not present °° Mixed cell type of FCC lymphoma most common in skin, then large cleaved type; small cleaved is least common
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Fig. 1.24 This case of follicle center cell lymphoma is composed predominantly of small centrocyte-like cells with cleaved nuclei and inconspicuous nucleoli
Fig. 1.25 This case of follicle center lymphoma shows a mixture of small and large centrocyte-like cells with scattered centroblast-like cells that show large nuclei and prominent nucleoli (arrows)
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–– Immunologic features °° Predominance of CD20+ or CD79a + cells in infiltrate with scattered reactive CD3/CD43+ lymphocytes °° Either kappa or lambda restriction in many cases °° Bcl-2 expression uncommon in primary cutaneous FCC lymphomas (common in nodal based lymphomas) °° Bcl-6 expression helpful in confirming follicular nature of cells °° CD10 expression seen only in follicular pattern, not in diffuse growth pattern lymphomas °° CD5 and CD43 are negative –– Molecular features °° Clonality can be established in most cases, but t(14;18) is not seen in primary cutaneous FCC lymphoma –– Treatment protocols °° °° °° °°
Orthovolt radiation therapy to local lesions Surgical excision has been used (less desirable) Radiation also effective for recurrent lesions Chemotherapy indicated only when noncontiguous regions are affected
–– Prognosis °° Local relapses present in 25% of cases (disease-free interval was 27 months (mean)) °° Systemic spread of disease in 95% independent of growth pattern (nodular vs. diffuse), multi-focality vs. localized, or percentage of blasts °° Strong bcl-2 expression and a diffuse large-cell growth pattern may be associated with less favorable prognosis • Primary cutaneous large B-cell lymphoma of the leg –– Epidemiologic features °° Only in elder patients (median age 76) °° 85% greater than 70 years of age °° 3:1 female predominance in one study
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Fig. 1.26 Primary cutaneous diffuse B-cell lymphoma of the leg has a non-epidermotropic infiltrate filling the dermis
–– Clinical features °° Large blue-red tumor nodules appearing on lower legs, mostly multiple °° Almost always confined to lower leg at time of presentation, but associated with rapid dissemination °° Has been associated with lymphedematous leg –– Histologic features (Figs. 1.26 and 1.27) °° Dermis filled diffusely with large cells including centrocytes and immunoblasts °° High mitotic rate, abundant necrosis °° No epidermotropism
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Fig. 1.27 The dermal infiltrate in primary cutaneous diffuse B-cell lymphoma is composed of large cells with centrocyte and centroblast morphology
–– Immunologic features (Fig. 1.28) °° Cells express CD20 and CD79a (pan B-cell markers) and strongly express bcl-2 (unlike most FCC lymphomas in the skin) °° Bcl-2 expression cited as evidence in favor of classifying as a separate B cell lymphoma (not follicular center cell-related) °° Usually bcl-6 positive and CD10 negative –– Treatment protocols °° Usually starts with local radiation as first choice therapy for patients with single, small lesion °° Systemic chemotherapy for relapses, more extensive disease –– Prognosis °° 50% relapse rate °° Median survival is 28 months (range 8–97 months) °° 2-year survival 77%, 5 year survival 55%
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Fig. 1.28 The neoplastic cells in primary cutaneous B-cell lymphoma of the leg co-express CD79a (A) and bcl2 (B)
°° Patients with multiple lesions at time of presentation with significantly worse prognosis than those with a single lesion °° Considered an intermediate prognosis lymphoma in EORTC classification
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• Intravascular B cell lymphoma (malignant angioendothe liomatosis) –– Epidemiologic features °° Also known as angiotropic lymphoma (not angiocentric) °° Usually in adults ages 50–70 but can occur at any age °° No gender predilection –– Clinical features °° Most commonly involves skin, lungs, and central nervous system at time of presentation °° Skin findings may appear as telangiectasias, panniculitis, or erythematous nodules, most commonly on trunk and lower extremities °° Constitutional symptoms including fever and myalgias are common °° Hematopoietic tissues are rarely involved °° Mild anemia –– Histologic features (Figs. 1.29 and 1.30) °° Ectatic vessels in dermis and subcutis occluded by noncohesive proliferation of large, cytologically atypical lymphocytes °° Lymphocytes are hyperchromatic with prominent nucleoli and abundant mitoses °° Fibrin thrombi may be present °° Small- and medium-sized vessels are involved –– Immunologic features °° Most cases express CD20 and CD79a (rare cases are CD3+ T cell lymphomas) –– Treatment protocols °° Aggressive chemotherapy and radiation therapy °° Lymphoma responds poorly to both regimens °° Some evidence that better results occur with aggressive polychemotherapy early in course
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Fig. 1.29 Intravascular B-cell lymphoma shows dermal vessels distended with large atypical B-cells
Fig. 1.30 The cells filling the dermal vessels in intravascular B-cell lymphoma have irregular nuclei, prominent nucleoli, mitoses, and apoptosis
