Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics.

Hyun Hee Koh,Hyun-Soo Kim,Eunhyang Park

doi:10.3390/diagnostics12020326

Hyun Hee Koh, Hyun-Soo Kim + Show 1 more

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https://doi.org/10.3390/diagnostics12020326

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Abstract

Mesonephric-like adenocarcinoma (MLA) arising in the ovary is a rare malignant tumor of the female genital tract. Although the clinicopathological and molecular characteristics of uterine MLA have been accumulated, those of ovarian MLA have not been firmly clarified. In this study, we investigated the clinicopathological, immunohistochemical, and genetic features of five ovarian MLAs. A review of electronic medical records and pathology slides, immunostaining, and targeted sequencing was performed. On imaging, ovarian MLA presented as either a mixed solid and cystic mass or a purely solid mass. One, three, and one patient were diagnosed as having FIGO stage IA, IC, and II MLA, respectively. Four patients with stage IC–II tumor underwent post-operative adjuvant chemotherapy. Three of the four patients whose follow-up information was available did not experience recurrence. In contrast, the remaining patient with stage IA tumor who did not receive any adjuvant treatment developed multiple metastatic recurrences at post-operative 13 months. Histologically, ovarian MLAs characteristically displayed architectural diversity, compactly aggregated small tubules, and eosinophilic intraluminal secretions. Four tumors were found to be associated with endometriotic cysts. Two cases showed some areas of high-grade nuclear atypia, brisk mitotic activity, and necrosis. Immunohistochemically, all cases showed positive immunoreactivities for at least three of the four examined mesonephric markers (GATA3, PAX2, TTF1, and CD10), lack of WT1 expression, non-diffuse p16 immunoreactivity, and wild-type p53 immunostaining pattern. Targeted sequencing analysis revealed that all four examined cases harbored pathogenic KRAS mutations: p.G12V (2/4); p.G12D (1/4); and p.G12C (1/4). In addition, we reviewed the previous literature reporting 60 cases of ovarian MLA. Our findings corroborate those of the previous data regarding the clinical presentation, histological features, immunophenotypes, and molecular alterations. Our observations should encourage pathologists to recognize and accurately diagnose this rare but distinct entity.

Highlights

Mesonephric tubules and ducts are precursors of the male genital tract present during human embryogenesis [1]
Of four cases with available tissue for immunostaining of CD10, PTEN, and mismatch repair (MMR) proteins, CD10 characteristically highlighted the luminal membrane in three cases, and all cases showed no loss of PTEN and MMR protein expression
No pathogenic mutation was detected in neuroblastoma rat sarcoma viral oncogene homolog (NRAS), tumor protein 53 (TP53), Erb-B2 receptor tyrosine kinase 2 (ERBB2), AT-rich interaction domain 1A (ARID1A), PTEN, phosphatidylinositol-4,5bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and β-catenin (CTNNB1)

Summary

Introduction

Mesonephric tubules and ducts are precursors of the male genital tract present during human embryogenesis [1]. It is thought to arise from the embryonal remnants of mesonephric tubules and ducts, and is typically located in the uterine cervix and vagina; several cases of malignant mesonephric lesions arising in the uterine corpus and adnexa have been reported [4]. Within this context, MA of the upper female genital tract has been referred to as mesonephric-like adenocarcinoma (MLA) because the association with mesonephric remnants has not been firmly established [3,4]. Our observations will allow pathologists to recognize and accurately diagnose this rare entity

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