Abstract

Desmoplastic melanoma is a rare subtype of melanoma that is associated with chronic UV exposure. It usually arises on the head and neck of older adults. It is often large and deeply invasive at the time of diagnosis, necessitating aggressive surgical excision with high morbidity.  Anti-PD1 inhibition has shown incredible promise in the treatment of advanced desmoplastic melanomas; preliminary data from the SWOG phase II S1512 trial have shown that neoadjuvant treatment with single-agent pembrolizumab can induce complete pathological response in a significant subset of unresectable desmoplastic melanomas.  We present a case of a 75-year-old man with unresectable desmoplastic melanoma on the scalp who was treated with 4 cycles of neoadjuvant nivolumab and ipilimumab, with remarkable clinical response. Six months after initial biopsy, he underwent excision of the melanoma site with split-thickness skin graft repair. Histologic examination revealed extensive dermal and subcutaneous fibrosis with lymphocyte aggregates and mixed inflammation; no melanoma cells were detected on H&E or by immunohistochemistry. Follow-up imaging 3 months after surgery revealed no evidence of local or metastatic disease. To our knowledge, this case represents the first report of desmoplastic melanoma showing complete pathologic response after neoadjuvant dual checkpoint-inhibitor therapy targeting CTLA-4 and PD-1. These results provide additional support for the use of neoadjuvant immunotherapy for unresectable desmoplastic melanoma. Although more cases with longer follow up are needed to show the durability of this response, it suggests the possibility that immunotherapy could eventually replace surgical excision in select cases of desmoplastic melanoma.