S100 expression in molecularly confirmed dermatofibrosarcoma protuberans, including fibrosarcomatous variants

Dermatofibrosarcoma protuberans (DFSP) is a superficial, locally aggressive spindle cell neoplasm, characterised by diffuse CD34 expression and the presence of COL1A1::PDGFB or related fusions. S100 expression is not a feature of DFSP. Prompted by a recent case of classic DFSP with significant S100 expression, we sought to explore the prevalence of S100 expression in DFSP, including its fibrosarcomatous variants.

We reviewed our institutional and consultation archives for cases of DFSP that had undergone S100 immunohistochemical staining. A total of 176 cases were identified. Pigmented DFSP (Bednar tumour) cases were excluded from this study. S100 positivity expression was observed in 9 of 176 cases (5.1%), all of which lacked SOX10 expression. The mean patient age was 46.2 years, and there was a male predominance (M:F 3.5:1). The majority of tumours were located in the head and neck region (6/9), with the scalp being the most common location (n = 4). Pan-TRK staining was variably positive in 5 of the 7 cases tested. Fibrosarcomatous transformation was present in 7 of the 9 cases. Molecular confirmation was achieved in all 9 cases.

S100 expression occurs in a small subset of DFSP, with a notable association with fibrosarcomatous transformation and head and neck location. The co-expression of CD34 and S100, in the absence of SOX10, mirrors the immunoprofile of emerging 'NTRK-rearranged spindle cell tumours'. Awareness of this unexpected immunophenotypic finding is essential to avoid misdiagnosis and to ensure appropriate molecular workup, which carries important prognostic and therapeutic implications.