PTEN Loss and ARID1A Mutation in an HPV-positive Metastatic Adenocarcinoma Diagnosed Almost 18 yr After an Intact Cone Excision for Endocervical Adenocarcinoma In Situ.

ABSTRACT

There have been previous reports of neoplasms with the morphology of endocervical adenocarcinoma in situ (AIS) that secondarily involve the ovaries, presumably through transtubal spread, with a smaller subset metastasizing to distant sites. These ovarian metastases have been discovered up to 7 yr postexcision of the endocervical lesion, consistent with the known potential for overtly invasive cervical carcinomas to recur late after primary curative management. Herein, we present a case of a premenopausal woman with a pelvic mass classified as metastatic human papillomavirus (HPV)-associated endocervical adenocarcinoma (p16-block immunoreactive, high-risk HPV positive by in situ hybridization with PTEN loss, ARID1A, and PBRM1 mutations detected by qualitative next-generation sequencing), identified 17.7 yr (212 mo) after a fertility-sparing cone excision with negative margins for endocervical AIS [HPV-associated, p16-block immunoreactive; PTEN, and BAF250a (ARID1a) expression retained]. Our case highlights (1) the potential for a subset of lesions with the morphology of AIS to metastasize, and the extraordinarily long timeframe (almost 18 y, the longest reported to date) during which metastases may still be identified; (2) alterations in PTEN and ARID1A may play a role in the progression of a subset of endocervical carcinomas; and (3) the need for studies to evaluate the utility of incorporating ovarian/pelvic imaging into surveillance protocols following fertility-sparing excisions or ovarian-preserving hysterectomies, during the management of endocervical adenocarcinomas, as well as the need to counsel patients about the small but real risk of delayed discovery of ovarian metastases following fertility-preserving surgeries for AIS.