Cutaneous Melanoma

Charles M. Balch • Michael B. AtkinsClaus Garbe • Jeffrey E. GershenwaldAllan C. Halpern • John M. KirkwoodGrant A. McArthur • John F. ThompsonArthur J. SoberEditors

Cutaneous Melanoma

Sixth Edition

With 371 Figures and 115 Tables

EditorsCharles M. BalchDepartment of Surgical OncologyThe University of Texas MD AndersonCancer CenterHouston, TX, USA

Michael B. AtkinsDepartment of OncologyGeorgetown University Medical CenterLombardi Comprehensive Cancer CenterWashington, DC, USA

Claus GarbeCentre for DermatooncologyDepartment of DermatologyEberhard Karls UniversityTuebingen, Germany

Jeffrey E. GershenwaldDepartments of Surgical Oncology andCancer BiologyMelanoma and Skin CenterThe University of Texas MD AndersonCancer CenterHouston, TX, USA

Allan C. HalpernDermatology Service, Departmentof MedicineMemorial Sloan Kettering Cancer CenterNew York, NY, USA

John M. KirkwoodDepartments of Medicine,Dermatology, and Translational ScienceUniversity of Pittsburgh andUPMC Hillman Cancer CenterPittsburgh, PA, USA

Grant A. McArthurDivisions of CancerMedicine and ResearchPeter MacCallum Cancer CentreMelbourne, VIC, Australia

John F. ThompsonMelanoma Institute AustraliaFaculty of Medicine and HealthThe University of SydneySydney, NSW, Australia

Arthur J. SoberDepartment of DermatologyMassachusetts General HospitalHarvard Medical SchoolBoston, MA, USA

ISBN 978-3-030-05068-9 ISBN 978-3-030-05070-2 (eBook)ISBN 978-3-030-05069-6 (print and electronic bundle)https://doi.org/10.1007/978-3-030-05070-2

1st and 2nd edition: © J. B. Lippincott Company, Philadelphia 1985, 19913rd and 4th edition: © Quality Medical Publishing Inc., St. Louis, MO 1997, 20035th edition: © Quality Medical Publishing Inc., St. Louis, MO. Transfer: copyright transferredfrom the editors and individual contributors by written agreement 20096th edition: © Springer Nature Switzerland AG 2020This work is subject to copyright. All rights are reserved by the Publisher, whether the whole orpart of the material is concerned, specifically the rights of translation, reprinting, reuse ofillustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,and transmission or information storage and retrieval, electronic adaptation, computer software, orby similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in thispublication does not imply, even in the absence of a specific statement, that such names are exemptfrom the relevant protective laws and regulations and therefore free for general use.The publisher, the authors, and the editors are safe to assume that the advice and information in thisbook are believed to be true and accurate at the date of publication. Neither the publisher nor theauthors or the editors give a warranty, expressed or implied, with respect to the material containedherein or for any errors or omissions that may have been made. The publisher remains neutral withregard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Switzerland AG.The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Tomy wife, Carol, and our children, Glen, Alan, Laura, andMarkC.M.B.

To my wife, Susan Crockin, and our children, Ben, Melea, andJonM.B.A.

To my wife, Eva, and my daughters, Anna, Lisa, and SophieC.G.

To my wife, Donna, and my children, Sophie and EllieJ.E.G.

To my wife, Judy, and our children, Josh, Orly, and DebA.C.H.

To my wife, Gayle, and my children, Gerrit and GordonJ.M.K.

To my wife, Maree, and our children, Sarah, Ethan, and ChloeG.A.M.

To my children, Sally, James, Julia, and AnnaJ.F.T.

To my wife, Cheryl, and our children, Felicia and StephanieA.J.S.

To the Memory of:Seng-jaw Soong Ph.D. (1942–2012)

Statistician extraordinaire and Editor of the first five editions ofCutaneous Melanoma

Seng-jaw Soong with Charles Balch (circa 1985)Donald L. Morton, M.D. (1934–2014)

Consummate melanoma investigator and pioneer of thetechnique of lymphatic mapping and sentinel node biopsy formelanoma

Preface to the Sixth Edition

For over 34 years, we have been privileged to write six editions of a compre-hensive text describing the biology and clinical management of melanoma.Cutaneous Melanoma has now become the authoritative and comprehensivetreatise on this subject, which is used worldwide. It has a special emphasis ondata presentation and collectively incorporates the clinical outcomes of morethan 50,000 patients treated at major melanoma centers throughout the world.This book spans the entire spectrum of the disease, from precursors of mela-noma to advanced stages of metastatic disease, from melanoma genes topopulation-based epidemiology, and from prevention of melanoma to allforms of multidisciplinary treatments. It incorporates the basic principles ofdiagnosis and pathologic examination with treatment approaches for thedisease’s many clinical presentations. Each facet of clinical management issupported by statistical data about natural history, prognosis, and treatmentresults.

During the past decade, there have been major advances in the clinicalmanagement of melanoma, most notably in the effectiveness of new immu-notherapy and targeted therapies. As a result, this sixth edition has beencompletely rewritten by acknowledged experts in a wide variety of disciplines.Cutaneous Melanoma has grown considerably larger since the last edition,reflecting the vast amount of new information available on the topic and theincreased incidence of melanoma throughout the world. The book contains52 chapters and is organized into 7 major parts focusing on biology, diagnosisand staging, pathology, epidemiology and prevention, management of local-ized melanoma, management of regional metastases, diagnosis and treatmentof distant metastases, systemic treatment of metastatic disease, and history ofmelanoma. The chapters are either completely new or extensively revised andupdated. These chapters provide the latest data on melanoma staging andprognosis as well as on randomized prospective clinical trials involvingsurgical treatment and systemic treatments of melanoma. There are newchapters on clinical genetics, sentinel lymph node and other regional metasta-ses, adjuvant systemic therapy, immune modulators, melanoma-specifictargeted therapies, management of central nervous systemic metastases, andbiomarkers. Chapters are also devoted to special types of melanomas, such aschildhood melanomas, mucosal melanomas, and subungual melanomas.Finally, every clinical variation of recurrent and metastatic melanoma isaddressed, with treatment options included for each clinical entity. These

vii

topics include detailed descriptions about local recurrences and their manage-ment, regional recurrences, in-transit metastases, and specific sites of distantmetastases (e.g., lung, gastrointestinal tract). There is also an emphasis onprevention, screening, and early detection of melanoma.

