Oral Cavity Neuroendocrine Neoplasms: Review Highlights Diagnostic Challenges and Management Gaps for Rare Malignancies.

Neuroendocrine neoplasms (NENs) of the oral cavity are exceptionally rare, accounting for less than 1% of all head and neck malignancies. This rarity, coupled with nonspecific clinical features and significant histopathologic overlap with other intraoral tumors, makes their definitive diagnosis particularly challenging. Unlike more common NENs, such as gastroenteropancreatic NENs, there is a critical lack of specific international guidelines for managing oral cavity NENs, forcing clinicians to extrapolate from broader head and neck protocols. This gap in specialized guidance underscores the need for a comprehensive understanding of their unique presentation and optimal management strategies.

This narrative review systematically summarized current evidence regarding the epidemiology, pathogenesis, diagnosis, and management of head and neck neuroendocrine neoplasms, with a specific focus on those arising in the oral cavity. The authors encompassed both well-differentiated and poorly differentiated forms of these rare tumors. The review synthesized available literature to outline typical clinical presentations, key immunohistochemical markers for diagnosis, and current therapeutic approaches, including surgical, chemotherapeutic, and emerging novel modalities.

Oral cavity NENs most frequently manifest as painless nodules or ulcerated masses, primarily affecting the gingiva and buccal mucosa. Definitive diagnosis hinges on integrating morphologic findings with immunohistochemistry, typically demonstrating positivity for synaptophysin, chromogranin A, and CD56. Given the absence of specific international guidelines for oral cavity NENs, current management largely follows established protocols for general head and neck NENs. > For localized disease, surgical excision remains the treatment of choice, often followed by adjuvant chemoradiotherapy. In advanced or metastatic stages, platinum-based chemotherapy may offer transient disease control but provides limited survival benefit. While novel therapeutic modalities, including immune checkpoint inhibitors and peptide receptor radionuclide therapy (PRRT), show preliminary promise, the review highlights their lack of robust clinical validation due to the rarity and heterogeneity of these tumors.