Primary large-cell neuroendocrine carcinoma of the submandibular gland arising from a long-standing benign tumor: case report

Abstract

Background: Large-cell neuroendocrine carcinoma (LCNEC) is an aggressive malignancy that commonly arises in the lungs. Primary salivary gland involvement is exceptional, presenting a major diagnostic challenge in differentiating it from metastatic pulmonary disease. Case presentation: A 62-year-old man presented with a right submandibular mass that had been stable for 16 years before rapidly expanding. Imaging revealed a massive 11 cm necrotic submandibular tumor with disseminated pulmonary and hepatic metastases. Following partial debulking, pathology revealed a high-grade neuroendocrine tumor (Ki-67 index 85%) arising alongside a benign mesenchymal component. Immunohistochemistry showed diffuse CD56 positivity and TTF-1 negativity. Discussion: While histology mimics pulmonary variants, the dominant pre-existing cervical mass and chronologic evolution strongly suggest a primary salivary origin, likely representing malignant transformation of a benign lesion. Conclusion: This case highlights the rare phenomenon of primary salivary LCNEC developing within a long-standing benign mass. It underscores the importance of including high-grade neuroendocrine carcinoma in the differential diagnosis of rapidly expanding salivary lesions.