Actinic Keratosis
Current Problems in Dermatology Vol. 46 Series Editors Peter Itin Basel Gregor B.E. Jemec Roskilde
Actinic Keratosis Volume Editors H. Peter Soyer Brisbane, Qld. Tarl W. Prow Brisbane, Qld. Gregor B.E. Jemec Roskilde 33 figures, 29 in color, and 4 tables, 2015 Basel Freiburg Paris London New York Chennai New Delhi Bangkok Beijing Shanghai Tokyo Kuala Lumpur Singapore Sydney
Current Problems in Dermatology H. Peter Soyer Tarl W. Prow Dermatology Research Centre The University of Queensland School of Medicine Translational Research Institute Princess Alexandra Hospital Brisbane, QLD 4102 (Australia) Gregor B.E. Jemec Department of Dermatology University of Copenhagen Roskilde Hospital DK 4000 Roskilde (Denmark) Library of Congress Cataloging-in-Publication Data Actinic keratosis / volume editors, Peter H. Soyer, Tarl W. Prow, Gregor B.E. Jemec. p. ; cm. -- (Current problems in dermatology, ISSN 1421-5721 ; vol. 46) Includes bibliographical references and indexes. ISBN 978-3-318-02762-4 (hard cover : alk. paper) -- ISBN 978-3-318-02763-1 (electronic version) I. Soyer, Peter H., editor. II. Prow, Tarl W., editor. III. Jemec, G. B. E. (Gregor B. E.) IV. Series: Current problems in dermatology ; v. 46. 1421-5721 [DNLM: 1. Keratosis, Actinic. W1 CU804L v.46 2015 / WR 500] RL435 616.5 44--dc23 2014041120 Bibliographic Indices. This publication is listed in bibliographic services, including MEDLINE/Pubmed. Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 2015 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland) www.karger.com Printed in Germany on acid-free and non-aging paper (ISO 9706) by Kraft Druck GmbH, Ettlingen ISSN 1421 5721 e-issn 1662 2944 ISBN 978 3 318 02762 4 e-isbn 978 3 318 02763 1
Contents VII Preface Soyer, H.P.; Prow, T.W. (Brisbane, Qld.); Jemec, G.B.E. (Roskilde) 1 Epidemiology of Actinic Keratoses Green, A.C. (Brisbane, Qld./Manchester) 8 Patients Perspectives on Actinic Keratosis Esmann, S. (Roskilde) 14 Photodamage: All Signs Lead to Actinic Keratosis and Early Squamous Cell Carcinoma Wei, J.; Kok, L.F.; Byrne, S.N.; Halliday, G.M. (Sydney, N.S.W.) 20 Dysregulation of Epidermal Growth Factor Receptor in Actinic Keratosis and Squamous Cell Carcinoma Joseph, S.R.; Endo-Munoz, L.; Gaffney, D.C.; Saunders, N.A.; Simpson, F. (Brisbane, Qld.) 28 The Actinic Keratosis Virome: Can We Prevent Squamous Cell Carcinoma with a Vaccine? Frazer, I.H. (Brisbane, Qld.) 36 Do Actinic Keratoses and Superficial Squamous Cell Carcinomas Have a Specific Immunoprofile? Wells, J.W. (Brisbane, Qld.) 42 Mouse Models for Actinic Keratosis and Squamous Cell Carcinoma Handoko, H.Y.; Ferguson, B.; Walker, G.J. (Brisbane, Qld.) 49 Keratinocyte Cancer and Its Precursors in Organ Transplant Patients Jenni, D.; Hofbauer, G.F.L. (Zürich) 58 Clinical Features of Actinic Keratoses and Early Squamous Cell Carcinoma Wheller, L.; Soyer, H.P. (Brisbane, Qld.) 64 The Many Clinico-Pathologic Faces of Actinic Keratosis: An Atlas Massone, C.; Cerroni, L. (Graz) 70 Dermoscopy of Actinic Keratosis, Intraepidermal Carcinoma and Squamous Cell Carcinoma Zalaudek, I. (Graz); Argenziano, G. (Reggio Emilia) 77 The Future of Keratinocyte Skin Cancer Surveillance: Automated Image Analysis to Identify and Monitor Keratinocyte Dysplasia Hames, S.C.; Prow, T.W. (Brisbane, Qld.) 85 Reflectance Confocal Microscopy: Hallmarks of Keratinocyte Cancer and Its Precursors Prow, T.W.; Tan, J.-M. (Brisbane, Qld.); Pellacani, G. (Modena) V
95 Optical Coherence Tomography and Its Role for Delineating the Thickness of Keratinocyte Dysplasia and Neoplasia Themstrup, L.; Jemec, G.B.E. (Roskilde) 101 Teledermatology: Its Use in the Detection and Management of Actinic Keratosis Janda, M. (Brisbane, Qld.) 108 Conventional Treatment of Actinic Keratosis: An Overview Peris, K.; Fargnoli, M.C. (Rome) 115 Field Cancerization: From Molecular Basis to Selective Field-Directed Management of Actinic Keratosis Philipp-Dormston, W.G. (Cologne) 122 Update on Photodynamic Treatment for Actinic Keratosis Wiegell, S.R. (Roskilde) 129 Laser Treatment and Its Implications for Photodamaged Skin and Actinic Keratosis de Vries, K.; Prens, E.P. (Rotterdam) 136 Ingenol Mebutate: From Common Weed to Cancer Cure Zarchi, K.; Jemec, G.B.E. (Roskilde) 143 Oral Nicotinamide and Actinic Keratosis: A Supplement Success Story Kim, B.; Halliday, G.M.; Damian, D.L. (Sydney, N.S.W.) 150 Author Index 151 Subject Index VI Contents
