Color atlas of melanocytic lesions of the skin

H. P. Soyer, G. Argenziano, R. Hofmann-Wellenhof, R. H. Johr (Eds.) Color Atlas of Melanocytic Lesions of the Skin

H. P. Soyer G. Argenziano R. Hofmann-Wellenhof R. H. Johr (Eds.)

Color Atlas of Melanocytic Lesions of the Skin With 366 Figures and 26 Tables

123

H. Peter Soyer, MD, FACD Professor of Dermatology The Queensland Institute of Dermatology School of Medicine University of Queensland Princess Alexandra Hospital Brisbane, QLD 4102 Australia Giuseppe Argenziano, MD Professor of Dermatology  Department of Dermatology  Second University of Naples  Nuovo Policlinico – Edificio 13  Via Pansini 5 I-80131 Naples Italy

Rainer Hofmann-Wellenhof, MD Professor of Dermatology  Department of Dermatology Medical University Graz Auenbruggerplatz 8 A-8036 Graz Austria Robert H. Johr, MD Clinical Professor of Dermatology and Pediatrics Director, Pigmented Lesion Clinic University of Miami, School of Medicine Miami, FL 33136 USA

Library of Congress Control Number: 2007924719 ISBN 978-3-540-35105-4  Springer Berlin Heidelberg New York 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-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer is a part of Springer Science+Business Media springer.com © Springer-Verlag Berlin Heidelberg 2007 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. Editor: Marion Philipp, Heidelberg, Germany Desk Editor: Ellen Blasig, Heidelberg, Germany Production: LE-TEX Jelonek, Schmidt & Vöckler GbR, Leipzig, Germany Cover design: Frido Steinen-Broo, EStudio, Calamar, Spain Reproduction and typesetting: am-productions GmbH, Wiesloch, Germany Printed on acid-free paper  24/3180/YL 5  4  3  2  1  0



This book is dedicated to the memory of Paolo Carli an outstanding scientist and a special human being. H. Peter Soyer and Giuseppe Argenziano on behalf of all authors

Foreword

Melanocytic tumors of the skin deserve special attention because of the following important facts Melanoma is frequent and early detection is critical. ■ A correct interpretation is necessary because the implications may be very serious. ■ It is a dynamically developing field where major progress has been made over the past decade. ■

This atlas, written in a concise way, is a highly useful presentation that focuses on the full spectrum of pigmented skin tumors. The prominent features include classical clinical as well as histopathological criteria for diagnosis, illustrations of excellent quality, as well as new concepts and practical aspects of management. Of special interest are modern diagnostic techniques with emphasis on dermatoscopy. Case studies and core messages indicating pathways of the diagnostic approach are at the end of each chapter.

All these features characterize the book as an impressive contribution to the literature in the area of melanocytic tumors. My co-workers in Graz, Dr. H. Peter Soyer and Dr. Rainer Hofmann-Wellenhof, as well as Dr. Giuseppe Argenziano from Naples and Dr. Robert Johr from Miami, together with many international contributors who are all experts in their respective disciplines, have produced a splendid piece of work which presents highly relevant information on a complex and challenging subject. This book will greatly assist physicians in providing optimal care for patients with melanocytic skin lesions.

Helmut Kerl Professor & Chairman Department of Dermatology Medical University of Graz Austria

Preface

At the beginning of many scientific endeavors there is an idea shared by a small group of enthusiastic people. This was the case with our group, friends and colleagues from Austria, Italy, and the United States. Our idea was to write a color atlas of melanocytic skin lesions, with particular emphasis on the morphological dimension, using a systematic and logical approach. As practicing dermatologists with backgrounds in dermoscopy and dermatopathology, we wanted to describe the many faces of benign and malignant pigmented skin lesions based on clinico-pathological and dermoscopic−pathological correlations. Together with a large group of distinguished dermatologists from around the world, we prepared this atlas.

In 1894 Paul Gerson Unna published the textbook Histopathology of Skin Diseases. His wellknown saying on the relationship between dermatology and histopathology has been slightly modified by us and now reads as follows: “The dermatologist is fortunate in being able to study the clinical and dermoscopic picture with his/ her histologically trained eye and the microscopic picture with his/her clinically and dermoscopically trained eye.” In this spirit we hope that you enjoy reading this atlas and that it will help you in your daily practice.

H. Peter Soyer Giuseppe Argenziano Rainer Hofmann-Wellenhof Robert Johr

Contents

I.1

The Morphologic Dimension in the Diagnosis of Melanocytic Skin Lesions. . . . . . . . . . . . . . . . . . . . . . . 1 H. Peter Soyer and Elisabeth M.T. Wurm

III.3 Agminated Nevus. . . . . . . . . . . . . . . . . 75 Ulrike Weigert and Wilhelm Stolz

Clinical Examination of Melanocytic Neoplasms Including ABCDE Criteria . . . . . . . . . . 3 Alfred W. Kopf

III.5 Atypical (Dysplastic) Nevus. . . . . . . . 87 Rainer Hofmann-Wellenhof and H. Peter Soyer

I.3

Dermoscopic Examination. . . . . . . . . . 7 Ralph P. Braun, Harold S. Rabinovitz, Margaret Oliviero, Alfred W. Kopf, Jean-Hillaire Saurat, Luc Thomas

III.6

Combined Nevus . . . . . . . . . . . . . . . . . 97 Horacio Cabo

III.7

I.4

Melanoma: the Morphological Dimension. . . . . . . . . . . . . . . . . . . . . . . 23 Lorenzo Cerroni

Common Nevus . . . . . . . . . . . . . . . . . 102 Rainer Hofmann-Wellenhof and H. Peter Soyer

III.8

II.1 Laser-Scanning Confocal Microscopy. . . . . . . . . . . . . . . . . . . . . . . 39 Salvador González and Allan Halpern

Congenital Melanocytic Nevi. . . . . . 106 A lon Scope, Cristiane BenvenutoAndrade, Ashfaq A. Marghoob

III.9

II.2 Automatic Diagnosis . . . . . . . . . . . . . . 47 Josef Smolle



Melanocytic Nevi on the Genitalia and Melanocytic Nevi on Other Special Locations. . . . . . . . 119 Ingrid H. Wolf

I.2



II.3

Multispectral Image Analysis. . . . . . . 52 Dina Gutkowicz-Krusin and Harold Rabinovitz

II.4

Teledermatology. . . . . . . . . . . . . . . . . . 57 Cesare Massone, Elisabeth M.T. Wurm, Rainer Hofmann-Wellenhof, Gian Piero Lozzi, H. Peter Soyer

III.1

The Life of Melanocytic Nevi. . . . . . . 61 Harald Kittler

III.2 Acral Nevus. . . . . . . . . . . . . . . . . . . . . . 66 Masaru Tanaka, Masayuki Kimoto, Toshiaki Saida

III.4

Blue Nevus. . . . . . . . . . . . . . . . . . . . . . . 78 Gerardo Ferrara and Giuseppe Argenziano

III.10 Halo Nevus . . . . . . . . . . . . . . . . . . . . . 124 A lessandro Di Stefani and Sergio Chimenti III.11 Irritated Nevus and Meyerson’s Nevus. . . . . . . . . . . . 129 Regina Fink-Puches, Iris Zalaudek, Rainer Hofmann-Wellenhof III.12 Melanocytic Lesions in Darker Racial Ethnic Groups. . . . 135 Heather Woolery-Lloyd III.13 Miescher Nevus. . . . . . . . . . . . . . . . . . 139 Steven Q. Wang, Harold H. Rabinovitz, Alfred W. Kopf



XII

Contents

III.14 Nevi with Particular Pigmentation: Black, Pink, and White Nevus . . . . . 142 Iris Zalaudek, Robert Johr, Bernd Leinweber III.15 Recurrent Nevus. . . . . . . . . . . . . . . . . 147 Andreas Blum III.16 Spitz Nevus and Its Variants. . . . . . . 151 Gerardo Ferrara, Elvira Moscarella, Caterina M. Giorgio, Giuseppe Argenziano III.17 Syndromes Involving Melanocytic Lesions. . . . . . . . . . . . . . 164 Cheryl G. Aber, Elizabeth Alvarez Connelly, Lawrence A. Schachner III.18 Nail Apparatus Nevus (Subungual Nevus, Nail Matrix Nevus). . . . . . . . 173 Luc Thomas III.19 Unna Nevus. . . . . . . . . . . . . . . . . . . . . 181 Susana Puig and Josep Malvehy IV.1

Epidemiology of Melanoma . . . . . . . 185 Scott Kitchener

IV.2 Acral Melanoma. . . . . . . . . . . . . . . . . 196 Toshiaki Saida, Hiroshi Koga, Yoriko Yamazaki, Masaru Tanaka IV.3 Amelanotic Melanoma. . . . . . . . . . . 204 Jürgen Kreusch IV.4

Early Evolution of Melanoma (Small-Diameter Melanoma) . . . . . . 213 Robert J. Friedman, Melanie Warycha, Michele Farber, Dina GutkowiczKrusin, Harold Rabinovitz, David Polsky, Margaret Oliviero, Darrell S. Rigel, Lori Kels, Edward R. Heilman, Alfred W. Kopf

IV.5

False-Negative Melanomas. . . . . . . . 221 Robert Johr and Giuseppe Argenziano

IV.6

Genital Melanoma . . . . . . . . . . . . . . . 229 Ingrid H. Wolf

IV.7

Melanoma of the Face . . . . . . . . . . . . 233 Ulrike Weigert and Wilhelm Stolz

IV.8

Melanoma of the Trunk and Limbs Including Superficial and Nodular Melanoma. . . . . . . . . . . 237 Josep Malvehy and Susana Puig

