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 I-80131 Naples Italy Rainer Hofmann-Wellenhof, MD Professor of Dermatology Department of Dermatology Medical University Graz Auenbruggerplatz 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 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 I.2 The Morphologic Dimension in the Diagnosis of Melanocytic Skin Lesions 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 Alfred W Kopf III.5 Atypical (Dysplastic) Nevus 87 R ainer Hofmann-Wellenhof and H Peter Soyer III.4 Blue Nevus 78 G erardo Ferrara and Giuseppe Argenziano III.6 Combined Nevus 97 Horacio Cabo III.7 Melanoma: the Morphological Dimension 23 Lorenzo Cerroni Common Nevus 102 R ainer 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.3 Dermoscopic Examination R alph P Braun, Harold S Rabinovitz, Margaret Oliviero, Alfred W Kopf, Jean-Hillaire Saurat, Luc Thomas I.4 II.3 Multispectral Image Analysis 52 D ina Gutkowicz-Krusin and Harold Rabinovitz II.4 Teledermatology 57 C esare 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 M asaru Tanaka, Masayuki Kimoto, Toshiaki Saida III.10 Halo Nevus 124 A lessandro Di Stefani and Sergio Chimenti III.11 Irritated Nevus and Meyerson’s Nevus 129 R egina 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 S teven Q Wang, Harold H Rabinovitz, Alfred W Kopf XII Contents III.14 Nevi with Particular Pigmentation: Black, Pink, and White Nevus 142 I ris Zalaudek, Robert Johr, Bernd Leinweber III.15 Recurrent Nevus 147 Andreas Blum III.16 Spitz Nevus and Its Variants 151 G erardo Ferrara, Elvira Moscarella, Caterina M Giorgio, Giuseppe Argenziano III.17 Syndromes Involving Melanocytic Lesions 164 C heryl 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 T oshiaki Saida, Hiroshi Koga, Yoriko Yamazaki, Masaru Tanaka IV.3 Amelanotic Melanoma 204 Jürgen Kreusch 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 I ris 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 I ris Zalaudek, Jason Giacomel, Bernd Leinweber Early Evolution of Melanoma (Small-Diameter Melanoma) 213 R obert 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 Subject Index 329 IV.6 Genital Melanoma 229 Ingrid H Wolf IV.4 V.5 Vascular Lesions 303 Fezal Özdemir V.6 Seborrheic Keratosis Including Lichen Planus-like Keratosis 313 Robert Johr 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: caber@med.miami.edu 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: econnelly@med.miami.edu A Blum Associate Professor of Dermatology Seestraße 3a 78464 Konstanz Germany E-mail: a.blum@derma.de R.P Braun Department of Dermatology University Hospital Zurich 8091 Zurich Switzerland E-mail: braun@melanoma.ch H Cabo Section of Dermatology Instituto de Investigaciones Médicas “A Lanari” University of Buenos Aires Argentina E-mail: hcabo@fibertel.com.ar G Argenziano Department of Dermatology Second University of Naples Nuovo Policlinico − Edificio 13 Via Pansini 80131 Naples E-mail: argenziano@tin.it 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 Sul Porte Alegre Brazil E-mail: cris@fornix.com.br L Cerroni Department of Dermatology Medical University of Graz Auenbruggerplatz 8036 Graz Austria E-mail: lorenzo.cerroni@meduni-graz.at Seborrheic Keratosis Chapter V.6 Fig. V.6.10. Fingerprinting on the right and a variation of the fissure and ridge pattern on the left characterize this seborrheic keratosis Fig. V.6.11. This seborrheic keratosis demonstrates typical hairpin-shaped blood vessels Another network-like pattern with foci of thicker-branched and dark-brown or black-line segments often with an abrupt cut-off at the periphery can be seen Histopathologically, it represents melanin in keratinocytes or melanocytes along the dermo-epidermal junction At times, the differentiation of all of these forms of network will not be possible One must formulate a dermoscopic differential diagnosis and search for more criteria to make a diagnosis Hairpin-shaped fine telangiectatic blood vessels are commonly seen in seborrheic keratosis (Fig. V.6.11) At times they can have a white halo surrounding them, indicating the keratinizing nature of the tumor They are also seen in melanocytic nevi, keratoacanthomas, basal cell carcinomas, and when thick and irregular, in melanomas The less pressure applied to the skin with instrumentation, the easier it will be to see these fine vessels Skill and minimal pressure is needed to capture good images of hairpin vessels with digital photography Flat seborrheic keratosis can also have irregular borders with small or large concave indentations that have been compared to moth-eaten garments “Moth-eaten” borders are a widely accepted criterion that can also be seen in solar lentigines Finally, if one looks carefully, the pigment on the surface of the skin in flat seborrheic keratosis can appear to be like “jelly