Desmoplastic Melanoma

Abstract

Desmoplastic melanoma is a rare subtype of melanoma accounting for 1–4% of all melanomas. There are a number of clinical and pathological features that distinguish desmoplastic melanoma from conventional melanoma. Desmoplastic melanoma usually occurs in the elderly, particularly males, and on chronically sun-damaged skin, especially on the head and neck region. Lesions often present in an innocuous fashion, and are frequently unrecognized or misdiagnosed clinically. The pathological diagnosis of desmoplastic melanoma can also be very challenging, because the tumor is often very subtle and its morphological features overlap with nonneoplastic conditions such as scars, as well as benign and malignant neoplasms. Histologically, desmoplastic melanoma is characterized by malignant spindle cells in which individual tumor cells are separated by collagen fibers. There are two subtypes of desmoplastic melanoma, namely pure and mixed. In the pure subtype, the overwhelming majority of invasive tumor is desmoplastic, while in the mixed subtype (which may consist of spindled or epithelioid cells, or both), the desmoplastic areas account for less than 90% of the invasive tumor. Desmoplastic melanoma has an affinity for nerves and a propensity for local recurrence. Compared with other melanoma subtypes, desmoplastic melanoma more frequently metastasizes to the lungs and less frequently to lymph nodes. The molecular landscape of desmoplastic melanoma is quite different from that of conventional melanoma; it has a higher mutation rate and almost always lacks BRAF, NRAS, or KIT mutations, commonly present in other subtypes. Recent genomic studies have highlighted the very high DNA mutation load of desmoplastic melanoma and clinical studies suggest patients with metastatic desmoplastic melanoma have higher response rates to immunotherapy. Primary desmoplastic melanoma should be treated by wide local excision of the primary tumor. The role of sentinel lymph node biopsy in patients with desmoplastic melanoma is controversial; a number of early studies showed the rate of sentinel lymph node metastasis in patients with pure subtype desmoplastic melanoma was very low (approximately 1%), while much higher rates have been reported in more recent studies.