Cutaneous epithelioid hemangiosarcoma with granular cell differentiation in a dog: a case report and review of the literature.

We report a case of cutaneous epithelioid hemangiosarcoma in a dog in which the majority of the neoplastic cells displayed histologic and ultrastructural features similar to those seen in granular cell tumors (GCTs). This intersection of hemangiosarcoma and granular cell change adds to the argument that GCTs are heterogeneous in histologic origin and underlines the fact that pathologists should not consider all GCTs as a single entity. The combination of histology in typical areas of the tumor with ultrastructural changes and the correct immunohistochemical markers can facilitate the accurate diagnosis of tumors with granular cell differentiation. Besides characteristic intracytoplasmic PAS-positive granules and ultrastructural proteinaceous accumulation within single membrane vesicles (presumably lysosomes and phagolysosomes), we suggest the following combination of markers for the diagnosis of granular cell angiosarcoma and/or hemangiosarcoma: vimentin positive, NSE and/or S100 negative, CD31 positive. We propose that the histologic granular appearance represents a metabolic defect of the neoplastic cells, which supports variability in cell origin for granular cell differentiation.