An Ovarian Adenocarcinoma With Combined Low-grade Serous and Mesonephric Morphologies Suggests a Müllerian Origin for Some Mesonephric Carcinomas

Abstract

Mesonephric carcinomas are rare adenocarcinomas of the female genital tract that occur most commonly in the uterine cervix. They are classically thought to arise from benign mesonephric remnants, and are rarely reported at other sites in the gynecologic tract. Here we present an interesting biphenotypic ovarian adenocarcinoma with intimately associated but distinct components of both low-grade serous carcinoma and mesonephric-like carcinoma. A serous borderline tumor was present adjacent to the invasive carcinoma, and no benign mesonephric precursors were identified. Numerous invasive peritoneal metastases were present, including multiple metastases with both low-grade serous and mesonephric-like elements. Consistent with recent reports, foci of mesonephric-like carcinoma were morphologically and immunohistochemically identical to classic mesonephric carcinoma of the cervix. On molecular analysis, the serous borderline tumor, primary and metastatic low-grade serous carcinoma, and primary and metastatic mesonephric-like carcinoma each harbored a shared NRAS p.Q61R hotspot mutation, shared gains in chromosome 1q and 18p, and shared losses in chromosomes 1p, 18q, and 22. These shared molecular features indicate a clonal relationship between all morphologic elements of this ovarian adenocarcinoma, suggesting that at least some mesonephric carcinomas may arise from Müllerian precursors.

Mesonephric Adenocarcinoma Arising From The Uterine Corpus：Case Reports and Literature Review

“…Another recently published two papers presented two ovarian adenocarcinomas with combined low-grade serous and mesonephric morphologies, also suggest a Müllerian Origin for some Mesonephric Carcinomas. [22,24] Given the previously documented association with endometriosis (ovarian neoplasms) [24] and the prominent endometrial involvement (uterine corpus neoplasms) [21] , these tumors are best regarded as of Mullerian origin and representing adenocarcinomas which differentiate along mesonephric lines.…”

“…Mesonephric adenocarcinoma (MNAC) is a rare carcinoma that originates from mesonephric remnant of the female genital tract [1][2][3] , and are predominantly located on the lateral walls of the cervix and vagina [4] . Of the cases reported to date, the vast majority of MNAC are from uterine cervix [1,2,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] ., , comprising<1% of all carcinomas at this site [20] , several cases of MNAC are from ovary [21][22][23][24] , and rare cases are from vagina [4,7,[25][26][27][28][29] and uterine corpus [4,11,21,[30][31][32][33][34][35][36][37][38][39][40]…”

“…Although the authors presume that these neoplasms might represent a new type of endometrioid adenocarcinomas, considering the immunohistochemical and histologic characteristics they found, they were in favor of that these tumors were "true" mesonephric neoplasms but admitted the uncertainty in their pathogenesis, so they termed them as "mesonephric-like" adenocarcinomas [21] . Molecular analyses suggest that MLACs are characterized by recurrent KRAS-mutations as well as unique immunohistochemical features and an aggressive clinical course [24,44,46] .One research demonstrated that PIK3CA mutations, which have not previously been identi ed in cervical MNAC, were found in 3 of 7 (43%) MLAC in uterine corpus, and thus raised the question about possible Mullerian origin of the uterine corpus MLAC [46] .…”

Endometriosis‐related pathology: a discussion of selected uncommon benign, premalignant and malignant lesions

“…65 Recently, two studies reported single ovarian neoplasms with distinct areas of mesonephric-like carcinoma and serous borderline tumour/low-grade serous carcinoma. 66,67 In the two cases, both components contained an identical KRAS or NRAS mutation, suggesting that they were clonally related and did not represent collision tumours. It was concluded in both studies that it was likely that the serous tumour was the 'parent' neoplasm and that the mesonephric-like carcinoma developed from the serous component, and these studies provide additional evidence that mesonephric-like carcinomas are of Mullerian origin.…”

“…Recently, two studies reported single ovarian neoplasms with distinct areas of mesonephric‐like carcinoma and serous borderline tumour/low‐grade serous carcinoma . In the two cases, both components contained an identical KRAS or NRAS mutation, suggesting that they were clonally related and did not represent collision tumours.…”