Cutaneous Melanoma is oriented to all health-care providers andresearchers involved in the care of patients with melanoma, including sur-geons, dermatologists, medical and surgical oncologists, radiation oncologists,and other physicians and nurses who diagnose and treat patients with mela-noma. There are valuable sections for geneticists, cell biologists, and immu-nologists as well as epidemiologists and public health workers to provide themwith current reviews by the experts in those fields. We have attempted topresent a balanced perspective of the risks and benefits involved in eachtreatment modality and how these can be optimized in various clinical settings.This book also provides a reliable reference for general physicians, internists,and other health-care workers to help them recognize cutaneous melanomas atthe earliest possible stage, learn how to biopsy them properly for both diag-nosis and micro-staging, and clinically manage these patients during and aftertreatment.

Cutaneous Melanoma represents the accumulated wisdom of our col-leagues throughout the world who have contributed significantly to the amaz-ing progress that is being made in the study and treatment of melanoma. Thisprogress is built on the solid foundation that was laid by the pioneers in thefield, whose interest in this topic led to many of the discoveries that have beenmade to date. It is our hope that this book will help to further the understandingof melanoma, its biologic and clinical characteristics, and lead to furtheradvances in treatment.

We have been sustained throughout our professional careers by the courageand warmth of the large number of patients for whom it has been our privilegeto care. Personal rewards from these relationships and a desire to help improvethe care of other patients are the main reasons we continue to update this book.

Houston, USA Charles M. BalchWashington, USA Michael B. AtkinsTuebingen, Germany Claus GarbeHouston, USA Jeffrey E. GershenwaldNew York, USA Allan C. HalpernPittsburgh, USA John M. KirkwoodMelbourne, Australia Grant A. McArthurSydney, Australia John F. ThompsonBoston, USA Arthur J. SoberDecember 2019

viii Preface to the Sixth Edition

Acknowledgments

So many colleagues and coworkers have contributed to this book that it isdifficult to select only a few for specific recognition. This sixth edition ofCutaneous Melanoma was edited to a greater degree than any other edition.For this we thank all the authors and coauthors for their cooperation andwillingness to make this edition even more consistent and integrated in itscontents and treatment recommendations. Since publication of the fifth editionin 2009, there have been revolutionary changes in melanoma diagnosis andtherapy, making this sixth edition the most extensively updated of all editions(since 1985) and a must read for everyone interested in current information onmelanoma management.

We also want to thank those in our academic offices who helped us inso many ways to facilitate the manuscript flow and editorial review process,as well as typing our manuscripts. These include Ms. Brigitte Nelson (forDr. Balch), Ms. Kaye Oakley and Dr. Gabrielle Williams (for Dr. Thompson),Clara Florentino (for Dr. Sober), Ms. Julia Tijerina (for Dr. Atkins),Peg Grossman (for Dr. Halpern), Catherine Ringin (for Dr. McArthur), LisaHuntley and Victoria Alisasis (for Dr. Kirkwood), and Irma Wintle (forDr. Gershenwald).

We are privileged to work with a dynamic and talented publishing team atSpringer Publishing, led by Andrew Spencer, Senior Editor, who coordinatedall aspects of this book, and Purva Ashok Kumar who was the point person onthe production team. The Project Manager for this book was Kate Emery, whoworked diligently and patiently with the authors on their chapter submissions.She was particularly valuable in coordinating the flow of all the manuscriptsamong the multiple authors and editors and functioning as the primary inter-face with the publisher.

The research and data management represented in this book would not havebeen possible without the financial support and generous assistance of numer-ous institutions and individuals: NCI Center Core Grants and (P30 CA051008)to Georgetown Lombardi Comprehensive Cancer Center, TheMarion GardnerJackson Trust, and the Jason Sabbag Melanoma Research Fund (Massachu-setts General Hospital), and support from the NCI Cancer Center Core Grantand the NIH SPORE grants in melanoma at The University of Texas MDAnderson Cancer Center (MD Anderson), Houston, Texas (1P50CA221703),and the University of Pittsburgh SPORE in Melanoma and Skin Cancer(CA121973); the Robert and Lynne Grossman Family Foundation and theMichael and Patricia Booker Melanoma Research Endowment (MD

ix

Anderson), the Sandra and Thomas Usher/Frances and James McGlothlinendowments (University of Pittsburgh Cancer Institute at UPMC Hillman);and grants from the National Health and Medical Research Council ofAustralia and the Victorian Cancer Agency. The Melanoma Institute Australiadatabase and its data managers have been supported by the Melanoma Foun-dation of the University of Sydney.

Our families have provided vital emotional support and graciously forfeitedsome of their time with us to the additional effort required to complete thisbook. As only they know, considerable personal sacrifices were required thatthey willingly made. For this reason, we have chosen to dedicate this bookto them.

This edition is also dedicated to the memory of Drs. Donald L. Morton andSeng-jaw Soong. Dr. Morton was a visionary leader as a clinical investigator inthe field of melanoma, a consummate clinician, and a dedicated teacher. Hewas a mentor and a friend to many of us. He contributed enormously to thefield over the years (see chapter “A History of Melanoma: From Hunter toMorton” for more details). Dr. Soong brought a unique statistical dimension tothe entire field of melanoma research and was an editor of in all five previouseditions of Cutaneous Melanoma. He provided a valuable, meticulouslyassembled statistical database that facilitated our understanding of the biologyand natural history of melanoma as well as treatment outcomes. Their legacylives on through the pages of this melanoma book, and we will miss them bothgreatly. Their impact will last for many years to come.

x Acknowledgments

Contents

Volume 1

Part I Biology and Immunology of Melanoma . . . . . . . . . . . . . . . 1

Biology of Melanocytes and Primary Melanoma . . . . . . . . . . . . . . 3M. Raza Zaidi, David E. Fisher, and Helen Rizos

Immunology of Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41Paul F. Robbins and Yong-Chen Lu

Biomarkers for Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73Dirk Schadendorf, Keith T. Flaherty, Lyn M. Duncan,Mohammed Kashani-Sabet, and Selma Ugurel

Part II Diagnosis and Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

Clinical Presentations of Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . 107Allan C. Halpern, Ashfaq A. Marghoob, Arthur J. Sober,Victoria Mar, and Michael A. Marchetti

Dermoscopy/Confocal Microscopy for Melanoma Diagnosis . . . . . 145Katie J. Lee, Nicola di Meo, Oriol Yélamos, Josep Malvehy,Iris Zalaudek, and H. Peter Soyer

Biopsy of Suspected Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195Noah Smith, Timothy M. Johnson, John W. Kelly, Arthur J. Sober,and Christopher Bichakjian

Lymphoscintigraphy in Patients with Melanoma . . . . . . . . . . . . . . 205Roger F. Uren, Omgo E. Nieweg, and John F. Thompson

Biopsy of the Sentinel Lymph Node . . . . . . . . . . . . . . . . . . . . . . . . . 239Mark B. Faries, Alistair J. Cochran, Michael McLemore,Vernon K. Sondak, Sandra L. Wong, and John F. Thompson

Melanoma Prognosis and Staging . . . . . . . . . . . . . . . . . . . . . . . . . . 271Emily Z. Keung, Charles M. Balch, John F. Thompson,John M. Kirkwood, Richard A. Scolyer, Vernon K. Sondak, andJeffrey E. Gershenwald

xi

Models for Predicting Melanoma Outcome . . . . . . . . . . . . . . . . . . . 299Lauren E. Haydu, Phyllis A. Gimotty, Daniel G. Coit,John F. Thompson, and Jeffrey E. Gershenwald

Part III Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315

Classification and Histopathology of Melanoma . . . . . . . . . . . . . . . 317Richard A. Scolyer, Victor G. Prieto, David E. Elder,Alistair J. Cochran, and Martin C. Mihm Jr.

Molecular Pathology and Genomics of Melanoma . . . . . . . . . . . . . 381Klaus Georg Griewank, Rajmohan Murali, and Thomas Wiesner

Part IV Epidemiology and Prevention of Melanoma . . . . . . . . . 423

Clinical Epidemiology of Melanoma . . . . . . . . . . . . . . . . . . . . . . . . 425Catherine M. Olsen and David C. Whiteman

Molecular Epidemiology of Melanoma . . . . . . . . . . . . . . . . . . . . . . 451Anne E. Cust, Hensin Tsao,Marianne Berwick, Graham J.Mann, andMark M. Iles

Clinical Genetics and Risk Assessment of Melanoma . . . . . . . . . . . 471V. Bataille, Hensin Tsao, S. Raimondi, and S. Gandini

Acquired Precursor Lesions and Phenotypic Markersof Increased Risk for Cutaneous Melanoma . . . . . . . . . . . . . . . . . . 501Cristian Navarrete-Dechent, Alon Scope, Hensin Tsao,Nadeem G. Marghoob, Arthur J. Sober, and Ashfaq A. Marghoob

Melanoma Prevention and Screening . . . . . . . . . . . . . . . . . . . . . . . . 525Susan M. Swetter, Alan C. Geller, Sancy A. Leachman,JohnM. Kirkwood, Alexander Katalinic, and Jeffrey E. Gershenwald

Part V Management of Primary Melanoma andLocoregional Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 571

Treatment of Primary Melanomas . . . . . . . . . . . . . . . . . . . . . . . . . . 573John F. Thompson, Michael A. Henderson, Gabrielle Williams, andMerrick I. Ross

Reconstructive Options Following Surgery of PrimaryMelanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595MarcMoncrieff, Brian Gastman, Rogerio Izar Neves, Howard Peach,and Anthony P. Tufaro

Axillary and Epitrochlear Lymph Node Dissection forMelanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 657Sandra L. Wong, Douglas S. Tyler, Charles M. Balch,John F. Thompson, and Kelly M. McMasters

xii Contents

Inguinofemoral, Iliac/Obturator, and PoplitealLymphadenectomy for Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . 669Keith A. Delman, Lesly A. Dossett, Clara R. Farley,Kelly M. McMasters, and Omgo E. Nieweg

Neck Dissection and Parotidectomy for Melanoma . . . . . . . . . . . . . 689Brian Gastman, Rebecca Knackstedt, Ryan P. Goepfert,Baran Sumer, Ashok Shaha, and Michael E. Kupferman

Local and Recurrent Regional Metastases of Melanoma . . . . . . . . 705Matthew C. Perez, Kenneth K. Tanabe, Charlotte E. Ariyan,John T. Miura, Dorotea Mutabdzic, Jeffrey M. Farma, andJonathan S. Zager

Radiotherapy for Primary and Regional Melanoma . . . . . . . . . . . 739Angela M. Hong and Graham Stevens

Adjuvant Systemic Therapy for High-Risk MelanomaPatients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 747Yana G. Najjar, Ryan Massa, Vernon K. Sondak,Alexander M. M. Eggermont, Helen Gogas, and John M. Kirkwood

Neoadjuvant Systemic Therapy for High-Risk MelanomaPatients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 767Emily Z. Keung, Rodabe N. Amaria, Vernon K. Sondak,Merrick I. Ross, John M. Kirkwood, and Jennifer A. Wargo

Hyperthermic Regional Perfusion for Melanoma ofthe Limbs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795Douglas S. Tyler, Douglas L. Fraker, Harald J. Hoekstra, andH. Richard Alexander Jr.

