Primary Sublingual S100-Positive Undifferentiated Pleomorphic Sarcoma in a Cat: A Case Report with Comprehensive Exclusionary Immunohistochemistry

Undifferentiated pleomorphic sarcoma (UPS) is an exceptionally rare mesenchymal neoplasm in the feline oral cavity, presenting significant diagnostic and therapeutic challenges. A 10-year and 10-month-old, castrated male Korean Shorthair cat presented with a progressively enlarging sublingual mass measuring 2.77 cm × 3.02 cm × 1.86 cm. Computed tomography revealed a well-circumscribed, non-osteolytic sublingual mass without detectable mandibular bone erosion or regional lymphadenopathy. Gross complete surgical excision was performed via a transoral approach without mandibulectomy. Histopathological examination revealed a highly pleomorphic, sheet-like proliferation of atypical spindle to epithelioid cells with prominent giant binucleated cells and a low mitotic count (3 per 10 high-power fields). To establish a diagnosis of exclusion, an extensive immunohistochemical (IHC) panel was performed. The neoplastic cells were strongly positive for vimentin and diffusely positive for S100, but immunonegative for pancytokeratin (PanCK), Melan-A, Iba-1, desmin, and α-smooth muscle actin (α-SMA). These exclusionary IHC findings did not support epithelial, histiocytic, or myogenic differentiation, though amelanotic melanoma cannot be completely excluded based on Melan-A negativity alone. Rather than confirming definitive neural differentiation, the diffuse S100 immunoreactivity supported a final diagnosis of an S100-positive UPS. The patient achieved rapid functional recovery, with owner-reported absence of clinical signs of local recurrence over a 90-day follow-up period. This report underscores the necessity of a broad exclusionary IHC panel to accurately diagnose feline oral UPS and highlights surgical resection as a viable local management option.