Current Management of Melanoma 9783030453466, 9783030453473

Table of contents :
Foreword
Preface
Contents
Contributors
1: The History of Melanoma: From Incas to the Third Millennium
1.1 From Ancient Times to the Beginning of the Twentieth Century
1.2 Recent History
1.3 The Present
1.4 Conclusion
References
2: Epidemiology, Prevention and Clinical Diagnosis of Melanoma
2.1 Epidemiology
2.2 Prevention
2.3 Risk Factors
2.4 Clinical Features and Growth Pattern of Primary Melanoma
2.5 Diagnosis
References
3: Treatment of Primary Melanoma
3.1 Current Skin Biopsy for Suspected Melanoma
3.1.1 Excisional Biopsy
3.1.2 Incisional Biopsy
3.2 Surgery: Wide Local Excision
3.2.1 Melanoma In Situ (pTis)
3.2.2 Invasive Melanoma (pT1–pT4)
3.3 Reconstruction Strategies after a Wide Excision
References
4: Histopathological Examination: The Keystone of Treatment of Melanoma
4.1 Primary Lesion
4.2 Histotype
4.3 Growth Phases
4.4 Breslow Thickness
4.5 Clark Level
4.6 Ulceration
4.7 Mitotic Index
4.8 Tumor-Infiltrating Lymphocytes
4.9 Regression
4.10 Satellitosis
4.11 Lymphovascular Invasion
4.12 Neurotropism
4.13 Conclusion
References
5: Molecular Assessment in Patients with Melanoma: When and Why?
5.1 Introduction
5.2 Diagnostic Approaches
5.3 Indications for Molecular Assessment: Timing
5.4 Assessment of Non-BRAF Mutations
5.5 Indications on Molecular Assessment in Summary. Advantages and Disadvantages
5.6 Conclusion
References
6: New Melanoma Staging: Prognostic Factors
6.1 Introduction
6.2 The Eighth Edition of the AJCC Melanoma Staging System
6.3 Prognostic Biomarkers in the Metastatic Setting
References
7: The Role of Nuclear Medicine in Mapping Sentinel Lymph Nodes and Staging Metastatic Melanoma
7.1 Nuclear Medicine
7.2 Lymphoscintigraphy and Sentinel Lymph Node Biopsy
7.2.1 Clinical Indications
7.2.2 Efficacy and Value of Sentinel Lymph Node Biopsy
7.3 New Tracers for Sentinel Lymph Node
7.3.1 Blue Dyes
7.3.2 Radioactive Tracers
7.3.3 Fluorescent Agents
7.3.4 Hybrid Tracers
7.4 18F-FDG PET
7.5 Role of PET/CT in the Primary Staging of Malignant Melanoma
7.5.1 Early-Stage Melanoma
7.5.2 Advanced-Stage Melanoma
7.5.3 FDG-PET/CT in Follow-Up and Recurrence of Melanoma
7.5.4 FDG-PET/CT in the Evaluation of Therapeutic Response
7.6 PET/MRI
7.7 Conclusion
References
8: Methodological and Technological Evolution of Sentinel Lymph Node Biopsy: An 8-Year Experience
8.1 Introduction
8.2 Overall Clinical Experience
8.3 First Set of Patients
8.3.1 Technique
8.3.2 Pathologic Examination
8.3.3 Clinical and Pathological Findings
8.3.4 Comment
8.4 Second Set of Patients
8.4.1 Clinical and Pathological Findings
8.4.2 Comment
References
9: The Rationale of Sentinel Lymph Node Biopsy
9.1 Introduction
9.2 Balch’s Model
9.3 Morton and the Advent of Sentinel Lymph Node Biopsy
9.4 Randomized Clinical Trials and Meta-Analysis on Sentinel Lymph Node Biopsy
9.4.1 Multicenter Selective Lymphadenectomy Trial-I
9.4.2 Multicenter Selective Lymphadenectomy Trial-II
9.4.3 Dermatologic Cooperative Oncology Group Trial
9.5 Conclusions
References
10: Surgical Technique and Indications for Radical Dissection: Axilla
10.1 Introduction
10.1.1 Rationale
10.1.2 Aim
10.1.3 Indications
10.2 Anatomy
10.3 Surgical Technique
10.3.1 Positioning
