Biopsy Pathology of Melanocytic Disorders

BIOPSY PATHOLOGY SERIES

General Editors

Professor Leonard S. Gottlieb, MD, MPH Mallory Institute of Pathology, Boston, USA

Professor A. Munro Neville, PhD, DSc, MD, FRC Path. Ludwig Institute for Cancer Research, London, UK

Professor F. Walker, MD, PhD, FRC Path. Department of Pathology, University of Aberdeen, UK

Other titles in the series

1. Biopsy Pathology of the Small Intestine F. D. Lee and P. G. Toner

2. Biopsy Pathology of the Liver R. S. Patrick and]. O'D. McGee

3. Brain Biopsy ]. H. Adams, D. I. Graham and D. Doyle

4. Biopsy Pathology of the Lymphoreticular System D. H. Wright and P. G. Isaacson

5. Biopsy Pathology of Muscle M. Swash and M. S. Schwartz

6. Biopsy Pathology of Bone and Bone Marrow B. Frisch, S. M. Lewis, R. Burkhardt and R. Bartl

7. Biopsy Pathology of the Breast ]. Sloane

8. Biopsy Pathology of the Oesophagus, Stomach and Duodenum D. W. Day

9. Biopsy Pathology of the Bronchi E. M. McDowell and T. F. Beals

10. Biopsy Pathology in Colorectal Disease I. C. Talbot and A. B. Price

11. Biopsy Pathology and Cytology of the Cervix D. V. Coleman and D. M. D. Evans

12. Biopsy Pathology of the Liver (2nd edn) R. S. Patrick and]. O'D. McGee

13. Biopsy Pathology of the Pulmonary Vasculature C. A. Wagenvoort and W. ]. Mooi

14. Biopsy Pathology of the Endometrium C. H. Buckley and H. Fox

15. Biopsy Pathology of Muscle (2nd edn) M. Swash and M. S. Schwartz

16. Biopsy Pathology of the Skin N. Kirkham

17. Biopsy Pathology of Melanocytic Disorders W. ]. Mooi and T. Krausz

Biopsy Pathology of Melanocytic Disorders

W. J. MOOI MD Head of Department of Pathology; Head of Division of Tumour Biology The Netherlands Cancer Institute Amsterdam The Netherlands

and

T. KRAUSZ MD, MRCPath Senior Lecturer and Consultant Histopathology and Cytopathology Royal Postgraduate Medical School Hammersmith Hospital London UK

With a Foreword by

J. G. AZZOPARDI MD, FRCPath Emeritus Professor of Oncology Royal Postgraduate Medical School University of London Honorary Consultant Pathologist Hammersmith Hospital London

I u !11 SPRINGER-SCIENCE+BUSINESS MEDIA, B.V.

First edition 1992

© 1992 W.J. Mooi and T. Krausz

Originally published by Chapman & Hall in 1992

Softcover reprint of the hardcover 1st edition 1992

Typeset in 10/12 Palatino by Best-set Typesetter Ltd, Hong Kong

ISBN 978-0-412-32350-8 ISBN 978-1-4899-6908-8 (eBook)

DOI 10.1007/978-1-4899-6908-8

Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the UK Copyright Designs and Patents Act, 1988, this publication may not be reproduced, stored, or transmitted, in any form or by any means, without the prior permission in writing of the publishers, or in the case of reprographic reproduction only in accordance with the terms of the licences issued by the Copyright Licensing Agency in the UK, or in accordance with the terms of licences issued by the appropriate Reproduction Rights Organization outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to the publishers at the London address printed on this page.

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A catalogue record for this book is available from the British Library

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Contents

Colour plates appear in Chapter 13 Preface X

Foreword xiii

1 Melanin and melanocytes 1 1.1 Embryology 3 1.2 Light microscopy 4 1.3 Biochemistry of melanin synthesis 8 1.4 Electron microscopy 10

2 Biopsy, tissue processing and histological investigation 17 2.1 Skin biopsy of a pigmented lesion: clinical considerations 17 2.2 Macroscopical description and dissection of skin biopsy 19

specimens 2.3 Dissection of lymphadenectomy specimens 20 2.4 Dissection of other specimens containing metastases 21 2.5 Tissue processing and staining methods 21 2.6 Electron microscopy 26 2.7 Other techniques in the diagnosis of malignancy 27 2.8 Histological investigation and description 27 2.9 Criteria for diagnosis: usefulness and limitations 28

