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

  • Lars-Christian HornEmail author
  • Anne Kathrin Höhn
  • Irene Krücken
  • Mathias Stiller
  • Ulrike Obeck
  • Christine E. Brambs
Original Article – Clinical Oncology



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.


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.


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).


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.


Endometrium Cancer Mesonephric Adenocarcinoma TTF-1 Prognosis KRAS-mutation PD-L1 



The authors declare that there was no funding of the study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. Ando H, Watanabe Y, Ogawa M, Tamura H, Deguchi T, Ikeda K, Fujitani M, Shioji M, Tsujie T, Doi R, Wakimoto A, Adachi S (2017) Mesonephric adenocarcinoma of the uterine corpus with intracystic growth completely confined to the myometrium: a case report and literature review. Diagn Pathol 12(1):63CrossRefGoogle Scholar
  2. Bagué S, Rodríguez IM, Prat J (2004) Malignant mesonephric tumors of the female genital tract: a clinicopathologic study of 9 cases. Am J Surg Pathol 28(5):601–607CrossRefGoogle Scholar
  3. Byron SA, Gartside M, Powell MA, Wellens CL, Gao F, Mutch DG, Goodfellow PJ, Pollock PM (2012) FGFR2 point mutations in 466 endometrioid endometrial tumors: relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and clinicopathological features. PLoS ONE ONE 7(2):e30801CrossRefGoogle Scholar
  4. Clement PB, Young RH, Keh P, Ostör AG, Scully RE (1995) Malignant mesonephric neoplasms of the uterine cervix. A report of eight cases, including four with a malignant spindle cell component. Am J Surg Pathol 19(10):1158–1171CrossRefGoogle Scholar
  5. Corey L, Valente A, Wade K (2019) Personalized medicine in gynecologic cancer: fact or fiction? Obstet Gynecol Clin N Am 46(1):155–163CrossRefGoogle Scholar
  6. Dierickx A, Göker M, Braems G, Tummers P, Van den Broecke R (2016) Mesonephric adenocarcinoma of the cervix: case report and literature review. Gynecol Oncol Rep 17:7–11CrossRefGoogle Scholar
  7. Ervine A, Leung S, Gilks CB, McCluggage WG (2014) Thyroid transcription factor-1 (TTF-1) immunoreactivity is an adverse prognostic factor in endometrioid adenocarcinoma of the uterine corpus. Histopathology 64(6):840–846CrossRefGoogle Scholar
  8. Fregnani JH, Soares FA, Novik PR, Lopes A, Latorre MR (2008) Comparison of biological behavior between early-stage adenocarcinoma and squamous cell carcinoma of the uterine cervix. Eur J Obstet Gynecol Reprod Biol 136(2):215–223CrossRefGoogle Scholar
  9. Howitt BE, Nucci MR (2018) Mesonephric proliferations of the female genital tract. Pathology 50(2):141–150CrossRefGoogle Scholar
  10. Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA (2013) Integrated genomic characterization of endometrial carcinoma. Nature 497(7447):67–73CrossRefGoogle Scholar
  11. Kim SS, Nam JH, Kim GE, Choi YD, Choi C, Park CS (2016) Mesonephric adenocarcinoma of the uterine corpus: a case report and diagnostic pitfall. Int J Surg Pathol 24(2):153–158.CrossRefGoogle Scholar
  12. Kolin DL, Costigan DC, Dong F, Nucci MR, Howitt BE (2019) A combined morphologic and molecular approach to retrospectively identify KRAS-mutated mesonephric-like adenocarcinomas of the endometrium. Am J Surg Pathol 43(3):389–398CrossRefGoogle Scholar
  13. Labi FL, Evangelista S, Di Miscia A, Stentella P (2008) FIGO Stage I endometrial carcinoma: evaluation of lung metastases and follow-up. Eur J Gynaecol Oncol 29(1):65–66PubMedGoogle Scholar
