Mesonephric carcinoma (MC) is a rare cervical adenocarcinoma originating from mesonephric remnants, characterized by diverse architectural patterns and a distinct immunophenotype. A subset of adenocarcinomas in the endometrium and ovary with similar morphology but lacking association with mesonephric remnants is classified as mesonephric-like adenocarcinoma (MLA). This review synthesizes current knowledge on the clinicopathological and molecular features of MC and MLA, emphasizing their diagnostic challenges, differential diagnoses, and clinical behavior.
Mesonephric Remnants and Hyperplasia
Mesonephric remnants are vestiges of the Wolffian ducts, commonly found in the lateral cervical wall (up to one-third of specimens). Histologically, they consist of small tubules lined by cuboidal cells with eosinophilic secretions, lacking cilia or mucin. Mesonephric hyperplasia, a benign proliferation, may form discrete masses and must be distinguished from MC. Both remnants and hyperplasia exhibit positivity for PAX8, GATA3, TTF1, and luminal CD10, while being negative for ER, PR, and p16. Unlike MC, hyperplasia lacks KRAS/NRAS mutations.
Mesonephric Carcinoma
MC primarily arises in the cervix (mean age: 53 years) and is often associated with mesonephric remnants. It displays a mixture of growth patterns (tubular, papillary, ductal, solid, spindled, etc.) and PTC-like nuclear features. Immunohistochemically, MC is positive for GATA3 (95%), PAX8, TTF1 (focal), and luminal CD10, with wild-type p53 and intact MMR. Molecularly, KRAS/NRAS mutations are universal, accompanied by gain of 1q, loss of 1p, and alterations in chromatin remodeling genes (*ARID1A/B*, SMARCA4). Mutations in PIK3CA or PTEN are absent.
Mesonephric-like Adenocarcinoma
MLA occurs in the endometrium or ovary (mean age: 60 years) and lacks association with mesonephric remnants. Morphologically, it mimics MC but often shows diffuse TTF1 positivity and weaker GATA3 expression. MLA is frequently associated with Müllerian precursors (e.g., endometriosis, atypical hyperplasia). Molecularly, it shares KRAS/NRAS mutations and chromosomal gains/losses with MC but also harbors PIK3CA, PTEN, or CTNNB1 mutations, suggesting a Müllerian origin with mesonephric differentiation.
Differential Diagnosis
The morphological diversity of MC/MLA necessitates distinction from:
Endometrioid Adenocarcinoma: ER/PR-positive, often with squamous/mucinous differentiation.
Clear Cell Carcinoma: Positive for Napsin A, HNF1-beta, and AMACR.
High-Grade Serous Carcinoma: Exhibits TP53 mutations and significant nuclear atypia.
FATWO and STK11 Adnexal Tumors: FATWO is PAX8-negative; STK11 tumors show STK11 alterations.
Conclusions
MC and MLA are aggressive neoplasms with overlapping morphological and immunophenotypic features. MC arises from mesonephric remnants, while MLA likely originates from Müllerian epithelium undergoing mesonephric differentiation. Molecular profiling (KRAS/NRAS mutations with/without *PIK3CA/PTEN* alterations) aids in distinguishing these entities. Both exhibit a propensity for distant metastasis, underscoring the need for accurate diagnosis and vigilant monitoring.
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The study was recently published in the Journal of Clinical and Translational Pathology .
Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.