3 Cutaneous pigmented lesions not related to melanocytic 36 naevi

3.1 Generalized and regional hyperpigmentation 36 3.2 Ephelis (freckle) 38 3.3 Solar lentigo (senile lentigo, 'liver spot') 39 3.4 Cafe-au-lait spot 40 3.5 Becker's naevus (pigmented hairy epidermal naevus) 41 3.6 Xeroderma pigmentosum 42 3.7 Reactive pigmentation and melanocyte colonization of 43

tumours

vi Contents

3.8 Pigmented dermatofibrosarcoma protuberans (Bednar 51 tumour)

4 Common acquired melanocytic naevi 56 4.1 Lentigo simplex (simple lentigo, naevoid lentigo) 57 4.2 Junctional naevus 61 4.3 Compound naevus 64 4.4 Intradermal naevus 74 4.5 Halo naevus (Sutton's naevus, leukoderma acquisitum 85

centrifugum) 4.6 Balloon cell naevus 90 4.7 Cockarde naevus 93 4.8 Deep penetrating naevus 93 4.9 Recurrent naevus after incomplete removal 97

('pseudomelanoma') 4.10 'Active' naevi (so-called 'hot naevi') 99 4.11 Vulvar naevi 100

5 Cutaneous blue naevi and related lesions 106 5.1 Common blue naevus 107 5.2 Cellular blue naevus 113 5.3 Plaque-type blue naevus 125 5.4 Target blue naevus 125 5.5 Combined naevus 126 5.6 Mongolian spot, Ota's and Ito's naevus, and related 130

lesions

6 Congenital melanocytic naevi 136 6.1 Clinical features 136 6.2 Pathological features 138 6.3 The distinction between congenital and acquired naevi 150 6.4 Malignant transformation of congenital naevi 152 6.5 Subtypes of congenital naevus 152 6.6 Meningeal melanocytic lesions associated with congenital 154

naevi (neurocutaneous melanosis) 6.7 Placental naevus cell aggregates 154

7 Spitz naevus, desmoplastic Spitz naevus and pigmented 157 spindle cell naevus

7.1 Terminology 157 7.2 Clinical features 158 7.3 Histological features 160

Contents vii

7.4 Differential diagnosis 172 7.5 Desmoplastic Spitz naevus 175 7.6 Pigmented spindle cell naevus ('Reed's pigmented spindle 178

cell tumour')

8 Dysplastic naevus 186 8.1 Familial melanoma and the dysplastic naevus syndrome 188 8.2 Sporadic dysplastic naevus syndrome and solitary 190

dysplastic naevus 8.3 Clinical features 192 8.4 Pathological features 192 8.5 Histological criteria for the diagnosis 201 8.6 Dysplastic naevi vs in situ melanoma 204 8.7 Additional diagnostic techniques 206 8.8 Histological grading of dysplastic naevi to identify 207

dysplastic naevi associated with high risk 8.9 Histological evidence of dysplastic naevi_as precursors of 208

melanoma 8.10 Conclusion 210

9 Cutaneous melanoma 215 9.1 Macroscopical appearance 217 9.2 Histological diagnosis 219 9.3 Clinicopathological subtyping of melanoma 233 9.4 Superficial spreading melanoma 237 9.5 Nodular melanoma 239 9.6 Lentigo maligna and lentigo maligna melanoma 240 9.7 Acrallentiginous melanoma 246 9.8 Spindle cell melanoma 250 9.9 Desmoplastic and neurotropic melanoma 253 9.10 Borderline and minimal deviation melanoma 260 9.11 Balloon cell melanoma 270 9.12 Intradermal melanoma arising in intradermal naevus 273 9.13 Malignant blue naevus 274 9.14 Congenital melanoma; materno-fetal metastasis 274 9.15 Childhood melanoma 275 9.16 Melanoma arising in congenital naevus 275 9.17 Multiple melanoma 277 9.18 Primary and metastatic melanoma simulating other 281

neoplasms 9.19 Cutaneous and generalized melanosis in metastatic 294

melanoma

viii Contents

10 Prognostic factors in cutaneous melanoma 10.1 Clinical and pathological tumour stage 10.2 Site, sex and age 10.3 Levels of invasion 10.4 Tumour thickness 10.5 Mitotic rate, and related prognostic index 10.6 Ulceration 10.7 Satellites 10.8 Regression 10.9 Vascular invasion 10.10 Pre-existent naevus 10.11 Dermal inflammatory infiltrate 10.12 Cytological features 10.13 Late recurrence of melanoma 10.14 Prognosis of metastatic melanoma 10.15 Metastatic melanoma with unknown primary

