Histopathology · 2026
Clinicopathological and molecular genetic characteristics of Epstein-Barr virus-positive small cell neuroendocrine carcinoma of the nasopharynx.
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Jian-Ping Lu, Yun-Li Xie, Xiao-Jiang Wang, Huan-Huan Zhu, Shu-Yi Lu, Wen-Wen Zhang, Long-Feng Ke, Gang Chen, Yan-Ping Chen
Аннотация
BACKGROUND: Epstein-Barr virus (EBV)-positive small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx) is exceptionally rare and aggressive, with poorly characterized molecular features.
METHODS: Clinicopathological, immunohistochemical (synaptophysin, INSM1, chromogranin A, CK-pan, EGFR, NUT, INI1), and molecular profiles of 15 EBV-positive SCNEC-nasopharynx cases (2012-2025) were analysed. EBV status was confirmed by EBER-ISH. Exploratory next-generation sequencing compared nine SCNEC with five EBV-positive nasopharyngeal non-keratinizing carcinomas (NKUC).
RESULTS: Patients (median age 51; male:female = 2:1) presented with advanced-stage disease and cervical lymphadenopathy. Histology showed solid nests of small cells with high-grade features. All tumours were diffusely positive for synaptophysin and EBER, showed perinuclear dot-like CK-pan staining, and were negative for squamous markers and EGFR. NUT was negative and INI1 retained. Comparative genomics revealed greater mutational burden and unique alterations enriched in cell cycle/DNA damage pathways in SCNEC versus NKUC. After multimodal therapy, median overall survival was 33 months.
CONCLUSION: This largest integrated study defines the distinct clinicopathological and molecular profile of EBV-positive SCNEC-nasopharynx. The identified diagnostic immunophenotype and potential oncogenic pathways provide a foundation for precise diagnosis and future targeted therapy development.
METHODS: Clinicopathological, immunohistochemical (synaptophysin, INSM1, chromogranin A, CK-pan, EGFR, NUT, INI1), and molecular profiles of 15 EBV-positive SCNEC-nasopharynx cases (2012-2025) were analysed. EBV status was confirmed by EBER-ISH. Exploratory next-generation sequencing compared nine SCNEC with five EBV-positive nasopharyngeal non-keratinizing carcinomas (NKUC).
RESULTS: Patients (median age 51; male:female = 2:1) presented with advanced-stage disease and cervical lymphadenopathy. Histology showed solid nests of small cells with high-grade features. All tumours were diffusely positive for synaptophysin and EBER, showed perinuclear dot-like CK-pan staining, and were negative for squamous markers and EGFR. NUT was negative and INI1 retained. Comparative genomics revealed greater mutational burden and unique alterations enriched in cell cycle/DNA damage pathways in SCNEC versus NKUC. After multimodal therapy, median overall survival was 33 months.
CONCLUSION: This largest integrated study defines the distinct clinicopathological and molecular profile of EBV-positive SCNEC-nasopharynx. The identified diagnostic immunophenotype and potential oncogenic pathways provide a foundation for precise diagnosis and future targeted therapy development.