Isolated Limb Infusion for Melanoma . . . . . . . . . . . . . . . . . . . . . . . 827Georgia Marie Beasley, John T. Miura, Jonathan S. Zager,Douglas S. Tyler, John F. Thompson, and Hidde M. Kroon

Surveillance and Follow-Up of Melanoma Patients . . . . . . . . . . . . 851Rachael L. Morton, Anne Brecht Francken, and Mbathio Dieng

Local Melanoma Recurrence, Satellitosis, and In-transitMetastasis: Incidence, Outcomes, and Selection of TreatmentOptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 867John F. Thompson, Nicola Mozzillo, and Merrick I. Ross

Volume 2

Part VI Uncommon Presentations of Melanoma . . . . . . . . . . . . . 895

Acral Lentiginous Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 897Yukiko Teramoto, Hector Martinez-Said, Jun Guo, and Claus Garbe

Contents xiii

Lentigo Maligna Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 925Cristian Navarrete-Dechent, Kelly C. Nelson, Anthony M. Rossi,Erica H. Lee, Christopher A. Barker, Kishwer S. Nehal, andSusan M. Swetter

Mucosal Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 953Michael A. Henderson, Charles M. Balch, Claus Garbe,Alexander N. Shoushtari, Bin Lian, Chuanliang Cui, and Jun Guo

Melanoma in Children and Teenagers . . . . . . . . . . . . . . . . . . . . . . . 969Ines B. Brecht, Ira J. Dunkel, and Claus Garbe

Pregnancy and the Use of Hormones in Melanoma Patients . . . . . 983Alexandra Gangi, Robyn Saw, and Vernon K. Sondak

Diagnosis of Stage IV Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . 997Ahmad A. Tarhini, Sanjiv S. Agarwala, Arjun Khunger,Richard L. Wahl, and Charles M. Balch

Part VII Management of Distant Metastases . . . . . . . . . . . . . . . . 1045

Evolving Role of Chemotherapy-Based Treatment of MetastaticMelanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1047Sanjiv S. Agarwala, Mark R. Middleton, and Michael B. Atkins

Targeted Therapies for BRAF-Mutant Metastatic Melanoma . . . . 1067Douglas B. Johnson, Reinhard Dummer, Keith T. Flaherty, andKeiran S. Smalley

Molecularly Targeted Therapy for Patients with BRAFWild-Type Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1087Sunandana Chandra, Grant A. McArthur, and Jeffrey Sosman

Cytokines (IL-2, IFN, GM-CSF, etc.) Melanoma . . . . . . . . . . . . . . 1109John B. A. G. Haanen, Ryan J. Sullivan, John M. Kirkwood,Michael B. Atkins, and Douglas J. Schwartzentruber

Checkpoint Inhibitors in the Treatment of MetastaticMelanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1141Alison Weppler, Peter Lau, and Grant A. McArthur

Novel Immunotherapies and Novel Combinations ofImmunotherapy for Metastatic Melanoma . . . . . . . . . . . . . . . . . . . 1165Daniel J. Olson, Rodolfo Gutierrez, Salah Eddine Bentebibel,Randy F. Sweis, Omid Hamid, Adi Diab, Douglas B. Johnson, andJason J. Luke

Managing Checkpoint Inhibitor Symptoms and Toxicity forMetastatic Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1187Anna Pavlick and Jeffrey Weber

Sequencing and Combinations of Molecularly Targeted andImmunotherapy for BRAF-Mutant Melanoma . . . . . . . . . . . . . . . . 1215Paolo A. Ascierto and Michael B. Atkins

xiv Contents

Melanoma Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1243Peter Hersey, Stuart J. Gallagher, John M. Kirkwood, andJonathan Cebon

Cellular Therapy for Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1267Udai S. Kammula and Michael T. Lotze

Systemic Therapy for Mucosal, Acral, and Uveal Melanoma . . . . 1301Suthee Rapisuwon, Yong Qin, Jason Roszik, Fernando Carapeto,Sapna Patel, and Richard D. Carvajal

Dermatological Complications of Systemic Therapiesfor Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1337Egle Ramelyte, Reinhard Dummer, Cristina Libenciuc,Gregory S. Phillips, Mario E. Lacouture, and Caroline Robert

Surgical Management of Distant Melanoma Metastases . . . . . . . . 1359John F. Thompson, Mark B. Faries, Erica B. Friedman,Jeffrey E. Lee, and Charles M. Balch

Radiotherapy for Distant Melanoma Metastases . . . . . . . . . . . . . . 1403Angela M. Hong and Christopher A. Barker

Melanoma Brain Metastases: Unique Biology and Implicationsfor Systemic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1421Kim Margolin, Michael Davies, Harriet Kluger, and Hussein Tawbi

Part VIII History of Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1455

A History of Melanoma: From Hunter to Morton . . . . . . . . . . . . . 1457Arthur J. Sober, Charles M. Balch, John F. Thompson, andJohn M. Kirkwood

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1477

Contents xv

Editorial Board

Charles M. Balch Department of Surgical Oncology, The University ofTexas MD Anderson Cancer Center, Houston, TX, USA

Michael B. Atkins Georgetown Lombardi Comprehensive Cancer Center,Washington, DC, USA

Department of Oncology, Georgetown University Medical Center, Washing-ton, DC, USA

Claus Garbe Centre for Dermatooncology, Department of Dermatology,Eberhard Karls University, Tuebingen, Germany

Jeffrey E. Gershenwald Departments of Surgical Oncology and CancerBiology, Melanoma and Skin Center, The University of Texas MD AndersonCancer Center, Houston, TX, USA

Allan C. Halpern Dermatology Service, Department of Medicine, MemorialSloan Kettering Cancer Center, New York, NY, USA

JohnM.Kirkwood Departments ofMedicine,Dermatology, and TranslationalScience, University of Pittsburgh and UPMCHillmanCancer Center, Pittsburgh,PA, USA

Grant A. McArthur Divisions of Cancer Medicine and Research, PeterMacCallum Cancer Centre, Melbourne, VIC, Australia

University of Melbourne, Parkville, VIC, Australia

John F. Thompson Melanoma Institute Australia, Faculty of Medicine andHealth, The University of Sydney, Sydney, NSW, Australia

Department of Melanoma and Surgical Oncology, Royal Prince AlfredHospital, Sydney, NSW, Australia

Arthur J. Sober Department of Dermatology, Massachusetts General Hos-pital, Harvard Medical School, Boston, MA, USA

xvii

Contributors

Sanjiv S. Agarwala Department of Medical Oncology, St Luke’s UniversityHospital and Health Network, Easton, PA, USA

Temple University School of Medicine, St. Luke’s University Hospital, Beth-lehem, PA, USA