11 Extracutaneous melanocytic lesions 11.1 Eye and orbital cavity 11.2 Nasal cavity and paranasal sinuses 11.3 Labial mucosa, oral cavity, and oropharynx 11.4 Larynx 11.5 Oesophagus 11.6 Lower respiratory tract 11.7 Gallbladder 11.8 Anal canal and rectum 11.9 Genitourinary tract 11.10 Lymph node 11.11 Melanoma of soft tissues (clear cell sarcoma) 11.12 Central nervous system 11.13 Adrenal gland 11.14 Miscellaneous sites

12 Other extracutaneous melanotic lesions 12.1 Conjunctiva 12.2 Labial and oral melanotic lesions 12.3 Salivary gland 12.4 Dermatopathic lymphadenopathy 12.5 Endocrine organs and neuroendocrine tumours 12.6 Melanotic schwannoma and neurofibroma 12.7 Other pigmented tumours of the nervous system 12.8 Tumours of uveal pigment epithelium

304 305 305 308 309 313 313 314 316 317 318 318 318 320 320 322

331 333 344 345 349 350 351 353 353 356 362 366 369 374 374

384 385 385 386 386 387 387 392 394

Contents ix

12.9 Pigmented neuroectodermal tumour of infancy ('melanotic 394 progonoma')

12.10 Pigmented tumours of the genital tract 398

13 Cytological diagnosis of melanoma 404 13.1 Methods 405 13.2 Microscopic features: general remarks 408 13.3 Epithelioid-cell melanoma 410 13.4 Spindle cell melanoma 413 13.5 Melanomas of mixed cell type 415 13.6 Uveal melanomas 415 13.7 Cytological features of melanoma in specimens other than 416

FNA

Index 421

Preface

The incidence of cutaneous melanoma has risen considerably over the last decades, and both the medical profession and the general public have become increasingly aware of the importance of early diagnosis of this tumour. As a consequence, pigmented lesions of the skin are submitted for pathological diagnosis more often, and melanomas are generally detected at an earlier stage of their development. Clinically important new entities such as dysplastic naevus have been iden­tified and have added to the complexity of the differential diagnosis. Presently, several controversies continue to generate intense debate, e.g. the existence of dysplastic naevus as a distinct entity and the diagnosis of in situ melanoma. As a result, the diagnosis of melanocytic lesions has become more complex and difficult. Needless to say, the clinical consequences of over-diagnosis and under-diagnosis of melanoma are often far-reaching.

Reed and colleagues (1975) wrote that 'for the diagnostic histo­pathologist, the diagnosis of common melanocytic nevus is gestalt. He seldom, if ever, enumerates those features which clearly distinguish either a nevus or nevus cells (dermal melanocytes). When faced with an unusual melanocytic lesion, his gestalt may fail him'. In order to avoid this problem, it is important for the pathologist to follow a systematic procedure of differential diagnosis, based on concrete histo­logical criteria. We have attempted to adhere as rigidly as possible to the use of well-defined histological features that can be used as criteria in differential diagnosis. Tables of diagnostic features are included for the large majority of entities discussed, in order to facilitate quick reference for the reader. In the text, the criteria and potential pitfalls are discussed at length, since by themselves tables are not a safe basis for pathological diagnosis. Relevant clinical data are briefly outlined, in order to enhance pathological diagnostic accuracy as well as to outline the clinical consequences of various diagnoses. Because the book is intended for surgical pathologists, we only briefly refer to aspects of molecular biology, cell biology and biochemistry of melanocytes and melanocytic lesions.