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–– Prognosis °° Very poor °° 13-month median survival after diagnosis °° Patients with only skin lesions have a 56% 3-year survival °° Patients with other organ involvement have a 22% 3-year survival
Chapter 2
Vascular Tumors
• Vascular tumors (Table 2.1) • Telangiectasias (Table 2.2) • Port wine stain –– Clinical
°° Presents at birth or shortly thereafter °° Progressively darkens, thickens, and becomes more °° °°
nodular with age Associated with Sturge–Weber syndrome, Klippel– Trenaunay syndrome, and Cobb syndrome Progressive ectasia believed to be caused by abnormal autonomic regulation – decreased nerves present in lesional skin
–– Histologic (Figs. 2.1 and 2.2)
°° Ectatic, thin-walled vessels in superficial to mid-dermis °° Vascular ectasia becomes more prominent with increas°°
ing age Difficult to diagnose in young children (without clinical history) – appears virtually normal
• Hereditary hemorrhagic telangiectasia –– Clinical
°° Autosomal dominant inheritance °° Nosebleeds in children °° Telangiectasias appear on mucosal surfaces and diffusely on skin
B.R. Smoller, K.M. Hiatt, Dermal Tumors: The Basics, DOI: 10.1007/978-3-642-19085-8_2, © Springer-Verlag Berlin Heidelberg 2011
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38 Table 2.1 Vascular tumors Telangiectias Intravascular papillary endothelial hyperplasia Hemangiomas Lymphangiomas Non-hemangiomatous tumors Table 2.2 Telangiectasias Nevus flammeus (port wine stains) Hereditary hemorrhagic telangiectasia Angiokeratoma Venous lake
Fig. 2.1 Port wine stain demonstrates vascular ectasia but no increase in numbers of dermal blood vessels. Original magnification 40×
–– Histologic
°° Ectatic post-capillary venules °° Thin-walled vessels °° No inflammation
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Fig. 2.2 Widely ecstatic vessels are present in the papillary and superficial reticular dermis in port wine stains. Original magnification 100×
• Angiokeratoma –– Clinical
°° Acquired telangiectasia °° Epidermal hyperplasia is secondary °° Mibelli type – multiple telangiectasias on dorsa and sides °° °° °°
of fingers Fordyce type – multiple telangiectasias on scrotum Associated with Fabry’s disease – multiple angiokeratomas, renal disease Angiokeratoma circumscriptum is probably a true hemangioma (not a telangiectasia) – is probably misnamed
–– Histologic (Figs. 2.3 and 2.4)
°° Dermal papillae expanded by dermal capillaries °° Epidermal acanthosis with elongated rete ridges engulf°°
ing ectatic vessels Deeper vessels may rarely be involved
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Fig. 2.3 Ectatic vessels are located high in the papillary dermis and surrounded by acanthotic epidermis in angiokeratoma. Original magnification 40×
Fig. 2.4 The superficial, ecstatic vessels in angiokeratoma are usually congested and often thrombosed. Original magnification 100×
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• Venous lake –– Clinical
°° Slowly enlarging ectatic vascular lesion usually in elderly men with marked sun exposure
–– Histologic (Fig. 2.5)
°° Dilated vessel, usually filled with erythrocytes and often thrombosed surrounded by marked solar elastosis
• Intravascular Papillary Endothelial Hyperplasia (IVPEH) –– Clinical
°° Also known as Masson’s lesion °° Tender-painful red-blue dermal nodule, often sudden appearance and growth
–– Histologic (Figs. 2.6 and 2.7)
°° Proliferation of endothelial cells confined to lumen of °° °°
larger, thrombosed vessel Papillary infoldings may resemble angiosarcoma, but no mitoses or cellular atypia Represents a recanalized, thrombosed blood vessel
Fig. 2.5 A venous lake consists of a single ecstatic vessels in the superficial dermis, often surrounded by marked solar elastosis. Original magnification 40×
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Fig. 2.6 Intravascular papillary endothelial hyperplasia is a proliferation of endothelial cells confined to within the lumen of a vessel. Original magnification 40×
Fig. 2.7 Higher magnification demonstrates a florid proliferation of endothelial cells forming interanastamosing channels and extravasated erythrocytes in intravascular papillary endothelial hyperplasia. Original magnification 200×
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• Hemangiomas (Table 2.3) • Acquired capillary hemangioma –– Clinical
°° Small, red lesions acquired in adolescence and later in life °° Associated with increased estrogens, liver disease –– Histologic (Fig. 2.8)
°° Proliferation of dilated capillaries in the superficial dermis Table 2.3 Hemangiomas Acquired capillary hemangioma Infantile capillary hemangioma Cavernous hemangioma Verrucous hemangioma Lobular capillary hemangioma (pyogenic granuloma) Arteriovenous hemangioma Acquired tufted hemangioma Targetoid hemangioma (hobnail hemangioma)
Fig. 2.8 Capillary hemangioma is characterized by a proliferation of bland appearing blood vessels in the superficial portion of the dermis. These vessels may be fully congested with erythrocytes. Original magnification 100×
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• Infantile capillary hemangioma –– Clinical
°° Usually present within days of birth and grow rapidly for °° °°
up to a year May involute in up to 75% of cases, usually starting at about age 5 Usually in area surrounding parotid gland, but can grow to involve airways and to be life-threatening
