Definitive Chemoradiation for Unresectable Hyalinizing Clear Cell Carcinoma of the Base of the Tongue: A Molecularly Confirmed Case.

Hyalinizing clear cell carcinoma (HCCC) is a rare malignancy of the minor salivary glands, most often managed by surgical resection. We report a case of a 63-year-old woman with an unresectable base-of-tongue tumor initially presumed to be squamous cell carcinoma. Histopathologic evaluation and molecular testing ultimately confirmed HCCC with an EWSR1-ATF1 fusion. Given the tumor's extent, she was treated with definitive chemoradiation using weekly cisplatin and 70 Gy in 35 fractions. Her course was complicated by pulmonary embolism, neutropenia, and severe mucositis requiring percutaneous endoscopic gastrostomy tube placement. Post-treatment imaging showed decreased FDG avidity, and circulating tumor DNA remained negative for minimal residual disease. This case highlights the importance of molecular diagnostics in distinguishing HCCC from other clear cell neoplasms and suggests a potential role for chemoradiation in unresectable cases, though treatment-related toxicity remains a significant concern. Further investigation into systemic and targeted therapies for HCCC is warranted.