Clinicopathologic Characteristics of Mesonephric Adenocarcinomas and Mesonephric-like Adenocarcinomas in the Gynecologic Tract

Abstract

Mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) are uncommon neoplasms of the gynecologic tract that have until recently been poorly understood. Although their morphologic, immunohistochemical, and molecular profiles have been recently defined, little is known about their clinical behavior. Small studies have demonstrated inconsistent findings and no large studies have examined the clinical behavior of these adenocarcinomas. In this multi-institutional study, representing the largest and most stringently defined cohort of cases to date, we examined the clinicopathologic features of 99 MAs and MLAs (30 MAs of the uterine cervix, 44 MLAs of the endometrium, and 25 MLAs of the ovary). Only tumors with characteristic mesonephric morphology and either immunohistochemical or molecular support were included. Our results demonstrate that the majority of mesonephric neoplasms presented at an advanced stage (II to IV) (15/25 [60%] MA of the cervix, 25/43 [58%] MLA of the endometrium, and 7/18 [39%] MLA of the ovary). The majority (46/89 [52%] overall, 12/24 [50%] MA of the cervix, 24/41 [59%] MLA of the endometrium, and 10/24 [42%] MLA of the ovary) developed recurrences, most commonly distant (9/12 [75%] MA of the cervix, 22/24 [92%] MLA of the endometrium, and 5/9 [56%] MLA of the ovary). The 5-year disease-specific survival was 74% (n=26) for MA of cervix, 72% (n=43) for MLA of endometrium, and 71% (n=23) for MLA of ovary. Our results confirm that mesonephric neoplasms are a clinically aggressive group of gynecologic carcinomas that typically present at an advanced stage, with a predilection for pulmonary recurrence.

Mesonephric-Like Adenocarcinoma of the Endometrium: Diagnostic Advances to Spot This Wolf in Sheep’s Clothing. A Review of the Literature

“…In the literature, 115 uterine and 39 ovarian cases have been reported. Of these, 16 MLA had associated findings of Müllerian origin: adenomyosis [ 22 , 23 ], endometriosis [ 4 , 22 , 31 ], atypical hyperplasia of the endometrium (or EIN) [ 10 ], serous cystadenoma [ 4 ], mixed serous and mucinous cystadenoma [ 4 ], serous borderline tumor [ 3 , 4 , 30 ], borderline endometrioid adenofibroma [ 4 ], low-grade endometrioid endometrial carcinoma [ 28 ], low-grade serous ovarian carcinoma [ 3 , 4 ].…”

“…CD10 shows in most of the cases at least focal expression with staining of the luminal/apical surface and has a reported sensitivity of 73% and specificity of 83% [ 10 ]. Calretinin positivity can support the diagnosis but is frequently negative.…”

“…MLAs have aggressive biological behavior with more than half of the published cases presented with advanced stage (FIGO ≥ II) at diagnosis. They are associated with a considerable risk of recurrent disease with a tendency to metastasize to the lungs [ 6 , 7 , 8 , 9 , 10 ]. Not only high stage disease but also stage I disease frequently metastasizes [ 9 , 12 , 14 , 28 , 29 , 31 ].…”

“…This was confirmed by Pors et al who calculated that the stage at diagnosis was not significant for progression-free survival. They reported a 5-year overall survival of 71 to 72% for mesonephric adenocarcinomas of the uterine body and ovary [ 10 ]. Six characteristics were significantly associated with the development of metastasis, including large tumor size (>4 cm), ill-defined tumor border, advanced FIGO stages (III to IV), presence of coagulative tumor cell necrosis, high mitotic activity (>10/10 high-power fields), and presence of lymphovascular invasion.…”

“…Whole proteomic analysis, however, could not distinguish MA from MLA [ 5 ]. Most importantly, MLA is often misdiagnosed as other endometrial neoplasms, but has an aggressive clinical behavior and tend to metastasize early to the lungs [ 6 , 7 , 8 , 9 , 10 ].…”