–– Histologic (Fig. 2.9)
°° Early lesions – marked cellularity, may have jig-saw °° °° °°
puzzle-like appearance at low magnification Difficult to find vessels – very small Mitoses are abundant Older lesions with less cellularity and more prominent vessels
• Lobular capillary hemangioma (pyogenic granuloma) –– Clinical
°° Rapid onset of exophytic red nodule
Fig. 2.9 Juvenile (infantile) capillary hemangioma demonstrates a markedly cellular proliferation with scattered blood vessels that are often devoid of erythrocytes. Original magnification 200×
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°° Usually ulcerated °° Most common on fingers, mucous membranes, but can occur anywhere
°° Increased numbers associated with pregnancy °° Can occur in any age patient –– Histologic (Figs. 2.10 and 2.11)
°° Collarette of rete ridges surrounds proliferation of wellformed small vessels
°° Feeder vessel at deep margin ramifies into many smaller vessels
°° Endothelial cell mitoses and mild cytologic atypia may be present
°° Infiltrate of inflammatory cells most prominent at surface where ulceration is common
Fig. 2.10 Lobular capillary hemangioma (pyogenic granuloma) is characterized by an exophytic proliferation of small blood vessels surrounded by an epidermal collarette. Original magnification 40×
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Fig. 2.11 Lobular capillary hemangioma demonstrates many small blood vessels with a proliferation of spindle-shaped cells between the vessels. Inflammatory cells may also be present. Original magnification 200×
• Acquired tufted angioma (angioblastoma) –– Clinical
°° Benign, progressive angiomatosis most common in chil°° °°
dren and younger adults Slowly enlarging erythematous macules Usually on trunk and upper extremities
–– Histologic (Figs. 2.12 and 2.13)
°° °° °° °°
Cellular lobules dispersed throughout the reticular dermis Ovoid or spindle-shaped cells without atypia Cleft-like luminal spaces Masses of cells protrude into and distort surrounding thin-walled vessels
• Targetoid hemosiderotic hemangioma –– Clinical
°° Most common in young to middle-aged men °° Usually single, on trunk and proximal extremities °° Central papular area with centrifugal areas of bronze discoloration
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Fig. 2.12 Acquired tufted angioma demonstrates a lobular pattern of dermal involvement. Original magnification 20×
Fig. 2.13 The lobules consist of angulated blood vessels surrounded by spindle-shaped cells in acquired tufted angioma. Original magnification 100×
–– Histologic (Figs. 2.14 and 2.15)
°° Vascular spaces lined by plump endothelial cells with °° °°
papillary projections into lumen Abundant hemosiderin deposits, especially laterally Poorly circumscribed and infiltrative growth pattern at periphery
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Fig. 2.14 Targetoid hemosiderotic hemangioma demonstrates thin vessels with prominent endothelial cells and surrounding hemosiderin. Original magnification 200×
Fig. 2.15 Targetoid hemosiderotic hemangioma (hobnail hemangioma) demonstrates prominent endothelial cell protrusion into the lumen in a hobnail-like pattern. Original magnification 400×
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• Lymphangiomas (Table 2.4) • Lymphangioma circumscriptum –– Clinical
°° Grouped vesicular papules, often on flank and thighs °° May appear fluid filled or dark (if hemorrhagic and thrombosed)
–– Histologic (Fig. 2.16)
°° Indistinguishable from angiokeratoma except if vessels °°
are devoid of erythrocytes Epidermal collarette surrounds ectatic vessels in papillary dermis
• Non-hemangiomatous tumors (Table 2.5) Table 2.4 Lymphangiomas Lymphangioma circumscriptum Cystic hygroma Acquired progressive lymphangioma
Fig. 2.16 Thin-walled vessels, often containing serum but few cells, are present in the superficial dermis in lymphangioma circumscriptum. There is often an epidermal collarette. Original magnification 200×
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Table 2.5 Non-hemangiomatous tumors Angiolymphoid hyperplasia with eosinophilia (ALHE) Spindle cell hemangioendothelioma Glomus tumor (glomangioma) Hemangiopericytoma
• ALHE –– Clinical
°° °° °° °°
One or several erythematous papules, nodules Most common around ears and on face Young to middle-aged adults Synonymous with epithelioid hemangioma
–– Histologic (Figs. 2.17–2.19)
°° Abundant small vessels with swollen endothelial cells, °° °°
often occluding lumen – difficult to identify as vessels in some cases Dense inflammatory infiltrate of lymphocytes and eosinophils surrounding vascular proliferation Often completely filling dermis, may be germinal centers present
Fig. 2.17 Angiolymphoid hyperplasia with eosinophilia demonstrates a marked inflammatory infiltrate at lowest magnification. Original magnification 40×
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Fig. 2.18 At high magnification, swollen endothelial cells may make vessels appear to be small granulomas in angiolymphoid hyperplasia with eosinophilia. The percentage of eosinophils present in the infiltrate is highly variable. Original magnification 400×
Fig. 2.19 In some cases of angiolymphoid hyperplasia with eosinophilia, there are many eosinophils surrounding the thickened blood vessels. Original magnification 400×
