Small Cell Neuroendocrine Carcinomas of the Uterine Cervix: A Histological, Immunohistochemical, and Molecular Genetic Study

Abstract

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.

Clinicopathological features and prognosis of small cell carcinoma of the cervix

“…Generally speaking, SCCC is highly aggressive with regard to its biological behaviors. A previous study showed that the undifferentiated carcinoma of SCCC was closely related to HPV18 infection [11][12][13] . Herrington et al [14] believed that the absence of expression of pRb immunocompetence was likely to result from the combination of pRb with E7 protein of HPV virus, and, in SCCC, the lack of immunocompetence of pRb was related with the endocrine phenotype of small cells, which contributes to its aggressive behaviors.…”

Neuroendocrine Small Cell Carcinoma of the Cervix Associated with Endocervical Adenocarcinoma

“…The coexistence of a non-small cell component has recently been molecularly analyzed in SCCs of the cervix 7 and urinary bladder 9 and has led to the tentative conclusion that both components may have originated from undifferentiated multipotential or stem cells in the mucosa. Similarly, and despite the evidence of biphenotypical differentiation, the nearly identical pattern of allelic loss in our SCC and concomitant ADC support the hypothesis that they shared the same cellular origin.…”

“…Although originally believed to be an uncommon subtype of SCC, cervical SCC 6 is now recognized as a rare but distinct entity belonging to the neuroendocrine group of cervi- cal carcinomas, morphologically resembling SCC of the lung and clinically characterized by an aggressive course and unfavorable outcome. 7,8 Because some cervical SCCs (up to 70% according to some authors 7 ) may show a mixed or adjacent non-SCC component (ADC or squamous carcinoma) in the presence of SCC tumoral cells, it is important to seek malignant squamous or glandular cells. We failed to recognize the glandular component in our case on first screening and only found it on subsequent examination, when we were aware of the histologic diagnosis.…”

Human Papillomavirus Genotype Distribution among Thai Women with High-Grade Cervical Intraepithelial Lesions and Invasive Cervical Cancer: a Literature Review

“…Available evidences based on only a constrained number of NECA cases demonstrate that almost all of NECA cases are associated with HPV 16 and/or HPV 18. However, in contrast to that noted in SCCA, the most prevalent HPV type among NECA cases is HPV 18, followed by HPV 16 (Masumoto et al, 2003;Ishida et al, 2004;Wang et al, 2006). In a study from Northern Thailand which is the largest study conducted to determine HPV genotype distribution in NECA, almost 90% of cases of NECA are HPV 16 and/or HPV 18-related.…”