Vol. 29. No. 4


Melanoma remains one of the most vexing problems faced by dermatologists. The incidence of melanoma is increasing faster than any other cancer in the United States,1,2 with the lifetime risk now estimated to be 1 in 59 (1 in 39 for white men).3 It is not simply a matter of earlier, more aggressive diagnosis because tumors of all thickness have shown increases in incidence. More than 68,130 new cases of invasive melanoma are expected to be diagnosed this year.4 It is now the sixth most common cancer in the United States and is presently the leading cause of cancer deaths in women between the ages of 20 and 35.5 Fortunately there is also some good news about melanoma. There have been significant advances recently in our ability to identify patients at high risk, to diagnose melanoma at an earlier and more curable point in the disease process, and to treat melanoma of all stages. Now more than 85% of newly diagnosed melanoma patients have the disease limited to the primary cutaneous site (American Joint Committee on Cancer stage I and II) and have an excellent prognosis. The ability to sequence and analyze the human genome has altered our traditional dysplastic nevus to melanoma model and identified multiple divergent oncogenic pathways leading to melanoma. This new information is having a significant impact on both bench research and clinical trials and, as medicine becomes more personalized, will likely help create more customized and targeted therapy. In addition, there are new noninvasive technologies developed each year that help clinicians evaluate suspicious lesions. As experience with dermoscopy increases, so too does the ability to recognize patterns more clearly and an associated increase in the sensitivity and specificity of diagnosing pigmented lesions. This helps reduce the number of unnecessary biopsies as well as minimize the risk of missing potentially serious lesions. In addition, bedside confocal microscopy, optical coherence tomography, reflex transmission imaging, and other imaging systems, such as SIAscopy and MelaFind, have shown real potential to improve our ability to quickly and accurately determine a pigmented lesion’s malignant potential. Sentinel lymph node biopsies have been shown to accurately stage regional lymph node basins in stage I and II melanoma patients, and as histologic examination of the biopsied nodes become more sensitive and more thorough, our ability to define true positive and negative subsets will be even further enhanced. In this issue of the journal we will examine many of the aspects of melanoma and discuss where the experts in our field believe we stand in 2011 and where we may be headed in the future. We begin with an in-depth look at the epidemiology of melanoma. Dr Darrel Rigel discusses the alarming increase in both the incidence and mortality of melanoma and evaluates the exogenous and endogenous risk factors that may help us identify those at higher risk for the disease and potential avenues to reduce their risk. This article is followed by a review of the latest discoveries on the divergent pathways of melanoma development from Drs Velez, Ko, and Tsao. New mutations have been identified that may have significant practical implications in patient care. Drs Wasserman and Monheit present an update on the most recent bedside technology available to help clinicians diagnose melanoma. Dr Marghoob and colleagues continue in the next article with an in-depth discussion on dermoscopy of pigmented lesions and other tumors with particular attention to the pediatric population. Dr Merrik Ross, a surgical oncologist from the M D Anderson Cancer Center, presents an update on sentinel node biopsies and its implications in clinical practice after 20 years of experience. Dr Jose Lutzky, a medical oncologist from Mount Sinai, addresses new therapeutic options in the medical management of advanced melanoma. Dr Marc Brown sums up the material and details a practical clinical approach to the melanoma patient. Likewise, Dr Eric Parlette discusses melanoma in situ and a practical approach to treatment. We are indebted to these thought leaders in our field for sharing their experience with us.

Epidemiology of Melanoma

Darrell S. Rigel, MD

Malignant melanoma represents a significant and growing public health burden in the US and worldwide. It is estimated that 68, 130 cases of invasive malignant melanoma and at least 48,000 cases of melanoma in-situ will be diagnosed in the US this year. Melanoma is also one of the few remaining cancers with increasing US incidence. In the 1930s, the lifetime risk of an American developing invasive malignant melanoma was 1 in 1,500. Currently, that risk is 1 in 59. Deaths from malignant melanoma are also increasing. The mortality rate from malignant melanoma has risen about 2% annually since 1960. This year, it is estimated that 8,700 Americans will die from this cancer. The identification of individuals at high risk for malignant melanoma is important for the development of focused and efficient prevention efforts. Acute sun exposure resulting in sunburn remains a significant risk factor for the development of melanoma, but numerous other potential risk factors have been cited. Included among these are atypical mole syndrome/dysplastic nevus syndrome, blistering sunburns, immunosuppression, prior therapy with psoralen with ultraviolet A light (UVA) light, UV exposure at tanning salons, elevated socioeconomic status, and history of melanoma in a first-degree relative. With a better understanding of the reasons for the increasing rate of this cancer, and with enhanced early detection approaches, we may be able to decrease the incidence and mortality of malignant melanoma.
Semin Cutan Med Surg 29:204-209 © 2010 Published by Elsevier Inc.