H. Richard Alexander Jr. Departments of Surgery, Biochemistry andMolecular Biology and Pathology, Rutgers Cancer Institute of New Jersey,New Brunswick, NJ, USA

Rodabe N. Amaria Department of Melanoma Medical Oncology, The Uni-versity of Texas MD Anderson Cancer Center, Houston, TX, USA

Charlotte E. Ariyan Memorial Sloan-Kettering Cancer Center, New York,NY, USA

Paolo A. Ascierto Unit of Melanoma, Cancer Immunotherapy and Develop-ment Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale,Naples, Italy

Michael B. Atkins Georgetown Lombardi Comprehensive Cancer Center,Washington, DC, USA

Department of Oncology, Georgetown University Medical Center, Washing-ton, DC, USA

Charles M. Balch Department of Surgical Oncology, The University ofTexas MD Anderson Cancer Center, Houston, TX, USA

Christopher A. Barker Department of Radiation Oncology, Memorial SloanKettering Cancer Center, New York, NY, USA

V. Bataille Department of Twin Research and Genetic Epidemiology, King’sCollege London | KCL, London, UK

Georgia Marie Beasley Department of Surgery, Duke University MedicalCenter, Durham, NC, USA

Salah Eddine Bentebibel Department of Melanoma Medical Oncology,Division of Cancer Medicine, MD Anderson Cancer Center, The Universityof Texas, Houston, TX, USA

xix

Marianne Berwick Department of Internal Medicine, University of NewMexico Cancer Center, University of New Mexico, Albuquerque, NM, USA

Christopher Bichakjian Department of Dermatology, University of Michi-gan, Ann Arbor, MI, USA

Ines B. Brecht Department of Pediatric Oncology and Hematology, EberhardKarls University, Tuebingen, Germany

Fernando Carapeto Department of Melanoma Medical Oncology, Divisionof Cancer Medicine, The University of Texas MD Anderson Cancer Center,Houston, TX, USA

Richard D. Carvajal Department of Medicine, Division of Hematology/Oncology, Columbia University Medical Center; Herbert Irving Comprehen-sive Cancer Center, New York, NY, USA

Jonathan Cebon Cancer and Neurosciences, Clinical Services Unit, AustinHealth, Melbourne, VIC, Australia

Cancer Immunobiology Program, Olivia Newton-John Cancer Research Insti-tute, LaTrobe University, Heidelberg, VIC, Australia

Sunandana Chandra Division of Hematology Oncology, NorthwesternUniversity Feinberg School of Medicine, Chicago, IL, USA

Alistair J. Cochran Departments of Pathology, Laboratory Medicine andSurgery, David Geffen School of Medicine at UCLA and Jonsson Compre-hensive Cancer Center, UCLA, Los Angeles, CA, USA

Daniel G. Coit Department of Surgery, Memorial Sloan Kettering CancerCenter, New York, NY, USA

Chuanliang Cui Department of Renal Cancer and Melanoma, Key Labora-tory of Carcinogenesis and Translational Research, Ministry of Education,Peking University Cancer Hospital and Institute, Beijing, China

Anne E. Cust Cancer Epidemiology and Prevention Research, SydneySchool of Public Health, The University of Sydney, Sydney, NSW, Australia

Melanoma Institute Australia, The University of Sydney, Sydney, NSW,Australia

Michael Davies Department ofMelanomaMedical Oncology, Department ofSystems Biology, Department of Translational Molecular Pathology, Depart-ment of Investigational Cancer Therapeutics, Division of Cancer Medicine,The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Keith A. Delman Division of Surgical Oncology, Department of Surgery,Emory University School of Medicine, Atlanta, GA, USA

Nicola di Meo Department of Dermatology and Venereology, University ofTrieste, Trieste, Italy

xx Contributors

Adi Diab Department of Melanoma Medical Oncology, Division of CancerMedicine, MD Anderson Cancer Center, The University of Texas, Houston,TX, USA

Mbathio Dieng NHMRC Clinical Trials Centre, The University of Sydney,Camperdown, NSW, Australia

Lesly A. Dossett Division of Surgical Oncology, Department of Surgery,University of Michigan, Ann Arbor, MI, USA

Reinhard Dummer Department of Dermatology, University HospitalZurich, Zurich, Switzerland

Department of Dermatology, University of Zurich, Zurich, Switzerland

Lyn M. Duncan Department of Pathology, Massachusetts General Hospitaland Harvard Medical School, Boston, MA, USA

Ira J. Dunkel Department of Pediatrics, Memorial Sloan-Kettering CancerCenter, New York, NY, USA

AlexanderM.M. Eggermont Gustave Roussy Cancer Campus Grand Paris,Villejuif, France

David E. Elder Department of Pathology and LaboratoryMedicine, Hospitalof the University of Pennsylvania, Philadelphia, PA, USA

Mark B. Faries Cedars Sinai Medical Center, The Angeles Clinic andResearch Institute, Los Angeles, CA, USA

Clara R. Farley Division of Surgical Oncology, Department of Surgery,Emory University School of Medicine, Atlanta, GA, USA

Jeffrey M. Farma Department of Surgical Oncology, Fox Chase CancerCenter, Philadelphia, PA, USA

David E. Fisher Department of Dermatology, Harvard/MGH CutaneousBiology Research Center, and Melanoma Program, MGH Cancer Center,Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Keith T. Flaherty Department of Medicine, Massachusetts General Hospital,Boston, MA, USA

Cancer Center, Massachusetts General Hospital, Boston, MA, USA

Douglas L. Fraker Department of Surgery, Division of Endocrine andOncologic Surgery, Hospital of the University of Pennsylvania, Philadelphia,PA, USA

Anne Brecht Francken Centre of Oncology, Isala, Zwolle, Netherlands

Erica B. Friedman Division of Surgical Oncology, New York University,School of Medicine, NY, USA

Stuart J. Gallagher Melanoma Research, Central Clinical School, Cente-nary Institute, University of Sydney, Camperdown, Sydney, NSW, Australia

