Extrauterine Mesonephric-like Neoplasms: Expanding the Morphologic Spectrum

Area of Science:

• Gynecologic Pathology
• Oncology
• Molecular Pathology

Background:

• Mesonephric-like adenocarcinomas (MLA) are rare neoplasms recently classified by the WHO, found in the uterine corpus and ovary.
• These tumors share morphological and immunophenotypic similarities with cervical mesonephric adenocarcinomas, with debated origins (mesonephric vs. Mullerian).

Purpose of the Study:

• To describe the clinical, pathological, immunohistochemical, and molecular features of five rare extrauterine mesonephric-like proliferations.
• To identify novel associations and features of MLA, including origins in endometriosis and co-occurrence with other ovarian tumors.
• To investigate the potential Mullerian versus true mesonephric origin of these lesions using molecular data.

Main Methods:

• Case series analysis of five patients with extrauterine mesonephric-like proliferations.
• Detailed clinical, pathological, and immunohistochemical evaluation.
• Molecular testing (KRAS, PIK3CA variants) to analyze neoplastic components and origins.

Main Results:

• Reported novel features including MLA originating in extraovarian endometriosis and associations with high-grade serous carcinoma, mixed germ cell tumors, and mature teratomas.
• Identified a borderline ovarian endometrioid tumor with mesonephric differentiation, a previously unreported finding.
• Detected KRAS variants in four cases and PIK3CA variants in three cases, aiding in lesion confirmation and relationship determination.

Conclusions:

• These findings expand the spectrum of tumors associated with MLA and highlight a borderline tumor exhibiting mesonephric differentiation.
• Molecular testing is valuable for confirming mesonephric-like lesions and understanding relationships between neoplastic components.
• Evidence suggests a Mullerian origin in some cases, and MLA may arise from germ cell tumors in specific instances.