10.3.2 Incision
10.3.3 Flap
10.3.4 Dissection
10.3.5 Closure
10.4 Complications
10.5 Quality Assurance
References
11: Surgical Technique and Indications of Radical Dissection: Groin
11.1 Introduction
11.2 Indications for Surgery
11.3 Prognostic Role of CLND After Positive SLNB
11.4 Therapeutic Role of CLND After Positive SLNB
11.5 Therapeutic Lymph Node Dissection (TLND)
11.6 Palliative Lymph Node Dissection
11.7 Technical Aspects
11.7.1 VIIOL Technique [28]
11.7.2 VIIOL Technique Discussion
References
12: Surgical Technique and Indications for Radical Dissection: Head and Neck
12.1 Introduction
12.1.1 Rationale and Aim
12.1.2 Indication
12.2 Anatomy
12.3 Surgical Technique
12.3.1 Comprehensive Neck Dissection
12.3.1.1 Positioning
12.3.1.2 Technique
12.3.2 Selective Neck Dissection
12.3.2.1 Technique
12.3.2.2 Selective Dissection of Level II–V
12.3.2.3 Supraclavicular Dissection
12.3.3 Parotidectomy
12.4 Complications
12.5 Quality Assurance
References
13: Management and Prevention of Lymphatic Complications of Radical Dissections
13.1 Introduction
13.2 Prevention
13.2.1 Tips and Tricks
13.3 Treatment of Complications
13.3.1 Lymphorrhea and Lymphocele
13.3.2 Lymphedema
References
14: Local Treatments of Locoregional Disease in the Setting of Melanoma
14.1 Introduction
14.2 Prognosis in Patients with ITM Disease
14.2.1 In-Transit Metastasis and Clinically Negative Regional Nodal Disease
14.2.2 In-Transit Metastasis and Clinically Positive Regional Nodal Disease
14.3 Locoregional Treatments
14.3.1 Laser
14.3.2 Intralesional Agents
14.3.2.1 PV-10
14.3.2.2 IL-2
14.3.2.3 T-VEC
14.3.3 Topical Agents
14.3.3.1 DPCP
14.3.3.2 Imiquimod
14.3.4 HILP and ILI
14.3.4.1 Repeated HILP
14.3.4.2 Minimally Invasive HILP [52]
14.3.4.3 Technique [52]
14.3.5 Electrochemotherapy
14.4 Conclusions
References
15: Role of Surgery for Metastatic Melanoma
15.1 Introduction
15.2 Collection of Biological Material
15.3 Treatment of Oligometastatic Disease
15.4 Treatment Beyond (Oligo)Progression
15.5 Palliative Treatment
15.6 Treatment of Urgencies and Emergencies
15.6.1 Complications of Surgical Relevance in Melanoma
References
16: Medical Treatment of Melanoma: Adjuvant and Neoadjuvant Therapies
16.1 Introduction
16.2 Interferon Alpha
16.3 Anti-CTLA-4: Ipilimumab
16.4 Anti-PD-1: Nivolumab and Pembrolizumab
16.5 Targeted Therapy: Vemurafenib and Dabrafenib Plus Trametinib
16.6 Algorithm of Adjuvant Treatment in Everyday Clinical Practice
16.7 Future Directions: Neoadjuvant Therapy
References
17: Systemic Treatment in Advanced Melanoma
17.1 Introduction
17.2 Immunotherapy
17.3 Targeted Therapies
17.4 Future Perspectives
17.5 Concluding Remarks
References
18: The Management of Melanoma Brain Metastases
18.1 The Puzzling Biology of Melanoma Brain Metastases
18.1.1 The Blood-Brain Barrier
18.1.2 Molecular Cascades, Neo-Angiogenesis, and Proliferation
18.1.3 The Microenvironment
18.1.4 Immunoregulatory Mechanisms
18.2 New Boundaries after the Revolution of Systemic Therapy
18.3 Targeted Therapies and MBM
18.4 Immunotherapy and MBM
18.5 Clinical Indications for Local Therapies
18.5.1 The Role of Neurosurgery in MBM
18.5.2 The Role of Whole-Brain Radiotherapy in MBM
18.5.3 The Role of Stereotactic Radiosurgery in MBM
References