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• Spindle cell hemangioendothelioma –– Clinical
°° °° °° °° °°
May be reactive, and not neoplastic 50% of cases in people F Single, blue – violaceous nodules and plaques 15% 5-year survival
°° Arising in lymphedematous limbs (Stewart–Treves) 12.5 years post-surgery
°° Post-irradiation 10–20 years post-irradiation
Fig. 2.25 Angiosarcoma is characterized by a proliferation of angulated, interanastamosing channels throughout the dermis. The early lesions may be subtle. Original magnification 100×
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Fig. 2.26 The interanastamosing channels are lined by prominent protruding endothelial cells in angiosarcoma. Original magnification 400×
Fig. 2.27 In some cases, the proliferating endothelial cells may be markedly spindly in shape. Original magnification 100×
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Fig. 2.28 In other cases, the endothelial cells may demonstrate pronounced atypia and have an epithelioid morphology, making it difficult to determine the nature of the malignant process. Original magnification 200×
–– Histologic (Figs. 2.25–2.28)
°° Poorly circumscribed proliferation of interanastamosing °° °° °° °°
vascular spaces Vessels lined with atypical endothelial cells May be solid areas Dense lymphocytic infiltrate in some cases may obscure vascular proliferation Well-differentiated can resemble benign angiomatous process, poorly differentiated can be difficult to identify as vascular
Chapter 3
Histiocytic Proliferations
• Histiocytic proliferations −− X-histiocytoses – Langerhans cell histiocytoses (LCH) −− Non-X histiocytoses • Langerhans cell histiocytosis −− −− −− −− −−
Letterer–Siwe disease Hand–Schuller–Christian disease Eosinophilic granuloma Congenital self-healing reticulohistiocytosis Indeterminate cell disorder
• Langerhans cell histiocytosis −− Proliferation of Langerhans cells −− Distinction between subtypes is not sharp (nor important) −− Letterer–Siwe °° Clinical Infants Fever, anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy 80% with cutaneous lesions – first sign Papules and petechiae – may be scaly Extensive, involving face, scalp, trunk Resembles seborrheic dermatitis or Darier’s disease Poor prognosis B.R. Smoller, K.M. Hiatt, Dermal Tumors: The Basics, DOI: 10.1007/978-3-642-19085-8_3, © Springer-Verlag Berlin Heidelberg 2011
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−− Hand–Schuller–Christian disease °° Clinical Diabetes insipidus, exophthalmos, bony defects Other organs may be involved Cutaneous lesions in about 30% of cases Plaques with ulceration mainly in mouth, anogenital region, axillae Rarely, xanthematous, yellow lesions May resemble Letterer–Siwe clinically (rare) 30% mortality without treatment
−− Eosinophilic granuloma °° Clinical Least severe form Lesions are few or solitary Mostly bone lesions, diabetes insipidus may be present Skin only rarely involved – lesions resemble other subtypes
Fig. 3.1 Langerhans cell histiocytosis showing a dense papillary dermal infiltrate of histiocytosis with marked epidermotropism
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Fig. 3.2 The dermal infiltrate in Langerhans cell histiocytosis is accompanied by numerous eosinophils in this case
Fig. 3.3 Langerhans cell histiocytosis showing diffuse expression of CD1a
−− Histologic (Figs. 3.1–3.3) °° Proliferative lesions Abundant infiltrate of Langerhans cells close to epidermis with marked exocytosis and spongiosis Cells may be atypical Variable numbers of eosinophils in infiltrate
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°° Granulomatous lesions Seen with infiltrated plaques Aggregates of Langerhans cells extending deep into dermis and subcutis Giant cells may be present Variable numbers of eosinophils −− Xanthomatous lesions °° Only in Hand–Schuller–Christian subtype °° Abundant foam cells seen in conjunction with other patterns °° Can also be foreign body or Touton-type giant cells • Congenital self-healing reticulohistiocytosis −− Clinical °° °° °° °°
Present at birth or within weeks Multiple scattered papules and nodules Rarely solitary lesion All resolve within 12 months (usually within 2–3)
−− Histologic (Figs. 3.4 and 3.5) °° Abundant large giant cells with extensive eosinophilic cytoplasm °° Can see “ground glass” cytoplasm °° Admixture of lymphocytes, neutrophils, eosinophils °° Occasional foam cells °° Exocytosis and spongiosis °° Mitotically active −− Histogenesis °° °° °° °°
Langerhans cell proliferation Cells express CD1 and S100 Demonstrate Birbeck granules on electron microscopy Clonality demonstrated in many cases
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Fig. 3.4 Congenital self-healing reticulohistiocytosis shows epidermotropism and spongiosis
Fig. 3.5 Giant cells with eosinophilic cytoplasm with “ground glass” appearance are seen in the dermal infiltrate in congenital self-healing reticulohistiocytosis
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• Indeterminate Cell Proliferative Disorder −− No characteristic clinical or histologic features −− Previously regarded as “nodular non-X histiocytosis” or “generalized eruptive histiocytoma” −− Dermis filled with S100+, OKT6+ cells that do not contain Birbeck granules – incompletely developed Langerhans cells? • Benign Non-X histiocytoses (Table 3.1) • Reticulohistiocytosis (multicentric) −− Clinical Cutaneous nodules associated with polyarthritis Usually in middle-aged women Lasts for about 8 years Destructive arthritis, mostly in interphalangeal joints Skin-colored papules on head and hands 50% with oral lesions Underlying malignancy in 25% of cases, thyroid disease in 15%, hypercholesterolemia in 33% °° May be solitary (reticulohistiocytoma) – no systemic associations