spread over the skin.” The jelly sign would be one of the most difficult criterion to identify and least important in diagnosing seborrheic keratosis using dermoscopy V.6.4 elevant Clinical Differential R Diagnosis In most cases the clinical diagnosis of seborrheic keratosis, stuccokeratosis, and dermatosis papulosa nigra poses no problems; however, clinically atypical lesions can be challenging If in doubt, never hesitate to cut one out, because melanomas are not uncommonly misdiagnosed as seborrheic keratosis Clinical and dermoscopic features of both can be found in a single lesion In a retrospective study of 9204 cases submitted for histopathological examination with the clinical diagnosis of seborrheic keratosis, or a differential diagnosis including seborrheic keratosis, a significant number of cases turned out to be melanomas Verrucous melanomas might be especially difficult to differentiate clinically from seborrheic keratosis (Figs. V.6.12–V.6.14) [14] Clinically, they can also be confused with actinic keratosis, melanocytic nevi (Fig. V.6.15), verruca vulgaris, condyloma acuminatum, solar lentigines, in-situ and invasive squamous cell carcinoma, acrochordon, eccrine poromas, and epidermal nevi The patient’s personal and fam- 319 320 R Johr Fig. V.6.12. At times it is very difficult to differentiate melanoma from a seborrheic keratosis In this case it was a seborrheic keratosis If one does not have a good clinicopathological correlation, another biopsy or another pathologist’s opinion can be considered Fig. V.6.13. This large, well-demarcated scaly and greasy-appearing lesion was present for years without a history of any changes With dermoscopy multiple milialike cysts were thought to be seen reinforcing the diagnosis of a seborrheic keratosis V.6 ily history, plus the history of the lesion, should be taken into consideration For example, a seborrheic keratosis-like lesion in a 7-year-old most probably is an epidermal nevus Actinic keratosis tend to be more erythematous with poorly defined borders Melanocytic nevi are soft, compressible, non-scaly with a positive wobble sign If one observes a seborrheic keratosis-like lesion in the genital area, most probably it is a condyloma acuminatum Seborrheic keratosis is generally regarded as a benign tumor; however, melanocytic, nonmelanocytic, benign, and malignant pathologies have been associated with them (Fig. V.6.16) Seborrheic Keratosis Fig. V.6.14. Another general dermoscopy principle is to eliminate scale to get a better picture After the scale was removed with a swipe of an alcohol prep, a different picture emerged This nodular melanoma demonstrated asymmetry of color and structure, irregular pigment network, globules and blotches, plus a diffuse blue-white structure Chapter V.6 321 Fig. V.6.16. A collision lesion consisting of a melanocytic nevus and a seborrheic keratosis Fig. V.6.15. The clinical and dermoscopic differential diagnosis includes a melanocytic nevus vs seborrheic keratosis In this case it was a seborrheic keratosis The association might be by chance, or seborrheic keratosis could be a precursor lesion since it contains all of the cells found in the normal skin Basal cell carcinoma, in-situ and invasive squamous cell carcinoma, keratoacanthomas, lentigo maligna, superficial spreading melano- ma, melanocytic and dysplastic nevi, actinic keratosis, actinic lentigo, and eccrine porocarcinoma have been reported to be associated with seborrheic keratosis Some researchers believe that the reticulated sub-type of seborrheic keratosis arises from solar lentigines The frequency of these associations varies from study to study [15–17] 322 R Johr Fig. V.6.17. On the left is a collision tumor consisting of a basal cell carcinoma and a seborrheic keratosis On the right is another collision tumor, a squamous cell carci- V.6.5 istopathology H V.6 Seborrheic keratosis are true neoplasms and not a hyperplasia of the epidermis that have a variable proliferation of basaloid and squamous cells with pseudohorn cyst formation (Fig. V.6.17) Acanthotic, hyperkeratotic, reticulated, irritated, and clonal are the most common histological subtypes, and many show a mixture of patterns There are varying amounts of hyperkeratosis, acanthosis, papillomatosis, pigmentation, and inflammation Cytological atypia and perivascular, diffuse, or lichenoid chronic inflammatory infiltrates can be seen with irritated lesions The acanthotic subtype is most common with little hyperkeratosis or pap- noma with a seborrheic keratosis Did the malignancies arise from the seborrheic keratosis, a benign proliferation of basaloid and squamous cells? illomatosis and a greatly thickened epidermis The hyperkeratotic variant is the histological reverse of the acanthotic type with prominent hyperkeratosis, and papillomatosis while the reticulated