Mesonephric-Like Adenocarcinoma Of The Endometrium: A Potential Diagnostic Pitfall and Institutional Experience

Amin, N, Bidla, G, Nica, A, Boutross, Tadross O, Sur, M
2025 · doi:10.5281/zenodo.17239668 · W7084045445
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This paper presents an institutional case series of eight mesonephric-like adenocarcinoma (MLA) cases, highlighting the diagnostic challenges posed by its morphological similarity to low-grade endometrioid, clear cell, and mucinous carcinomas. The authors emphasize that accurate diagnosis requires a combination of morphology, immunohistochemistry, and molecular testing due to MLA’s aggressive clinical course, frequent recurrence, and tendency for distant metastasis, particularly to the lungs. A key observation noted is that some MLA cases arise in a background of atypical hyperplasia or endometriosis, which can complicate differentiation from more common endometrial subtypes. Relevance to endometriosis: The paper mentions endometriosis as a potential histological background for some MLA cases, but it is centrally about diagnosing a rare uterine cancer subtype rather than studying endometriosis itself.

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Abstract

Abstract: Background: Mesonephric-like adenocarcinoma (MLA) of the female gential tract is a recently described rare adenocarcinoma of the uterine corpus and ovary. This subtype can be very challenging to diagnose as it can mimic other endometrial carcinomas, particularly low grade endometrioid adenocarcinoma and rarely clear cell carcinoma and mucinous carcinoma. MLA of the endometrium often present at an advanced stage with frequent recurrence and distant metastasis, with the most common site being the lung. Misdiagnosis of MLA may prevent patients from benefiting from treatment that is reserved for more aggressive endometrial carcinomas. Post hysterectomy and staging, these patients receive radiation only (stage 1 or 2); and in the metastatic setting (stage 3 or 4) a combination of chemotherapy and radiation. In this case series, a total of eight MLA cases including two metastatic cases are described from a tertiary care Gynecologic Oncology disease site from the regional cancer center. Conclusion: MLA diagnosis on morphology is challenging as it can mimic a wide range of histologic patterns including endometrioid, mucinous, serous and clear cell carcinoma. Some MLA can have a background of atypical hyperplasia or endometriosis similar to endometrioid adenocarcinoma. Morphology, immunohistochemistry and molecular testing are invaluable in arriving at the diagnosis of MLA given its aggressive clinical course. Clues that may lead to further characterization include but are not limited to glomeruloid, tubular and villous morphology with bland cytology and brisk mitosis, ER/PR negativity, TTF1/GATA3 inverse positivity, PAX-8 positive, p16 negative and KRAS mutations only. All uterine carcinomas resembling low grade ER/PR negative endometrioid adenocarcinoma should have additional immunohistochemical work up and next generation sequencing testing to reach the correct diagnosis and get appropriate treatment.
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Abstract

Background: Mesonephric-like adenocarcinoma (MLA) of the female gential tract is a recently described rare adenocarcinoma of the uterine corpus and ovary. This subtype can be very challenging to diagnose as it can mimic other endometrial carcinomas, particularly low grade endometrioid adenocarcinoma and rarely clear cell carcinoma and mucinous carcinoma. MLA of the endometrium often present at an advanced stage with frequent recurrence and distant metastasis, with the most common site being the lung. Misdiagnosis of MLA may prevent patients from benefiting from treatment that is reserved for more aggressive endometrial carcinomas. Post hysterectomy and staging, these patients receive radiation only (stage 1 or 2); and in the metastatic setting (stage 3 or 4) a combination of chemotherapy and radiation. In this case series, a total of eight MLA cases including two metastatic cases are described from a tertiary care Gynecologic Oncology disease site from the regional cancer center.

Conclusion

MLA diagnosis on morphology is challenging as it can mimic a wide range of histologic patterns including endometrioid, mucinous, serous and clear cell carcinoma. Some MLA can have a background of atypical hyperplasia or endometriosis similar to endometrioid adenocarcinoma. Morphology, immunohistochemistry and molecular testing are invaluable in arriving at the diagnosis of MLA given its aggressive clinical course. Clues that may lead to further characterization include but are not limited to glomeruloid, tubular and villous morphology with bland cytology and brisk mitosis, ER/PR negativity, TTF1/GATA3 inverse positivity, PAX-8 positive, p16 negative and KRAS mutations only. All uterine carcinomas resembling low grade ER/PR negative endometrioid adenocarcinoma should have additional immunohistochemical work up and next generation sequencing testing to reach the correct diagnosis and get appropriate treatment. Files Mesonephric-Like-Adenocarcinoma-Of-The-Endometrium-A-Potential-Diagnostic-Pitfall- and-Institutional-Experience-2025.pdf Files (528.1 kB) | Name | Size | Download all | |---|---|---| | md5:e7c1883734e631a5ce9031c284c47cb6 | 528.1 kB | Preview Download | Additional details Dates - Accepted - 2025-09-19

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