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Abstract

Desmoplastic melanoma poses significant diagnostic challenges, both clinically and histologically. Immunohistochemistry is crucial for diagnosis, with SOX10 and S100 considered highly sensitive and specific markers. We report a rare case of SOX10- and S100-negative desmoplastic melanoma in a patient with a history of solid organ transplant on immunosuppressive therapy. Initial shave biopsy revealed an atypical compound melanocytic proliferation composed of pleomorphic cells with enlarged nuclei, prominent nucleoli, frequent dermal mitoses, and prominent junctional pagetoid spread. Wide local excision and sentinel lymph node biopsy were performed. Histology showed melanoma with both in-situ and invasive components. Two of three sentinel nodes were positive, staging the tumor as T4b. The invasive tumor displayed two morphologic populations: conventional epithelioid melanocytes and a desmoplastic component with sarcomatoid features. As transplant patients are at increased risk for both desmoplastic melanoma and squamous cell carcinoma the distinction is critical. Molecular studies showed BRAF wild-type status. Immunohistochemistry revealed scattered reactivity to p63, nonspecific cytoplasmic staining for SOX10, and absence of S100, MART 1, HMB 45 as well as cytokeratin AE1/AE3, CAM 5.2, p40. Additional stains showed MITF positivity—strong in conventional and patchy in desmoplastic melanocytic populations. Multiplex MITF/DE-40 highlighted focal lymphovascular invasion. Loss of SOX10 and S100 in desmoplastic melanoma is exceptionally rare, with only one prior case reported. This case illustrates a unique diagnostic pitfall with the aberrant p63 staining and underscores the need for additional comprehensive histopathologic and immunohistochemical evaluation in suspected cases of desmoplastic melanoma when conventional markers are absent.