or adenoid type demonstrates delicate strands of epithelium branching from the epidermis Intraepithelial nesting gives rise to the Borst–Jadassohn appearance of the clonal seborrheic keratosis and intradermal or inverted proliferation characterizes the inverted follicular keratosis Stuccokeratosis has histopathological features of hyperkeratotic seborrheic keratosis, usually without pseudohorn cyst formation, whereas dermatosis papulosa nigra has features of the acanthotic variant with pseudohorn cysts [18] Seborrheic Keratosis V.6.6 anagement M Seborrheic keratosis comes to clinical attention for cosmetic reason if they become symptomatic or appear to break into pieces for no apparent reason They account for a large number of o ffice visits and significant health care costs Seborrheic keratosis that have undergone recent change, are symptomatic, or look suspicious clinically should be considered for der moscopic and histopathological evaluation Significant pathology, such as melanoma or basal cell carcinoma, could be surrounded by numerous seborrheic keratosis, or individual seborrheic keratosis could have malignant changes themselves Careful physical examination is essential Complete excision, rather than a shave or curettage, will be more helpful to the pathologist to evaluate for malignancy Treatment is most often for cosmetic reasons, so the least destructive method should be used Cryotherapy, with and without curettage, is the treatment of choice Shave excision, electrodesiccation, and CO2 laser vaporization are other methods of treatment that have increased risks of scarring V.6.7 ichen Planus-like Keratosis L V.6.7.1 efinition D Lichen planus-like keratosis (synonyms: benign lichenoid keratosis; solitary lichen planus; involuting lichenoid plaque) is a common benign tumor of adulthood V.6.7.2 linical Features C The pathogenesis of lichen planus-like keratosis is thought to be an immunologically mediated regression of an existing lesion This theory does not account for the lesions that develop de novo Ninety percent of these lesions are solitary macules or papules, occasionally nodules or plaques that develop between the third to seventh decade in Caucasians and which are occasionally seen in Hispanics, Asians, or African-Americans With a 2:1 female to male inci- Chapter V.6 dence, they are typically found on the upper trunk, distal upper extremities, and uncommonly, on the head and neck A small percentage of people can have two or three of these lesions There is a correlation of the clinical appearance with their chronicity and histopathological findings Acute, rapidly developing lichen planus-like lesions of less than 3 months tend to be erythematous or pinkish Subacute lesions of 3 months to 1 year have a dusky-red or violaceous color, and if present for more than 1 year, they are regularly or irregularly pigmented with shades of brown or gray The diagnosis can be suspected even before dermoscopy is used by seeing a small lesion with a combination of brown and gray colors The surface can be scaly, verrucous, or smooth and pearly They range in size from a few millimeters to a centimeter or more, and can be asymptomatic, slightly pruritic, or have a mildly stinging sensation Malignant degeneration of lichen planus-like keratosis has never been reported V.6.7.3 ermoscopy D Erythematous or pinkish lichen planus-like keratosis are featureless or feature poor with remnants of pigment network, subtle blotches of brown color, plus dotted, irregular linear, and other-shaped telangiectatic blood vessels (Fig. V.6.18) They cannot be distinguished clinically or dermoscopically from melanocytic, non-melanocytic benign, malignant, or inflammatory lesions that have the same characteristics including amelanotic melanoma With the pigmented variant, the dermoscopic picture depends on the age of the lesion Early lesions can have the dermoscopic features of a solar lentigo or flat seborrheic keratosis with “moth-eaten” borders, fingerprinting, milialike cysts, comedo-like openings plus small foci of melanophages Also referred to as peppering or granular dust, melanophages have a distinctive dermoscopic appearance with fine irregular dots that can be black, shades of brown, gray, or blue Typically they are smaller than the dots and globules seen in melanocytic lesions (Fig. V.6.19) 323 324 R Johr Fig. V.6.18. Pinkish macules and papules can be melanocytic, non-melanocytic, benign, malignant, or inflammatory This worrisome papule was discovered hidden on the chest of a very hairy patient It is feature poor with dotted and linear irregular-shaped blood vessels It turned out to be a lichen planus-like keratosis and not amelanotic melanoma Fig. V.6.19. Fingerprinting of a flat seborrheic keratosis can be seen on the right side of this lesion The grayishcolored fine dots representing