Citation preview

Updates in Surgery

Ferdinando Cafiero Franco De Cian   Editors

Current Management of Melanoma

Updates in Surgery

The aim of this series is to provide informative updates on hot topics in the areas of breast, endocrine, and abdominal surgery, surgical oncology, and coloproctology, and on new surgical techniques such as robotic surgery, laparoscopy, and minimally invasive surgery. Readers will find detailed guidance on patient selection, performance of surgical procedures, and avoidance of complications. In addition, a range of other important aspects are covered, from the role of new imaging tools to the use of combined treatments and postoperative care. The topics addressed by volumes in the series Updates in Surgery have been selected for their broad significance in collaboration with the Italian Society of Surgery. Each volume will assist surgical residents and fellows and practicing surgeons in reaching appropriate treatment decisions and achieving optimal outcomes. The series will also be highly relevant for surgical researchers. More information about this series at http://www.springer.com/series/8147

Ferdinando Cafiero  •  Franco De Cian Editors

Current Management of Melanoma Foreword by Paolo De Paolis

Editors Ferdinando Cafiero Department of Surgery IRCCS Ospedale Policlinico San Martino Genoa Italy

Franco De Cian Department of Surgery IRCCS Ospedale Policlinico San Martino Genoa Italy

The publication and the distribution of this volume have been supported by the Italian Society of Surgery ISSN 2280-9848     ISSN 2281-0854 (electronic) Updates in Surgery ISBN 978-3-030-45346-6    ISBN 978-3-030-45347-3 (eBook) https://doi.org/10.1007/978-3-030-45347-3 © Springer Nature Switzerland AG 2021 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, 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. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Revision and editing: R. M. Martorelli, Scienzaperta (Novate Milanese, Italy) This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Foreword

The incidence rates of melanoma continue to rise in Italy and in most European countries. Therefore, it is a pleasure for me to introduce this high-quality and very useful book edited by Ferdinando Cafiero and Franco De Cian, focusing on the state of the art of melanoma clinical practice. Ferdinando and Franco, top experts in the field, engaged coworkers whose experience and scientific excellence have produced a complete collection of the most advanced aspects related to the epidemiology, diagnosis, and treatment of melanoma. Particular attention is paid to the role of nuclear medicine in mapping sentinel lymph nodes and staging metastatic melanoma, and to the sentinel lymph node biopsy. In effect, surgery for melanoma has recently changed, and completion lymph node dissection is now reserved for a limited number of patients. Furthermore, the book discusses the histopathological examination and prognostic factors. All the strictly surgical aspects related to primary melanoma and radical dissections are also extensively addressed. The volume is exhaustive and up-to-date in every aspect, and it represents a point of reference for both the very experienced and less experienced surgeons who deal with this condition. On behalf of the Italian Society of Surgery, I would like to thank all the eminent authors who collaborated in producing this important monograph. Turin, Italy September, 2020 

Paolo De Paolis President Italian Society of Surgery

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Preface

Melanoma is a neoplasm whose incidence is steadily increasing, especially in the Western world. It is certainly true that we tend to see more thin melanomas than in previous years, thanks to prevention and education campaigns for the population, which has come to see “the sun as a friend.” The use of sunscreens and the avoidance of exposure during the warmer hours, especially for subjects with certain phenotypes, have led to a significant reduction of advanced forms of melanoma, with an increase of diagnoses in the early stages. As in all cancers, early diagnosis implies a better prognosis and less invasive and more effective treatments. Regarding this monograph, we aimed to illustrate the most innovative aspects of surgical and medical therapy for melanoma, taking into consideration the criticality of some treatments, which have seen their indications change dramatically within a few years. The volume starts with a short history of melanoma to make clear that the first reports of melanoma had already appeared 2000 years ago and that the problem of lymph node involvement and wide excision of the primary lesion had already arisen in the 1800s. With regard to epidemiology, prevention, and clinical diagnosis, we have emphasized the importance of dermoscopy and digitalization of images to be able to have comparisons over time. One chapter, edited by plastic surgeons, concerns the removal of the primary lesion, excision margins, and types of reconstruction in certain districts such as the face, in which the removal can be more limited without implying a higher risk of oncological relapse. The contribution of pathological anatomy, both morphological and immunohistochemical, is fundamental for the prognostic factors related to infiltration and other features of melanoma. As far as diagnostic imaging is concerned, it seemed fundamental to include the role of nuclear medicine both in detecting distant metastases with positron-emission tomography (PET) and in identifying the sentinel lymph node also with the new tracers now available. Since this textbook is mainly concerned with surgical technique, we wished to discuss in detail the technique of sentinel lymph node biopsy, the rationale for selective dissection as well as its implications. The surgical technique is discussed with

