Fibroblastic and myofibroblastic differentiation of cutaneous pleomorphic sarcomas in rabbits

Cutaneous and subcutaneous soft tissue sarcomas of undetermined differentiation are common in pet rabbits and are often diagnosed as sarcoma not otherwise specified (sarcoma NOS). Such sarcomas with marked cellular pleomorphism and presence of multinucleated giant cells are also referred to as undifferentiated pleomorphic sarcoma, anaplastic sarcoma, or giant cell sarcoma. However, these terminologies do not define any cellular differentiation. In this study, we aimed to identify the line of differentiation of cutaneous pleomorphic sarcomas in rabbits. Histopathological, histochemical, and immunohistochemical analyses were performed on 48 cutaneous masses in rabbits, previously diagnosed as sarcoma NOS. Histologically, the tumors were characterized by proliferation of pleomorphic mesenchymal cells, primarily spindle cells, with frequent presence of multinucleated giant cells (58% of the cases). Sirius red staining revealed fine collagen fibers directly extending from the neoplastic cells in all cases. Some cases showed immunoreactivity for calponin (35%), α-smooth muscle actin (31%), and pan-muscle actin (25%). Almost all the case were negative for SOX10, ionized calcium binding adapter molecule-1 and CD204. Based on the findings above, rabbit cutaneous pleomorphic sarcomas are considered to differentiate towards fibroblasts and myofibroblasts. In addition, our follow-up data revealed a high recurrence rate and short survival times, indicating aggressive biological behavior of rabbit cutaneous pleomorphic sarcomas.