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

Hyunjin Kim,Hyun-Soo Kim,Go Eun Bae,Kiyong Na

doi:10.3390/diagnostics11112042

Abstract

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.

Highlights

Mesonephric adenocarcinoma (MA) is a rare malignant tumor of the female genital tract that is thought to derive from the embryonal remnant of the mesonephric tubules and ducts [1,2]
Twenty-five cases of uterine mesonephric-like adenocarcinoma (MLA) were diagnosed by characteristic histological features (Figure 1), including the presence of (1) a tubular growth pattern with small, closely packed, back-to-back tubules lined by cuboidal cells and containing eosinophilic intraluminal secretions, and (2) diverse architectural patterns [1,5,6,7,8,9,10,11,12,13,14,15]
Since the immunophenotypes of endometrial endometrioid carcinoma (EC) and serous carcinoma (SC) are familiar to most surgical pathologists, they are likely to perform immunohistochemical staining (IHC) using a panel of antibodies typical for common endometrial carcinomas: estrogen receptor (ER), progesterone receptor (PR), p16, and p53

Summary

Introduction

Mesonephric adenocarcinoma (MA) is a rare malignant tumor of the female genital tract that is thought to derive from the embryonal remnant of the mesonephric tubules and ducts [1,2]. It comprises less than 1% of all gynecological malignancies [3]. MA of the upper female genital tract has been referred to as mesonephric-like adenocarcinoma (MLA), as its relationship with the mesonephric remnant has not been firmly established [3,4]. MLA of the uterine corpus is only recently described: its first mention in the World Health Organization (WHO). Uterine MLA has already been vigorously studied due to its aggressive behavior, poor prognosis, and the difficulty of differentiating it from two common histological subtypes of endometrial carcinoma: endometrioid carcinoma (EC) and serous carcinoma (SC) [5,6,7,8]

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