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Preface

regard to axillary dissection, groin and iliac-obturator dissection, and neck dissection, which is perhaps the most demanding procedure. Aspects related to surgical complications have also been addressed, in particular early and late complications. The treatment of metastatic lymph nodes has changed radically in the last 3 years, with completion dissection becoming less and less frequent, to the benefit of medical therapies now recognized as less invasive and more effective. It was also felt appropriate to describe the treatment of metastatic lesions. The role of surgery for metastases is reserved for oligometastatic subjects or patients under medical treatment with solitary growing lesions. Additional surgical indications are represented by palliative treatment in urgent settings for bleeding, perforation, and occlusion, or just palliation in order to improve quality of life. As for medical treatment, it seemed essential that a monograph on melanoma should discuss neoadjuvant therapy. As with many other solid tumors, it is possible to give chemotherapy or, in this case, immunotherapy or target therapy, and then to perform a more conservative surgical procedure and continue medical therapy. Adjuvant medical therapy is also increasingly tailored. The last two chapters deal with the medical treatment of advanced forms with survival effects that were unimaginable until a few years ago. Finally, the local and systemic treatment of brain metastases, in particular the use of radiotherapy and gamma knife are discussed. At the end of this complex endeavor, we wish to thank first of all the authors who provided their contributions, often under pressure of time. A special thanks goes to Matteo Mascherini, who was the true soul of the project and the true glue that held the authors of this monograph together: he was always punctual and precise. Finally, a heartfelt thanks to all Springer’s staff and to our “Cerberus” Marco Martorelli. Good reading! Genoa, Italy Genoa, Italy September 2020

Ferdinando Cafiero Franco De Cian

Contents

1 The History of Melanoma: From Incas to the Third Millennium ��������   1 Ferdinando Cafiero, Matteo Mascherini, and Pietro Paolo Tavilla 2 Epidemiology, Prevention and Clinical Diagnosis of Melanoma����������   7 Pietro Quaglino, Paolo Fava, Paolo Broganelli, Lorenza Burzi, Elena Marra, Simone Ribero, and Maria Teresa Fierro 3 Treatment of Primary Melanoma������������������������������������������������������������  17 Ilaria Baldelli, Pier Luigi Santi, and Edoardo Raposio 4 Histopathological Examination: The Keystone of Treatment of Melanoma������������������������������������������������������������������������  27 Marina Gualco 5 Molecular Assessment in Patients with Melanoma: When and Why?����������������������������������������������������������������������������������������  39 Bruna Dalmasso, Irene Vanni, William Bruno, Virginia Andreotti, Lorenza Pastorino, Francesco Spagnolo, and Paola Ghiorzo 6 New Melanoma Staging: Prognostic Factors������������������������������������������  47 Francesco Spagnolo, Andrea Boutros, Elena Croce, Enrica Tanda, Federica Cecchi, and Paola Queirolo 7 The Role of Nuclear Medicine in Mapping Sentinel Lymph Nodes and Staging Metastatic Melanoma����������������������������������  55 Giuseppe Villa and Federico Schenone 8 Methodological and Technological Evolution of Sentinel Lymph Node Biopsy: An 8-Year Experience ������������������������������������������  71 Marco Gipponi, Nicola Solari, and Ferdinando Cafiero 9 The Rationale of Sentinel Lymph Node Biopsy��������������������������������������  85 Ferdinando Cafiero, Marco Gipponi, Nicola Solari, Matteo Mascherini, and Franco De Cian 10 Surgical Technique and Indications for Radical Dissection: Axilla������  97 Carlo Riccardo Rossi and Saveria Tropea

