Human Papilloma Virus 18-Positive Submucosal Small Cell Neuroendocrine Carcinoma of the Vagina: An Immunohistochemical and Genomic Study

• Published in: International journal of surgical pathology Vol. 29; no. 8; p. 870
• Main Authors: Kitazono, Ikumi, Akahane, Toshiaki, Sakihama, Mika, Yanazume, Shintaro, Matsushita, Michiko, Tabata, Kazuhiro, Kobayashi, Yusuke, Kobayashi, Hiroaki, Umekita, Yoshihisa, Tanimoto, Akihide
• Format: Journal Article
• Language: English
• Published: United States 01.12.2021
• Subjects: Aged; Biomarkers, Tumor - genetics; Carcinoma, Neuroendocrine - diagnosis; Carcinoma, Neuroendocrine - genetics; Carcinoma, Neuroendocrine - pathology; Carcinoma, Neuroendocrine - virology; Carcinoma, Small Cell - diagnosis; Carcinoma, Small Cell - genetics; Carcinoma, Small Cell - pathology; Carcinoma, Small Cell - virology; DNA Mutational Analysis; Female; Genomics; High-Throughput Nucleotide Sequencing; Human papillomavirus 18 - isolation & purification; Humans; Immunohistochemistry; Mutation; Neurofibromin 1 - genetics; Papillomavirus Infections - diagnosis; Papillomavirus Infections - genetics; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; Receptors, Androgen - genetics; Vagina - pathology; Vaginal Neoplasms - diagnosis; Vaginal Neoplasms - genetics; Vaginal Neoplasms - pathology; Vaginal Neoplasms - virology; histopathology; human papillomavirus 18; next-generation sequencing; Merkel cell carcinoma morphology; vaginal neuroendocrine carcinoma
• ISSN: 1940-2465
• DOI: 10.1177/10668969211007569

Primary vaginal neuroendocrine carcinoma (NEC) is extremely rare among female genital tract tumors. Here, we report 2 cases of vaginal small cell NEC (SCNEC) using immunohistochemistry and next-generation sequencing (NGS) analysis. The 2 patients were in their mid-to-late 70s, presented with abnormal vaginal bleeding and had a vaginal submucosal mass. The biopsied or resected tumors showed a typical neuroendocrine morphology consisting of solid nests of atypical tumor cells, with no specific organoid patterns, and proliferating in the vaginal submucosa. Immunohistochemical analysis showed strong and diffuse expression of chromogranin A, synaptophysin, and p16, but no thyroid transcription factor 1 expression. Additionally, both cases were positive for human papillomavirus (HPV) 18. An NGS-based cancer panel analysis revealed that the tumors carried and mutations, but no major driver mutations were detected. The results of this study suggested that HPV18 infection is linked to vaginal SCNEC.