IV.9

Cutaneous Metastatic Melanoma. . . 260 Maria Antonietta Pizzichetta

IV.10 Scalp Melanoma . . . . . . . . . . . . . . . . . 265 Iris Zalaudek, Jason Giacomel, Bernd Leinweber IV.11 Nail Apparatus Melanoma (Subungual Melanoma, Nail Matrix Melanoma). . . . . . . . . . . 270 Luc Thomas V.1

Pigmented Basal Cell Carcinoma. . . 279 Scott W. Menzies

V.2

Dermatofibroma. . . . . . . . . . . . . . . . . 286 Domenico Piccolo and Ketty Peris

V.3 Lentigines Including Lentigo Simplex, Reticulated Lentigo and Actinic Lentigo . . . . . . . . . . . . . . 290 Paolo Carli and Camilla Salvini V.4



Squamous Cell Carcinoma Including Actinic Keratosis, Bowens Disease, Keratoacanthoma, and Its Pigmented Variants . . . . . . . . . . . . . . 295 Iris Zalaudek, Jason Giacomel, Bernd Leinweber

V.5

Vascular Lesions. . . . . . . . . . . . . . . . . 303 Fezal Özdemir

V.6

Seborrheic Keratosis Including Lichen Planus-like Keratosis. . . . . . . 313 Robert Johr



Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . 329

List of Contributors

C. Aber Division of Pediatric Dermatology Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine Cedars Medical Center 1295 NW 14th Street, Suite K Miami, Florida 33125 E-mail: [email protected] E. Alvarez Connelly Division of Pediatric Dermatology Department of Dermatology and Cutaneous Surgery University of Miami, Miller School of Medicine Cedars Medical Center 1295 NW 14th Street, Suite K Miami, Florida 33125 USA E-mail: [email protected]

A. Blum Associate Professor of Dermatology Seestraße 3a 78464 Konstanz Germany E-mail: [email protected] R.P. Braun Department of Dermatology University Hospital Zurich 8091 Zurich Switzerland E-mail: [email protected] H. Cabo Section of Dermatology Instituto de Investigaciones Médicas “A. Lanari” University of Buenos Aires Argentina E-mail: [email protected]

G. Argenziano Department of Dermatology Second University of Naples Nuovo Policlinico − Edificio 13 Via Pansini 5 80131 Naples E-mail: [email protected]

P. Carli † Dipartimento di Scienze Dermatologiche Universita’ di Firenze Via degli Alfani, 37 50121 Florence Italy † Deceased

C. Benvenuto-Andrade Research Dermatologist Photomedicine and Telemedicine Laboratory Federal University of Rio Grande do Sul Porte Alegre Brazil E-mail: [email protected]

L. Cerroni Department of Dermatology Medical University of Graz Auenbruggerplatz 8 8036 Graz Austria E-mail: [email protected]



XIV

List of Contributors

S. Chimenti Department of Dermatology University of Rome “Tor Vergata” PTV − Policlinico di Tor Vergata Viale Oxford 81 00133 Rome Italy E-mail: [email protected] A. Di Stefani Department of Dermatology University of Rome “Tor Vergata” PTV − Policlinico di Tor Vergata Viale Oxford 81 00133 Rome Italy E-mail: [email protected] M. Farber Department of Dermatology New York University School of Medicine 550 First Avenue New York, NY 10016 USA E-mail: [email protected] G. Ferrara Pathologic Anatomy Service Gaetano Rummo General Hospital Via dell’Angelo 1 82100 Benevento Italy E-mail: [email protected] R. Fink-Puches Department of Dermatology Medical University Graz Auenbruggerplatz 8 8036 Graz Austria E-mail: [email protected] R.J. Friedman Oncology Section Department of Dermatology New York University School of Medicine 550 First Avenue New York, NY 10016 USA E-mail: [email protected]

J.S. Giacomel Private Practice 11 Mends Street South Perth Western Australia 6151 Australia E-mail: [email protected] C.M. Giorgio Department of Dermatology Second University of Naples Via S. Pansini 5 80131 Naples Italy E-mail: [email protected] S. González Dermatology Service Memorial Sloan-Kettering Cancer Center New York, NY 10022 USA E-mail: [email protected] D. Gutkowicz-Krusin Electro-Optical Sciences, Inc. 1 Bridge Street Irvington, NY 10533 USA E-mail: [email protected] A. Halpern Dermatology Service Memorial Sloan-Kettering Cancer Center New York, NY 10022 USA E-mail: [email protected] E.R. Heilman Department of Dermatology SUNY Health Science Center at Brooklyn Brooklyn, N.Y. USA E-mail: [email protected]

List of Contributors

R. Hofmann-Wellenhof Department of Dermatology Medical University of Graz Auenbruggerplatz 8 8036 Graz Austria E-mail: [email protected] R.H. Johr Pigmented Lesion Clinic School of Medicine University of Miami Miami, FL 33136 USA E-mail: [email protected] M. Kimoto Department of Dermatology Keio University School of Medicine 35 Shinanomachi, Shinjyuku-ku Tokyo 160-8582 Japan E-mail: [email protected] S. Kitchener Primary Care Skin Cancer Medicine Unit School of Medicine University of Queensland Herston Road Herston 4006 Australia E-mail: [email protected] H. Kittler Department of Dermatology Medical University of Vienna Waehringer Guertel 18−20 1090 Vienna Austria E-mail: [email protected] H. Koga Department of Dermatology Shinshu University School of Medicine 3-1-1 Asahi Matsumoto 390-8621 Japan E-mail: [email protected]

A.W. Kopf The Ronald O. Perelman Department of Dermatology New York University School of Medicine 550 First Avenue New York, NY 10016 USA E-mail: [email protected] J. Kreusch Dermatological Practice Skin Cancer Diagnostic Center Moislinger Allee 95 23558 Luebeck Germany E-mail: juergen.kreusch @web.de B. Leinweber Department of Dermatology Medical University of Graz, Austria Auenbruggerplatz 8 8036 Graz Austria E-mail: [email protected] G.P. Lozzi Department of Dermatology University of L’Aquila, Italy Via Vetoio − Coppito 2 67100 L’Aquila Italy E-mail: [email protected] J. Malvehy Melanoma Unit Department of Dermatology Hospital Clinic Villarroel 170 08036 Barcelona Spain E-mail: [email protected] A.A. Marghoob Section of Dermatology Memorial Sloan-Kettering Cancer Center 160 East 53rd Street, 2nd floor New York, NY 10022 USA E-mail: [email protected]

XV



XVI

List of Contributors

C. Massone Department of Dermatology Medical University Graz Auenbruggerplatz 8 A-8036 Graz Austria E-mail: [email protected]

D. Piccolo Department of Dermatology University of L’Aquila Via Vetoio − Coppito 2 67100 L’Aquila Italy E-Mail: [email protected]

S.W. Menzies Sydney Melanoma Diagnostic Centre 2nd Floor, Gloucester House Royal Prince Alfred Hospital Missenden Road Camperdown NSW 2050 Australia E-mail: [email protected]

M.A. Pizzichetta Division of Medical Oncology C Oncology Prevention Centro di Riferimento Oncologico National Cancer Institute Via Pedemontana Occidentale 12 33081 Aviano –PN Italy E-mail: [email protected]

E. Moscarella Department of Dermatology Second University of Naples Via S. Pansini 5 80131 Naples Italy E-mail: [email protected] M. Oliviero Department of Dermatology University of Miami School of Medicine Miami, FL 33324 USA E-mail: [email protected] F. Özdemir Department of Dermatology Medical Faculty Ege University 35100 Bornova Izmir Turkey E-mail: [email protected] K. Peris Department of Dermatology University of L’Aquila Via Vetoio − Coppito 2 67100 L’Aquila Italy E-Mail: [email protected]

D. Polsky Department of Dermatology New York University School of Medicine 550 First Avenue New York, NY 10016 USA E-mail: [email protected] H.S. Rabinovitz Skin and Cancer Associates 201 N.W. 82nd Avenue Plantation, FL 33324 USA E-mail: [email protected] D.S. Rigel Department of Dermatology New York University School of Medicine Adjunct Clinical Professor Department of Dermatology Mount Sinai School of Medicine New York, NY USA E-mail: [email protected] S. Puig Melanoma Unit Department of Dermatology Hospital Clínic Villarroel 170 08036 Barcelona Spain E-mail: [email protected]

List of Contributors

T. Saida Department of Dermatology Shinshu University School of Medicine 3-1-1 Asahi Matsumoto 390-8621 Japan E-mail: [email protected] C. Salvini Department of Dermatological Sciences University of Florence Via della Pergola 58−60 50121 Florence Italy E-mail: [email protected] J.-H. Saurat Pigmented Skin Lesion Unit Department of Dermatology University Hospital Geneva 24 rue Micheli Du Crest 1211 Geneva 14 Switzerland E-mail: [email protected] L.A. Schachner Division of Pediatric Dermatology University of Miami, Miller School of Medicine Department of Dermatology and Cutaneous Surgery 1600 NW 10th Avenue Rosenstiel Bldg. Room 2023A Miami FL 33136 USA E-mail: [email protected] L. Schneider-Kels Department of Dermatology New York University School of Medicine 550 First Avenue New York, NY 10016 USA E-mail: [email protected] A. Scope Section of Dermatology Memorial Sloan-Kettering Cancer Center 160 East 53rd Street, 2nd floor New York, NY 10022 USA E-mail: [email protected]