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11 Surgical Technique and Indications of Radical Dissection: Groin�������� 107 Nicola Solari, Ferdinando Cafiero, and Matteo Mascherini 12 Surgical Technique and Indications for Radical Dissection: Head and Neck ������������������������������������������������������������������������������������������ 115 Carlo Riccardo Rossi and Saveria Tropea 13 Management and Prevention of Lymphatic Complications of Radical Dissections�������������������������������������������������������������������������������� 125 Francesco Boccardo and Sara Dessalvi 14 Local Treatments of Locoregional Disease in the Setting of Melanoma ���������������������������������������������������������������������������������������������� 135 Nicola Solari and Matteo Mascherini 15 Role of Surgery for Metastatic Melanoma���������������������������������������������� 147 Franco De Cian and Matteo Mascherini 16 Medical Treatment of Melanoma: Adjuvant and Neoadjuvant Therapies���������������������������������������������������������������������� 157 Francesco Spagnolo, Enrica Tanda, Andrea Boutros, Federica Cecchi, and Paola Queirolo 17 Systemic Treatment in Advanced Melanoma������������������������������������������ 167 Francesco Spagnolo, Andrea Boutros, Enrica Tanda, Federica Cecchi, and Paola Queirolo 18 The Management of Melanoma Brain Metastases �������������������������������� 175 Stefano Vagge and Francesco Lupidi

Contributors

Virginia  Andreotti  Genetics of Rare Cancers, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Ilaria Baldelli  Plastic and Reconstructive Surgery Unit, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Francesco Boccardo  Lymphatic Surgery and Microsurgery Unit, Department of Cardio-Thoracic, Vascular and Endovascular Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Andrea  Boutros  Medical Oncology Unit 2, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Paolo  Broganelli  Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy William  Bruno  Genetics of Rare Cancers, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Lorenza Burzi  Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy Ferdinando  Cafiero  Surgery Unit 1, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Federica  Cecchi  Medical Oncology Unit 2, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Elena Croce  Medical Oncology Unit 2, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Bruna  Dalmasso  Genetics of Rare Cancers, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Franco De Cian  Surgical Clinic Unit 1, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Sara Dessalvi  Lymphatic Surgery and Microsurgery Unit, Department of CardioThoracic, Vascular and Endovascular Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy xi

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Paolo Fava  Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy Maria  Teresa  Fierro  Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy Paola  Ghiorzo  Genetics of Rare Cancers, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Marco Gipponi  Breast Unit, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Marina Gualco  Department of Pathological Anatomy and Histology, Villa Scassi Hospital, Genoa, Italy Francesco Lupidi  Neurosurgery Unit, Ospedali Galliera, Genoa, Italy Elena Marra  Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy Matteo  Mascherini  Surgical Clinic Unit 1, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Lorenza  Pastorino  Genetics of Rare Cancers, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Pietro Quaglino  Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy Paola Queirolo  Division of Medical Oncology for Melanoma, Sarcoma and Rare Tumors, IEO-European Institute of Oncology IRCCS, Milan, Italy Edoardo  Raposio  Plastic and Reconstructive Surgery Unit, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Simone Ribero  Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin, Italy Carlo Riccardo Rossi  Department of Surgical Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy Pier Luigi Santi  Plastic and Reconstructive Surgery Unit, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Federico  Schenone  Nuclear Medicine Unit, Department of Diagnostic Imaging and Radiation Oncology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Nicola  Solari  Minimally Invasive Surgery Unit, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Francesco  Spagnolo  Medical Oncology Unit 2, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

Contributors

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Enrica Tanda  Medical Oncology Unit 2, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Pietro Paolo Tavilla  Plastic and Reconstructive Surgery at Dermatologic Clinic, Department of Specialist Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Saveria  Tropea  Department of Surgical Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy Stefano Vagge  Oncological Radiotherapy Unit, Department of Diagnostic Imaging and Radiation Oncology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Irene Vanni  Genetics of Rare Cancers, Department of Oncology and Hematology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy Giuseppe  Villa  Nuclear Medicine Unit, Department of Diagnostic Imaging and Radiation Oncology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

1

The History of Melanoma: From Incas to the Third Millennium Ferdinando Cafiero, Matteo Mascherini, and Pietro Paolo Tavilla