melanophages on the left side are the most important clues in diagnosing this lichen planus-like keratosis V.6 As time passes increasingly more melanophages are seen, and they might be the only dermoscopic criteria found in older lesions (Fig. V.6.20) One can also see larger clumps of pigment plus foci of whitish color In the later stages of development, the dermoscopic differ- ential diagnosis could include regressive melanoma The clinical, dermoscopic, and histopathological differentiation might not be possible Special staining, such as S-100 and a good clinicopathological correlation, is advised Seborrheic Keratosis Chapter V.6 325 Fig. V.6.20. Surgery can be avoided with this small oval lichen planus-like keratosis filled with melanophages There is no suggestion with dermoscopy that this could be a regressive melanoma; therefore, dermoscopy over rides the atypical clinical picture With experience one will not excise many lesions with this dermoscopic appearance V.6.7.4 elevant Clinical Differential R Diagnosis In most, but not all, cases the diagnosis of lichen planus-like keratosis is made after a skin biopsy The clinical impression does not usually correlate with the histopathology Past experience and a high index of suspicion are helpful The differential diagnosis includes basal cell carcinoma, especially when the surface is smooth and pearly, in-situ and invasive squamous cell carcinoma, actinic or seborrheic keratosis, pigmented dermatofibromas, and solar lentigines Older pigmented variants, especially if there is a history of change, should be differentiated from banal and dyspastic nevi or melanoma An erythematous or pinkish macule or papule cannot be differentiated clinically from amelanotic banal and dyspastic nevi, amelanotic melanoma, and even solitary inflammatory lesions such as psoriasis or granuloma annulare V.6.7.5 istopathology H In general, lichen planus-like keratosis are characterized by epidermal and dermal changes that reflect the age of the lesion The epidermis can be normal, acanthotic, or atrophic with hyperkeratosis, focal parakeratosis, and hypergranulosis Civatte colloid body formation representing necrotic keratinocytes is frequently found There are variable amounts of vacuolar degeneration of the basal cell layer plus a band-like lymphocytic infiltrate that can obscure the dermo-epidermal junction Melanin incontinence with melanophages, dermal scarring, plus variable numbers of eosinophils, plasma cells, histiocytes, and neutrophils can also be found Features of solar lentigo or seborrheic keratosis are often seen at the periphery of the lesion In a study of 1040 lichen planus-like keratosis, five histopathological subtypes were identified [19]: the classic and early interface types, plus bullous lesions with intra- and subepidermal vesiculation There was an atypical variant with at least five atypical lymphocytes and an absence of criteria to diagnose mycosis fungiodes In another retrospective study, 15 cases of mycosis-fungoides-pattern, lichen planuslike keratoses were presented that had Pautrier micro-abscesses, epidermotropism, and lymphocytes with hyperconvoluted nuclei [20] Atrophic late lesions were the last subtype identified 326 R Johr The classic, atypical, and bullous patterns were associated with erythematous or pinkish lesions Interface subtypes were erythematous to brown macules, whereas the late atrophic lesions tended to be grayish, violaceous, or irregularly pigmented The histopathological differential diagnosis is extensive and includes other conditions with a band-like infiltrate such as lichen planus, lichenoid lupus erythematosus, and lichenoid drug reactions Inflamed actinic and seborrheic keratosis, porokeratosis, melanocytic lesions, including melanoma, are also in the differential diagnosis Melanomas simulating lichen planus-like keratosis have increased numbers of atypical melanocytes that can be partially obscured by a dense lymphocytic infiltrate Pathologists considering the diagnosis of mycosis fungoides should search for criteria that might indicate that the lesion is a lichen planus-like keratosis Clinicopathological correlation plus dermoscopic examination will help the clinician make the differentiation V.6 V.6.7.6 anagement M In most cases lichen planus-like keratosis is found by physicians that perform careful skin examinations Baseline gross and digital dermoscopic images can be taken of minimally suspicious lesions to follow over time Side-byside comparisons of the baseline and follow-up images can be checked for significant changes When a more suspicious lesion is found, a complete excision, rather than an incisional biopsy, is recommended Since melanoma is in the differential diagnosis of pigmented and pinkish lesions, the pathologist will need the entire specimen for a complete evaluation