Management of Cutaneous Melanoma, With a Special Focus on Desmoplastic Melanoma

Abstract

Not all melanomas are the same. They differ in presentation, mutational status, and behavior. Desmoplastic melanoma (DM) is a rare subtype of melanoma which carries a high tumor mutation burden and is found in highly sun-exposed areas. Although many cutaneous melanomas are pigmented, DM is amelanotic and frequently mistaken for more benign lesions. It is composed of spindle cells surrounded by a dense fibrinous matrix. It frequently carries NF1 mutations. It is exquisitely sensitive to single-agent PD1 blockade resulting in deep, rapid responses at all stages. These responses with single-agent pembrolizumab are durable with a 96% 3-year melanoma specific survival rate. This has influenced recommended treatments for unresectable and resectable disease. Single-agent PD1 blockade is recommended first line for unresectable disease with a reported overall response rate of 89%. The first prospective neoadjuvant study in DM demonstrated a pathologic complete response of 57% after three cycles of pembrolizumab, suggesting potential benefit to the use of neoadjuvant therapy in resectable disease. Owing to the low incidence of sentinel lymph node positivity and lack of correlation with overall survival, sentinel lymph node biopsy can be eliminated in patients with pure DM. Adjuvant radiation has been shown to result in improved local control in cases of high-risk DM, but studies have not demonstrated an impact on distant metastasis-free survival. For DM, less is more.