S100 expression in molecularly confirmed dermatofibrosarcoma protuberans, including fibrosarcomatous variants.

Aims: 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.

Methods and results: 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.

Conclusion: 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.