Although the technique is controversial, skilled clinicians can accomplish this easily with a deep-shave excision Skin biopsies are not always needed, especially if the lesion is examined with dermoscopy and no high-risk criteria are identified Once the diagnosis is confirmed histopathologically, if part of the lesion remains, liquid nitrogen or electrosurgery and curettage can be performed Topical steroids can also be used, or they can be left alone Seborrheic Keratosis C Chapter V.6 Core Messages ■ Seborrheic keratosis are ubiquitous benign epidermal neoplasms that, in most but not all cases, can be diagnosed clinically and with dermoscopy; some will need a histopathological diagnosis ■ It is important to be aware of the clinical differential diagnosis of atypical lesions ■ Melanomas can be misdiagnosed as seborrheic keratosis, especially the verrucous variant Any lesion that looks suspicious clinically or with dermoscopy to be symptomatic or changing should be considered for histopathological evaluation ■ Seborrheic keratoses can be associated with melanocytic, non-melanocytic benign, or malignant pathology ■ Cutaneous malignancies can be surrounded and camouflaged by multiple seborrheic keratoses, or an individual seborrheic keratosis could undergo malignant change Careful physical examination is essential ■ The sudden appearance, irritation of pre-existing lesions, or regression of seborrheic keratosis is called the sign of Leser–Trelat and can be a cutaneous manifestation of an internal malignancy References Hefferman MP, Khavari PA Raindrop seborrheic keratosis: a distinctive pattern on the backs of elderly patients Arch Dermatol 1998; 134:382–383 Hsu C, Abraham S Campanelli A et al Sign of Leser–Trelat in a heart transplant recipient Br J Dermatol 2005; 153(4):861–862 Patton T, Zirwas M, Nieland-Fisher N, Jukie D Inflammation of seborrheic keratoses caused by cytarabine: a pseudo sign of Leser–Trelat J Drugs Dermatol 2004; 3(5):565–566 Pentenero M, Carrozzo M, Pagano M, Gandolfo S Oral acanthosis nigricans, tripe palms and sign of Leser–Trelat in a patient with gastric adenocarcinoma Int J Dermatol 2004; 43(7):530–532 If the diagnosis is made, a comprehensive systemic work-up is indicated ■ Treatment is most often for cosmetic reasons and the least destructive and scarring method should be used ■ Lichen planus-like keratosis are usually diagnosed histopathologically Excisional, rather than incisional, techniques are recommended ■ The more skilled clinician can make the diagnosis by putting the clinical and dermoscopic findings together, thus avoiding surgery ■ There is an extensive clinical and histopathological differential diagnosis which includes melanoma, nonmelanoma skin cancer, and mycosis fungoides A good clinicopathological correlation is essential ■ Solitary erythematous or pinkish macules and papules could be melanocytic, non-melanocytic, benign, malignant, or inflammatory Dermoscopy is usually not helpful with these lesions ■ Once the diagnosis of a lichen planuslike lesion is made, aggressive therapy is not indicated Reassurance to the patient of the benign nature of this pathology will be appreciated Inamadar AC, Palit A Eruptive seborrheic keratosis in human immunodeficiency virus infection: a coincidence or “the sign of Leser–Trelat?” Br J Dermatol 2003; 149(2):435–436 Flugman SL, McClain SA, Clark RA Transient eruptive seborrheic keratosis associated with erythrodermic psoriasis and erythrodermic drug eruption: report of two cases J Am Acad Dermatol 2001;45(6 Suppl):S212–S214 Vielhauer V, Herzinger T, Korting HC The sign of Leser–Trelat: a paraneoplastic cutaneous syndrome that facilitates early diagnosis of occult cancer Eur J Med Res 2000; 5(12):512–516 McCrary ML, Davis LS Sign of Leser–Trelat and mycosis fungoides J Am Acad Dermatol 1998; 38(4):644 327 328 R Johr Braun RP, Rabinovitz HS, Krischer J et al Dermoscopy of pigmented seborrheic keratosis: a morphological study Arch Dermatol 2002; 138:1556–1560 10 Elgart GW Seborrheic keratosis, solar lentigines and lichenoid keratosis Dermatoscopic features and correlation to histology and clinical signs Dermatol Clin 2001; 19(2):347–357 11 Zalaudek I, Ferrara G, Argenziano G Clonal seborrheic keratosis: a dermoscopic pitfall Arch Dermatol 2004; 140:1169–1170 12 Hirata SH, Almeida FA, Tomimori-Yamashita J et al “Globulelike” dermoscopic structures in seborrheic keratosis Arch Dermatol 2004; 140:128–129 13 Argenziano G, Rossiello L, Scalvenzi M et al Melanoma simulating seborrheic keratosis: a Dermoscopy pitfall Arch Dermatol 2003; 139:389–391 14 Izikson L, Sober AJ, Mihm MC et al Prevalence of melanoma clinically resembling seborrheic keratosis Arch Dermatol 2002; 138:1562–1566 15 Vun Y, De’ambrosis B, Spelman L, et al Seborrheic keratosis and malignancy: collision tumour or malignant