The American Cancer Society estimates that approximately 76,380 cases of invasive cutaneous melanoma will be diagnosed in the United States in 2016.1 Despite recent advances in the management of patients with advanced disease through immunotherapy and targeted agents, the number of deaths in the United States from metastatic melanoma is estimated to exceed 10,000 for the first time in 2016. It therefore remains of paramount importance that additional tools are developed to aid in the early diagnosis and accurate prognostication of primary cutaneous melanoma.
Currently, the diagnosis of melanoma relies primarily on histopathologic and immunohistochemical findings. Several characteristics of the primary tumor (eg, Breslow thickness, presence or absence of ulceration, and number of dermal mitoses per mm2) and the presence or absence of occult nodal metastasis identified by sentinel lymph node biopsy (SLNB) are known to correlate with outcome. These prognostic parameters are currently incorporated in the AJCC staging system, which is used to risk-stratify patients and determine appropriate stage-based treatment and surveillance management. Several models have been developed in the United States and abroad to provide individualized prognostication for patients with localized or regional cutaneous melanoma, incorporating known prognostic parameters.2–8 However, diagnostically challenging melanocytic lesions, such as atypical Spitz tumors, remain difficult to risk stratify based on conventional criteria.
Most patients are diagnosed with early-stage melanoma, for whom current AJCC staging provides excellent prognostication (93% 10-year survival rate for stage IA), which allows for definitive treatment with limited morbidity and appropriate follow-up.9 For clinically node-negative patients with higher-risk melanoma based on currently known criteria, in whom the risk of regional lymph node metastasis generally exceeds 10%, the sentinel lymph node (SLN) status is the most powerful predictor of survival and determines the indication for additional surgery (ie, complete lymph node dissection), systemic adjuvant therapy, surveillance imaging, and frequency of clinical follow-up. However, controversy remains regarding the most appropriate criteria to perform SLNB, particularly in T1 melanoma (≤1 mm). Moreover, SLN status is not perfect in predicting recurrence; the occasional occurrence of metastatic disease in patients with SLN-negative status underscores the need for additional, more discriminant prognostic indicators.
In recent years, several molecular techniques have emerged in an attempt to augment current methods in the diagnosis, prognosis, and management of melanoma, fueled by successful efforts in breast cancer and other malignancies. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) have been explored primarily to aid in the differentiation among diagnostically challenging melanocytic lesions. Gene expression profiling (GEP) has been studied both from a diagnostic and a prognostic perspective, which has led to 2 currently commercially available assays in the United States. This review summarizes some of the ongoing efforts to bring molecular techniques into clinical practice, specifically with regard to the diagnosis and prognosis of primary cutaneous melanoma. It also provides several reasonable benchmarks needed to successfully launch molecular profiling into routine clinical practice, largely based on the ongoing success in the management of breast cancer.
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CancerMath.netMelanoma Outcome Calculator. Available at: http://www.lifemath.net/cancer/melanoma/outcome/. Accessed March 14, 2016.
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Gerami P, Li G, Pouryazdanparast P et al.. A highly specific and discriminatory FISH assay for distinguishing between benign and malignant melanocytic neoplasms. Am J Surg Pathol 2012;36:808–817.
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. A retrospective study of the influence of a gene expression signature on the treatment of melanocytic tumors. Rock C Cockerell C Tschen J Poster presented at The 52nd Annual Meeting of the American Society of Dermatopathology; October 8–11, 2015; San Francisco, California. Number 457.
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. Flaherty LE Othus M Atkins MB Southwest Oncology Group S0008: a phase III trial of high-dose interferon Alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma—an intergroup study of Cancer and Leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. J Clin Oncol 2014; 32: 3771– 3778.