Abstract
BACKGROUND This report describes the case of a 78-year-old man with neuroendocrine carcinoma of the submandibular gland. This is an exceptionally rare and aggressive malignancy, with only a limited number of cases reported in the literature. Due to its low incidence and histopathologic overlap with other tumors, its diagnosis and management remain challenging. CASE REPORT We report the case of a 78-year-old White man with no history of smoking or alcohol use and with no relevant comorbidities, who presented with a painless, rapidly enlarging left submandibular mass measuring approximately 6×4.5 cm. Contrast-enhanced CT revealed a large tumor with central necrosis extending into the subcutaneous plane. The patient underwent en bloc surgical resection of the tumor with associated cervical lymph nodes. Histopathological examination demonstrated a high-grade neuroendocrine carcinoma, characterized by large nests and trabeculae of tumor cells with a high nucleus-to-cytoplasm ratio, nuclear hyperchromasia, high mitotic activity, and areas of necrosis. Immunohistochemistry showed positivity for chromogranin A, cytokeratin AE1/AE3, and CD56, supporting the diagnosis of neuroendocrine carcinoma. Postoperative management included adjuvant medical therapy, and long-term radiological follow-up demonstrated no evidence of recurrence at 4 years. In addition, a systematic review of the literature was performed, identifying 27 well-documented cases of submandibular gland neuroendocrine carcinoma. CONCLUSIONS Submandibular gland neuroendocrine carcinoma is a rare and highly aggressive neoplasm requiring a multidisciplinary diagnostic and therapeutic approach. Given the lack of standardized treatment protocols, further research, molecular profiling, and multicentric studies are needed to develop personalized therapeutic strategies and improve patient outcomes.