Clinical and Histopathologic Analyses of Nasopharyngeal Hyalinizing Clear Cell Carcinoma

The aim of this study was to evaluate the clinicopathologic features, molecular characteristics, treatment strategy, and prognosis of nasopharyngeal hyalinizing clear cell carcinoma (HCCC). Retrospective observational case series. Institutional pathology records between 2006 and 2022 were searched for all cases of nasopharyngeal HCCC. We included 10 male and 16 female patients aged 30 to 82 years (median: 60.5 y, mean: 54.6 y). The most common symptoms were blood-stained rhinorrhea and nasal obstruction. Tumors most often involved the lateral wall of the nasopharynx, followed by the superior posterior wall. Microscopically, all tumor cells were arranged in sheets, nests, cords, and single cells in a hyaline/myxoid/fibrous stroma. The tumor cells were polygonal, with or without distinct cell borders, and displayed abundant clear-to-eosinophilic cytoplasm. All 26 cases were positive for pancytokeratin, CK7, p40, and p63 but negative for myoepithelial differentiation markers. Ki-67 labeling was low and ranged from 1% to 10%. All 26 cases demonstrated EWSR1 and EWSR1-ATF1 rearrangements, and no case demonstrated MAML2 rearrangement. Complete follow-up data were available for 23 patients: 14 patients underwent endoscopic surgery alone, 5 underwent radiation therapy followed by endoscopic surgery, 3 underwent radiation therapy followed by biopsy, and 1 underwent cisplatin chemotherapy before endoscopic surgery. Clinical follow-up ranged from 6 to 195 months; 13 patients (56.5%) were alive without tumor, 5 patients (21.7%) died of disease, 5 patients (21.7%) survived with tumor. HCCCs of the nasopharynx are rare tumors. The definitive diagnosis depends on histopathology, immunohistochemistry, and molecular studies. The optimal treatment for patients with nasopharyngeal HCCC is wide local excision. Radiation and chemotherapy might be good options for managing locally advanced cases. Nasopharyngeal HCCC is less indolent than previously thought. Tumor stage and the choice of treatment are key factors affecting the prognosis of nasopharyngeal HCCC patients.