Melanoma Institute Australia, Crows Nest, NSW, Australia

Contributors xxi

S. Gandini Department of Experimental Oncology, European Institute ofOncology, Milan, Italy

Alexandra Gangi Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Claus Garbe Centre for Dermatooncology, Department of Dermatology,Eberhard Karls University, Tuebingen, Germany

Brian Gastman Department of Plastic Surgery, Cleveland Clinic, LernerResearch Institute, Cleveland, OH, USA

Alan C. Geller Department of Social and Behavioral Sciences, Harvard THChan School of Public Health, Boston, MA, USA

Jeffrey E. Gershenwald Departments of Surgical Oncology and CancerBiology, Melanoma and Skin Center, The University of Texas MD AndersonCancer Center, Houston, TX, USA

Phyllis A. Gimotty Department of Biostatistics, Epidemiology and Informat-ics, Perelman School of Medicine, The University of Pennsylvania, Philadel-phia, PA, USA

Ryan P. Goepfert Department of Head and Neck Surgery, UTMDAndersonCancer Center, Houston, TX, USA

Helen Gogas First Department of Medicine, Laiko Hospital, University ofAthens, Athens, Greece

Klaus Georg Griewank Department of Dermatology – University Hospital,University Duisburg-Essen, Essen, Germany

Dermatopathologie bei Mainz, Nieder-Olm, Germany

Jun Guo Department of Renal Cancer and Melanoma, Key Laboratory ofCarcinogenesis and Translational Research, Ministry of Education, PekingUniversity Cancer Hospital and Institute, Beijing, China

Rodolfo Gutierrez Hematology and Oncology, Translational Research andImmunotherapy, Melanoma Therapeutics, The Angeles Clinic and ResearchInstitute, Los Angeles, CA, USA

John B. A. G. Haanen Antoni van Leeuwenhoek Hospital, Division ofMedical Oncology, The Netherlands Cancer Institute, Amsterdam, TheNetherlands

Allan C. Halpern Dermatology Service, Department of Medicine, MemorialSloan Kettering Cancer Center, New York, NY, USA

Omid Hamid Translational Research and Immunotherapy, Melanoma Ther-apeutics, The Angeles Clinic and Research Institute, Los Angeles, CA, USA

Lauren E. Haydu Department of Surgical Oncology, The University ofTexas MD Anderson Cancer Center, Houston, TX, USA

Michael A. Henderson Division of Cancer Surgery, Peter MacCallum Can-cer Centre, Melbourne, VIC, Australia

xxii Contributors

Peter Hersey Melanoma Research, Central Clinical School, Centenary Insti-tute, University of Sydney, Camperdown, Sydney, NSW, Australia

Melanoma Institute Australia, Crows Nest, NSW, Australia

Harald J. Hoekstra Surgical Oncology Department of Surgery, Universityof Groningen, Groningen, The Netherlands

Angela M. Hong Radiation Oncology, Melanoma Institute Australia, TheUniversity of Sydney, North Sydney, NSW, Australia

MarkM. Iles Leeds Institute for Data Analytics, University of Leeds, Leeds,UK

Douglas B. Johnson Division of Hematology/Oncology Department ofMedicine, Vanderbilt University Medical Center and Vanderbilt Ingram Can-cer Center, Nashville, TN, USA

Timothy M. Johnson Department of Dermatology, University of Michigan,Ann Arbor, MI, USA

Udai S. Kammula Solid Tumor Cell Therapy Program, Division of SurgicalOncology, University of Pittsburgh, UPMC Hillman Cancer Center, Pitts-burgh, PA, USA

Mohammed Kashani-Sabet Center for Melanoma Research and Treatment,California Pacific Medical Center Research Institute, San Francisco, CA, USA

Alexander Katalinic Department of Medicine, University Lübeck, Institutefor Social Medicine and Epidemiology, Lübeck, Schleswig-Holstein,Germany

John W. Kelly Victorian Melanoma Service, The Alfred Hospital, Mel-bourne, VIC, Australia

Emily Z. Keung Department of Surgical Oncology, The University of TexasMD Anderson Cancer Center, Houston, TX, USA

Arjun Khunger Department of Hematology and Oncology, Taussig CancerCenter, Cleveland Clinic, Cleveland, OH, USA

John M. Kirkwood Departments of Medicine, Dermatology, and Transla-tional Science, University of Pittsburgh and UPMC Hillman Cancer Center,Pittsburgh, PA, USA

Harriet Kluger Internal Medicine, Medical Oncology; Skin DiseasesResearch Center; Dermatology, SPORE in Skin Cancer; Urology, UrologicOncology; Yale Cancer Center, Yale Medical School, New Haven, CT, USA

Rebecca Knackstedt Department of Plastic Surgery, Cleveland Clinic,Cleveland, OH, USA

Hidde M. Kroon Melanoma Institute Australia, The University of Sydney,Sydney, NSW, Australia

Department of General Surgery, The University of Adelaide, Royal AdelaideHospital, Adelaide, SA, Australia

Contributors xxiii

Michael E. Kupferman Department of Head and Neck Surgery,The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Mario E. Lacouture Department ofMedicine, Dermatology Service, Memo-rial Sloan Kettering Cancer Center, New York, NY, USA

Peter Lau Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Sancy A. Leachman Department of Dermatology, Oregon Health and Sci-ence University, Portland, OR, USA

Erica H. Lee Dermatology Service, Memorial Sloan Kettering Cancer Cen-ter, New York, NY, USA

Jeffrey E. Lee Department of Surgical Oncology, The University of TexasMD Anderson Cancer Center, Houston, TX, USA

Katie J. Lee Dermatology Research Centre, The University of Queensland,The University of Queensland Diamantina Institute, Brisbane, QLD, Australia

Bin Lian Department of Renal Cancer and Melanoma, Key Laboratory ofCarcinogenesis and Translational Research, Ministry of Education, PekingUniversity Cancer Hospital and Institute, Beijing, China

Cristina Libenciuc Oncology Department, Dermatology Service, GustaveRoussy Cancer Campus, Villejuif-Grand Paris, France

Michael T. Lotze Department of Surgery, Immunology, and Bioengineering,University of Pittsburgh, UPMCHillman Cancer Center, Pittsburgh, PA, USA

