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

Abstract

Mesonephric-like adenocarcinoma is a recently described rare neoplasm occurring in the uterine corpus and ovary. This under-recognized subtype of carcinoma can be very challenging to diagnose. In mesonephric adenocarcinoma a variety of growth patterns can be present within the same tumor, as a result of which they can be misinterpreted and diagnosed as low-grade endometrioid adenocarcinoma, clear cell carcinoma, or even serous carcinoma and carcinosarcoma. We report a case of mesonephric-like adenocarcinoma misdiagnosed as a low-grade endometrioid endometrial adenocarcinoma that had an early local recurrence and metastasized to the liver and the lungs. Histopathological, immunohistochemical and molecular analysis were performed and compared to published literature, providing a comprehensive overview of the current knowledge. Databases (Pubmed, Web of Science, Google Scholar) were searched with a combination of the following search terms: mesonephric-like, mesonephric, adenocarcinoma, carcinoma, uterine body, uterine corpus, endometrium. Mesonephric-like adenocarcinoma is a difficult-to-diagnose entity. Advanced diagnostics, including improved morphologic, immunohistochemical and molecular knowledge can help develop new therapeutic strategies against this specific subtype of endometrial cancer with an aggressive clinical behavior.

Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors

“…It has been well known that uterine MLA has a poor prognosis with frequent metastasis, particularly to the lungs in nearly half of the metastatic cases [36]. In the largest multiinstitutional study by Pors et al [7], 58.1% (25/43) of the uterine MLAs were advanced FIGO stage (II or higher) tumors at the time of diagnosis.…”

Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma

“…Data concerning the immunostaining for ER and PR on MLA obtained in this study are quite heterogeneous, while most of the previously reported cases showed negative results [4,7,17,35]. Some authors have reported that the extent of hormone receptor positivity tends to be focal to patchy, with faint-to-weak staining intensity [5,36,37].…”

“…Previous studies have indicated that the prognosis of patients with uterine MLA is significantly different from that of patients with endometrial EC [4,7,10,35]. A multiinstitutional study confirmed that uterine MLA is a clinically aggressive tumor that typically presents at an advanced stage, with a predilection for recurrent pulmonary metastasis [10].…”

“…Several studies have documented the molecular characteristics of MLAs [7,19,24,35,42]. Most MLAs harbor pathogenic KRAS mutations, and some of them also have chromosomal gains in chromosomes 1 q, 10, 12, and 20.…”

Sustained response to lenvatinib and pembrolizumab in two patients with KRAS-mutated endometrial mesonephric-like adenocarcinoma

“…Treatment of endometrial MLA varies widely. Almost all patients undergo upfront surgery, but adjuvant treatments differ and include radiation therapy, hormone therapy, or chemotherapy; the optimal adjuvant treatment regimen remains unknown ( Deolet et al, 2021 ). The use of platinum-based chemotherapy regimens in the recurrent setting has shown mixed results ( Montagut et al, 2003 ).…”