J. Smolle Institute of Medical Informatics, Statistics and Documentation Medical University of Graz Billrothgasse 18a/7 8010 Graz Austria E-mail: [email protected] H.P. Soyer The Queensland institute of Dermatology School of Medicine University of Queensland Princess alexandra Hospital Brisbane, QlD 4102 Australia E-mail: [email protected] W. Stolz Abteilung für Dermatologie, Allergologie und Umweltmedizin Krankenhaus München Schwabing Kölner Platz 1 80804 Munich Germany E-mail: [email protected] M. Tanaka Department of Dermatology Tokyo Women’s Medical University Medical Center East 2-1-10 Nishi-Ogu, Arakawa-ku Tokyo 116-8567 Japan E-mail: [email protected] L. Thomas Department of Dermatology Hotel Dieu 69288 Lyon Cedex 02 France E-mail: [email protected] S.Q. Wang Department of Dermatology Mayo Mail Code 98 420 Delaware Street S.E. Minneapolis, MN 55455 USA E-mail: [email protected]

XVII



XVIII

List of Contributors

M. Warycha Department of Dermatology New York University School of Medicine 550 First Avenue New York, NY 10016 USA E-mail: [email protected]

E.M.T. Wurm Department of Dermatology Medical University of Graz Auenbruggerplatz 8 8036 Graz Austria E-mail: [email protected]

U. Weigert Abteilung für Dermatologie, Allergologie und Umweltmedizin Krankenhaus München Schwabing Kölner Platz 1 80804 München Germany E-mail: [email protected]

Y. Yamazaki Department of Dermatology Shinshu University School of Medicine 3-1-1 Asahi Matsumoto 390-8621 Japan E-mail: [email protected]

I.H. Wolf Department of Dermatology Medical University Graz Auenbruggerplatz 8 8036 Graz Austria E-mail: [email protected] H. Woolery-Lloyd Department of Dermatology and Cutaneous Surgery School of Medicine University of Miami Miami, FL 33136 USA E-mail: [email protected]

I. Zalaudek Department of Dermatology Medical University Graz Auenbruggerplatz 8 8036 Graz Austria E-mail: [email protected]

Chapter I.1

The Morphologic Dimension in the Diagnosis of Melanocytic Skin Lesions

I.1

H. Peter Soyer and Elisabeth M.T. Wurm

Contents I.1.1 A Color Atlas of Melanocytic Lesions of the Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 I.1.2

The Benign/Malignant Threshold in Morphology. . . . . . . . . . . . . . . . . . . . . . . . . . 1

I.1.3 A New Era of “Clinicoimaging” Diagnosis in Dermatology. . . . . . . . . . . . . . . . 2 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

I.1.1 A Color Atlas of Melanocytic Lesions of the Skin The book in your hands has been designed basically as an atlas entitled Color Atlas of Melanocytic Lesions of the Skin and focuses on the morphologic dimension of melanocytic skin lesions. It encompasses all the classical methods of morphology such as the clinical and dermoscopic examination and dermatopathology, as well as the most up-to-date diagnostic approaches such as laser scanning in-vivo microscopy, multispectral image analysis, automatic diagnosis, and teledermatology. With the exception of the chapters on automatic diagnosis and on multispectral analysis, all chapters focus on the morphologic dimension, albeit in its various facets, thus justifying the title of this book. The core of this book represents an atlas with clinical, dermoscopic, and histopathologic images of the many faces of melanocytic nevi, the various types of melanomas, as well as the variable features of non-melanocytic pigmented skin tumors. Each of these well-illustrated entities are presented following the same ductus characterized by definition, clinical and dermo-

scopic features, relevant clinical differential diagnosis, histopathology, as well as practical aspects of management. Core messages recapitulate the most pertinent facets of each entity. This introductory chapter, therefore, can be considered a plea for recognition of the significance, and the unchanging importance, of the human eye and the human neural network for achieving diagnosis in the protean field of melanocytic skin lesions. We currently are on the edge of the development of new technologies, such as imaging technologies and molecularbiologic tests, for identifying individuals at risk and for refining the benign/malignant threshold. These new technologies are challenging the currently well-accepted morphologic methods including histopathology. However, the present reality, even in high-tech countries, is that dermatologists are, and most probably will remain, at the forefront of diagnosing and treating skin cancers as well as managing melanocytic skin lesions.

I.1.2 The Benign/Malignant Threshold in Morphology The boundary between benignity and malignancy is not as sharp as our established categories would like them to be. Dermoscopic – but also histopathologic – diagnoses, not to mention clinical diagnosis, are subjective as well as objective. In 1962 these facts were well depicted for the histopathologic diagnosis by Rambo who stated that “pathologists are physicians and human beings. They […] traditionally have been regarded to be more scientific than many of their colleagues. A mystic perversion of this assumption prevails among those clinicians who





I.1

H. P. Soyer, E. M.T. Wurm

believe that the pathologist, given only a piece of the patient’s tissue, has all the other ingredients necessary to produce a statement of absolute truth at the end of his report. More dangerous to the mankind is a pathologist with the same concept…” [1]. Even today it is not easy at all to find references which indicate that expert pathologists sometimes have great difficulties in recognizing, for example, the threshold separating carcinoma in situ or melanoma in situ from atypia or dysplasia. Interestingly, many dermoscopists reveal more insight with regard to their diagnostic limitations. In a recent issue of the “Archives of Dermatology” an article by Skvara et al. entitled “Limitations of dermoscopy in the recognition of melanoma” focuses on the limitations of dermoscopy in the diagnosis of very early, and mainly featureless, melanomas [2]. The authors report that baseline dermoscopic patterns of 262 melanocytic nevi and 63 melanomas, which were followed by digital dermoscopy and finally excised because of changes over time, did not differ substantially from each other. Suffice it to say that histopathology represented the gold standard in this study.

I.1.3 A New Era of “Clinicoimaging” Diagnosis in Dermatology In 2005 June Robinson, the editor of the “Archives of Dermatology,” wrote in an editorial titled “Biotechnology succeeds in revolutionizing medical sciences” the following statement: “Given the unique visual learning patterns of our discipline, it is not surprising that we eager­ ly adapt emerging bioimaging techniques. [...] We are beginning to move away from clinicopathologic diagnosis into an era of ‘clinicoimaging’ diagnosis” [3]. The introduction of these new ‘clinicoimaging’ techniques in the near future certainly will have a major impact on the current dermatologic practice, although there will be a need to define new quality standards in order to integrate these techniques into the daily workflow. We should not forget, however, that all of these new “clinicoimaging” techniques have, like every other purely morphologic meth-

od, limitations due to methodologic drawbacks, and sometimes even due to personal restraints. In addition, we are presently also on the edge of a period of radical change in histopathology, as DNA and RNA can be analyzed by advanced technologies even from archival paraffin-embedded material, allowing us to make diagnostic leaps and bounds [4]. This “new biology” will certainly also affect the benign/malignant threshold in pathology, and a more functional approach to establish the risk associated with sharply defined categories will substitute the fanciful separation of benign from malignant [4, 5]; thus, one can easily foresee that in the future the conventional morphologic methods will probably be substituted by these new “clinicoimaging” techniques and by novel microbiologic methods. Until then, a combined approach linking the most legitimate and effective morphologic methods, namely, clinical examination, dermoscopy, and histopathology, will strengthen the validity of classical morphology [6, 7]. In this spirit this introductory chapter, and this atlas, has been written.

References 1. Rambo ON. The limitations of histologic diagnosis. Progr Radiat Ther 1962; 2: 215–224 2. Skvara H, Teban L, Fiebiger M, Binder M, Kittler H. Limitations of dermoscopy in the recognition of melanoma. Arch Dermatol 2005; 141: 155–160 3. Robinson JK, Callen JP. Biotechnology succeeds revolutionizing medical sciences. Arch Dermatol 2005; 141: 133–134 4. Quirke P, Mapstone N. The new biology: histopathology. Lancet 1999; 354: SI26–SI31 5. Foucar E. Carcinoma-in-situ of the breast: Have pathologists run amok? Lancet 1996; 347: 707–708 6. Soyer HP, Massone C, Ferrara G, Argenziano G. Limitations of histopathologic analysis in the recognition of melanoma: a plea for a combined diagnostic approach of histopathologic and dermoscopic evaluation. Arch Dermatol 2005; 141: 209–211 7. Bauer J, Leinweber B, Metzler G, Blum A, HofmannWellenhof R, Leitz N, Dietz K, Soyer HP, Garbe C. Correlation with digital dermoscopic images can help dermatopathologists to diagnose equivocal skin tumours. Br J Dermatol 2006;155: 546–551

Chapter I.2

Clinical Examination of Melanocytic Neoplasms Including ABCDE Criteria

I.2

Alfred W. Kopf

Contents I.2.1

Clinical Recognition of Melanoma. . . . . . . . . 3

I.2.2 ABCDE Criteria and Other Diagnostic Methods . . . . . . . . . . . . . . . . . . . . . 3

I.2.1 Clinical Recognition of Melanoma The clinical recognition of melanoma in its early phases of progression is exceedingly important since the total surgical removal of such ­lesions is almost invariably curative. When the clinical recognition is delayed, the opportunity for distant metastases increases and the prognosis is guarded since treatment of such metastases is problematic. Since dysplastic nevi and melanomas can ­occur on any area of the cutaneous surface, it is mandatory that a complete cutaneous examination be performed on every patient regardless of age. All new patients should have a complete cutaneous examination either at the initial visit or in the near future. The frequency for an established patient depends on their history. Those patients with a history of actinic keratosis, dysplastic nevi, non-melanoma skin cancer or melanoma should be seen every 6 months for a complete cutaneous examination. The examining room should have proper ­illumination and the temperature should be comfortable for the patient, who should be ­completely undressed except – maybe – for the examination gown, which should be provided. The examiner should have available a simple magnifying lens, an instrument for dermoscopy, and an ultraviolet lamp (“Woods light”) for special examinations such as looking for areas of hyper- or hypopigmentation on the skin.