Yong-Chen Lu Surgery Branch, National Cancer Institute, National Insti-tutes of Health, Bethesda, MD, USA

Jason J. Luke Department of Medicine, University of Pittsburgh and UPMCHillman Cancer Center, Pittsburgh, PA, USA

Josep Malvehy Department of Dermatology, Melanoma Unit, HospitalClínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain

Graham J. Mann Melanoma Institute Australia, The University of Sydney,Sydney, NSW, Australia

Centre for Cancer Research, Westmead Institute for Medical Research, TheUniversity of Sydney, Sydney, NSW, Australia

Victoria Mar Victorian Melanoma Service, Alfred Hospital, Melbourne,VIC, Australia

Michael A. Marchetti Dermatology Service, Department of Medicine,Memorial Sloan Kettering Cancer Center, New York, NY, USA

Ashfaq A. Marghoob Dermatology Service, Department of Medicine,Memorial Sloan Kettering Cancer Center, New York, NY, USA

Nadeem G. Marghoob New York Institute of Technology College of Oste-opathic Medicine, OMSIII, Old Westbury, New York, NY, USA

xxiv Contributors

Kim Margolin Departments of Medical Oncology and TherapeuticsResearch, City of Hope National Medical Center, Duarte, CA, USA

Hector Martinez-Said Melanoma Clinic, Surgical Oncology, InstitutoNacional de Cancerología, México City, Mexico

Ryan Massa Hematology/Oncology, University of Pittsburgh Medical Cen-ter, Pittsburgh, PA, USA

Grant A. McArthur Divisions of Cancer Medicine and Research, PeterMacCallum Cancer Centre, Melbourne, VIC, Australia

University of Melbourne, Parkville, VIC, Australia

Michael McLemore Department of Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Kelly M. McMasters Department of Surgery, University of LouisvilleSchool of Medicine, Louisville, KY, USA

MarkR.Middleton Department of Oncology, University of Oxford, Oxford,UK

Martin C. Mihm Jr. Dermatology Department, Brigham and Women’sHospital, Harvard Medical School, Boston, MA, USA

John T. Miura Department of Cutaneous Oncology, Moffitt Cancer Center,Tampa, FL, USA

Marc Moncrieff Department of Plastic and Reconstructive Surgery, Norfolk& Norwich University Hospital, Norwich, UK

Rachael L. Morton NHMRC Clinical Trials Centre, The University ofSydney, Camperdown, NSW, Australia

Nicola Mozzillo Department Melanoma and Soft Tissue, Istituto Nazionaledei Tumori, Napoli, Italy

Rajmohan Murali Department of Pathology, Memorial Sloan KetteringCancer Center, New York, NY, USA

Dorotea Mutabdzic Department of Surgical Oncology, Fox Chase CancerCenter, Philadelphia, PA, USA

Yana G. Najjar Division of Hematology-Oncology, UPMC Hillman CancerCenter, Pittsburgh, PA, USA

Cristian Navarrete-Dechent Melanoma and Skin Cancer Unit, Departmentof Dermatology, Facultad de Medicina, Pontificia Universidad Catolica deChile, Santiago, Chile

Dermatology Service, Memorial Sloan Kettering Cancer Center, New York,NY, USA

Kishwer S. Nehal Dermatology Service, Memorial Sloan Kettering CancerCenter, New York, NY, USA

Contributors xxv

Kelly C. Nelson Department of Dermatology, MD Anderson Cancer Center,The University of Texas, Houston, TX, USA

Rogerio Izar Neves Department of Plastic Surgery, College of Medicine,Penn State University, Hershey, PA, USA

Omgo E. Nieweg Melanoma Institute Australia, Department of Surgery, TheUniversity of Sydney Central Clinical School, Royal Prince Alfred Hospital,Department of Melanoma and Surgical Oncology, Sydney, NSW, Australia

Catherine M. Olsen Cancer Control Group, QIMR Berghofer MedicalResearch Institute, Brisbane, QLD, Australia

Faculty ofMedicine, The University of Queensland, Brisbane, QLD, Australia

Daniel J. Olson Department of Medicine, Section of Hematology/Oncology,The University of Chicago, Chicago, IL, USA

Sapna Patel Department of Melanoma Medical Oncology, Division of Can-cer Medicine, The University of TexasMDAnderson Cancer Center, Houston,TX, USA

Anna Pavlick Laura and Isaac Perlmutter Cancer Center, NYU LangoneHealth, New York, NY, USA

Howard Peach Department of Plastic and Reconstructive Surgery, LeedsTeaching Hospitals NHS Trust, Leeds, UK

Matthew C. Perez Department of Cutaneous Oncology, Moffitt CancerCenter, Tampa, FL, USA

Gregory S. Phillips Department of Medicine, Dermatology Service, Memo-rial Sloan Kettering Cancer Center, New York, NY, USA

Victor G. Prieto Departments of Pathology and Dermatology, The Univer-sity of Texas MD Anderson Cancer Center, Houston, TX, USA

Yong Qin Department of Melanoma Medical Oncology, Division of CancerMedicine, The University of Texas MD Anderson Cancer Center, Houston,TX, USA

S. Raimondi Department of Experimental Oncology, European Institute ofOncology, Milan, Italy

Egle Ramelyte Dermatology Department, University Hospital Zurich,Zurich, Switzerland

Suthee Rapisuwon Department of Medicine, Division of Hematology/Oncology, Georgetown University; Lombardi Comprehensive Cancer Center,Washington, DC, USA

Helen Rizos Department of Biomedical Sciences, Faculty of Medicine andHealth Sciences, Macquarie University, and Melanoma Institute Australia,Sydney, NSW, Australia

xxvi Contributors

Paul F. Robbins Surgery Branch, National Cancer Institute, National Insti-tutes of Health, Bethesda, MD, USA

Caroline Robert Oncology Department, Dermatology Service, GustaveRoussy Cancer Campus, Villejuif-Grand Paris, France

Université Paris-Sud, Kremlin Bicêtre, France

Merrick I. Ross Department of Surgical Oncology, The University of TexasMD Anderson Cancer Center, Houston, TX, USA

