Mesonephric-like adenocarcinomas of the uterine corpus: report of a case series and review of the literature indicating poor prognosis for this subtype of endometrial adenocarcinoma

Purpose: Endometrial mesonephric-like adenocarcinoma (ML-AC) represents a recently recognized subtype of endometrial adenocarcinoma (AC) associated with a subtle immunophenotype with a characteristic KRAS-mutation. Detailed clinico-pathologic analyses and prognostic data on ML-AC are limited.

Methods: We report a series of four cases with histopathological, immunohistochemical, and molecular analyses. These cases as well as the data of previously published cases were reviewed for clinico-pathologic variables and clinical follow-up information.

Results: Forty cases of ML-AC were identified. ML-AC represents about 1% of all endometrial carcinomas. Similar to other types of endometrial AC, vaginal bleeding was the leading presenting symptom, and the mean age was 60.0 years (range 31-91). More than a half of the patients presented with locally advanced disease (≥ FIGO stage II) at time of diagnosis, developed a recurrence or died of the disease within a mean follow-up period of 24.7 months (range 3-144.5 months). The most common site of distant disease was pulmonary involvement. Microscopically, ML-ACs present with mixed morphology and show a co-expression of so-called mesonephric and Müllerian markers, suggesting a Müllerian origin of the tumors. Immunostaining for PD-L1 was negative in all tested cases, using different antibodies against PD-L1. Retained staining for mismatch repair proteins on immunohistochemistry and a POLE-mutation suggest a copy number low phenotype within the molecular classification of endometrial carcinomas. Almost all cases showed a KRAS-mutation at codon 12 (mostly G12V).

Conclusion: Uterine ML-AC represents a distinct subtype of invasive endometrial AC, associated with KRAS-mutations and characteristic immunohistochemical findings. Clinically, ML-AC may show an aggressive behavior with a high rate of recurrent disease and a substantial risk for distant metastatic disease, especially to the lungs.