Mesonephric adenocarcinoma (MNAC) is a rare tumor of the female genital tract mainly occurring in the uterine cervix. To date, only a few cases of MNAC arising from of the uterine body (UB-MNAC) have been reported. The clinicopathologic and molecular characteristics of UB-MNAC remain unknown. In this study, we investigated the clinical, histopathologic, immunohistochemical, and genetic features of UB-MNAC. In total, 11 cases were included. Six patients developed metastatic disease, most commonly in lungs (5/6). Histopathologically, UB-MNAC was characterized by an admixture of tubular, glandular, papillary, retiform, glomeruloid, sex cord-like, and comedonecrosis-like architectural patterns. Three adverse pathologic characteristics, including advanced International Federation of Gynecology and Obstetrics stage, high mitotic activity, and presence of lymphovascular the invasion, were independent factors predicting the development of metastasis. All cases were positive for GATA-binding protein 3 and paired box 2 expression and showed wild-type p53, patchy p16, and preserved PTEN expression, as indicated by immunohistochemistry. Next-generation sequencing using 12 samples (11 primary tumors and 1 metastatic tumor) revealed 42 single nucleotide variations in 16 genes, mostly in KRAS (10/12) and ARID1A (9/12). Copy number variation was found in 16 genomic regions, and consisted of 57 gains and 10 losses, with 1q gain (11/12) being the most prevalent. In conclusion, UB-MNAC displays an aggressive biological behavior, with a tendency to metastasize to the lungs. Adverse pathologic characteristics reflect the aggressive nature of UB-MNAC. Distinct molecular features of UB-MNAC include frequent somatic mutations of KRAS and ARID1A and gain of 1q.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Mesonephric-like adenocarcinoma (MLA) of the uterine corpus is a rare but distinct malignant tumor of the female genital tract, demonstrating a characteristic morphology and unique immunohistochemical profiles and molecular alterations. We conducted immunohistochemical staining (IHC) to make precise differential diagnoses of uterine MLAs from common histological subtypes of endometrial carcinomas. We collected 25 uterine MLAs and performed IHC for GATA3, TTF1, CD10, ER, PR, p16, p53, and HER2. Seventeen cases (68.0%) showed at least moderate nuclear GATA3 immunoreactivity in ≥25% of tumor cells. Most cases expressed TTF1 (17/21, 81.0%) and CD10 (luminal; 17/21, 81.0%). Heterogeneous TTF1 expression was noted in 12 cases. An inverse pattern of GATA3 and TTF1 staining was observed in eight cases (32.0%). Three cases (12.0%) showed moderate-to-strong ER expression in ≥25% of tumor cells, and two cases (8.0%) showed moderate-to-strong PR expression in ≥5% of tumor cells. These hormone receptor-positive MLAs varied in intensity and proportion of GATA3 staining. None of the 25 cases exhibited either diffuse and strong p16 expression or aberrant p53 expression. Five cases (20.0%) showed equivocal HER2 immunoreactivity (score 2+), but HER2 FISH confirmed that none of them exhibited HER2 gene amplification. In summary, a small subset of uterine MLAs displayed atypical IHC results: focal but strong expression of ER or PR, the complete absence of GATA3 immunoreactivity, the concurrent expression of mesonephric and hormone receptors, and the inverse pattern of GATA3 and TTF1 staining. These unusual immunophenotypes may complicate the differential diagnosis of MLA. Moreover, pathologists should be encouraged to interpret the IHC results cautiously.