1.1

 rom Ancient Times to the Beginning F of the Twentieth Century

• The first evidence of melanoma belongs to the diffuse melanotic metastases found in the skeletons of pre-Columbian mummies in Peru, radiocarbon dated to the fourth century BC [1]. • In 1787, John Hunter, working in London, successfully removed a recurrent melanoma from the jaw of a 35-year-old man. Hunter reported the tumor to be “soft and black” and labeled it as a “cancerous fungous excrescence” [2]. The preserved tumor was later diagnosed as a melanoma in 1968, and is still housed in the Hunterian Museum at Lincoln’s Inn Fields in London, UK [3]. • René Laennec, the inventor of the stethoscope, was the father of the term “mélanose”, from the ancient Greek μέλᾱς, μέλαινᾰ, μέλᾰν. During a lecture in Paris in 1804, he used this noun to describe lung metastases [4]. • The natural history of the disease was first described by William Norris in 1820. In his “Case of fungoid disease” he particularized a case of a patient affected by melanoma, from local recurrence to death for metastases. He wrote “When removed, it recurred rapidly in the scar; groin nodal metastases preceded the development of F. Cafiero (*) Surgery Unit 1, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy e-mail: [email protected] M. Mascherini Surgical Clinic Unit 1, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy e-mail: [email protected] P. P. Tavilla Plastic and Reconstructive Surgery at Dermatologic Clinic, Department of Specialist Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy e-mail: [email protected] © Springer Nature Switzerland AG 2021 F. Cafiero, F. De Cian (eds.), Current Management of Melanoma, Updates in Surgery, https://doi.org/10.1007/978-3-030-45347-3_1

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multiple subcutaneous lesions, a cough, and death” [5]. Norris continued to collect several cases of melanoma and, in his paper published in 1857, he proposed a “wide excision” to prevent local recurrence. He was also the first to notice the correlation between pale phototype or high number of nevi and incidence of melanoma [6]. In 1840, Samuel Cooper wrote “The first lines of the theory and practice of surgery” and observed that the advanced stages of melanomas were untreatable, stating “the only chance for benefit depends upon the early removal of the disease” [7]. In 1851, Fergusson performed the first groin radical dissection for lymph nodal metastases. The surgical intervention was published in The Lancet [8]. In 1853, Sir James Paget described the transition from the radial growth to the vertical growth phase [9], and he identified this process as the breaking point for the development of distant recurrence. Sir Jonathan Hutchinson made the first description of subungual melanoma (1857) and determined that “early amputation is demanded” to prevent a high risk of recurrence of disease. In the second half of nineteenth century, the interest in lymph node recurrence and surgery increased. Based on previous studies and publications, the first site of melanoma metastases seemed to be the locoregional nodal basin. The development of anesthesia helped in the surgical treatment, which could be more invasive than in the past. In 1892, Herbert Snow, a London surgeon, proposed that all melanoma should be treated by a wide local excision and anticipatory gland excision. Snow stated that “it is essential to remove, whenever possible, those lymph glands which first receive the infective protoplasm, and bar its entrance into the blood, before they have undergone increase in bulk” and that “palpable enlargement of these glands is unfortunately but a late symptom of deposit therein: by the time it occurs there is almost always implication of deeper organs or tissues” [10]. On the basis of this concept of anticipation of disease, in the twentieth century some trials tried to compare prophylactic or elective lymph node dissection (ELND) to observational follow-up. In 1907, William Handley strongly recommended that the wide excision should be of 2 in. (5 cm) laterally and should include 2 in. (5 cm) of subcutaneous layer, to prevent the dissemination of disease through the just discovered lymphatic vessels [11]. This led to a very aggressive approach to treating the primary tumor, which lasted for more than half a century. The trend was similar to breast cancer treatment, in which Halsted advocated radical mastectomy as the best way to prolong survival. For many years, a wide excision of more than 2 cm, regardless of local stage, with or without prophylactic lymph nodal dissection, was the gold standard for melanoma treatment.

1.2

Recent History

• The first isolated limb perfusions (ILP) were performed in the 50s by the North American surgeons Creech and Krementz, for palliation of in-transit disease as an alternative to amputation; after a difficult start due to toxicity of the drugs escaping into the systemic circulation, the surgical technique improved together with patient outcomes.

1  The History of Melanoma: From Incas to the Third Millennium

3

• In the 60s and 70s Wallace Clark and Alexander Breslow proposed a standard scale to assess the prognosis of melanoma based upon the histological examination. Clark based his scale on the level of invasion from epidermis, to dermis and subcutaneous tissue [12]. Breslow stratified melanoma patients considering the total vertical depth of the melanoma from the granular layer of the epidermis to the area of deepest penetration into the skin [13, 14]. In both classifications, the lower the level or depth of invasion, the better the prognosis. With regard to the Clark and Breslow levels, clinicians could select patients for prophylactic lymph node dissection. • According to the relation between local stage and prognosis, Handley’s very wide excision was thought to be excessive and several randomized, prospective trials were performed: –– WHO trial: 1 cm vs. 3 cm (Breslow