Preface xi

Extracutaneous melanocytic lesions are much less common, and only occasionally come to attention. However, many of them are of con­siderable clinical importance. Naevus cells within a lymph node may erroneously be considered to represent a micrometastasis of melanoma or carcinoma; benign naevi of the conjunctiva and iris may be misdiagnosed as melanoma; melanin-containing non-melanocytic tumours, such as pigmented schwannoma and melanotic progonoma, may baffle the pathologist insufficiently familiar with these entities. A lymph node metastasis of a histologically 'undifferentiated' malignant tumour as the first presentation of melanoma occasionally poses diag­nostic problems. Cytology of metastatic melanoma is discussed in the final chapter, again emphasizing practical aspects and potential errors in diagnosis.

The diagnostic challenge posed by some melanocytic lesions is con­siderable and the authors dare to hope that in this respect the present book will be of some help.

The authors wish to thank the numerous fellow clinicians and pathologists who have in many ways contributed significantly to this book. We especially would like to thank Professor J. G. Azzopardi (Hammersmith Hospital, London), for his valuable advice, encourage­ment and detailed criticism, and for agreeing to write a foreword to this volume.

Also, we thank Professors Ph. Riimke (Netherlands Cancer In­stitute, Amsterdam) and N. A. Wright (Hammersmith Hospital, London) for valuable criticism. Many colleagues have contributed cases; we specifically would like to mention Dr J. Alons-van Kordelaer (Amsterdam), Dr D. De Wolff-Rouendaal (University of Leiden), Dr K. P. Dingemans (University of Amsterdam), Dr C. D. M. Fletcher (StThomas's Hospital Medical School, London), Dr P. van Heerde and Dr J. L. Peterse (Netherlands Cancer Institute, Amsterdam), Dr R. Salm (Hammersmith Hospital, London), Dr M. B. Satti (King Fahd Hospital, Al-Khoubar, Saudi Arabia), Dr P. J. Slootweg (Un~versity of Utrecht), and Dr N. P. Smith (StJohn's Dermatology Centre, London).

We have been greatly helped by the expert assistance of the staff of the Library and the Department of Medical Illustration of the Netherlands Cancer Hospital and by Mr W. P. Meun, Department of Medical Illustration, University of Amsterdam.

Finally, we owe a heartfelt debt of gratitude to Suzie and Hanneke, who have put up with so much for so long during the preparation of this book.

W. J. Mooi MD T. Krausz MD MRCPath

xii Preface

Reference

Reed, R. J., Ichinose, H., Clark, W. H. and Mihm, M. C. (1975) Common and uncommon melanocytic nevi and borderline melanomas. Semin. Oncol., 2, 119-47.

Foreword

Malignant melanoma, with its variants and its m1m1cs, constitutes a major diagnostic challenge for histopathologists. The problem is an increasingly important one with the increased frequency of melanoma in many countries. The types of benign pigmented naevi proliferate remorselessly, because of increased knowledge about new clinico­pathological entities. Melanomas have acquired a certain mystique which does not apply to the same extent to lesions of, say, the gut or the thyroid. This does little to boost the confidence of the surgical pathologist approaching a difficult case. There have been many refine­ments of diagnosis in recent years and it clearly requires an expert to bring together the diverse strands of knowledge into an integrated whole and present the information in a way which is easily understood by a general histopathologist.

Drs Mooi and Krausz have done this admirably. The authors are primarily surgical pathologists and this has no doubt contributed to the way they tackle the subject. Histology, cytology, electron microscopy, cytochemistry and immunocytochemistry, together with some bio­chemical and embryological facets and, not least, clinical aspects are integrated in a sophisticated yet simple way. The merits and pitfalls of new methods are critically assessed. Loose undergrowth is raked away to reveal the essentials in stark relief. At the end, one is almost left wondering why one ever had difficulties, although the authors admit that the 'Spitzoid melanoma' and so-called 'malignant Spitz naevus' remain somewhat enigmatic. One could say the same of the 'deep penetrating naevus'. The reader will find topics like 'dysplastic naevus' discussed with great clarity.

I have little doubt that the Mooi-Krausz approach will meet with the approval of their peers and that this splendid monograph will come to be regarded as an essential part of the armoury of the surgical pathologist.

J. G. Azzopardi