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

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.

Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Analyses of Clinicopathological, Molecular, and Prognostic Characteristics With Retrospective Review of 237 Endometrial Carcinoma Cases

“…For CD10, we examined the subcellular localization of positive immunoreactivity. In particular, CD10 immunoreactivity along the luminal surfaces of neoplastic tubules and ducts was considered as positive expression, supporting the diagnosis of MLA (2,5). p53 expression was interpreted as having a mutated pattern when one of the following staining patterns was observed: diffuse and strong nuclear immunoreactivity in ≥75% of the tumor cells (over-expression pattern); no nuclear immunoreactivity in any of the tumor cells (complete absence pattern); or an unequivocal cytoplasmic staining accompanied by variable nuclear staining (cytoplasmic pattern) (28).…”

“…A unique immunophenotype of MLA has also been documented in the literature (2,6,13,14). The following expression patterns support the diagnosis of MLA: positive immunoreactivities for mesonephric markers, including GATA-binding protein 3 (GATA3), paired box 2 (PAX2), transcription termination factor 1 (TTF1), and cluster of differentiation 10 (CD10); negative or only focal expression of hormone receptors; non-diffuse p16 positivity; and wild-type p53 immunostaining pattern (1,2,5,6,8,9). Molecular studies using targeted next-generation sequencing (NGS) revealed that patients with uterine MLA frequently harbor a pathogenic mutation in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, as well as alterations in neuroblastoma viral oncogene homolog, AT-rich interaction domain (ARID1A), phosphatidylinositol-4,5bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), βcatenin, patched 2, and tumor protein 53 (TP53) (1,8,9,15).…”

“…Four-micrometer-thick, formalinfixed, paraffin-embedded (FFPE) slices were deparaffinized and rehydrated using a xylene and alcohol solution. Immunostaining was performed using an automated instrument (Leica Biosystems, Buffalo Grove, IL, USA) (1,2,5,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). After antigen retrieval, the FFPE slices were incubated with primary antibodies against GATA3 (1:200, clone L50-823, Cell Marque, Rocklin, CA, USA), PAX2 (1:200, clone EP3251, Abcam, Cambridge, UK), CD10 (1:50, clone NCL-L-CD10-270, Novocastra, Leica Biosystems, Vista, CA, USA), TTF1 (1:1,000, clone 8G7G3/1, Dako, Agilent Technologies, Santa Clara, CA, USA), estrogen receptor (ER; 1:200, clone NCL-L-ER-6F11, Novocastra), progesterone receptor (PR; 1:200, clone PGR-312-L-CE, Novocastra), p16 (prediluted, clone E6H4, Ventana Medical Systems, Roche, AZ, USA), and p53 (1:200, clone DO-7, Dako).…”

Mesonephric-Like Adenocarcinoma of the Endometrium: Review of the Literature and Practical Diagnostic Recommendations

“…9 However, the subset of mesonephric-like tumors with frankly malignant sarcomatous elements or heterologous differentiation may be classified as mesonephric-like carcinosarcoma. 25,26,42 As the sarcomatous elements of mesonephric-like carcinosarcoma are negative for GATA3 and TTF1 14,26 and heterologous elements may be seen in both mesonephric-like and conventional uterine carcinosarcoma, careful examination of the associated carcinomatous elements is necessary for classification. The natural history of mesonephric-like carcinosarcoma (and thus the significance of distinguishing this rare entity from conventional uterine carcinosarcoma) is uncertain.…”

Mesonephric-Like Adenocarcinoma of Uterine Corpus: A Clinicopathological and Targeted Genomic Profiling Study in a Single Institution

“…However, accumulated evidence disclose MLAs do not infrequently harbor PIK3CA and PTEN alterations which are commonly seen in endometrial endometrioid carcinomas (EECs) but are very rare in MAs (11,13,16). Furthermore, extra-uterine MLAs are often associated with Müllerian lesions such as endometriosis and serous tumors (17)(18)(19)(20). This evidence has led some pathologists to suggest that MLA may represent mesonephric-like transdifferentiation of a Müllerian tumor rather than a true mesonephric tumor (9,11,13,16).…”