Small cell neuroendocrine carcinoma of uterine cervix with expressions of KIT, PDGFRA and bcl-2 and with long survival

Abstract

Primary small cell neuroendocrine carcinoma (SNEC) of uterine cervix is very rare; about 30 cases have been reported in literature. However, there have been no studies of KIT, PDGFRA, and bcl-2 in SNET of cervix. A 91-year-old woman presented vaginal bleeding which subsided by hemostatic drugs and balloon catheterization. Colposcopy showed a small tumor (6 mm) cervix and biopsy showed necrotic tissue and small atypical cells. They showed epithelioid features, small size, increased nucleo-cytoplasmic ratio, hyperchomatic nuclei, molded nuclei, scant cytoplasm, and absent nucleoli, thus fulfilling the criteria of SNEC of WHO. Immunohistochemically, tumor cells were positive for cytokeratin (CK) CAM5.2, CK AE1/3, CK7, CK8, CK18, CK19, NSE, synaptophysin, NCAM, KIT, PDGFRA, bcl-2, p53, and Ki-67 (labeling index = 100%). The tumor cells were negative for CK5, CK6, CK34BE12, CK14, CK20, EMA, chromogranin, CD45, CD138, CD20, CD3, CD99 (MIC-2), vimentin, S100 protein, α-smooth muscle actin, desmin, and myoglobin. Since neuroendocrine antigens (NSE, NCAM, synaptophysin, KIT and PDGFRA) were positive, a diagnosis of primary SNEC of cervix was made. Post-biopsy whole body studies revealed no other tumors. The patient rejected medical, surgical interventions because of very old age. She was followed-up, a mass of 5 cm was found in pelvic cavity. The patient is now alive 8 years after the diagnosis. The present case is the first of primary SNEC of cervix demonstrating positive KIT, PDGFRA, and bcl-2 proteins in a very old woman. The tumor was positive for many stem cells antigens, suggesting that the SNEC is a stem cell malignancy.