Neuroendocrine cells and associated malignancies of the oral mucosa: a review

Abstract

Neuroendocrine cells of the oral mucosa constitute an under-recognized component of the diffuse neuroendocrine system with diverse subpopulations and elusive biologic roles in the oral cavity. Primary malignant oral tumors that show a neuroendocrine phenotype display histomorphologic heterogeneity thereby giving rise to a spectrum of lesions in this rare category of oral malignancy. These lesions can be divided into neuroendocrine carcinomas (NECs) of small cell or non-small cell type. The former is further subdivided into the Merkel cell type or the pulmonary type while the latter includes atypical carcinoid tumor and large cell NEC. All histologic subtypes of oral NEC appear to have a strong predilection for men in their fifth or sixth decade and arise predominantly in the non-keratinized oral mucosa. The biologic behavior of oral Merkel cell carcinomas appears to be more aggressive than those of skin. It remains to be determined whether histologic categorization of the remaining tumor subtypes is predictive of patient survival in oral neuroendocrine tumors.