Anthony M. Rossi Dermatology Service, Memorial Sloan Kettering CancerCenter, New York, NY, USA

Jason Roszik Department of Melanoma Medical Oncology, Division ofCancer Medicine, The University of Texas MD Anderson Cancer Center,Houston, TX, USA

Robyn Saw Melanoma Institute Australia, University of Sydney, RoyalPrince Alfred Hospital, Sydney, NSW, Australia

Dirk Schadendorf Department of Dermatology, University Hospital Essen,Essen, Germany

German Cancer Consortium, Heidelberg, Germany

Douglas J. Schwartzentruber Indiana University Health, Bloomington, IN,USA

Richard A. Scolyer Tissue Pathology and Diagnostic Oncology, RoyalPrince Alfred Hospital, Sydney, NSW, Australia

Melanoma Institute Australia, Central Clinical School, The University ofSydney, Sydney, NSW, Australia

Alon Scope Medical Screening Institute, Sheba Medical Center, Ramat Gan,Israel

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Ashok Shaha Department of Otolaryngology, Memorial Sloan KetteringCancer Institute, New York, NY, USA

Alexander N. Shoushtari Memorial Sloan Kettering Cancer Center, WeillCornell Medical College, New York, NY, USA

Keiran S. Smalley Tumor Biology, H. Lee Moffitt Cancer Center andResearch Institute, Tampa, FL, USA

Noah Smith Department of Dermatology, University of Michigan, AnnArbor, MI, USA

Arthur J. Sober Department of Dermatology, Massachusetts General Hos-pital, Harvard Medical School, Boston, MA, USA

Vernon K. Sondak Department of Cutaneous Oncology, H. Lee MoffittCancer Center, Tampa, FL, USA

Contributors xxvii

Jeffrey Sosman Division of Hematology Oncology, Northwestern Univer-sity Feinberg School of Medicine, Chicago, IL, USA

H. Peter Soyer Dermatology Research Centre, The University of Queens-land, The University of Queensland Diamantina Institute, Brisbane, QLD,Australia

Dermatology Department, Princess Alexandra Hospital, Brisbane, QLD,Australia

Graham Stevens Radiation Oncology, Orange General Hospital, Orange,NSW, Australia

Bathurst Rural Clinical School, School of Medicine, Western Sydney Univer-sity, Bathurst, NSW, Australia

Ryan J. Sullivan Massachusetts General Hospital, Boston, MA, USA

Baran Sumer Department of Otolaryngology, UT Southwestern MedicalCenter, Dallas, TX, USA

Randy F. Sweis The University of Chicago, Department of Medicine, Sec-tion of Hematology / Oncology, Chicago, IL, USA

Susan M. Swetter Department of Dermatology, Pigmented Lesion and Mel-anoma Program, Stanford University Medical Center and Cancer Institute,Stanford, CA, USA

Dermatology Service, Veterans Affairs Palo Alto Health Care System, PaloAlto, CA, USA

Kenneth K. Tanabe Division of Surgical Oncology, Department of Surgery,Massachusetts General Hospital Cancer Center, Boston, MA, USA

Ahmad A. Tarhini Department of Cutaneous Oncology, H. Lee MoffittCancer Center and Research Institute, Tampa, FL, USA

Hussein Tawbi Department of Melanoma Medical Oncology, Department ofSystems Biology, Department of Translational Molecular Pathology, Depart-ment of Investigational Cancer Therapeutics, Division of Cancer Medicine,The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Yukiko Teramoto Department of Skin Oncology/Dermatology, SaitamaMedical University International Medical Center, Saitama, Japan

John F. Thompson Melanoma Institute Australia, Faculty of Medicine andHealth, The University of Sydney, Sydney, NSW, Australia

Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hos-pital, Sydney, NSW, Australia

Hensin Tsao Skin Cancer Genetics Laboratory/Wellman Center for Photo-medicine, Melanoma and Pigmented Lesion Center/Department of Dermatol-ogy/Melanoma Genetics Program, Massachusetts General Hospital, CancerCenter, Harvard Medical School, Boston, MA, USA

xxviii Contributors

Anthony P. Tufaro Department of Surgery, Division of Plastic Surgery andSurgical Oncology, The University of Oklahoma Health Science Center,Oklahoma City, OK, USA

Douglas S. Tyler Department of Surgery, University of Texas MedicalBranch, Galveston, TX, USA

Department of Surgery, Duke University Medical Center, Durham, NC, USA

Selma Ugurel Department of Dermatology, University Hospital Essen,Essen, Germany

Roger F. Uren Melanoma Institute Australia, The University of Sydney,Sydney, NSW, Australia

Alfred Nuclear Medicine and Ultrasound, RPAH Medical Centre, Newtown,NSW, Australia

Central Clinical Schools, The University of Sydney, Sydney, NSW, Australia

Richard L. Wahl Mallinckrodt Institute of Radiology, Washington Univer-sity School of Medicine, St. Louis, MO, USA

Jennifer A. Wargo Department of Surgical Oncology, The University ofTexas MD Anderson Cancer Center, Houston, TX, USA

Jeffrey Weber Laura and Isaac Perlmutter Cancer Center, NYU LangoneHealth, New York, NY, USA

Alison Weppler Peter MacCallum Cancer Centre, Melbourne, VIC,Australia

David C. Whiteman Cancer Control Group, QIMR Berghofer MedicalResearch Institute, Brisbane, QLD, Australia

Thomas Wiesner Department of Dermatology, Medical University ofVienna, Vienna, Austria

GabrielleWilliams Melanoma Institute Australia, The University of Sydney,Sydney, NSW, Australia

Sandra L. Wong Department of Surgery, Geisel School of Medicine atDartmouth-Hitchcock Medical Center, Lebanon, NH, USA

Oriol Yélamos Department of Dermatology,Melanoma Unit, Hospital Clínicde Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain

Jonathan S. Zager Department of Cutaneous Oncology, Moffitt CancerCenter, Tampa, FL, USA

M. Raza Zaidi Fels Institute for Cancer Research and Molecular Biology,Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA

Iris Zalaudek Department of Dermatology and Venereology, University ofTrieste, Trieste, Italy

Contributors xxix