Melanoma

Melanoma is the most common cause of skin-cancer mortality; it is the fifth most common incident cancer in men and the most common cancer among women aged 20-29 years. Early detection of melanoma is important because early definitive therapy drastically improves survival. When detected in later stages, melanoma is associated with a poor prognosis. Until recently, the median survival for stage IV (metastatic) melanoma was 6-10 months. Fortunately, basic and translational science have revolutionized advanced melanoma management with the introduction of molecular target inhibitors as well as immunotherapies. A 2016 in-depth review of advanced melanoma therapeutics is available here.

Key Risk Factors

• white men older than age 60 (this population has the greatest incidence of melanoma)

• immunosuppression

• personal or family history of melanoma

• high-intensity, intermittent sun exposure (i.e., prior sunburns, especially blistering sunburns)

• tanning-bed use

• red hair

• genetic disorders (i.e., xeroderma pigmentosum)

(Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines®] for Melanoma V.1.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed June 1, 2017. To view the most recent and complete version of the guideline, go online to NCCN.org.)

Clinical Manifestations

Melanoma is most commonly (but not always) a darkly pigmented lesion that may or may not be symptomatic. In the early stages, and for an untrained clinician, melanoma can be difficult to differentiate from other benign pigmented lesions (e.g., nevi, ephelides, seborrheic keratoses).

The ABCD criteria (area, border, color, dimension), first developed in 1985, highlight the typical features of the most common melanomas. Lesion change over time (“E” or evolution) was added in 2004 and is recognized to be the most important factor for detection of melanoma.

(Source: Information provided courtesy of the Melanoma Research Foundation at www.melanoma.org.)

The ugly duckling sign refers to any pigmented lesion that is unlike all others, and thus, possibly indicative of melanoma. The sign was introduced in 1998 as another helpful tool, given some of the limitations of the ABCDE criteria for detecting melanoma.

The clinical images and links provided below show the wide range of clinical presentations of melanoma, as well as some common imitators.

Common Melanoma Mimickers

Images of seborrheic keratosis:

• Seborrheic keratosis

• Mature seborrheic keratosis (figure 10)

• Stucco keratoses (figure 11)

• Dermatofibroma (figure 12)

• Dermatofibroma (figure 13)

Examples of Melanomas

(Source: National Cancer Institute.)

(Source: Eyelid Melanoma. N Engl J Med 2016.)

(Source: Acral Lentiginous Melanoma. N Engl J Med 2015.)

(Source: Gingival Melanoma. N Engl J Med 2013.)

(Source: Melanoma of the Oral Cavity. N Engl J Med 2013.)

(Source: Conjunctival Melanoma. N Engl J Med 2015.)

(Source: Red Melanoma. N Engl J Med 2013.)

(Source: Plantar Melanoma. N Engl J Med 2006.)

(Source: Malignant Melanoma. N Engl J Med 1994.)

Diagnosis

• Histology, via skin biopsy, is necessary to confirm the diagnosis of melanoma. Per NCCN guidelines, an excisional biopsy (punch, deep shave, or elliptical) with 1- to 3-mm margins is preferred. In cases where the lesion of concern is not amenable to a full-lesion biopsy (e.g., very large size, challenging anatomical location), the guidelines recommend sampling the most atypical or darkly pigmented area.

• Staging of melanoma is done using the tumor-node-metastasis (TNM) system. The Breslow thickness defines the primary tumor stage. For the thinnest (stage IA) melanoma (thickness <0.8 mm and no ulceration nor mitoses), the expected 5- and 10-year survival rates are 97% and 93% respectively; again emphasizing the importance of early detection. A melanoma that has a Breslow thickness >4 mm is associated with a 10-year survival rate of 39%. The details of the American Joint Committee on Cancer’s 8th edition TNM staging system can be found here.

Management

• The National Comprehensive Cancer Network (NCCN) guidelines define the standard of care for melanoma management.

• All cases of melanoma require a wide local excision. Prior to this surgery, a decision should be made about whether to perform sentinel-lymph-node biopsy. The topic of sentinel-lymph-node testing is controversial and further discussed in this case vignette.

• Management of melanoma that is beyond stage T1a should be discussed in a multidisciplinary group with surgical and/or medical oncology.

• In the last decade, novel small-molecule­-kinase inhibitors (e.g., vemurafenib, trametinib) and immunotherapies (e.g., ipilimumab, pembrolizumab, nivolumab) have revolutionized the management of metastatic melanoma. Management principles with these therapies are concisely discussed in the NCCN guidelines. Landmark studies include Hodi et al. and Chapman et al. (with recently published data on 5-year survival). Novel therapies are discussed on the American Academy of Dermatology website and more exhaustively in this review article.