Small cell neuroendocrine carcinomas of the uterine cervix: a histological, immunohistochemical, and molecular genetic study.

Small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. Although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. In this study, the authors tentatively defined small cell neuroendocrine carcinoma (SCNEC) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin A immunoreactivity, and synaptophysin immunoreactivity. We found 10 cases fulfilling these requirements. Five of the 10 tumors were composed mainly of small ("oat") cells and 5 of mainly larger "intermediate" cells. The majority of both subtypes showed an insular pattern. Three of the 10 SCNECs were pure, whereas the other seven were mixed with adenocarcinoma and/or squamous cell carcinoma or cervical intraepithelial neoplasia. In addition to the definitional markers noted earlier, the tumors were immunoreactive for serotonin (6 cases), somatostatin, gastrin, glucagon, and pancreatic polypeptide. No tumors were immunoreactive for cytokeratin 20. Human papillomavirus (HPV)-18 was detected in all of the pure tumors and both the SCNEC and adenocarcinomatous components in four of the mixed tumors. No other types of HPV were detected. The tumors showed a relatively low frequency of loss of heterozygosity for representative tumor suppressor gene sites; p53 mutations were found in only one case.