Pathways to Melanoma

Hensin Tsao, MD | Justin M. Ko, MD, MBA | Nicole F. Velez, MD

Melanoma is one of the most aggressive and yet poorly understood of human malignancies. Advances in genomics has allowed a more nuanced understanding of the disease, moving beyond the traditional dysplastic nevus-to-melanoma model and identifying multiple divergent oncogenic pathways leading to melanoma. An understanding of the molecular mechanisms driving melanoma has opened the doors for the development of targeted therapeutic approaches. As we enter the era of personalized medicine, it will be critical for clinicians to both appreciate and be able to determine the molecular profile of their patients’ melanoma because this profile will guide risk stratification, genetic counseling, and treatment customization. A review of the divergent pathways of melanoma development is presented here, with a particular emphasis on recently identified mutations, and their implications for patient care.
Semin Cutan Med Surg 29:210-217 © 2010 Published by Elsevier Inc.


Dermoscopy of Benign and Malignant Neoplasms in the Pediatric Population

A.A. Marghoob, MD | Christoph Lanschuetzer, MD | Helen C. Haliasos, MD | Helmut Hinter, MD | Iris Zalaudek, MD | Josep Malvehy, MD | Rainer Hofmann-Wellenhof, MD | Ralph P. Braun, MD

Dermoscopy is a noninvasive technique that enables visualization of subsurface colors and structures within the skin that are imperceptible to the naked eye. The dermatoscope allows
the physician to examine both the macroscopic and microscopic primary morphology of skin lesions, identify subtle clinical clues, confirm naked-eye clinical diagnoses, and monitor treatment progress while posing little threat to the young patient. Dermoscopic findings have been formulated into diagnostic criteria that assist experienced clinicians in differentiating benign and malignant neoplasms. In this review, clinical morphology of melanocytic nevi and melanoma in the pediatric population is examined and the relevant dermoscopic findings and histopathologic correlates that aid in the diagnosis and management of these lesions are described.
Semin Cutan Med Surg 29:218-231 © 2010 Published by Elsevier Inc.


Office Management of Melanoma Patients

Marc D. Brown, MD

As the incidence of melanoma continues to increase, so does the role of the dermatologist as both medical and surgical oncologist for these patients. The dermatologist holds a key role in all phases of care, including prevention, diagnosis, treatment, and follow-up. The dermatologist is best trained to complete a full and thorough skin examination and is best able to recognize a melanoma in its early stages of growth. Dermatologists have a unique opportunity to prevent melanoma through appropriate patient education concerning sun protection, self skin examinations, and the ABCDEs of melanoma recognition (ie, asymmetry, border irregularity, color variations, dimension and evolution). The dermatologist is well trained to obtain an appropriate full-thickness skin biopsy and is knowledgeable to interpret the pathologist report and understand the significance of the various histologic prognostic indexes. Most patients present with localized disease and with thinner Breslow depth and thus can be skillfully treated in an outpatient setting under local anesthesia by
a dermatologist.
Semin Cutan Med Surg 29:232-237 © 2010 Published by Elsevier Inc.


Sentinel Node Biopsy for Melanoma: An Update After Two Decades of Experience

Merrick I. Ross, MD

When detected and treated early, melanoma has an excellent prognosis. Unfortunately, as the tumor invades deeper into tissue the risk of metastatic spread to regional lymph nodes and beyond increases and the prognosis worsens significantly. Therefore, accurately detecting any regional lymphatic metastasis would significantly aid in determining a patient’s prognosis and help guide his or her treatment plan. In 1991, Don Morton and colleagues presented new paradigm in diagnosing regional lymphatic involvement of tumors termed sentinel lymph node biopsy (SLNB). By mapping the regional lymph system around a tumor and tracing the lymphatic flow, a determination of the most likely lymph node or nodes the cancer will spread to first is made. Then, a limited biopsy of the most likely nodes is performed rather than a more-invasive removal of the entire local lymphatic chain. In 20 years that have followed, a great deal of information has been gained as to its accuracy, prognostic value, appropriate candidates, and its impact on regional disease control and survival. The SLNB has been shown to accurately stage regional lymph node basins in stage I and II melanoma patients with minimal morbidity. More sensitive histologic techniques are now being applied that may allow even greater accuracy in the staging of melanoma patients. Although specific percent risk thresholds are still in question, recommendation for SLNB when melanomas are 1 mm or thicker has gained wide acceptance. SLNB may also be appropriate for patients with melanomas that are between 0.76 and 1 mm thick and have ulceration, high mitotic rates, or reach a Clark level IV. Therefore, melanomas with IB or greater staging should be considered for SLNB.
Semin Cutan Med Surg 29:238-248 © 2010 Published by Elsevier Inc.