Ideally, the patient should lie in a horizontal position on the examining table. The entire anterior and posterior cutaneous surface of the patient is examined with the patient assuming a supine, then a prone, position. Intertriginous areas, including the axillae, groin, and interdigital webs of the hands and feet, plus the nail apparatus, are included in the complete cutaneous examination. Finally, examination of the scalp is best accomplished by the use of a hair blower that parts the hair down to the skin of the scalp for viewing.

I.2.2 ABCDE Criteria and Other Diagnostic Methods The acronym ABCDE was created as a simple mnemonic to alert both the general community and health care workers of some of the key features of melanoma. The acronym stands for: A = Asymmetry. No matter where the lesion is bisected, the one half will not match the other in silhouette and/or lesion content. B = Border irregularity. The perimeter of the lesion is uneven, undulating, ragged, notched, or blurred. C = Color. Multiple shades of tan, brown, black, red, white, and blue are admixed, producing a mottled appearance. D = Diameter >6 mm. The largest diameters of most melanomas will exceed 6 mm at a point in their evolution that can be identified. This is not an inviolate rule, and currently a significant portion of melanomas are diagnosed by experts when these cancers are 6 mm or less in diameter.





I.2

A.W. Kopf

E = Evolving. While common melanocytic nevi evolve slowly and reach a final stage of growth usually within the first few decades of life, melanomas usually undergo constant change in size, shape, shades of color, symmetry, symptoms (especially pruritus, scaliness, oozing, bleeding), or surface alterations [erosion, ulceration, papule, and/or nodule formation and the development of areas of hypopigmentation and depigmentation (a clinical correlate of spontaneous regression)]. Another easy mnemonic are the three Cs of melanoma standing for: color, contour, and change. The diagnostic method of the Glasgow 7point checklist for diagnosis of melanoma includes: (a) change in size; (b) irregular shape; (c) irregular color (major criterion); (d) diameter at least 7 mm; (e) inflammation; (f) oozing/bleeding; and (g) change in sensation (minor criterion). The features described above are suggestive of melanoma (especially superficial spreading melanoma), but they also appear in benign lesions (such as atypical nevi), thus causing diagnostic difficulties. Nodular melanomas, on the other hand, often appear as small and symmetric round nodules, smaller than 6 mm in diameter, the only hint of malignancy being a clinical history of evolution and change. These limitations to specificity and sensitivity of naked-eye examination can be reduced by dermoscopy as a useful aid in the in-vivo differentiation of such lesions (see Chap. I.3). Furthermore, total cutaneous photography can be performed for patients who have many melanocytic nevi (especially when atypical). Baseline total-cutaneous photographs (Fig. I.2.1) are very helpful in identifying significant changes in pre-existing lesions and identifying new melanocytic neoplasms on subsequent followup clinical examinations. Last but not least, patients should be instructed and encouraged to regularly perform self-examination of their skin (Fig. I.2.2).

Fig. I.2.1.  Illustrations for different views taken of total-body photographs. Sites photographed are bound by dashed lines or solid-line rectangles. Top: On anterior and posterior surfaces of body, all demarcated areas (shaded and unshaded) are photographed. On lateral aspects of body, only shaded areas are photographed

Clinical Examination of Melanocytic Neoplasms

C

Chapter I.2

Core Messages ■ It is mandatory that a complete cutaneous examination be performed on every patient regardless of her/his age. ■ The examination should include examination of intertriginous areas including axillae, groin, and interdigital webs of hands and feet, as well as nail apparatus and scalp. ■ Features of melanoma can be memorized by the acronym ABCDE: Asymmetry; Borders; Color; Diameter; and Evolution.

■ The diagnostic method of the Glasgow 7-point checklist for diagnosis of melanoma includes: (a) change in size; (b) irregular shape; (c) irregular color (major criterion); (d) diameter at least 7 mm; (e) inflammation; (f) oozing/ bleeding; and (g) change in sensation (minor criterion). ■ Patients should be encouraged to regularly perform a self-examination of their skin.

Fig. I.2.2.  Self-examination of the skin (continuation see next page)







A.W. Kopf

I.2

Fig. I.2.2.  (continued)

Chapter I.3

Dermoscopic Examination Ralph P. Braun, Harold S. Rabinovitz, Margaret Oliviero, Alfred W. Kopf, Jean-Hillaire Saurat, Luc Thomas

Contents I.3.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . .   7 I.3.2 Physical Aspects. . . . . . . . . . . . . . . . . . . . . . . .   7

I.3

I.3.7.3.2 Menzies Method. . . . . . . . . . . . . . . . . . . . . . . . 20 I.3.7.3.3 Three-Point Checklist. . . . . . . . . . . . . . . . . . . 21

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

I.3.3 Equipment for Dermoscopy. . . . . . . . . . . . . .   8 I.3.4 Dermoscopic Criteria. . . . . . . . . . . . . . . . . . .   9 I.3.4.1 Colors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   9 I.3.4.2 Blood Vessels. . . . . . . . . . . . . . . . . . . . . . . . . . .  9 I.3.5 Dermoscopic Structures. . . . . . . . . . . . . . . . . 11 I.3.5.1 Pigment Network. . . . . . . . . . . . . . . . . . . . . . . 11 I.3.5.2 Dots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 I.3.5.3 Globules. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 I.3.5.4 Branched Streaks. . . . . . . . . . . . . . . . . . . . . . . 12 I.3.5.5 Streaks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 I.3.5.6 Structureless Areas . . . . . . . . . . . . . . . . . . . . . 13 I.3.5.7 Blotches. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 I.3.5.8 Regression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 I.3.5.9 Blue-White Veil . . . . . . . . . . . . . . . . . . . . . . . . 13 I.3.5.10 Milia-like Cysts . . . . . . . . . . . . . . . . . . . . . . . . 13 I.3.5.11 Comedo-like Openings (Crypts, Pseudofollicular Openings). . . . . . 13 I.3.5.12 Fingerprint-like Structures . . . . . . . . . . . . . . 14 I.3.5.13 Moth-Eaten Border. . . . . . . . . . . . . . . . . . . . . 14 I.3.5.14 Fissures and Ridges (“Brain-like” Appearance). . . . . . . . . . . . . . . 14 I.3.5.15 Leaf-like Areas. . . . . . . . . . . . . . . . . . . . . . . . . 14 I.3.5.16 Spoke-Wheel-like Structures. . . . . . . . . . . . . 14 I.3.5.17 Large Blue-Gray Ovoid Nests . . . . . . . . . . . . 14 I.3.5.18 Multiple Blue-Gray Globules. . . . . . . . . . . . . 14 I.3.6 Differential Diagnosis of Pigmented Lesions of the Skin. . . . . . . . . 15 I.3.7 ABCD Rule of Dermatoscopy [11, 12] . . . . . 19 I.3.7.1 Asymmetry. . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 I.3.7.2 Border. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 I.3.7.3 Colors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 I.3.7.3 Dermoscopic Structures. . . . . . . . . . . . . . . . . 19 I.3.7.3.1 Seven-Point Checklist. . . . . . . . . . . . . . . . . . . 20

I.3.1 Introduction Dermoscopy (also known as epiluminescence microscopy, dermatoscopy, amplified surface microscopy) is an in-vivo method that has been reported to be a useful tool for the early recognition of melanoma and the differential diagnosis of pigmented lesions of the skin [1, 2]. Its use increases diagnostic accuracy between 5 and 30% over clinical visual inspection, depending on the type of skin lesion and the experience of the physician. This was confirmed by two recent evidence-based publications from a meta-analysis of the literature [3].

I.3.2 Physical Aspects Light is either reflected, dispersed, or absorbed by the stratum corneum due to its refraction index and its optical density, which is different from air; thus, deeper underlying structures cannot be adequately visualized. The use of ­immersion liquids renders the skin surface translucent and reduces reflections, so that underlying structures will become visible. The application of a glass plate flattens the skin surface and provides an even surface. Optical magnification is used for examination. Taken together, these optical means allow the visualization of certain epidermal, dermo-epidermal, and dermal structures. As immersion liquid we recommend the use of 60° alcohol (ethanol) which can





I.3

R. P. Braun, H. S. Rabinovitz, M. Oliviero et al.

be applied directly on the skin using an eye dropper bottle [4]. The advantages are that ethanol results in the best image quality and the least air inclusions. It evaporates immediately, does not have to be wiped off, and does not stain the patient’s clothing or underwear. In areas close to the eyes or to the mucosa, as well as for the examination of the nail apparatus, we recommend instead the use of a gel (ultrasound gel, cosmetic gel, etc.). A cosmetic gel does not burn the eyes and, most importantly, it fills out very nicely the gap between the convex nail surface and the handheld device. As an alternative to the immersion technique, some devices use polarized light in order to reduce the surface reflections. This technique allows a faster examination of the patient, but if the patient has dry skin the use of immersion liquid is still required.

