Premature Classification of Early-stage Endometrioid Ovarian Carcinoma With Mesonephric-like Differentiation as Mesonephric-like Adenocarcinoma

Yu Miyama, Miyama Y, Aiko Ogasawara, Ogasawara A, Kosei Hasegawa, Hasegawa K, Masanori Yasuda, Yasuda M
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · 2024 · vol. 43(4) , pp. 362–372 · doi:10.1097/pgp.0000000000001002 · PMID:38870078 · W4392378042
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This study identified 10% of endometrioid ovarian carcinomas with mesonephric-like differentiation, characterized by specific morphological and immunophenotypic features and common KRAS mutations, suggesting they are a subtype of endometrioid carcinoma.

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This study investigates whether early-stage endometrioid ovarian carcinomas with mesonephric-like differentiation represent a distinct adenocarcinoma subtype or a variant of endometrioid carcinoma. Researchers analyzed 121 malignant endometrioid tumor cases and identified ten patients exhibiting mesonephric-like morphologic patterns and immunophenotypes, all of whom had pre-existing endometriosis. The findings revealed that these tumors shared common KRAS mutations with coexisting components and showed no significant prognostic differences compared to standard endometrioid carcinomas. Consequently, the authors argue that such cases should be classified as a subtype of endometrioid carcinoma rather than mesonephric-like adenocarcinoma to prevent overtreatment in early-stage disease. This paper is centrally about endometriosis — specifically its role as a precursor lesion for this rare ovarian cancer subtype.

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Abstract

Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.
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Premature Classification of Early-stage Endometrioid Ovarian Carcinoma With Mesonephric-like Differentiation as Mesonephric-like Adenocarcinoma - Yu Miyama - Aiko Ogasawara - Kosei Hasegawa - Masanori Yasuda Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.

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Condition tags

endometriosis

MeSH descriptors

Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid

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