Could cathepsin-k be a driver of the myofibroblastic differentiation observed in dermatofibroma, atypical fibroxanthoma and pleomorphic dermal sarcoma?

Dermatofibroma (BFH), atypical fibroxanthoma (AFX) and dermal pleomorphic sarcoma (DPS) are skin-based soft-tissue neoplasms of uncertain lineage. They are classified as “fibrohistiocytic” neoplasms, even if the World Health Organization stated that this term connotes a polymorphic group of lesions that histologically resemble fibroblasts and histiocytes. It is well-known that this group of lesions shows a “fibro-histiocytic-dendritic” and/or a “myofibroblastic” phenotype, even within the same lesion. We studied the expression of cathepsin-k in 34 cases (25 BFH, 5 AFX, 4 DPS) with a broad panel of antibodies. 20 cases (5 dermatofibrosarcoma protuberans, 5 melanomas, 5 basal cell carcinomas, 5 squamous cell carcinomas) were chosen as controls. Although our results need to be validated, they support a myofibroblastic and/or partial myofibroblastic (“proto-myofibroblastic”) phenotype and the lineage-plasticity of these neoplasms, highlighting the potential role of cathepsin-k in myofibroblastic trans-differentiation. Cathepsin-k proved to be an additional immunoistochemical marker potentially useful in the diagnostic algorithm.