transformation? Australas J Dermatol 2006; 47(2):106–108 V.6 16 Lim C Seborrheic keratosis with associated lesions: a restrospective analysis of 85 lesions Australas J Dermatol 2006; 47(2):109–113 17 Johr R, Saghari S, Nouri K Eccrine porocarcinoma arising in seborrheic keratosis evaluated with dermoscopy and treated with Moh’s technique Int J Dermatol 2003; 42:653–657 18 Mckee PH et al (eds) Tumors of the surface epithelium Pathology of the skin, 3rd edition with clinical correlations, 2005; Elsever Mosby, Amsterdam, pp 1158–1163 19 Morgan MB, Stevens GL, Switlyk S Benign lichnoid keratosis A clinical and pathologic reappraisal of 1040 cases Am J Dermatopathol 2005; 27(5):387– 392 20 Higail IA, Crawford RI Benign lichenoid keratosis with histologic features of mycosis fungoides: clinicopathologic description of a clinically significant histologic pattern J Cutan Pathol 2002; 29:291–294 Subject Index A ABCD criteria/rule 88, 91, 214 ABCDE criteria „Abtropfung“ 61, 63 acanthosis 199 achromia 271 achromic melanoma 273 – ungual 273 acquired monodactylic anonychia 271 acral – lentiginous melanoma 238 – melanoma – – Clark’s classification 196 – nevus 66 actinic – keratosis 234, 267, 295, 296 – lentigo, see also lentigo senilis 103, 225, 293 adenocarcinoma 315 adnexal neoplasm 82 agminated nevus 75, 80 albinismus perinaevicus, see also halo nevus 124 amelanotic melanoma 204, 221, 323 – vascular pattern 208 AMS, see atypical mole syndrome anaplasia 299 angiokeratoma 248, 261, 303 – solitary 307 angioma 261 – acquired plaque-type 310 anhidrosis 108 apocrine hydrocysroma 82 astrocytoma 168 arborizing vessel 82 artificial light source 189 atypical – dysplastic nevus 87 – melanoma 211 – mole syndrome (AMS) 88, 184, 187, 253 – nevus – – central hyperpigmen- tation 91 – – central hypopigmen- tation 90 – – dermoscopic pattern 90 – – eccentric hyperpigmen tation 91 – – multifocal hyperpigmen tation 91 – – multifocal hypopigmen tation 91 – spitzoid tumor 34 automated classification 47 automatic diagnosis 47 B baby Spitz nevus 159 basal cell carcinoma (BCC) 14, 15, 97, 144, 224, 279, 319 – black patients 137 – pigmented 234, 246 Becker’s nevus 111 Bednar tumor 247 benign – fibrous histiocytoma 288 – melanocytic proliferation 98 BK mole syndrome 88 black – heel 69 – lamella 13, 142, 143, 158 – nevus 93, 142 blood – spot 175 – vessel – – comma-shaped 139, 181 blotch 13, 48 blue nevus 179, 225, 247, 261, 265, 284 – atypical variants 78 – dendritic-sclerotic histotype 81 – hypochromic variants 80 – hypomelanotic 82 – mixed types 78 – with satellites 266 blue-white veil 13, 245 Bowenoid carcinoma 296 Bowen’s disease 273, 296, 297 – non-pigmented 298 – pigmented 298 B-RAF mutation 152 branched streak 244 C café-au-lait macule 111, 167, 168 capping 159 Carney syndrome 80, 169 CASH 17 CD4 gene 250 CDKN2A 168, 187, 250 cherry – angioma 17 – hemangioma 304 chromatin pattern 84 Civatte colloid body formation 325 Clark – level 25 – nevus 62, 63, 87, 97, 98, 147, 158, 286 – melanoma 64 clinico-imaging technique CNS melanocytosis 165 cobblestone 17 cockarde nevus 130 collagen 54 collision tumor 97 combined nevus 97 common nevus, see also typical nevus 102 condyloma acuminata 320 confocal – laser scanning 47 – microscopy 39 congenital melanocytic nevus 75, 106 – treatment 112, 113 330 Subject Index crista profunda – intermedia 200 – limitans 68, 70 crush artifact 24 cryosurgery 167 cutaneous – hemorrhagic macule 309 – metastatic melanoma – – in-transit type 260 – – satellite type 260 cyclin D1 196, 200 D Dandy-Walker complex 165 dermal – elastosis 188 – melanoma 27, 30 dermatofibroma 247, 248, 286 – hemosiderotic 288 dermatofibrosarcoma 247 – protuberans 288 dermatoglyphics 69 dermatoheliosis 166 dermatosis papulosa nigra 314, 322 dermoscopy/dermatoscopy – ABCD rule 19, 215 – attachments – blood vessels – colors – equipment – machine vision computergenerated 218 – score 19 desmoplasia 83, 159 digital camera DNA – nucleotide excision repair 166, 167 – repair 187 dots 11 dysplastic nevus syndrome, see also familial atypical multiple mole melanoma syndrome 88, 144, 168 E endothelin-1 284 epidermal hyperplasia 155, 157 epidermolysis bullosa 30 epidermotropism 325 exophytic tumor 306 extravasated erythrocyte 131 F familial atypical multiple mole melanoma syndrome (FAMMM) 88, 168 familiar dysplastic syndrome 93 FAMMM, see familial atypical multiple mole melanoma syndrome fibrillar pattern 67, 72 fibrin 131 fibroblast 288 fibroplasia 31, 91 fibrosis 241, 261 fibroxanthoma 247 fissure 14 flat seborrheic keratosis 319 5-fluorouracil 167, 199, 300, 301 follicular cyst 286 G genital – melanocytic nevus 119 – melanoma 28, 229 – melanosis 28 glabrous skin 197, 200 Glasgow 7-point checklist global positioning radio system (GPRS) 58 globular pattern 17 globule 11 – cobble-stone-like 110 GPRS, see global positioning radio