°° °° °° °° °° °° °°
−− Histologic (Figs. 3.6 and 3.7) °° Dense infiltrate of multinucleated and mononuclear histiocytes in superficial and mid dermis °° Histiocytes with pale, ground glass eosinophilic cytoplasm
Table 3.1 Benign non-X histiocytoses Juvenile xanthogranuloma (see Chap. 4) Reticulohistiocytosis (solitary and multiple) Xanthoma disseminatum Benign cephalic histiocytosis Verruciform xanthoma Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease)
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Fig. 3.6 A dense dermal infiltrate fills the superficial reticular and papillary dermis in reticulohistiocytoma
Fig. 3.7 The infiltrate in reticulohistiocytoma is composed of large cells with pale, eosinophilic cytoplasm
°° °° °° °°
Plasma cells and eosinophils may be present Overlying epidermis thinned Fibrosis in late lesions Cells are S100 negative
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• Xanthoma disseminatum −− Clinical °° Adult onset °° Red-brown papules and xanthomatous plaques °° Symmetrical, flexural surfaces and intertriginous regions °° 40% with mucous membrane involvement °° Normolipemic °° 40% with diabetes insipidus °° Good prognosis −− Histologic (Figs. 3.8 and 3.9) °° Dermal histiocytes with foamy cytoplasm °° Inflammatory infiltrate admixed with occasional eosinophils °° Numerous Touton-type giant cells °° Indistinguishable from JXG histologically • Benign cephalic histiocytosis −− Clinical °° °° °° °° °° °°
Onset during first 2 years of life M = F Many small yellow-red papules on face, neck, ears Trunk and extremities involved later May regress by age 4 without scarring No systemic anomalies described
−− Histologic °° °° °° °° °° °°
Well-demarcated, superficial infiltrate Atrophic epidermis infiltrated with histiocytes Histiocytes with pale, glassy cytoplasm Eosinophils not prominent Cells are S100 negative Comma-shaped bodies in 5–30% of histiocytes on EM – not specific
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Fig. 3.8 The xanthomatous plaques of xanthoma disseminatum show numerous histiocytes in the papillary dermis with a sparse inflammatory infiltrate consisting of lymphocytes and scattered eosinophils
Fig. 3.9 Multinucleate Touton-type giant cells and cells with abundant foamy cytoplasm make up the infiltrate in xanthoma disseminatum
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• Verruciform xanthoma −− Clinical °° Solitary verrucous lesion, most common in oral cavity or on genitals °° Also occurs as secondary lesion in association with conditions with marked epidermal hyperplasia (epidermal nevus, ILVEN) −− Histologic (Figs. 3.10 and 3.11) °° Elongated rete ridges °° Papillary dermis distended with foam cells pushed up against the dermal epidermal junction °° Uniform population of cells – minimal associated inflammation • Sinus histiocytosis with massive lymphadenopathy (Rosai– Dorfman disease) −− Clinical °° °° °° °° °°
Benign condition Massive cervical lymphadenopathy 10% of cases with skin involvement Most common site for extranodal disease Multiple papules, nodules
Fig. 3.10 Verruciform xanthoma shows an acanthotic epidermis with elongated rete. There are numerous foamy cells filling the papillary dermal tips
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−− Histologic (Figs. 3.12–3.14) °° Polymorphous dermal infiltrate with many histiocytes, some with foamy cytoplasm; Touton giant cells °° Emperipolesis (lymphophagocytosis and erythrophago cytosis)
Fig. 3.11 The papillary dermal tips in verruciform xanthoma are filled with cells with abundant foamy cytoplasm
Fig. 3.12 Sinus histiocytosis with massive lymphadenopathy shows a vaguely nodular dermal dense mixed infiltrate
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Fig. 3.13 Higher power of sinus histiocytosis with massive lymphadenopathy shows collections of histiocytosis with foamy cytoplasm accompanied by a dense lymphohistiocytic infiltrate
Fig. 3.14 Perivascular plasma cells are a characteristic feature of sinus histiocytosis with massive lymphadenopathy
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°° Plasma cells collaring blood vessels lined with swollen endothelial cells °° Histiocytes are S100+ • Malignant histiocytic proliferations −− Histiocytic cytophagic panniculitis – better known as subcutaneous panniculitis-like T cell lymphoma (at least in the majority of cases previously diagnosed as histiocytic cytophagic panniculitis) – see Chap. 1
Chapter 4
“Fibrohistiocytic” Proliferations
• Fibrocytic lesions –– Scar °° Normal scar °° Hypertrophic °° Keloid –– Fibrous papule °° Angiofibroma • Hypertrophic scar vs. keloid –– Clinical °° Initially identical °° Red, raised plaques with firm surface °° Hypertrophic scars flatten within years and do not extend beyond the original scar °° Keloids persist and enlarge beyond original scar • Keloid –– Clinical °° Familial predisposition °° More common in African American than Caucasian population °° Rubinstein–Taybi syndrome – spontaneous keloids during adolescence associated with microcephaly, mental retardation, breaking of nose, broadening of terminal phalanges of thumbs and great toes B.R. Smoller, K.M. Hiatt, Dermal Tumors: The Basics, DOI: 10.1007/978-3-642-19085-8_4, © Springer-Verlag Berlin Heidelberg 2011
