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

• Published in: Journal of cancer research and clinical oncology Vol. 146; no. 4; pp. 971 - 983
• Main Authors: Horn, Lars-Christian, Höhn, Anne Kathrin, Krücken, Irene, Stiller, Mathias, Obeck, Ulrike, Brambs, Christine E.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2020; Springer Nature B.V
• Subjects: Adenocarcinoma; Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Cancer Research; Carcinoma; Carcinoma, Endometrioid - diagnosis; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - metabolism; Carcinoma, Endometrioid - pathology; Case reports; Copy number; Diagnosis, Differential; Endometrial cancer; Endometrial Neoplasms - diagnosis; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endometrium; Female; Hematology; Humans; Immunohistochemistry; Internal Medicine; Invasiveness; K-Ras protein; Literature reviews; Lung diseases; Medicine; Medicine & Public Health; Metastases; Middle Aged; Mismatch repair; Mutation; Oncology; Original Article – Clinical Oncology; PD-L1 protein; Phenotypes; Prognosis; Tumors; Uterine cancer; Uterus; Vagina; Adenocarcinoma; mutation; Prognosis; PD-L1; Mesonephric; TTF-1; Endometrium; Cancer; KRAS-mutation
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-019-03123-7

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.