Primary Neuroendocrine Carcinoma in Oral and Maxillofacial Region: A Comprehensive Study of Twelve Rare Cases Including Mixed Neuroendocrine Non-Neuroendocrine Carcinoma

Neuroendocrine carcinomas (NEC) are extremely uncommon, representing 0.3% of head and neck cancers. Primary NEC arising in the oral and maxillofacial region are exceptionally rare, with <30 cases reported. Herein, we study the demographic, clinical, and pathologic features of these rare tumors, emphasizing the importance of accurate diagnosis at these sites.

Materials and Methods

A retrospective review was conducted on 12 cases of primary oral and maxillofacial NEC cases, excluding metastatic tumors and oropharynx, sinonasal, salivary, and middle ear origin cases.

Results

The cohort comprised 10 small-cell NEC (SCNEC), one large-cell NEC (LCNEC), and one mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN). With a median age of 57 years and a male-to-female ratio of 5:1, the tumors were distributed in the oral tongue (n=4), maxillary sinus (n=2), upper alveolus (2), hard palate (2), mandible (1), and buccal mucosa (1). Most (63.6%) patients were diagnosed at an advanced stage including one presenting with bone metastasis. The average tumor size was 3.5 cm. Microscopy of SCNEC cases displayed solid sheets of round cells with hyperchromatic nuclei, and scant cytoplasm while LCNEC revealed large cells with vesicular nuclei and conspicuous nucleoli. One rare MiNEN case comprised mixed small cell carcinoma and salivary duct carcinoma arising in a background of pleomorphic adenoma. Overall, the mitotic rate was 15–65/2mm2. All cases were positive for synaptophysin, chromogranin, and INSM1; seven were diffuse p16 positive. Ki67 ranged from 65-90%. Lymph node metastatic rate was 63.6%. With a median follow-up of 23 months, two patients developed recurrence, and three developed distant metastases.

Conclusions

Oral and maxillofacial NEC is an extremely rare and aggressive malignancy that mimics diverse neoplasms common in the head and neck region. Herein, we expand the morphologic spectrum of these rare tumors and underscore the importance of their accurate diagnosis for optimal patient management.