Evolving treatments and future therapeutic targets in desmoplastic melanoma.

Abstract

Desmoplastic melanoma (DM) is a rare and histopathologically distinct type of melanoma that is a subvariant of spindle cell melanoma [1]. It has a strong association with chronic sun exposure and usually occurs later in life. Incidence is reported to be less than four percent of cutaneous melanomas. Early diagnosis can be challenging because DM is predominantly dermal and often amelanotic [2]. The diagnosis can be difficult not only clinically but also histologically, as DM can be mistaken for a variety of benign and malignant nonmelanocytic spindle cell tumors. Histology of DM is divided into pure and mixed types, and this classification plays an important role in prediction of clinical outcomes [3]. Pure DM tends to have less potential for metastasis and as a result has a more favorable prognosis than mixed DM [4]. DM commonly demonstrates local invasion with poor circumscription due to its infiltrative nature which results in a high recurrence rate. It primarily affects patients with fair skin with age distribution of 60–80 years old and male-to-female ratio of two–one [5]. The overall survival for patients with DM is relatively favorable despite its depth at diagnosis with median survival at 5 and 10 years of 84.8 and 79.2 %, respectively [6]. Advanced age of the patient, higher stage of the tumor as well as increased Breslow depth were found to be independent positive factors associated with DM [7]. While established DM treatment options are surgical excision, sentinel lymph node biopsy, systemic chemotherapy and radiation therapy, a number of genetic mutations associated with DM have shown it to be responsive to targeted therapies. This review will focus on the future of DM therapy, which lies in better targeted therapy approaches and better penetration into the tumor core leading to more robust responses to therapeutic agents.