Neuroendocrine carcinoma of cervix: a clinicopathologic study of 82 cases

Abstract

Objective: To investigate the clinicopathological characteristics and prognostic factors of neuroendocrine carcinoma (NEC) of the cervix. Methods: Eight-two patients diagnosed as NEC of cervix from 2008 to 2016 at West China Second University Hospital were analyzed retrospectively including HE slide review, immunohistochemistry and HPV genotyping. Survival analysis was performed using Kaplan-Meier and Cox regression model. Results: The age of the patients ranged from 16 to 75 years with mean age of 43 years. According to International Federation of Gynecology and Obstetrics (FIGO) clinical stage, 52 cases were in stageⅠ, 10 cases in stageⅡ, 14 cases in stage Ⅲ and 6 cases in stage Ⅳ. The tumor size ranged from 0.5 to 6.5 cm, with an average of 3.6 cm. Upon histopathologic review, 74 tumors were classified as small cell carcinoma; 7 tumors as large cell NEC, and 1 as atypical carcinoid. Further evaluation showed 52 cases (63.4%) with deep stromal invasion, 73 cases (89.0%) with lymph-vascular invasion, and 28 cases (34.2%) with pelvic and (or) para-aortic lymph nodes involvement. Immunohistochemical staining showed neuroendocrine markers Syn, CD56, NSE, S-100 protein and CgA were positive in 93.9%, 84.2%, 74.4%, 64.6% and 51.2% of cases, respectively. The results of HPV-DNA detection were positive in 72 cases, high-risk HPV types were 70 cases and 49 cases were HPV18 positive. The median follow-up time was 37 months (range, 6-101 months). Twenty-nine cases were found recurrence or metastasis, including 23 cases of death. The univariate analysis demonstrated that the tumor size, lymph node metastasis, infiltration depth, FIGO stage and whether the lesion confined to the uterus were significant prognostic factors(P<0.05). Cox multivariate analysis showed that lymph node metastasis and FIGO stage were independent prognostic factors of NEC(P<0.05). Conclusions: NEC of the cervix is a highly aggressive malignancy with poor prognosis. The tumor is associated with HPV infection, especially type 18. Small cell NEC is the most common type of cervical NEC. Diagnosis is based on histological and immunohistochemical examination. Lymph node metastasis and FIGO stage are the independent factors affecting prognosis.