I.3.3 Equipment for Dermoscopy As mentioned, dermoscopy requires optical magnification and liquid immersion. Specially designed handheld devices with 10–20 times magnification are commercially available (Dermatoscope Delta 20, Heine, Herrsching, Germany; DermoGenius Basic, Biocam, Regensburg, Germany; Dermlite (3Gen, San Juan Capistrano, Calif.); see Fig. I.3.1). All devices mentioned above are devices of the second generation which have improved optics and illumi-

nation (LED) compared with the older devices [1]. The optic is designed in such a way that a lesion can be examined at distance from the skin. This is an advantage, because the examination is much faster and it is more comfortable for both, the physician and the patient, if the lesion is, for example, on the face or the genital area. Photographic documentation can be performed in different ways [1]: The digital camera is directly attached to a handheld dermatoscope (coupling adapters are available for most handheld devices). In this case, the camera uses the optics and the illumination of the handheld dermatoscope. Since the optics of the handheld devices are not designed to fit a camera, the dermoscopic image is always a bit blurred towards the periphery, but this is the most inexpensive way of taking dermoscopy images. Dermoscopy attachments (lenses) are directly attached to digital cameras. Their optics and illumination are designed to fit digital cameras and they provide the best image quality. These lenses can only be used with digital cameras and not for the examination of patients. There are many different attachments available, but we mainly use the Dermlite Foto attachment (3GEN; Fig. I.3.1) or a Dermaphot lens (Heine, AG) which can be attached to digital SLR cameras. The attachments can be used with different cameras and the resolution depends on the digital camera used. This solution enables conveniently taking images of excellent quality. Fig. I.3.1.  A choiceof handheld dermatoscopes of the latest generation (from left to right): DermoGenius Basic (Biocam); Delta 20 (Heine); Dermlite II pro HR (3GEN); and Dermlite Foto (3GEN) on a Coolpix 4500 (Nikon)

Dermoscopic Examination

Storage and retrieval remain tricky for both ways of photo documentation mentioned above, and by the end of the day one finds himself with a camera full of images which have to be attributed to patients and stored in a way that they can be easily retrieved. Systems for digital dermoscopy consist of a video camera which is linked directly to a computer. The lesion can be examined “live” on the computer screen. These systems offer physicians many more features than the previous solutions, such as the possibility of easy storage and retrieval of lesions, which is important for followup examinations of suspect lesions. This is a big advantage, because when the patient leaves the office, all images (lesions) are correctly stored and there is no additional work to be done. Some systems offer even the possibility of computerassisted diagnosis and/or teledermoscopy. Since these systems use a video camera, the resolution is not as good as with a digital consumer camera and a dermoscopy attachment, but the image quality is very good on the computer screen. Systems for digital dermoscopy offer many more features and can make life much easier, but their disadvantages are their high cost and their lack of portability.

I.3.4 Dermoscopic Criteria The use of dermoscopy allows the identification of many different structures, colors, and blood vessels not seen by naked-eye examination.

I.3.4.1 Colors Colors play an important role in dermoscopy. Common colors are light brown, dark brown, black, blue, blue-gray, red, yellow, and white. The most important chromophore of the skin, especially in melanocytic neoplasms, is melanin. The color of melanin as seen with dermoscopy depends on its localization in the skin. For

Chapter I.3

example, melanin appears black in the stratum corneum and the upper epidermis, light to dark brown in the epidermis, gray to blue-gray in the papillary dermis, and steel blue in the reticular dermis. Melanin appears to be blue when it is localized within the deeper parts of the skin, because the portions of the visible light with longer wavelengths (red end of visible spectrum) are more dispersed than the portions with shorter wavelengths (blue-violet end of the spectrum). The color red is associated with either an increased number or dilatation of blood vessels, trauma, or neo-vascularization (see vascular pattern). The color white is often due to regression and/or scaring (see Regression).

I.3.4.2 Blood Vessels In recent publications, blood vessels have gained much more importance and their morphological aspect enables the clinician in many cases to make the diagnosis, especially in non-pigmented lesions and lesions of non-melanocytic origin. The following types of blood vessels have been described: red lagoons; hairpin vessels; dotted vessels; “comma”-like vessels; glomerular vessels; string of pearls; crown vessels; corkscrew vessels; and arborizing vessels (Table I.3.1) [5]. An atypical vascular pattern, also called irregular (polymorphous) vessels, may include linear, dotted, or globular red vessels, irregularly distributed within the lesion. Some of the vascular patterns may be due to neo-vascularization. For the evaluation of blood vessels, there has to be as little pressure as possible on the lesion during the examination, because otherwise the vessels are simply compressed and will not be visible. The use of ultrasound gel for immersion helps to reduce the pressure. An excellent alternative is the use of non-contact polarized light examination as used in some handheld dermatoscopes.





10

R. P. Braun, H. S. Rabinovitz, M. Oliviero et al. Table I.3.1.  Vascular architecture of pigmented skin lesions. (From [5])

Morphological aspect

Correlation

Red lagoons

Sharply demarcated globular structures, red, violaceous, brownish, bluish, or black

Hemangiomas or angiokeratomas

Hairpin vessels

Elongated vessels resembling hairpins

Fine and surrounded by whitish halo, seborrheic keratosis, or keratinizing tumor

I.3

Irregular and thick melanoma or Spitz nevus Dotted vessels

Small vessels resembling the head of a pin

Vertical vessels seen in Spitz ­nevus or melanoma Observed also in psoriasis and squamous cell carcinoma

Comma-like vessels

Resembling the shape of a comma

Compound or dermal nevus

Clusters of glomerular vessels

Small- and fine-coiled vessels

Bowen’s disease

String of pearls

Globular vessels following a serpiginous distribution

Crown vessels

Radial wreath-like or individual Sebaceous gland hyperplasia vessels at the periphery of the tumor; white-yellow globules in the center of the tumor

Corkscrew vessels

Irregular and thick-coiled vessels

Melanoma including melanoma metastasis

Arborizing vessels

Resembling the branches of a tree

Basal cell carcinoma

Irregular poly­ morphous vessels

Multiple vessels with different shapes including comma, dotted irregular lines, corkscrew, glomerular, and others

Melanoma

Observed in melanoma and stasis dermatitis Clear cell acanthoma

Dermoscopic Examination

Chapter I.3

I.3.5 Dermoscopic Structures In this chapter we use the nomenclature as proposed by the Consensus Netmeeting on Dermoscopy with some revisions [6].

I.3.5.1 Pigment Network The pigment network is a honeycomb-like network that consists of pigmented “lines” and ­hypopigmented “holes.” The reticulation (network) represents the rete ridge pattern of the epidermis. Its histopathological correlation is either melanin pigment in keratinocytes, or in melanocytes along the dermo-epidermal junction. The hypopigmented holes in the network correspond to tips of the dermal papillae and the overlying supra-papillary plates of the epidermis. The pigment network can be classified as typical or atypical. A typical network is relatively uniform, regularly meshed, homogeneous in color, and usually thinning out at the periphery (Fig. I.3.2). An atypical network is non-uniform, with darker and/or broadened lines and “holes” that are heterogeneous in diameter and shape. The lines are often hyperpigmented and may end abruptly at the periphery.

I.3.5.2 Dots Dots are small, round structures of less than 0.1 mm in diameter which may be black, brown, gray, or blue-gray. Black dots are due to pigment accumulation in the stratum corneum and the upper part of the epidermis (see colors). Brown dots represent focal melanin accumulations at the dermo-epidermal junction. Gray-blue granules are due to tiny melanin structures in the papillary dermis. Gray-blue or blue granules are due to loose melanin, fine melanin particles, or melanin “dust” in melanophages, or exist freely in the deep papillary or reticular dermis.

Fig. I.3.2.  Clinical picture of a benign compound nevus. Dermoscopy shows a regular pigment network (reticular architecture) at the periphery and regular globules (globular architecture) in the center of the lesion.

I.3.5.3 Globules Globules are round to oval, well-demarcated structures that may be brown, black, or gray. They have a diameter larger than 0.1 mm and correspond to nests of pigmented melanocytes, clumps of melanin, and/or melanophages situated usually in the lower epidermis, at the dermo-epidermal junction, or in the papillary dermis. Both dots and globules may occur in benign as well as in malignant melanocytic proliferations. In benign lesions, they are regular in size and shape and evenly distributed (frequently in the center of a lesion; Fig. I.3.2). In melanomas, they tend to vary in size, color, and shape and are frequently found in the periphery of lesions.

11



12

R. P. Braun, H. S. Rabinovitz, M. Oliviero et al.

I.3

Fig. I.3.3.  Clinical image of a lesion which has criteria for melanoma on clinical examination. Dermoscopy shows an irregular pigment network but no other criteria for melanoma. Using the 7-point checklist this lesion would have a score of 2 and would be classified as nonmelanoma

I.3.5.4 Branched Streaks Branched streaks are an expression of an altered, perturbed pigment network in which the network becomes broken up (see ABCD Rule of Dermoscopy; Figs. I.3.3, I.3.4). Their pathological correlations are remnants of pigmented rete ridges and bridging nests of melanocytic cells within the epidermis and papillary dermis. This term is exclusively used in the ABCD rule of dermoscopy and should not be confounded with the term “streaks,” which is used in the 7-point checklist of dermoscopy.

Fig. I.3.4.  Clinical image of a melanoma. Dermoscopy shows atypical pigment network, irregular dots in the periphery, regression areas, irregular pigmentation, and irregular streaks (radial streaming)

I.3.5.5 Streaks Both radial streaming and pseudopods correspond histopathologically to intraepidermal or junctional confluent radial nests of melanocytes. This is why some authors prefer using the term “streaks” interchangeably with radial streaming or pseudopods. Streaks can be irregular (unevenly distributed in melanoma) or regular (symmetrical radial arrangement over the entire lesion); the latter is found particularly in the pigmented spindle cell nevi (Reed’s nevi).

Radial Streaming Radial streaming appears as radially and asymmetrically arranged, parallel linear extensions at the periphery of a lesion (Fig. I.3.4).

Dermoscopic Examination

Pseudopods Pseudopods represent finger-like projections of dark pigment (brown to black) at the periphery of the lesion. They may have small knobs at their tips, and are either connected to the pigment network or directly to the tumor body.

I.3.5.6 Structureless Areas Structureless areas represent areas devoid of any discernible structures (globules, network, etc.). They tend to be hypopigmented, which is due to the absence of pigment or diminution of pigment intensity within a pigmented skin lesion. A structureless or hypopigmented area cannot be lighter than the surrounding skin and does not have signs of granularity (peppering) in its periphery.

