Sinonasal undifferentiated carcinoma: clinical and pathologic features and a discussion on classification, cellular differentiation, and differential diagnosis

Abstract

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon, highly aggressive, and clinicopathologically distinctive carcinoma of uncertain histogenesis. SNUC typically presents as a rapidly enlarging tumor mass involving multiple (sinonasal tract) sites, often with evidence of extension beyond the anatomic confines of the sinonasal tract. The light microscopic features include the presence of a hypercellular proliferation with varied growth patterns, including trabecular, sheet-like, ribbon, lobular, and organoid patterns. The tumor cells are medium to large sized and round to oval and have pleomorphic and hyperchromatic nuclei, inconspicuous to prominent nucleoli, varying amount of eosinophilic cytoplasm, high nuclear-to-cytoplasmic ratio, marked increase in mitotic activity frequently with atypical mitoses, tumor necrosis, and apoptosis. Adjunct analyses (eg, immunohistochemistry, electron microscopy, and molecular biologic studies) are often required in the diagnosis of SNUC and in differentiating it from other undifferentiated malignant neoplasms. The treatment of SNUC includes aggressive multimodality therapy, including surgical resection and adjuvant therapy (ie, radiotherapy, chemotherapy). The prognosis associated with SNUC is poor, and death due to disease often occurs within short periods following the diagnosis. We believe that the histologic definition of SNUC can be expanded to include tumors with limited differentiated foci (ie, squamous cell differentiation) predicated on the caveats that the clinical parameters (ie, rapidly enlarging and destructive sinonasal lesions) and the majority of the histologic findings (ie, undifferentiated pleomorphic cell population) match those features that have heretofore defined SNUC. The presence of squamous cell differentiation would correlate to origin in the Schneiderian epithelium, thereby conferring an ectodermal derivation to these tumors. Irrespective of its cell of origin and perhaps even in the face of differentiated foci in limited parts of the tumor, given its rather unique clinicopathologic characteristics, this tumor should be identified and classified as SNUC, thereby differentiating it from the other specific types of sinonasal carcinomas and nonepithelial malignant tumors.