Neuroendocrine Cervical Carcinoma Research Articles

Multimodality Therapy in Early-Stage Neuroendocrine Carcinoma of the Uterine Cervix

Objective. Patients with early-stage neuroendocrine cervical carcinoma (NECC) have a high mortality rate despite aggressive therapy. The rarity of this tumor precludes initiation of a randomized, prospective trial. We reviewed our experience in early stage disease and performed a meta-analysis of the literature to identify prognostic factors and determine optimal multimodality therapy.Methods. Eleven women with International Federation of Gynecology and Obstetrics (FIGO) early stage (IB–IIA) NECC were treated with surgery and chemotherapy at our institutions between 1978 and 1998. Administration of radiation therapy was recorded, but not required for inclusion in this study. A gynecologic pathologist reviewed all histopathologic sections. Medical records were retrospectively reviewed and clinical data obtained. Twenty-three early-stage NECC patients who were similarly treated during the study interval were identified by a Medline search of the English literature and included in the analysis. The Kaplan–Meier method and log-rank test were used for survival analysis.Results. The overall 2-year survival rate for the 34 patients was 38%. The median age was 37 years (range, 20–75 years). Median cervical tumor diameter was 3.2 cm (range 0.5–11.0 cm). Lymphovascular space invasion was present in 21 (78%) of 27 patients (7 unknown). Fifteen (52%) of twenty-nine had lymph node metastases (5 unknown). Fifteen patients received postoperative platinum/etoposide (PE), seven received vincristine/adriamycin/cyclophosphamide (VAC), two received alternating cycles of VAC and PE, and ten received other chemotherapy regimens. Twenty women were treated with radiation therapy. The presence of lymph node metastases was a poor prognostic factor (P < 0.001). PE and VAC chemotherapy was associated with increased survival (P < 0.01).Conclusion. NECC is a highly lethal variant of cervical cancer. The presence of lymph node metastases is the most important prognostic variable. Postoperative VAC or PE appears most likely to improve chances for survival.

Coexistence of metastatic neuroendocrine carcinoma of the uterine cervix with human immunodeficiency virus infection

Abstract.Balega J, Ulbright TM, Look KY. Coexistence of metastatic neuroendorcine carcinoma of the uterine cervix with human immunodeficiency virus infection.Women now constitute 28% of new cases of human immunodeficiency virus (HIV) infection. Cervical cancer in HIV-infected women has a high recurrence and death rate, as well as decreased intervals to recurrence and death. Neuroendocrine carcinomas of the cervix are characterized by a high frequency of early nodal and distant metastases.We present the first report of a neuroendocrine carcinoma of the cervix in an HIV-positive patient. A 28 year old with a 9-year history of HIV succumbed to metastatic neuroendocrine carcinoma of the cervix 5 months after diagnosis.Given the aggressive nature of the cell type, an extended metastatic workup should be considered prior to surgery. The immune suppression present in HIV-positive patients with neuroendocrine cervical carcinoma may make such a workup particularly crucial, such that surgery is offered only to those who can be expected to benefit.

Small-Cell Neuroendocrine Carcinoma of the Cervix

Small-cell undifferentiated carcinomas comprise a rare but aggressive subset of uterine cervical neoplasms. Analogous to small-cell anaplastic carcinoma of the lung, these tumors frequently exhibit neuroendocrine differentiation. Although human papillomaviruses (HPV) types 16 and 18 are strongly associated with the development of cervical squamous carcinoma, there is as yet little information describing the relationship of these viruses to small-cell carcinomas. To address this question, we analyzed 20 cases of small-cell carcinoma of the cervix using in situ hybridization to detect HPV gene expression. In addition, immunohistochemistry was used to evaluate three markers of neuroendocrine differentiation. Eighteen of 20 tumors (90%) demonstrated some evidence of neuroendocrine differentiation; 17 of 20 (85%) expressed HPV type 16 or 18 messenger RNA. Of the neuroendocrine-positive cases, 14 of 18 expressed HPV 18 messenger RNA. In contrast, both of the cases with squamous differentiation were HPV 16 positive. These findings broaden the spectrum of HPV-associated cervical neoplasia and strongly suggest that HPV 18 is a viral type specifically associated with cervical small-cell neuroendocrine carcinomas.

Cervical Neuroendocrine Carcinoma

Fourteen primary cervical neoplasms with light microscopic features of neuroendocrine carcinoma were studied. Two were of intermediate cell type (IC), resembling the pulmonary atypical carcinoid; seven were small cell type (SC), analogous to pulmonary oat cell carcinoma; two were SC with foci of IC; three were SC with foci of squamous or adenocarcinoma. Four patients were Stage I, five were Stage II, two were Stage III, and three were Stage IV. One patient (Stage I) underwent hysterectomy and has completed radiation therapy. Two patients underwent radical hysterectomy and chemotherapy. One received radiation and chemotherapy; one received only chemotherapy; nine received radical radiation therapy. One patient (Stage I) is alive and well 10.5 years later; one (Stage II) died of other causes 24 months after diagnosis. One other is alive with the disease 12 months postdiagnosis. Eleven died secondary to tumor, four to 33 months (mean 14, median 12.5 months) after diagnosis. There was no significant difference in survival between IC and SC types, either mixed or pure. Cervical neuroendocrine carcinomas are biologically aggressive neoplasms, regardless of histologic type.