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–– Histologic (Figs. 4.1–4.4)
°° Hypertrophic scar vs. keloid: spectrum on microscopy °° Whorls and nodules of thickened collagen bundles – scant in hypertrophic scar, majority in keloids °° Collagen bundles are thickened, more hyalinized °° May be perpendicular to skin surface – unusual in normal scar formation or in unaffected dermis • Fibrous papule (Table 4.1) • Fibrous papule of the nose –– Clinical °° Most common on nose, but can occur anywhere (mainly face) °° Almost always single °° Dome-shaped, skin-colored papule up to about 5 mm
Fig. 4.1 Hypertrophic scar shows a dense collagen deposition in the dermis
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Fig. 4.2 Hypertrophic scar on higher power shows the thickened collagen bundles arranged in haphazard array
Fig. 4.3 Keloid, similar to hypertrophic scar, shows dense collagen deposition. However the collagen is thick and eosinophilic
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Fig. 4.4 This higher power image of keloid shows the comparison of the thick eosinophilic collagen compared to the adjacent normal dermal collagen Table 4.1 Variants of fibrous papule Fibrous papule of the nose Angiofibroma (adenoma sebaceum) Pearly penile papule Subungual fibroma (Koenan’s tumor)
–– Histologic (Figs. 4.5 and 4.6)
°° Papillary dermal fibrosis (appears as if reticular dermal collagen is overgrowing the papillary dermis) °° Concentric perifollicular fibrosis °° Ectatic blood vessels °° Stellate fibroblasts °° Occasionally slight increase in overlying epidermal melanocytes °° Dermal dendritic cells express factor XIIIa • Angiofibroma –– Histologically identical to fibrous papule –– Part of tuberous sclerosis constellation
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Fig. 4.5 Fibrous papule is composed of ecstatic superficial dermal vessels with concentric collagen deposition around the follicle and in the papillary dermis
Fig. 4.6 Many fibroblasts in the dermis of a fibrous papule show stellate forms
–– Tuberous sclerosis
°° Autosomal dominant °° Triad of mental retardation, epilepsy, and angiofibromas (adenoma sebaceum)
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°° May also see fibromas of face, scalp, subungium °° Shagreen patches – collagenomas °° Ash-leaf macules – often earliest manifestation (at birth or shortly thereafter) Ash leaf macules – normal numbers of melanocytes with decreased melanin production
°° Gliomas (calcified) in brain and retina °° Rhabdomyomas of heart °° Angiomyolipomas of kidneys (tend to be bilateral) • Pearly penile papule –– 1–2 mm papules along corona of penis –– Histologically identical to angiofibroma/fibrous papule of the nose • Miscellaneous fibrous conditions –– Fibrous hamartoma of infancy Acquired digital fibrokeratoma Recurrent infantile digital fibroma Myofibromatosis Nodular fasciitis
–– –– –– ––
• Fibrous hamartoma of infancy –– Clinical °° Presents within a year of birth °° Slight male predominance °° Occurs on shoulders, axilla, upper arm °° Rapidly growing 3–5 cm nodule –– Histologic (Figs. 4.7–4.9) °° Poorly circumscribed proliferation with three components Cellular fibrous tissue with spindle-shaped fibroblasts arranged in an organoid pattern Loosely arranged bundles of collagen with rounded, immature appearing fibroblasts resembling neural tissue Variable amounts of mature fat cells
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Fig. 4.7 Fibrous hamartoma of infancy is composed of a poorly circumscribed proliferation of fibroblasts and mature fat cells
Fig. 4.8 This section of fibrous hamartoma of infancy shows a cellular fibroblast proliferations surrounded by loosely arranged collagen and immature fibroblasts resembling neural tissue admixed with mature fat
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Fig. 4.9 Both the cellular and less cellular areas of fibrous hamartoma of infancy are composed of spindled cells lacking significant atypia and mitoses
• Acquired digital fibrokeratoma –– Clinical °° Solitary, round, firm, hyperkeratotic projection on finger or toe (rarely palm or sole) °° Usually in adults °° Differential diagnosis of supernumerary digit –– Histologic (Fig. 4.10)
°° Hyperkeratosis, acanthosis °° Thick, interwoven bundles of collagen oriented perpendicular to skin surface °° Only thin, scant elastic tissue fibers persist °° Loss of cutaneous appendages • Recurrent infantile digital fibroma –– Clinical °° Single or multiple nodules on fingers or toes °° Usually occur during first year of life or rarely later in childhood °° Rarely exceed 2 cm in diameter °° 75% recur during childhood
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Fig. 4.10 Acquired digital fibroma shows acanthotic acral-type skin with a vaguely papillomatous epithelium. Lack of adnexal structures and thick collagen in bundles perpendicular to the surface are seen in this lesion
–– Histologic (Figs. 4.11–4.13)
