Clinicopathological Features of Epstein-Barr Virus-Positive Neuroendocrine Carcinoma: Analysis of Twenty-Two Cases.

Abstract

Epstein-Barr Virus (EBV)-positive neuroendocrine carcinoma (NEC) is a rare neoplasm with limited histopathological and therapeutic data. This report presents 22 cases of EBV-positive NEC, analyzing age distribution, morphology, and immunophenotype. The median patient age was 47 years (range: 27-67 years), with a male-to-female ratio of 17:5. Most cases (86%, 19/22) were localized to the nasal cavity or nasopharynx, while the remaining three (14%, 3/22) involved the lung, eyelid, and chest wall. Tumors were identified as small cell neuroendocrine carcinoma (SCNEC) or large cell neuroendocrine carcinoma (LCNEC) based on cellular morphology. Immunohistochemical analysis showed positivity for at least one, but generally, two neuroendocrine markers and INI1, while negativity for NUT and squamous cell carcinoma markers, such as p63, p40, and CK5/6. In situ hybridization consistently revealed EBV early RNAs (EBERs) in all cases. Notably, eight patients benefited from chemoradiotherapy. Recognizing this rare tumor is essential for optimizing treatment strategies.