I.3.5.7 Blotches A blotch (black lamella) is a diffuse pigmen­ tation of black to dark brown color which obscures underlying structures. It is due to a large concentration of melanin pigment localized throughout the epidermis and/or dermis visually. A blotch can be regular, often in the center of a lesion (junctional nevus), or irregular (melanoma).

I.3.5.8 Regression Regression appears as white scar-like depigmentation (lighter than the surrounding skin) or “peppering” (speckled multiple blue gray granules within a hypopigmented area; see Fig. I.3.4). Histopathologically, regression shows fibrosis, loss of pigmentation, epidermal thinning, effacement of the rete ridges, and melanin granules free in the dermis or in melanophages scattered in the papillary dermis.

Chapter I.3

I.3.5.9 Blue-White Veil Blue-white veil is an irregular, indistinct, confluent blue pigmentation with an overlying white ground-glass haze. The pigmentation cannot occupy the entire lesion and is found mainly in the papular part of the lesion. Histopathologically this corresponds to an aggregation of heavily pigmented cells or melanin in the dermis (blue color) in combination with a compact orthokeratosis. Blue-white veil should not be confused with confluent peppering (granularity) in regression areas of melanomas; the ­latter is the dermoscopy aspect of (histopathological) melanosis. Both entities might have a similar dermoscopy aspect but do not have the same histopathological correlation. The bluewhite veil is, together with pigment-network structures, a highly specific criterion for the diagnosis of melanoma.

I.3.5.10 Milia-like Cysts Milia-like cysts are round whitish or yellowish structures which are seen mainly in seborrheic keratosis. They correspond to intraepidermal keratin-filled cysts and may also be seen in congenital nevi as well as in some papillomatous melanocytic nevi (Fig. I.3.5).

I.3.5.11 Comedo-like Openings (Crypts, Pseudofollicular Openings) Comedo-like openings (pseudocomedos) are seen mainly in seborrheic keratosis (Fig. I.3.5) or in some rare cases in papillomatous melanocytic nevi. Histopathologically they correspond to keratin-filled invaginations of the epidermis.

13



14

R. P. Braun, H. S. Rabinovitz, M. Oliviero et al.

I.3.5.12 Fingerprint-like Structures

I.3

Some flat seborrheic keratoses (also known as solar lentigines) can show tiny ridges running in parallel and producing a pattern which resembles fingerprints.

I.3.5.13 Moth-Eaten Border Some flat seborrheic keratoses (mainly on the face) have a concave border so that the pigment ends with a curved structure. This has been compared to a moth-eaten garment.

I.3.5.14 Fissures and Ridges (“Brain-like” Appearance) Fissures are irregularly, linear keratin-filled depressions, commonly seen in seborrheic keratosis (Fig. I.3.5). They may also be seen in melanocytic nevi with congenital patterns and in some dermal melanocytic nevi. Multiple fissures might give a “brain-like” appearance to the ­lesion. This pattern has also been named “gyri and sulci” by some authors.

I.3.5.15 Leaf-like Areas Leaf-like areas (maple-leaf-like areas) are seen as brown to gray-blue discrete bulbous blobs, sometimes forming a leaf-like pattern. Their distribution reminds one of the shape of finger pads. In the absence of a pigment network, they are suggestive of pigmented basal cell carcinomas.

I.3.5.16 Spoke-Wheel-like Structures Spoke-wheel-like structures are well-circumscribed brown to gray-blue-brown radial projections meeting at a darker brown central hub. In absence of a pigment network, they are highly suggestive of basal cell carcinoma.

Fig. I.3.5.  Clinical image of a pigmented seborrheic keratosis. Dermoscopy shows multiple milia-like cysts, pseudocomedos, some crypts (fissures), regular hairpin blood vessels, as well as a sharp demarcation

I.3.5.17 Large Blue-Gray Ovoid Nests Ovoid nests are large, well-circumscribed, confluent, or near-confluent pigmented ovoid areas, larger than globules, and not intimately connected to a pigmented tumor body (Fig. I.3.6). When a network is absent, ovoid nests are highly suggestive of basal cell carcinoma.

I.3.5.18 Multiple Blue-Gray Globules Multiple blue-gray globules are round well-circumscribed structures which are, in the absence of a pigment network, highly suggestive of a basal cell carcinoma (Fig. I.3.6). They have to be

Dermoscopic Examination

Chapter I.3

a

b

c

d

Fig. I.3.6.  a Clinical image of a partially pigmented basal cell carcinoma. b Dermoscopy shows arborized telangiectasia as well as an ovoid nest and multiple blue-gray dots and globules. c Clinical image of a pigmented basal

cell carcinoma. d Dermoscopy shows a spoke-wheel area, a blue-gray ovoid nest, a small area of ulceration, and multiple blue-gray dots and globules

differentiated from multiple blue-gray dots (which correspond to melanophages and melanin dust).

For the first decision (melanocytic vs nonmelanocytic) the following algorithm is used (Fig. I.3.8): Steps 1-2: Are pigment network, aggregated globules, branched streaks, homogenous blue pigmentation, or a parallel pattern (palms, soles, and mucosa) visualized? If this is the case, the lesion should be considered as a melanocytic lesion (Figs. I.3.2, I.3.3, I.3.4). Step 3: If this is not the case, the lesion should be evaluated for the presence of comedo-like plugs, multiple milia-like cysts, and comedolike openings, irregular crypts, light-brown fingerprint-like structures, or “fissures and ridges” (brain-like appearance) pattern; if so, the lesion is suggestive of a seborrheic keratosis (Fig. I.3.5) [7]. Step 4: If such is not the case, the lesion has to be evaluated for the presence of arborizing blood

I.3.6 Differential Diagnosis of Pigmented Lesions of the Skin The Board of the Consensus Netmeeting agreed on a two-step procedure for the classification of pigmented lesions of the skin (see Fig. I.3.7) [6]. The first step is the differentiation between a melanocytic and a non-melanocytic lesion. Once a lesion has been identified to be of melanocytic origin, it has to be determined in a second step whether the lesion is benign, suspicious, or malignant. This can be done with the help of different algorithms, which are discussed later.

15



16

R. P. Braun, H. S. Rabinovitz, M. Oliviero et al. Fig. I.3.7.  Two-step procedure for the classification of pigmented skin lesions (modified)

I.3

Fig. I.3.8.  Algorithm for the decision of melanocytic vs non-melanocytic lesion according to the proposition of the Board of the Consensus Netmeeting (modified)

vessels (telangiectasias), leaf-like areas, large blue-gray ovoid nests, multiple blue-gray globules, spoke-wheel areas, or ulceration. If present, the lesion is suggestive of basal cell carcinoma (Fig. I.3.6) [8]. Step 5: If such is not the case, one has to look for red or red-blue (to black) lagoons. If these structures are present, the lesion should be considered as hemangioma or an angiokeratoma (Fig. I.3.9).

Step 6: If all the preceding questions were answered with “no,” the lesion should still be considered as melanocytic in order not to miss a melanoma. Once the lesion is identified to be of melanocytic origin, the decision has to be made as to whether the melanocytic lesion is benign, suspect, or malignant. To accomplish this, the following algorithms are most common:

Dermoscopic Examination

Fig. I.3.9.  Clinical picture of a cherry angioma. Dermoscopy shows multiple red lagoons

1. Pattern analysis [9] Pattern recognition has historically been used by clinicians and histopathologists to differentiate benign lesions from malignant neoplasms. A similar process has been found to be useful with dermoscopy, and has been termed “pattern analysis.” It allows distinction between benign and malignant growth features. It was described by Pehamberger and colleagues based on the analysis of more than 7000 pigmented skin lesions [9]. Table I.3.2 shows the typical patterns of some common, pigmented skin lesions using pattern analysis.

2. Revised pattern analysis The revised pattern analysis distinguishes between global patterns and local features [10]. The general appearance of Color, Architectural order, Symmetry of pattern, and Homogeneity (CASH) are important components in benign le-

Chapter I.3

sions from melanoma. Benign melanocytic ­ lesions tend to have few colors, architectural ­order, symmetry of pattern, and homogeneity. Melanoma often has many colors, architectural disorder, asymmetry of pattern, and heterogeneity. The reticular pattern or network pattern is the most common feature in melanocytic lesions. This pattern represents the junctional component of a melanocytic nevus. Another pattern is the so-called globular pattern. It is characterized by the presence of numerous “aggregated globules.” This pattern is commonly seen in a congenital nevus, superficial type. The cobblestone pattern is very similar to the globular pattern but is composed of closer aggregated globules, which are somehow angulated, resembling cobblestones. The homogeneous pattern appears as diffuse pigmentation, which might be brown, gray-blue, gray black, or reddish black. No pigment network or any other distinctive dermoscopy structures are found. An example is the homogenous steel-blue color seen in blue nevi. The so-called starburst pattern is characterized by the presence of streaks in a radial arrangement, which is visible at the periphery of the lesion. This pattern is commonly seen in Reed nevi or Spitz’s nevi. The parallel pattern is exclusively found on the palms and soles due to the particular anatomy of these areas. The combination of three or more distinctive dermoscopic structures (i.e., network, dots, and globules, as well diffuse areas of hyper- and hypopigmentation) within a given lesion is called multicomponent pattern. This pattern is highly suggestive of melanoma but might be observed in some cases in acquired melanocytic nevi and congenital nevi. The term “lesions with indeterminate patterns” are dermoscopic patterns that can be seen in both benign and malignant pigmented lesions. Clinically and dermoscopically one cannot distinguish whether they are melanomas or atypical nevi. In addition to the global features mentioned above, the local features (dermoscopic structures such as the pigment network, dots, and globules, etc.) are important to evaluate melanocytic lesions (Table I.3.3).

17



18

R. P. Braun, H. S. Rabinovitz, M. Oliviero et al. Table I.3.2.  Pattern analysis. (Modified after [9])

I.3

Lentigo simplex

Junctional nevus

Compound nevus

Dermal nevus

Blue nevus

Regular pigment network without interruptions

Regular pigment network without interruptions

Regular pigment network without interruptions

No criteria for melanocytic lesion

Steel blue areas

Regular border, thins out at the periphery

Regular border, thins out at the periphery

Regular border, thins out at the periphery

No pigment network

No pigment network

Black dots over the grids of the pigment network

Heterogeneous holes of the pigment network

Heterogenous holes of the pigment network

Brown globules

Ill defined

Brown-black globules Brown globules at the center of the lesion

Brown globules

Homogenous colors

White veils are possible

Homogenous colors

Symmetric papular appearance

“Pseudonetwork”

No pseudonetwork

All criteria for melanocytic lesion possible

“Comma”-shaped blood vessels

Homogenous colors

Color heterogeneity possible Melanoma

Atypical (Clarks) nevus

Angioma

Seborrheic keratosis

Pigmented BCC

Heterogeneous (colors and structures)

Irregular pigment network with interruptions

No features of melanocytic lesion

No features for a melanocytic lesion

No features for melanocytic lesion

Asymmetry (colors and structures)

Heterogeneous holes

No pigment network

Pigment network usually absent

Maple-leaflike pigmentation

Irregular pigment network

Irregular border

Red, red-blue, or red-black lagoons (globules, saccules)

Milia-like cysts

Telangiectasis

Abrupt border cut-off

Pseudofollicular openings, comedolike openings (plugs)

Tree-like blood vessels

Rough surface

“Dirty” gray brown to gray-black colors

Irregular border with Heterogeneity abrupt peripheral of colors margin Structureless areas

Gray-white veil

Dermoscopic Examination

Chapter I.3

Table I.3.3.  Patterns of benign and malignant melanocytic lesions

Benign melanocytic lesions

Malignant melanocytic lesions

Dots

Centrally located or situated right on the network

Unevenly distributed and scattered focally at the periphery

Globules

Uniform in size, shape, and color symmetrically located at the periphery, centrally located, or uniform throughout the lesion as in a cobblestone pattern

Globules which are unevenly distributed and when reddish in color are highly suggestive of melanoma

Streaks

Radial streaming or pseudopods tend to be symmetrical and uniform at the periphery

Radial streaming or pseudopods tend to be focal and irregular at the periphery

Blue-white veil

Tends to be centrally located

Tends to be asymmetrically located or diffuse almost over the entire lesion

Blotch

Centrally located or may be a diffuse hyperpigmented area that extends almost to the periphery of the lesion

Asymmetrically located or there are often multiple asymmetrical blotches

Network

Typical network that consists of lightto-dark uniform pigmented lines and hypopigmented holes

Atypical network which may be non-uniform with black/brown or gray thickened lines and holes of different sizes and shapes

Network borders

Either fades into the periphery or is symmetrically sharp

Focally sharp

I.3.7 ABCD Rule of Dermatoscopy [11, 12] The ABCD rule of dermatoscopy, described by Stolz et al. in 1994 [11], was based on an analysis of 157 pigmented skin lesions. It is based on a scoring system for melanocytic neoplasms that differentiates them into benign, suspicious, and malignant categories. This is accomplished by calculating a total dermoscopy score (Table I.3.4).

I.3.7.1 Asymmetry The lesion is bisected by two lines that are placed 90° to each other. The first line attempts to bisect the lesion at the division of most symmetry and the other one is placed 90° to it. Symmetry takes into account the contour, colors, and structures within the lesion. Lesions that are symmetric in both axes are given zero points. Points for asymmetry are multiplied with a weighting factor of 1.3 to calculate the dermoscopy score.

I.3.7.2 Border First the lesion is divided into eight equal pieshaped pieces. Next, one counts the number of segments that have an abrupt perimeter cut-off; thus, the points range from 0 to 8, which have to be multiplied with a weighting factor of 0.1.

I.3.7.3 Colors Number the following colors present: light brown; dark brown; black; red; white; and bluegray. The points will range from 1 to 6, which have to be multiplied with a weighting factor of 0.5.

I.3.7.3 Dermoscopic Structures Number the following five structures: dots; globules; structureless areas; network; and branched streaks. The points range from 1 to 6, which have to be multiplied with a weighting factor of 0.5.

19



20

R. P. Braun, H. S. Rabinovitz, M. Oliviero et al. Table I.3.4.  The ABCD rule of dermoscopy. (Modified after [11])

Points

Weight factor

Sub-score range

Complete symmetry

0

1.3

0−2.6

Asymmetry in one axis

1

Asymmetry in two axes

2

Border

Eight segments, one point for abrupt cut-off of pigment

0−8

0.1

0−0.8

Color

One point for each color: white; red; light brown; dark brown; black; blue gray

1−6

0.5

0.5−3.0

Differential structures

One point for every structure: pigment network; structureless areas; dots; globules; branched streaks

1−5

0.5

0.5−2.5

Asymmetry

I.3

Total score range:

The individual points are multiplied with weighting factor which is specific for each criterion. The different sub-scores are then added together in order to obtain the total dermoscopy score (TDS). A lesion with a TDS 5.45 should be considered to be malignant and should be removed. Lesions with a TDS between 4.75 and 5.45 should be considered to be suspicious and should be either removed or monitored.

I.3.7.3.1 Seven-Point Checklist In 1998 Argenziano and colleagues described a 7-point checklist based on the analysis of 342 pigmented skin lesions [13]. They distinguished three major criteria (atypical pigment network, blue-whitish veil, atypical vascular pattern) and four minor criteria (irregular streaks, irregular pigmentation, irregular dots/globules, regression structures; Table I.3.5). Each major criterion has a score of 2 points and each minor criterion has a score of 1 point. A minimum total score of 3 is required for the diagnosis of melanoma. The 7-point checklist was the first algorithm which compromised the vascular architecture of a lesion.

1.0–8.9

Table I.3.5.  The 7-point checklist. (According to [6])

Criteria

7-point score

Major  Atypical pigment network   Blue-whitish veil  Atypical vascular pattern

2 2 2

Minor  Irregular streaks  Irregular pigmentation  Irregular dots/globules  Regression structures

1 1 1 1

I.3.7.3.2 Menzies Method In Menzies method for diagnosing melanoma, both of the following negative features have to be absent: single color (tan, dark brown, gray, black, blue, and red, but white is not considered) and “point and axial symmetry of pigmentation” (refers to pattern symmetry around any axis through the center of the lesion). This does not require the lesion to have symmetry of shape.

Dermoscopic Examination

Chapter I.3

Table I.3.6.  The Menzies method. (According to [8]) Negative features

C

Core Messages ■ Dermoscopy increases diagnostic accuracy by 5–30% ■ Features of skin lesions not seen by naked-eye examination can be visualized with dermoscopy: 1. Colors (brown, black, blue, blue-gray, red, yellow, and white) 2. Blood vessel types (red lagoons, string of pearls, hairpin, dotted, “comma”-like, glomerular, crown, corkscrew, arborizing, or irregular vessels) 3. Architectural criteria (pigment network, dots, globules, branched streaks, streaks, structureless areas, blotches, regression, blue-white veil, milia-like cysts, comedo-like openings, fingerprint-like structures, moth-eaten borders, fissures and ridges, leaf-like areas) ■ Potentially malignant lesions tend to show two of the following three features: asymmetry; atypical network; and blue-white structures (3-step checklist).

  Point and axial symmetry of pigmentation   Presence of a single color Positive features   Blue-white veil   Multiple brown dots   Pseudopods  Radial streaming   Scar-like depigmentation   Peripheral black dots−globules   Multiple colors (five or six)   Multiple blue/gray dots   Broadened network

In addition, at least one or more of the positive features that are described in Table I.3.6 has to be found.

I.3.7.3.3 Three-Point Checklist The three-point checklist [15] is based on a simplified pattern analysis and is intended for use by non-experts as a screening technique. The three-point checklist does not differentiate between melanocytic and non-melanocytic lesions. Its aim is to identify all potentially malignant lesions, including basal cell carcinoma and melanoma, with a high degree of sensitivity. Remarkably, the sensitivity for detecting malignancy by non-experts using the three-point checklist has reached 96.3%; however, as is true for all screening techniques, the specificity achieved by non-experts was much lower (32.8%) than that achieved by experts (94.2%). The three-point checklist requires the examiner to assess the lesion for only three der­ moscopic criteria: (a) asymmetry; (b) atypical network; and (c) blue-white structures. The presence of two or three features suggests that the lesion under investigation is suspect for ­malignancy.

