Undifferentiated small round cell tumor of the oral cavity with non-contributory immunohistochemistry: a diagnostic pitfall

The lack of lineage-specific markers and overlapping shape make undifferentiated round cell cancers of the oral cavity extremely difficult to diagnose. We describe a 47-year-old female patient who had a submucosal lesion affecting her mandibular gingiva and labial mucosa. Histopathological analysis showed that the stroma was infiltrated by sheets of monotonous round cells with hardly noticeable nucleoli without any epithelial involvement. The results of a comprehensive immunohistochemistry panel that included cytokeratin, CD45, S100, desmin, synaptophysin, CD99, CD117, MyoD1, CK20, TTF-1, ER, PR, and INI1 were negative, ruling out metastatic disease and epithelial, lymphoid, melanocytic, myogenic, and neuroendocrine differentiation. Certain poorly differentiated carcinomas were further ruled out by retained INI1 expression and negative NUT. A diagnosis of undifferentiated round cell sarcoma, not otherwise described, was made in the absence of an identifiable primary tumor and conclusive immunophenotype. This case thereby emphasizes the value of a methodical exclusion-based strategy and the necessity of supplementary molecular tests in the diagnosis of head and neck tumors that are difficult to diagnose.