Ovarian mesonephric-like adenocarcinoma arising in serous borderline tumor: a case report with complex morphological and molecular analysis

Abstract

Background: Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and immunohistochemical features with the more common mesonephric adenocarcinoma (MAC), which mostly arises the uterine cervix. Despite the similarities between these tumors, the histogenesis of M-LAC is still disputable. Case presentation: Sixty-one-year-old woman presented with an advanced tumor of the left ovary with intraabdominal spread and liver metastases. After receiving 5 cycles of neoadjuvant chemotherapy, she underwent a hysterectomy with bilateral salpingo-oophorectomy, and resection of the liver metastasis, omentum, and appendix. Histologically, the ovarian tumor consisted of two components, whose morphology and immunohistochemical results were typical of either a serous borderline tumor (immunohistochemical positivity for PAX8, WT1, ER and PR) or a mesonephric-like carcinoma (immunohistochemical positivity for PAX8, TTF1 and GATA3). Only the component of the mesonephric-like adenocarcinoma metastasized to the omentum and liver. A molecular analysis with a panel of 271 genes (size 1020 kbp) was performed separately on samples from the borderline tumor, primary ovarian mesonephric-like adenocarcinoma, and liver metastasis. The results showed the clonal origin of all samples, which shared the same KRAS (NM_004985.3:c.34G > T, p.(G12C)) and PIK3CA (NM_ 006218.2:c.1633G > A, p.(E545K)) somatic mutations. Moreover, in the sample from the primary mesonephric-like carcinoma and its liver metastasis a likely pathogenic somatic MYCN mutation (NM_005378.4:c.131C > T, p.(P44L) was found. In all samples, the deletion of exons 9-10 in the CHEK2 gene was present, which is in concordance with the previously performed genetic testing of the blood specimen which revealed the hereditary CHEK2 mutation in this patient.

Mesonephric-like adenocarcinoma of the ovary with co-existent endometriosis: A case report and review of the literature

“…To the best of our knowledge this case represents the thirteenth reported case of ovarian MLA and the tenth case with a Mullerian associated lesion of the same ovary ( McFarland et al, 2016 , McCluggage et al, 2018 , Dundr, 2020 ). As MLA is heterogeneous in its architecture, it is often misdiagnosed as other malignant neoplasms.…”

“…Based on a systematic literature search of the databases PubMed, Scopus, and Cochrane Library using the search terms “mesonephric-like adenocarcinomas” AND “ovary” there has been a reported 12 cases of MLA in the ovary with 8 out of those 12 cases demonstrating coexistent Mullerian lesions ( Table 1 ) ( McFarland et al, 2016 , McCluggage et al, 2018 , Dundr, 2020 ). We present a case that provides potential evidence for the Mullerian origin of MLA, due to the presence of endometriosis in the same ovary as the MLA.…”

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

“…In the literature, 115 uterine and 39 ovarian cases have been reported. Of these, 16 MLA had associated findings of Müllerian origin: adenomyosis [ 22 , 23 ], endometriosis [ 4 , 22 , 31 ], atypical hyperplasia of the endometrium (or EIN) [ 10 ], serous cystadenoma [ 4 ], mixed serous and mucinous cystadenoma [ 4 ], serous borderline tumor [ 3 , 4 , 30 ], borderline endometrioid adenofibroma [ 4 ], low-grade endometrioid endometrial carcinoma [ 28 ], low-grade serous ovarian carcinoma [ 3 , 4 ].…”

“…High-grade cytological atypia is normally not the predominant feature. Hobnail cells are a rarely reported feature [ 6 , 30 ].…”

Molecular Mechanisms of MYCN Dysregulation in Cancers

“…In addition to deregulated expression of N-MYC due to gene amplification or dysregulation at mRNA and protein levels, a recurrent somatic mutation, proline 44 to leucine (P44L) ( Figure 1A ), is identified in various tumors ( 141 ), including, glioma ( 142 ), neoplastic cysts of the pancreas ( 143 ), medulloblastoma ( 144 ), neuroblastoma ( 145 ), Wilms tumor ( 67 ), skin basal cell carcinoma ( 146 ), T-lineage acute lymphoblastic leukemia ( 147 ), NUT midline carcinoma ( 148 ), Ovarian mesonephric-like adenocarcinoma ( 149 ). Notably, P44L mutation of N-MYC has occurred in 1.7% of high-risk neuroblastoma without MYCN amplification ( 145 ).…”