 



References 1. Marghoob AA, Braun RP, Kopf AW. Atlas of dermoscopy. New York: Taylor Francis; 2004 2. Braun RP, Rabinovitz HS, Oliviero M, Kopf AW, ­Saurat JH. Dermoscopy of pigmented skin lesions. J Am Acad Dermatol 2005; 52(1):109-121 3. Kittler H, Pehamberger H, Wolff K, Binder M. Diagnostic accuracy of dermoscopy. Lancet Oncol 2002; 3(3):159-165 4. Gewirtzman AJ, Saurat JH, Braun RP. An evaluation of dermoscopy fluids and application techniques. Br J Dermatol 2003; 149(1):59-63 5. Malvehy J, Puig S, Braun RP, Marghoob AA, Kopf AW. Handbook of dermoscopy. First ed. London and New York: Taylor and Francis; 2006 6. Argenziano G, Soyer HP, Chimenti S, Talamini R, Corona R, Sera F, et al. Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet. J Am Acad Dermatol 2003; 48(5 Pt 1):679– 693

21



22

I.3

R. P. Braun, H. S. Rabinovitz, M. Oliviero et al. 7. Braun RP, Rabinovitz H, Krischer J, Kreusch J, Oliviero M, Naldi L, et al. Dermoscopy of pigmented seborrheic keratosis. Arch Dermatol 2002; 138:1556–1560 8. Menzies SW, Westerhoff K, Rabinovitz H, Kopf AW, McCarthy WH, Katz B. Surface microscopy of pigmented basal cell carcinoma. Arch Dermatol 2000; 136(8):1012–1016 9. Pehamberger H, Steiner A, Wolff K. In vivo epiluminescence microscopy of pigmented skin lesions. I. Pattern analysis of pigmented skin lesions. J Am Acad Dermatol 1987; 17(4):571–583 10. Argenziano G, Soyer HP, Giorgio V de, Piccolo D, Carli P, Delfino M, et al. Dermoscopy a tutorial. First ed. Milan: EDRA; 2000 11. Stolz W, Riemann A, Cognetta AB, Pillet L, Abmayr W, Hölzel D, et al. ABCD rule of dermatoscopy: a new practical method for early recognition of malignant melanoma. Eur J Dermatol 1994; 4:521–527

12. Stolz W, Braun-Falco O, Bilek P, Landthaler M, Burgdorf WHC, Cognetta AB. Color atlas of dermatoscopy, 2nd ed. Berlin: Blackwell WissenschaftsVerlag; 2002 13. Argenziano G, Fabbrocini G, Carli P, Giorgio V de, Sammarco E, Delfino M. Epiluminescence microscopy for the diagnosis of doubtful melanocytic skin lesions. Comparison of the ABCD rule of dermatoscopy and a new 7-point checklist based on pattern analysis. Arch Dermatol 1998; 134(12):1563–1570 14. Menzies SW, Crotty KA, Ingvar C, McCarthy WH. An atlas of surface microscopy of pigmented skin lesions: Dermoscopy, 2nd edn. Roseville: McGrawHill; 2003 15. Soyer HP, Argenziano G, Zalaudek I, Corona R, Sera F, Talamini R, et al. Three-point checklist of dermoscopy. A new screening method for early detection of melanoma. Dermatology 2004; 208(1):27– 31

Melanoma: the Morphological Dimension Chapter I.4

Melanoma: the Morphological Dimension

I.4

Lorenzo Cerroni

Contents I.4.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . 23 I.4.2 General Remarks. . . . . . . . . . . . . . . . . . . . . . . 25 I.4.2.1 Morphological Observations. . . . . . . . . . . . . 25 I.4.2.2 Ancillary Techniques . . . . . . . . . . . . . . . . . . . 25 I.4.2.3 Particular Morphological Types of Melanoma. . . . . . . . . . . . . . . . . . . . . . . . . . . 25 I.4.3 Special Settings. . . . . . . . . . . . . . . . . . . . . . . . . 26 I.4.3.1 Melanocytic Tumors Biopsied in Newborns or Shortly After Birth. . . . . . . 26 I.4.3.2 Proliferations of Melanocytes Within Chronic Sun-Damaged Skin . . . . . . 27 I.4.3.3 Proliferations of Melanocytes Biopsied Shortly After Sun Exposure. . . . . . . . . . . . . . 28 I.4.3.4 Proliferations of Melanocytes Within Mucosal Epithelium (Genital and Oral Mucosa). . . . . . . . . . . . . . . 28 I.4.3.5 Melanocytic Proliferations at Other Special Skin Sites. . . . . . . . . . . . . . . 29 I.4.3.6 Proliferations of Melanocytes at Sites of Inflammatory Skin Disorders. . . . . . . . . . 30 I.4.4 Particular Histopathological Problems. . . . 30 I.4.4.1 Melanocytic Nevi with Several Cell Populations (“Combined” Nevi). . . . . . . . . . 30 I.4.4.2 Nodular Proliferations of Melanocytes Within Congenital Nevi. . . . . . . . . . . . . . . . . 30 I.4.4.3 Superficial Proliferations of Melanocytes with Prominent Pigmentation. . . . . . . . . . . . 31 I.4.4.4 Proliferations of Melanocytes Associated with Prominent Inflammatory Response and/or Regression . . . . . . . . . . . . . . . . . . . . . . 31 I.4.4.5 Recurrence (Persistence) of Melanocytic Lesions at the Site of a Previous Incomplete Excision (Recurrent Nevi, Recurrent Melanoma). . . 32 I.4.4.6 Atypical Melanocytic Nevi with Degenerative Changes (“Ancient” Melanocytic Nevi). . . . . . . . . . . . 32

I.4.4.7 Melanocytic Proliferations with “Spitzoid” Morphology. . . . . . . . . . . . . 33 I.4.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

I.4.1 Introduction The histopathological diagnosis of melanocytic tumors, including malignant melanoma (hence referred to as melanoma) and benign melanocytic nevi, has been the subject of countless studies published in the literature. Although precise histopathological criteria for distinction of benign from malignant melanocytic proliferations have been established, in some instances a precise diagnosis is not possible, a problem that is reflected by the use of various terms coined during the years, including “melanocytic tumors of uncertain malignant potential (MELTUMP)” or “superficial atypical melanocytic proliferation of uncertain significance (SAMPUS)” among others. Despite uncertainty in given cases, however, histological examination of a tissue specimen is still the gold standard in diagnosis of melanocytic tumors, and the most important prognostic criteria for primary melanoma (tumor thickness, ulceration) are established by the observation of the histopathological specimens as well. Sharing unusual or controversial cases in consultation with dermatopathologists with special expertise in melanocytic tumors is helpful in minimizing the risk of misdiag­noses that may be potentially fatal for the patients.



24

I.4

L. Cerroni

It is crucial to remember that under the microscope each single melanocytic lesion should first be analyzed at scanning magnification in order to evaluate properly overall symmetry and lateral circumscription. It is also important to emphasize that a proper biopsy is a pre-requisite for a specific diagnosis. This is true in dermatopathology in general, and even more so in the evaluation of melanocytic lesions. Incomplete biopsies (e.g., punch biopsies, shave biopsies) often do not allow a precise classification of the cases. In a similar manner, biopsies with surgical artifacts (crush artifacts) often cannot be interpreted properly. Finally, optimal preparation of the specimens in the dermatopathological laboratory is crucial as well. All too often we receive specimens in consultation that are either badly cut, or badly stained, or both. A precise diagnosis in these cases is often impossible. A good practice in the histopathological evaluation of melanocytic tumors is to study more than a single section of tissue. Step sections should be prepared routinely, particularly in cases that are controversial histopathologically, or that showed atypical features clinically. In this context, communication between clinicians and dermatopathologists is crucial. In addition, photographic documentation of each lesion deemed to be suspicious clinically should be attached to the referral sheet, in order to avoid mistakes in the grossing of the specimens. In fact, in melanomas arising within melanocytic nevi the specific histopathological changes may be found only focally, and a clinical picture with remarks by the clinicians allows precise identification of the suspicious areas before grossing. The occurrence of melanoma within pre-existing melanocytic nevi is probably underestimated [46]. The histopathological criteria for the diagnosis of melanoma are listed in Table I.4.1. They include general architectural criteria, features of the intraepidermal and dermal components, and cytomorphological features of the melanocytes (Fig. I.4.1) [1, 2]. No single criterion is specific for benign or malignant proliferations of melanocytes, and exceptions to any of these criteria exist; thus, only integration of all criteria can be helpful in establishing the correct diag-

Fig. I.4.1.  Melanoma shows scatter of melanocytes in small nests and as solitary units at all level of the epi­ dermis Table I.4.1.  Histopathological features of melanoma

Asymmetry of the lesion  Overall asymmetry  Asymmetry of pigment distribution  Asymmetry of inflammatory infiltrate Unsharp lateral circumscription Presence of ulceration “Consumption” of the epidermis (thinning of the epidermis with attenuation of the basal and suprabasal layers and loss of the rete ridges adjacent to collections of melanocytes) Solitary melanocytes predominate over melanocytes in nests within the epidermis Pagetoid spread of melanocytes within the epidermis (melanocytes distributed in all layers of the epidermis) Incohesive melanocytes within nests Sheets of melanocytes within the dermis “Pushing” lower margin of dermal complexes of melanocytes Obliteration and/or destruction of adnexal structures Presence of intravascular complexes of melanocytes Perineural growth and/or neurotropism Presence of atypical melanocytes Presence of several mitoses, especially at the base of the lesion

Melanoma: the Morphological Dimension

nosis. In this context, it is important to understand that in most cases application of the histopathological criteria listed in Table I.4.1 allows a precise diagnosis of melanoma, and that exceptions are relatively rare; however, exceptions do exist, and their recognition and precise classification is crucial in order to manage patients adequately. We discuss herein the general aspects of the histopathological diagnosis of melanoma and nevi, as well as some of the histopathological problems that may be encountered in the microscopic evaluation of pigmented lesions of the skin.

I.4.2 General Remarks I.4.2.1 Morphological Observations In recent years, many different studies have addressed specific aspects of melanoma diagnosis and prognosis, and many different suggestions have been proposed as to what information a histopathological report should include. Examples are, among others, presence/absence of tumor-infiltrating lymphocytes, vertical or horizontal growth phase, number of mitoses per unit area, presence of regression, presence of neo-angiogenesis, and details on histopathological classification according to the categories of superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, or acral melanoma [17, 19, 27, 28, 34, 43, 60, 73]. This last classification, in our opinion, is obsolete, and does not convey any meaningful information to physicians and/or patients. In addition, the prognostic value of most of the histopathological features listed above have yet to be validated in large studies, and at present the only accepted prognostic features for TNM classification of the tumors are the maximal thickness and the presence of ulceration [6, 7]. The Clark level needs to be mentioned only in the rare cases of thin melanoma (