Oral and Maxillofacial Neuroendocrine Carcinoma: A Systematic Review

Head Neck Pathol. 2022 Jun;16(2):525-537. doi: 10.1007/s12105-021-01398-2. Epub 2021 Dec 6.


The aim of the present study was to integrate the available data published in the literature on oral and maxillofacial neuroendocrine carcinomas concerning the demographic, clinical and histopathological features of this condition. An electronic search with no publication date restriction was undertaken in April 2021 in four databases. Eligibility criteria included reports published in English having enough data to confirm a definite diagnosis, always showing a neuroendocrine marker. Cases originating in the oropharynx, including base of the tongue and tonsils, were excluded. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. Twenty-five articles (29 cases) from nine different countries were detected. Mean patient age was 56.3 (± 17.5) years, with a slight male predilection. Symptomatology was present in 72.2% of informed cases. Regarding clinical presentation, a non-ulcerated nodule located in the gingiva with a mean size of 3.4 (± 2.0) cm was most frequently reported. Concomitant metastasis was identified in seven individuals. Histopathologically, most neoplasms were of the small cell type, and immunohistochemistry for both epithelial and neuroendocrine differentiation was used in 65.5% cases. Radical surgery was the treatment of choice in almost all cases, with or without adjuvant therapy. Mean follow-up was 20.5 (± 21.2) months, and only four patients developed recurrences. Eleven (44.0%) individuals died due to the disease. Ulcerated lesions were a prognostic factor. This study provides knowledge that can assist surgeons, oncologists, and oral and maxillofacial pathologists with the diagnosis and management of neuroendocrine carcinomas. Our findings demonstrated that the long-term prognosis of this lesion continues to be poor.

Keywords: High-grade neuroendocrine carcinoma; Large cell carcinoma; Neuroendocrine neoplasm; Neuroendocrine tumors; Poorly differentiated neuroendocrine carcinoma; Small cell carcinoma.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Neuroendocrine* / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis