Cervical small cell carcinoma frequently presented in multiple high risk HPV infection and often associated with other type of epithelial tumors

Abstract

BackgroundSmall cell carcinoma of the uterine cervix is a rare and highly malignant tumor, and its etiopathogenesis is strongly related to high-risk HPV infections.MethodsThe clinicopathological data of 30 cases of cervical primary small cell carcinoma were retrospectively analyzed. In situ hybridization, polymerase chain reaction and reverse dot-blot hybridization were employed to detect HPV DNA in both small cell carcinoma and other coexisting epithelial tumors. Immunohistochemistry was used to detect the protein expression of p16 and p53.ResultsAmongst 30 patients with cervical primary small cell carcinoma, 15 patients simultaneously exhibited other types of epithelial tumors, including squamous cell carcinoma, adenocarcinoma, squamous cell carcinoma in situ, and adenocarcinoma in situ. Most tumor cells infected with HPV presented integrated patterns in the nuclei by in situ hybridization. HPV DNA was detected in every small cell carcinoma case (100%) by polymerase chain reaction and reverse dot blot hybridization. 27 cases (90%) harbored type 18, and 15 (50%) displayed multiple HPV18 and 16 infections. The prevalence of HPV 18 infection in small cell carcinoma was higher than in cervical squamous and glandular epithelial neoplasms (P = 0.002). However, similar infection rates of HPV 16 were detected in both tumors (P = 0.383). Both small cell carcinoma and other types of epithelial tumors exhibited strong nuclear and cytoplasmic staining for p16 in all cases. Three cases of small cell carcinoma revealed completely negative p53 immunohistochemical expression in 15 cases of composite tumors, which suggested TP53 nonsense mutation pattern. The pure small cell carcinoma of uterine cervix had similar mutation or wild type pattern for TP53 compared with composite tumor (P = 0.224).ConclusionsCervical small cell carcinomas are often associated with squamous or glandular epithelial tumors, which might result from multiple HPV infections, especially HPV 16 infection. Multiple HPV infections were not correlated with tumor stage, size, lymphovascular invasion, lymph node metastasis, or prognosis. Furthermore, careful observation of specimens is very important in finding little proportion of small cell carcinoma in the composite lesions, specifically in cervical biopsy specimens, in order to avoid the missed diagnosis of small cell carcinoma.

Neuroendocrine small cell carcinoma of the cervix: A case report

“…Small Cell Neuroendocrine carcinoma (SCNEC) can be found anywhere in the gynecological tract, but is most commonly observed in the cervix (4). The causative agent underlying the development of this malignancy is Human Papilloma Virus (HPV) (5)(6)(7).…”

Histology-specific FGFR2 alterations and FGFR2-TACC2 fusion in mixed adenoid cystic and neuroendocrine small cell carcinoma of the uterine cervix

“…Few cases have been described whereby NESCC of the cervix is intermixed with a second cell lineage, including adenocarcinoma and squamous cell carcinoma ( Alphandery et al, 2007 , Toki et al, 1996 , Horn, 2006 , Li, 2018 , Ishida, 2004 ). Three cases have been reported where adenoid cystic carcinoma (ACC) were involved with squamous cell carcinoma in the cervix ( Shi, 2015 ).…”

Small Cell Carcinoma as an Independent Prognostic Factor for Cervical Cancer Patients: A Population-Based Analysis

“…The mechanism was not yet clear due to its rarity. Some studies have shown that most patients with SmCC of cervix were etiologically associated with high-risk HPV, especially HPV 18, and that HPV infection was involved at an early stage of oncogenesis in SmCC of cervix [30][31][32]. Moreover, SmCC of cervix are characterized by high mitosis, massive necrosis and common lymph-vascular involvement [33].…”