°° Numerous spindle-shaped cells in dermis °° Collagen in interlacing bundles – may extend into subcutis °° Eosinophilic cytoplasmic inclusion bodies in fibroblasts – often perinuclear °° Inclusions resemble erythrocytes – best seen with Masson’s (purple) or phosphotungstic acid-hematoxylin (PTAH) (deep red) –– Immunostains
°° Stains with smooth muscle actin antibodies °° Cells are myofibroblasts °° Infantile digital myoblastoma has been suggested as a name for these tumors
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Fig. 4.11 Recurrent infantile digital fibroma shows a dermal spindle cell proliferation
Fig. 4.12 Interlacing fascicles of fibroblasts is present in the dermis of this recurrent infantile digital fibroma
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Fig. 4.13 Eosinophilic perinuclear cytoplasmic inclusions (arrows) are characteristic of recurrent infantile digital fibroma
• Myofibromatosis –– Clinical °° Superficial – nodules confined to skin, subcutis, skeletal muscles, and bone – good prognosis °° Generalized – visceral nodules obstruct vital organs – 80% mortality within first few months °° Nodules appear at birth and continue to appear °° Spontaneous involution of superficial and deep lesions within first year –– Histologic (Fig. 4.14)
°° Well-circumscribed proliferations of spindle-shaped cells without atypia °° Arranged in short fascicles °° Collagen not abundant, areas with mucoid stroma °° Virtually all cells are myofibroblasts • Nodular fasciitis –– Clinical
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Fig. 4.14 Myofibromatosis is composed of a relatively well-circumscribed nodule of short fascicles of spindled cells, lacking atypia
°° Most common in young adults (10–50) °° Male = female incidence °° Most common on forearm, but can occur anywhere °° 75% with rapidly growing lesion ( 50% of patients with this tumor have neurofibromatosis –– 2–3 year mean survival –– Histologic (Fig. 5.19) °° Spindle cell proliferation with wavy bundles °° Alternating areas of dense cellularity with more myxoid areas °° Can be cellular with abundant mitoses and pleomorphism °° Can show divergent differentiation with other sarcomatous elements °° Express S100, neuron-specific enolase, neurofilament
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Fig. 5.19 Malignant peripheral nerve sheath tumor demonstrates a spindle cell proliferation with abundant, pleomorphism and bizarre, atypical forms. Original magnification 200×
• Smooth muscle proliferations –– Smooth muscle hamartoma –– Leiomyoma °° Angioleiomyoma °° Piloleiomyoma –– Leiomyosarcoma • Smooth muscle hamartoma –– Clinical °° May present with hyperpigmented patch with irregular surface –– Histologic features
°° Poorly circumscribed, diffuse proliferation of perfectly mature smooth muscle bundles °° Usually localized to superficial portion of reticular dermis
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°° No mitotic activity of cytologic atypia °° Often associated with enlarged terminal hairs and epidermal hyperplasia and hyperpigmentation (Becker’s nevus) • Leiomyoma –– Clinical °° Occasionally painful/tender dermal nodule with overlying hyperpigmentation and superficial dimpling (pseudoDarier’s sign) °° Most common on extremities –– Histologic features (Figs. 5.20 and 5.21) °° Poorly circumscribed, diffuse proliferation of perfectly mature smooth muscle bundles
Fig. 5.20 Leiomyoma is characterized by a proliferation of eosinophilic fascicles coursing in bundles throughout the dermis. Original magnification 40×
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Fig. 5.21 Spindle-shaped cells coursing in fascicles, with little nuclear atypia or pleomorphism characterize leiomyoma. Original magnification 400×
°° Usually more cohesive and circumscribed than smooth muscle hamartoma, but often difficult to distinguish based on histologic changes –– Angioleiomyoma °° Bundles of smooth muscle (eosinophilic with “cigar shaped nuclei”) surrounding large dermal blood vessel °° Usually in deeper dermis °° Well circumscribed °° No cytologic atypia °° Mitoses infrequent –– Piloleiomyoma °° Bundles of smooth muscle more diffusely scattered throughout the superficial portion of the reticular dermis °° Not obviously centered around arrector pili muscles °° No cytologic atypia °° Mitoses infrequent
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Fig. 5.22 Leiomyosarcoma demonstrates marked nuclear pleomorphism, bizarre atypical forms, and abundant mitoses within the proliferation of smooth muscle cells
• Leiomyosarcoma –– Histologic features (Fig. 5.22) °° Controversial as these tumors rarely, if ever, metastasize when dermally based °° De-differentiation with recurrence of leiomyoma has been reported °° Infiltrative growth pattern °° Bundles of smooth muscle cells demonstrating nuclear pleomorphism °° Abundant mitoses (exact numerical requirement not as clearly defined as leiomyosarcomas in other organs) °° Necrosis may be present (unlike in leiomyomas)
Chapter 6
Cutaneous Metastases
• Carcinoma metastatic to the skin (Tables 6.1 and 6.2) –– Occurs in 0.7–9.0% of all patients with cancer –– Most frequent sites on the body for metastases to appear:
–– –– –– –– ––
°° At sites of incision of primary tumors °° Three-fourths of metastases are on head and neck, despite only one-fourth surface area °° Extremities uncommon site for metastases Most common presentation is that of a painless, skin-colored, freely mobile cutaneous nodule; ulceration uncommon Indurated plaques, erysipelas-like patterns also seen Survival: 1–34 months following identification of cutaneous metastasis One-third of patients develop cutaneous metastases within 6 months of initial diagnosis One-half develop metastases within 1 year of initial diagnosis and >90% within 5 years
• Metastatic breast carcinoma –– Clinical °° Seen in 23.9% of patients with breast carcinoma °° Presenting sign in 3.5% of such patients °° Different clinical patterns: inflammatory (resembles erysipelas), en cuirasse (resembles morphea), telangiectatic pattern, nodular metastases, alopecia neoplastica, Paget’s disease B.R. Smoller, K.M. Hiatt, Dermal Tumors: The Basics, DOI: 10.1007/978-3-642-19085-8_6, © Springer-Verlag Berlin Heidelberg 2011
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Table 6.1 Most common carcinomas metastatic to skin in women Most frequent primary sources in women
Percent of total cutaneous metastases in women
Breast Colon Melanoma Lung Ovary
69 9 5 4 4
Table 6.2 Most common carcinomas metastatic to skin in men Most frequent primary sources in men
Percent of total cutaneous metastases in men
Lung Colon Melanoma Oral squamous cell carcinoma Stomach Kidney Esophagus
24 19 13 12 6 6 3
–– Histologic features (Figs. 6.1–6.4)
°° Inflammatory – tumor cells confined largely to dermal lymphatics °° Telangiectatic tumor altering blood flow leads to widely dilated and congested blood vessels °° Alopecia neoplastic – blood vascular spread to scalp °° Nodular-type most likely to be confused with primary eccrine adenocarcinoma °° May be separate nodules or diffusely infiltrating entire dermis °° Atypical cells prominent at low magnification °° Ductular differentiation may be present • Metastatic renal cell carcinoma –– Clinical °° Hemorrhagic tumor nodule °° Scalp is most common site (28% of cases)
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Fig. 6.1 Inflammatory breast carcinoma shows dermal lymphatics distended with tumoral cells
Fig. 6.2 Metastatic lobular breast carcinoma shows individual tumor cells in a single file infiltrating between collagen bundles
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Fig. 6.3 Cutaneous metastasis of ductal breast carcinoma shows nodules of tumor cells with ductal differentiation
Fig. 6.4 The ductal differentiation in metastatic ductal carcinoma can be so extensive as to mimic a primary eccrine carcinoma
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°° More common in men °° Ulceration uncommon –– Histologic features (Figs. 6.5 and 6.6) °° Highly vascular neoplasm °° Clear cytoplasm, some mitoses and cytologic atypia °° Differential diagnosis includes pyogenic granuloma which has spindle-shaped cells in surrounding stroma and less cytologic atypia. –– Immunohistochemical features °° RCC stains with EMA and cytokeratin cocktails, as does pyogenic granuloma °° RCC often S100 positive °° RCC stains with renal cell carcinoma antibodies and with PAX-2 –– Prognosis
°° Metastatic renal cell carcinoma – rarely can spontaneous regress with cure °° 5 -year survival with known primary RCC and a single cutaneous metastasis is 35%
Fig. 6.5 Metastatic renal cell carcinoma is characteristically highly vascular
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Fig. 6.6 The tumoral cells of metastatic renal cell carcinoma are often clear, or vacuolated
• Metastatic neuroendocrine carcinoma –– Histologic features °° Identical to Merkel cell carcinoma (Fig. 6.7) –– Immunohistochemical features °° Cytokeratin 20 (and CAM 5.2) stains almost all MCC with either punctate cytoplasmic pattern or membranous pattern °° Less frequent, but similar pattern can be seen in neuroendocrine carcinomas °° Thyroid transcription factor 1 – not seen in MCC, present in most metastatic small cell carcinomas from the lung and other sources • Melanoma – primary vs. metastatic –– Clinical features °° Individual lesions may be identical °° Primary lesions identified in >95% of cases, so history is crucial
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Fig. 6.7 Metastatic neuroendocrine carcinoma is histologically identical to primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) with small cells having open chromatin, minimal cytoplasm, and numerous mitoses
°° Multiple lesions favor metastasis over primary °° Proximal spread along cutaneous lymphatics also helpful °° Diffuse melanosis another pattern (rare) –– Histologic features (Fig. 6.8) °° Usual histology is a dermal nodule, often well-circumscribed without epidermal changes °° Differentiation from primary melanomas usually relatively straightforward °° Epidermotropic metastatic melanomas recently described °° Intraepidermal atypical melanocytes do not extend lateral to the dermal involvement in most cases – some exceptions reported °° Nesting pattern and Pagetoid invasion °° Inflammatory response often pronounced in these types of metastases °° Involvement may be limited to superficial dermis in nesting pattern °° Small size to these types of lesions also reported
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Fig. 6.8 Metastatic melanoma has cytologic features and immunohistochemical staining consistent with melanoma. An in situ component is not present in the overlying epidermis
°° Often vascular and lymphatic invasion seen °° May see thinning of epidermis or epidermal hyperplasia °° Can be seen in lesions