system granularity 13 granuloma of pregnancy, see also pyogenic granuloma 305 H hairpin loop 209 halo – nevus, see also albinismus perinaevicus, leukoderma acquisitum centrifugum, Sutton nevus 31, 124 – phenomenon 126, 152 hemangioma 170, 224, 248, 284, 303, 310 hematoma – subcorneal 309 – subungual 308 hemoglobin 54 hemorrhage 308 hepatocyte growth factor/scatter factor (HGF/SF) 107 heterochromic melanonychia striata 173 HGF/SF, see hepatocyte growth factor/scatter factor Hochsteigerung 61 homogeneous pattern 17 HRAS – amplification 152 – mutation 152 Hutchinson’s – melanotic freckle 233 – sign 29, 173, 174, 198, 276 hyperchromatism 26 hyperkeratosis 208, 224, 251, 300 hypermelanotic nevus 93, 142 hyperpigmentation 147 hyperplasia 131, 175, 293, 322 hypertrichosis 108, 111 hypomelanosis 124 hypomelanotic melanoma 222, 239 hyponychial volar skin 198 hypopigmentation 205 hypopigmented nevus 287 I imiquimod 167, 300, 301 immersion technique ink spot lentigo 225, 292 interferon alpha-2b 253 interleukin-2 253 in-transit metastasis 252 in-vivo confocal laser scanning microscopy 48 IR (near infrared) irregular crypt 181 irritated melanocytic nevus 129 K Kamino – body 33, 159 – nevus 82 keratin 210, 317 keratinization 299 keratinizing tumor 210 keratinocyte 40, 72, 135, 210, 295, 319 – demarcation 42 keratoacanthoma 297, 299, 319 keratosis – areola mammae 122 – lichen planus-like 323 Subject Index L LAMB 80, 169 large blue-gray ovoid nest 14 laser Doppler flowmetry 49 lattice-like pattern 67 Laugier-Hunziker syndrome 199, 272 leaf-like area 14 lense lentigines, see also lentigo simplex 175, 272, 290 lentigo – maligna 233, 236, 238, 265, 293, 316 – – melanoma 166, 188, 267 – – progression model 234 – senilis, see also actinic lentigo 236 – simplex, see also lentigines 103, 136, 290 LEOPARD syndrome 169 leptomeninges 107 lesion asymmetry parameter 55 leukoderma 108, 125 – acquisitum centrifugum, see also halo nevus 124 level of evidence 49 lichen – atrophicus 119 – planus-like keratosis 323 – sclerosus 30, 119 lipoma 170 liposarcoma 108 liquid nitrogen cryotherapy 235 Lisch nodule 167, 168 liver spot (see actinic lentigo) 293 lymphangiogenesis 251 lymphangitis 239 lymphoma 315 M macrophages 126 MAP-kinase (MAPK) pathway 107 MDP, see melanocytic differentiation pathway MED, see minimal erythema doses MelaFind 52 – dermoscopic image 54 melanin 9, 11, 29, 54, 69, 284, 299, 325 – caps 40 – deposits in the brain 114 – granules 73 – loss 207 – pigmentation 130, 204, 279 melanocortin-1 receptor gene 187 melanocyte 24, 26, 29, 106, 120, 135, 145, 149, 159, 215, 262, 319 – the CNS 165 in – malignant neoplasm 229 – necrosis 219 – nevus – – axilla 121 – – on the vulva 121 – – umbilicus 121 – proliferation 28 – stimulation 284 – suprabasal 131 melanocytic – differentiation pathway (MDP) 106 – hyperplasia 246 – nevus 71, 246, 319 – – nail apparatus 174 – – specific syndromes 164 – tumor 149 – non-melanocytic lesion algorhithm 16 melanocytosis 107 melanoma 64, 69, 82, 98, 108, 130, 286 – amelanotic 206 – asymmetry 244 – atypical 211 – balloon-cell 26 – black patients 136 – blood markers 253 – blotch 245 – blue-white veil 245 – childhood 160 – clinical recognition – desmoplastic 26 – diagnosis 25 – early stages 213 – epidemiology 185 – false negative 221 – feature-poor 225 – histopathological features 24 – hypopigmented 206 – situ 95, 217 in – the nail apparatus 270 in – incidence 185 – incognito 222 – latitude 188 – lentigo maligna 233, 265 – metastases 260 – migration 189 – minimal deviation 31 – mortality 186 – myxoid 26 – nevi 187 331 – nodular – occupational exposures 189 – the trunk 238 of – the vulva 229, 231 of – partially pigmented 206 – prevention 190 – screening 250 – skin colour 186 – small-diameter 213 – spitzoid 224, 226 – streaks 245 – exposure 188 sun – symmetry 244 – three Cs melanonychia 29 – striata 173, 174, 176, 270, 276 melanophage 82, 83, 323,325 melanosis 28 – Dubreuilh 233 of melanosome 135, 284 melanotic macule 230 melphalan 262 MELTUMP 23, 92 Menzies method 20, 21, 244 Merkel cell carcinoma 247 Meyerson phenomenon 315 Meyerson‘s nevus 129–131 micro-capping 159 microvesiculation 131 Miescher nevus 139, 181 milia-like cyst 13, 111, 317 milkline nevus 119, 122 minimal erythema doses (MED) 130 Mohs micrographic surgery 235 mongolian spot 79, 80 moth-eaten garment 14 multicomponent pattern 17 multiple – blue-gray globule 14 – dysplastic nevus 222, 224 multispectral – imaging 52 – system 55 mycosis fungoides 315 myxoma 169 N nail – matrix 176, 274 – melanoma 270 – nevus 173 NAME 80, 169 near infrared (IR) 52 neoangiogenesis 241 332 Subject Index neurocutaneous melanosis 108, 114, 115, 164 neurofibroma 167, 168 neurofibromatosis type I (NF-1), see also von Recklinghausen’s disease 167 neurotropism 26 nevoid – cell 26 – melanoma 131 nevus – acquired 62 – ancient 32 – congenital 30, 61 – dysplastic 42 – growth 63 – hypermelanotic 31 – melanocytic 30 – network 114 – Ito 79 of – midlife 142 of – Ota 79 of – outreach 114 – particular pigmentation 142 – recurrent (persistent) 32 – spilus 109, 111 NF-1, see neurofibromatosis type I nodal metastasis 251 nodular melanoma 238, 242, 243, 266, 267, 315 non-edge papillae 44 N-RAS mutation 152 O onychomycosis 274 optic nerve glioma 168 optical coherence tomography 49 orthokeratosis 307 – keratin layer 310 P pagetoid Spitz nevus 159 Paget’s disease 249 papillomatosis 322 parakeratosis 131, 156, 160, 299, 300 parallel – furrow pattern 66, 67, 70, 71 – pattern 17 – ridge pattern 198 pattern analysis 17 Pautrier’s microabscess 30, 325 PCR analysis 252 PDA, see personal digital assistant pebbles on the ridges 69 penile melanosis 230 pepper-like granule 266 persistent nevus, see also recurrent nevus 147 personal digital assistant (PDA) 58 Peutz-Jeghers syndrome 199 pigment network 11 pigmentation – drug-induced 175, 272 – ethnic 175 – the lunula 177 of pigmented – actinic keratosis 225 – basal cell carcinoma (BCC) 234, 246 – – telangiectasia 279 – – ulceration 279 – genital lesion 119 – parakeratosis 31 – spindle cell nevus 33 pink nevus 142 PITSLRE gene 87 plasma hemoglobin 253 poikiloderma 166 polymorphism 187 polyvinyl chlorid 189 pregnancy 305 pruritus 108 psammomatous melanotic schwannomas 169 pseudo-colour image 48 pseudocomedos 13 pseudohorn cyst 208, 322 pseudo-Hutchinson’s sign 174, 178 pseudomelanoma 27 pseudonetwork 293, 298 pseudopod 12, 13, 245, 308 pyogenic granuloma, see also granuloma of pregnancy 24, 248, 273, 303–305, 315 R radial streaming 12 Raman spectroscopy 48 RCM, see reflectance-mode laser scanning confocal microscopy real-time videoconferencing 57 recurrent nevus, see also persistent nevus 147, 225 Reed nevus 33, 62, 63, 82151, 158, 159 reflectance mode laser scanning confocal microscopy (RCM) 39 regression 13 reticular – depigmentation 153 – pattern 17 reticulated lentigo 292 revised pattern analysis 17 rhabdomyosarcoma 106, 108 S SAMPUS 23, 92 satellite metastasis 240 satellitosis 240, 251 scale crust 131 scalp melanoma, ABCDE criteria 265 schwannoma 32 sclerosing hemangioma 288 seborrheic keratosis 91, 97, 104, 111, 181, 183, 223, 234, 247, 248, 267, 313 – Borst-Jadassohn appearance 322 segmentation 54 self-examination of the skin 5, 213 senescence 62 senile freckle, see also actinic lentigo 293 sentinel-lymph-node biopsy 252, 300 serum lactate dehydrogenase 253 seven-point checklist 20 SIAscope 52 sign of Leser-Trelat 315 skin – fold freckling 168 – pigmentation 135 – self-examination 5, 213 – sun-damaged 27 – tumor – – two-step method 244 SkinCam system 49 solar – elastosis 300 – keratoses 188 – lentigines 14, 318 – lentigo, see also actinic lentigo 103, 293 speckled lentiginous nevus 109, 152 spectral analysis 48 SpectroShade 52 SPF, see sun protection factor spina bifida occulta 170 spinal dysraphism 170 Subject Index Spitz nevus 30, 33, 62, 75, 82, 97, 98, 120, 144, 208, 211, 224, 245, 247, 286 – atypical 151 – childhood 160 – metastasizing 152 spitzoid melanoma 151 squamous cell carcinoma 246, 249, 296 – the nail apparatus 273 of – precursor lesions 295 SSM, see superficial spreading melanoma starburst pattern 17 stratum – corneum 7, 40, 73 – granulosum 40 – spinosum 40 strawberry pattern 298 streak 245 – branched 12 stuccokeratosis 314, 322 Sturge-Weber syndrome 165 subcorneal hematoma 309 subungual – hemorrhage 272, 308 – melanoma 270 – tumoral syndrome 273, 276 sulcus superficialis 68 sun – exposure 188 – protection factor (see SPF) 190 superficial spreading melanoma (SSM) 238, 239, 267 Sutton nevus, see also halo nevus 124, 129 T target globule 111 targeted-chemotherapy 254 targetoid hemosiderotic – hemangioma 130 – nevus 123, 129 TDS, see total dermoscopy score telangiectasia 282 teledermatology 57 – mobile 58 teledermatopathology 58 teledermoscopy 9, 58 telomerase 87 telomere attrition 62 temozolamid 254 three-point checklist 21 total dermoscopy score (TDS) 20 traumatized nevus 129 Turner’s syndrome 125 Tyndall effect 78 typical nevus, see also common nevus 102 U ultra-violet index 186 Unna nevus 181 UV-irradiated nevus 129 333 V vaccine-based immunotherapy 254 vascular lesion 303 virtual slide system (VSS) 58 vitiligo 125 von Recklinghausen’s disease, see also neurofibromatosis type I 167 VSS, see virtual slide system vulvar – melanosis 230 – nevus 119 W web consultation 59 Wellman confocal criteria 43 white nevus 143 wireless local area network (WLAN) 58 WLAN, see wireless local area network wobble sign 181, 183 Wood’s light 3, 240 X xeroderma pigmentosum 166, 187 xerosis 108 XPD gene 187 .. .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. .. 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 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