Mixed small cell carcinomas of the uterine cervix: prognostic impact of focal neuroendocrine differentiation but not of Ki-67 labeling index

Horn, Lars-Christian; Hentschel, Bettina; Bilek, Karl; Richter, Christine E.; Einenkel, Jens; Leo, Cornelia

doi:10.1016/j.anndiagpath.2005.07.019

« Previous Next »Annals of Diagnostic Pathology
Volume 10, Issue 3 , Pages 140-143, June 2006

Mixed small cell carcinomas of the uterine cervix: prognostic impact of focal neuroendocrine differentiation but not of Ki-67 labeling index

Lars-Christian Horn, MD, PhD
- Institute of Pathology, Division of Gynecologic Pathology, University of Leipzig, Leipzig D-04103, Germany
- Corresponding author. Tel.: +49 341 97 150 46; fax: +49 341 97 150 09.
Bettina Hentschel, MA
- Institute of Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig D-04103, Germany
Karl Bilek, MD, PhD
- Department of Obstetrics and Gynecology, University of Leipzig, Leipzig D-04103, Germany
Christine E. Richter, MD
- Institute of Pathology, Division of Gynecologic Pathology, University of Leipzig, Leipzig D-04103, Germany
- Department of Obstetrics and Gynecology, University of Leipzig, Leipzig D-04103, Germany
Jens Einenkel, MD
- Department of Obstetrics and Gynecology, University of Leipzig, Leipzig D-04103, Germany
Cornelia Leo, MD
- Department of Obstetrics and Gynecology, University of Leipzig, Leipzig D-04103, Germany

Abstract

Small cell neuroendocrine carcinomas sometimes represent a non–small cell component. Because of infection with the high-risk human papillomavirus of small cell carcinomas (SmCCs), several host cell regulatory proteins are altered, thus causing altered proliferative activity. Knowledge regarding the prognostic impact of focal neuroendocrine differentiation in mixed SmCCs and the value of proliferative activity in these tumors is very limited. Small cell carcinomas were selected for immunohistochemical staining with neuroendocrine markers and Ki-67. In cases with mixed tumors, the percentage of the SmCC component was calculated and correlated with survival. Of 677 tumors, 9 (1.3%) were classified as SmCCs after Grimelius staining (8/9 positive tumors) and immunohistochemical reaction against neuron-specific enolase, chromogranin A, synaptophysin (7/9 positive tumors), and CD56 (8/9 positive tumors); all specimens were positive for at least 2 of these. CD99 staining was completely negative. Two thirds of the SmCCs showed non–small cell differentiation. Four patients died of the tumor after a median time of 36.7 months (range, 15-56 months). Even an SmCC component of 17% was associated with a fatal course. Small cell carcinoma represented a significantly lower proliferation (Ki-67 labeling index) than did the non–small cell component in the same tumor (12.8% vs 70.8%; P < .001). Even a small SmCC component in mixed carcinomas of the uterine cervix was associated with adverse outcome. Proliferative activity, determined by Ki-67 labeling index, is of no prognostic value.

Keywords: Small cell carcinoma, Cervix uteri, Ki-67, MIB-1, Prognosis