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.
Highlights
Small cell carcinoma of the uterine cervix is a rare and highly malignant tumor, and its etiopathogenesis is strongly related to high-risk human papillomavirus (HPV) infections
Clinicopathological features Among 30 patients with cervical primary small cell carcinomas included in this study, 15 patients were diagnosed with pure cervical small cell carcinoma
Our study extend these findings by demonstrating that all 30 cases of cervical small cell carcinomas are related to high-risk HPV types 18 and 16, Fig. 4 HPV typing using polymerase chain reaction-reverse dot blot hybridization with predominant HPV 18 infection and multiple infections with HPV 18 and 16
Summary
Small cell carcinoma of the uterine cervix is a rare and highly malignant tumor, and its etiopathogenesis is strongly related to high-risk HPV infections. Some studies report that cervical small cell carcinoma is often associated with other cervical cancer or intraepithelial neoplasia [5], the clinicopathological features of cervical composite tumors, including small cell carcinoma, were rarely characterized. In these studies, HPV infection was detected using a variety of methods [3, 6] such as immunohistochemistry, polymerase chain reaction (PCR), in situ hybridization (ISH), reverse dot blot hybridization (RDDH), and Southern blot hybridization. Many studies revealed the preponderant infection of HPV 18 in cervical small cell carcinoma [2], but multiple infections were rarely reported
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