Jay R Patibandla1, Julia E Fehniger1, Douglas A Levine1, Petar Jelinic2. 1. Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, United States. 2. Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, United States. Electronic address: petar.jelinic@nyumc.org.
Abstract
OBJECTIVE: Extra-pulmonary small cell carcinomas of the gynecologic tract (EPSCC-GTs) are a rare group of aggressive malignancies associated with poor prognoses and limited treatment options. Here, we review the clinical and molecular aspects of EPSCC-GTs and discuss how understanding their molecular features can assist in their diagnosis and the identification of novel effective treatments. METHODS: We searched PubMed and Scopus for articles using the following keywords: "small cell carcinoma" in combination with "neuroendocrine", "ovary", "vagina", "fallopian tube", "vulva", "endometrium", "uterus", "cervix", or "gynecologic". Articles were limited to those published in English from January 1984 to October 2017. RESULTS: EPSCC-GTs account for 2% of all gynecologic malignancies. The molecular features of EPSCC-GTs are largely understudied and unknown, with the exception of small cell carcinoma (SCC) of the ovary, hypercalcemic type (SCCOHT) and SCC of the cervix (SCCC). In nearly all cases, SCCOHT displays mutation in a single gene, SMARCA4, a member of the SWI/SNF chromatin remodeling complex. The loss of expression of the SWI/SNF protein SMARCA2 is another feature of SCCOHT. Dual negative staining for SMARCA2 and SMARCA4 is specific for SCCOHT and is generally used by gynecologic pathologists for the accurate diagnosis of this malignancy. Mutational analysis of SCCC has shown alterations in PIK3CA, KRAS and TP53, of which the last is the most common, although other actionable mutations have been identified. The molecular features of other EPSCC-GTs are largely unknown. CONCLUSIONS: Due to their rarity, the majority of EPSCC-GTs are understudied and poorly understood. As demonstrated in the case of SCCOHT, unraveling the mutational profiles of these tumors can lead to improved diagnosis and the identification of novel therapeutic targets.
OBJECTIVE:Extra-pulmonary small cell carcinomas of the gynecologic tract (EPSCC-GTs) are a rare group of aggressive malignancies associated with poor prognoses and limited treatment options. Here, we review the clinical and molecular aspects of EPSCC-GTs and discuss how understanding their molecular features can assist in their diagnosis and the identification of novel effective treatments. METHODS: We searched PubMed and Scopus for articles using the following keywords: "small cell carcinoma" in combination with "neuroendocrine", "ovary", "vagina", "fallopian tube", "vulva", "endometrium", "uterus", "cervix", or "gynecologic". Articles were limited to those published in English from January 1984 to October 2017. RESULTS:EPSCC-GTs account for 2% of all gynecologic malignancies. The molecular features of EPSCC-GTs are largely understudied and unknown, with the exception of small cell carcinoma (SCC) of the ovary, hypercalcemic type (SCCOHT) and SCC of the cervix (SCCC). In nearly all cases, SCCOHT displays mutation in a single gene, SMARCA4, a member of the SWI/SNF chromatin remodeling complex. The loss of expression of the SWI/SNF protein SMARCA2 is another feature of SCCOHT. Dual negative staining for SMARCA2 and SMARCA4 is specific for SCCOHT and is generally used by gynecologic pathologists for the accurate diagnosis of this malignancy. Mutational analysis of SCCC has shown alterations in PIK3CA, KRAS and TP53, of which the last is the most common, although other actionable mutations have been identified. The molecular features of other EPSCC-GTs are largely unknown. CONCLUSIONS: Due to their rarity, the majority of EPSCC-GTs are understudied and poorly understood. As demonstrated in the case of SCCOHT, unraveling the mutational profiles of these tumors can lead to improved diagnosis and the identification of novel therapeutic targets.
Authors: Julia A Beaver; Robert L Coleman; Rebecca C Arend; Deborah K Armstrong; Sanjeeve Bala; Gordon B Mills; Anil K Sood; Thomas J Herzog Journal: Clin Cancer Res Date: 2019-05-24 Impact factor: 12.531
Authors: Raffaella Soldi; Tithi Ghosh Halder; Alexis Weston; Trason Thode; Kevin Drenner; Rhonda Lewis; Mohan R Kaadige; Shreyesi Srivastava; Sherin Daniel Ampanattu; Ryan Rodriguez Del Villar; Jessica Lang; Hariprasad Vankayalapati; Bernard Weissman; Jeffrey M Trent; William P D Hendricks; Sunil Sharma Journal: PLoS One Date: 2020-07-10 Impact factor: 3.240
Authors: Guido Rindi; David S Klimstra; Behnoush Abedi-Ardekani; Sylvia L Asa; Frederik T Bosman; Elisabeth Brambilla; Klaus J Busam; Ronald R de Krijger; Manfred Dietel; Adel K El-Naggar; Lynnette Fernandez-Cuesta; Günter Klöppel; W Glenn McCluggage; Holger Moch; Hiroko Ohgaki; Emad A Rakha; Nicholas S Reed; Brian A Rous; Hironobu Sasano; Aldo Scarpa; Jean-Yves Scoazec; William D Travis; Giovanni Tallini; Jacqueline Trouillas; J Han van Krieken; Ian A Cree Journal: Mod Pathol Date: 2018-08-23 Impact factor: 7.842
Authors: Sarah H Kim; Arnaud Da Cruz Paula; Thais Basili; Higinio Dopeso; Rui Bi; Fresia Pareja; Edaise M da Silva; Rodrigo Gularte-Mérida; Zhen Sun; Sho Fujisawa; Caitlin G Smith; Lorenzo Ferrando; Ana Paula Martins Sebastião; Yonina Bykov; Anqi Li; Catarina Silveira; Charles W Ashley; Anthe Stylianou; Pier Selenica; Wesley R Samore; Achim A Jungbluth; Dmitriy Zamarin; Nadeem R Abu-Rustum; Kristian Helin; Robert A Soslow; Jorge S Reis-Filho; Esther Oliva; Britta Weigelt Journal: Nat Commun Date: 2020-01-02 Impact factor: 14.919