Preface The hardest thing to see is what is in front of your eyes. Was ist das Schwerste von allem? Was dir das Leichteste dünkt, Mit den Augen zu sehn, was vor den Augen dir liegt. Johann Christoph Friedrich von Schiller (1759 1805), German Poet This quote from Schiller, which is commonly attributed to Goethe, fits well with the dermatologic condition called actinic keratosis. In some aspects, actinic keratosis is the most common and most well-known pathology in dermatology. Actinic keratoses are found in significant numbers on the sun-exposed skin of Caucasians, especially those lucky enough to be living in sun-bathed countries such as Australia, as two of the editors and a considerable number of authors do. One may question why it is necessary to dedicate a book to this quite ordinary pathology. Everything about this condition seems crystal clear: the cause of its appearance, its pathogenesis, its clinical and pathologic features, its treatment, and also its prognosis. It is exactly because of this clarity that it is necessary to dedicate a book to actinic keratosis. This ordinary pathology provides insight into an extraordinary number of important biological and clinical processes. All of these thoughts came into my mind when asked by Gregor Jemec to consider compiling a book on actinic keratosis. However, reflection on my discussions with Tarl Prow and Gregor Jemec made it soon evident to all of us that actinic keratosis is actually one of the best examples in mankind for studying the potential evolution from benign erythaematous lesions, with some flaky scales, to more or less tender nodules that rarely, but still too often, lead to metastasis and death. Additionally, it is probably fair to say that actinic keratoses are a remarkable experiment of nature that allows us to study biologic questions in regards to carcinogenesis and its treatment in our patients in an unprecedented manner. There is quite a bit of controversial literature on the interpretation of actinic keratosis as a benign lesion, a precursor lesion, or a carcinoma en miniature, highlighting the different schools of thought and underlying divergent interpretations between researchers and clinicians. The attentive reader will realise that this intellectual diversity is also reflected by our chapters authors, who represent world-renowned experts in the field of actinic keratosis. We tried to encompass all the facets of this condition by inviting researchers and clinicians across the spectrum, from epidemiology to immunology and from molecular biology to behavioural psychology, and of course, pathologists and clinicians working at the coal face with patients who bear the many clinical facets of actinic keratoses. In this spirit, this book on actinic keratosis will be of interest for scientists and clinicians alike with a special interest in this common and VII
fascinating condition that affects our patients beyond cosmetics; often has an impact on morbidity; and rarely, when progressing uncontrolled, also has an impact on mortality. In conclusion, we are greatly indebted to all the authors contributing to the different chapters, and we wish to thank them all for a great collaborative effort. Finally, a special thank you goes to Sandra Braun from KARGER who accompanied us through the various stages of the process of getting this book to completion. H. Peter Soyer, Brisbane, Qld., Australia Tarl W. Prow, Brisbane, Qld., Australia Gregor B.E. Jemec, Roskilde, Denmark VIII Soyer Prow Jemec