  14. Malpica A, Euscher ED, Hecht JL, Ali-Fehmi R, Quick CM, Singh N, Horn LC, Alvarado-Cabrero I, Matias-Guiu X, Hirschowitz L, Duggan M, Ordi J, Parkash V, Mikami Y, Ruhul Quddus M, Zaino R, Staebler A, Zaloudek C, McCluggage WG, Oliva E (2019) Endometrial carcinoma, grossing and processing issues: recommendations of the international society of gynecologic pathologists. Int J Gynecol Pathol 38(Suppl 1):S9–S24CrossRefGoogle Scholar
  15. Marquette A, Moerman P, Vergote I, Amant F (2006) Second case of uterine mesonephric adenocarcinoma. Int J Gynecol Cancer 16(3):1450–1454CrossRefGoogle Scholar
  16. McFarland M, Quick CM, McCluggage WG (2016) Hormone receptor-negative, thyroid transcription factor 1-positive uterine and ovarian adenocarcinomas: report of a series of mesonephric-like adenocarcinomas. Histopathology 68(7):1013–1020CrossRefGoogle Scholar
  17. Mirkovic J, McFarland M, Garcia E, Sholl LM, Lindeman N, MacConaill L, Dong F, Hirsch M, Nucci MR, Quick CM, Crum CP, McCluggage WG, Howitt BE (2018) Targeted genomic profiling reveals recurrent KRAS mutations in mesonephric-like adenocarcinomas of the female genital tract. Am J Surg Pathol 42(2):227–233CrossRefGoogle Scholar
  18. Montagut C, Mármol M, Rey V, Ordi J, Pahissa J, Rovirosa A, Gascón P, Mellado B (2003) Activity of chemotherapy with carboplatin plus paclitaxel in a recurrent mesonephric adenocarcinoma of the uterine corpus. Gynecol Oncol 90(2):458–461CrossRefGoogle Scholar
  19. Murali R, Grisham RN, Soslow RA (2018) The roles of pathology in targeted therapy of women with gynecologic cancers. Gynecol Oncol 148(1):213–221CrossRefGoogle Scholar
  20. Na K, Kim HS (2019) Clinicopathologic and molecular characteristics of mesonephric adenocarcinoma arising from the uterine body. Am J Surg Pathol 43(1):12–25CrossRefGoogle Scholar
  21. Ordi J, Nogales FF, Palacin A, Márquez M, Pahisa J, Vanrell JA, Cardesa A (2001) Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation. Am J Surg Pathol 25(12):1540–1545CrossRefGoogle Scholar
  22. Patel V, Kipp B, Schoolmeester JK (2019) Corded and hyalinized mesonephric-like adenocarcinoma of the uterine corpus: report of a case mimicking endometrioid carcinoma. Hum Pathol 86:243–248CrossRefGoogle Scholar
  23. Pors J, Cheng A, Leo JM, Kinloch MA, Gilks B, Hoang L (2018) A comparison of GATA3, TTF1, CD10, and calretinin in identifying mesonephric and mesonephric-like carcinomas of the gynecologic tract. Am J Surg Pathol 42(12):1596–1606CrossRefGoogle Scholar
  24. Pors J, Ho J, Prentice L, Thompson E, Cochrane D, Gibbard E, Huntsman D, Gilks B, Hoang LN (2019) c-KIT analysis and targeted molecular sequencing of mesonephric carcinomas of the female genital tract. Am J Surg Pathol. CrossRefPubMedGoogle Scholar
  25. Proctor L, Pradhan M, Leung S, Cheng A, Lee CH, Soslow RA, Gilks CB, Talhouk A, McAlpine JM, Danielsen HE, Hoang LN (2017) Assessment of DNA Ploidy in the ProMisE molecular subgroups of endometrial cancer. Gynecol Oncol 146(3):596–602CrossRefGoogle Scholar
  26. Sorosky JI (2008) Endometrial cancer. Obstet Gynecol 111(2 Pt 1):436–447CrossRefGoogle Scholar
  27. Soslow RA, Tornos C, Park KJ, Malpica A, Matias-Guiu X, Oliva E, Parkash V, Carlson J, McCluggage WG, Gilks CB (2019) Endometrial carcinoma diagnosis: use of FIGO grading and genomic subcategories in clinical practice: recommendations of the international society of gynecological pathologists. Int J Gynecol Pathol 38(Suppl 1):S64–S74CrossRefGoogle Scholar
  28. Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N, Yang W, Senz J, Boyd N, Karnezis AN, Huntsman DG, Gilks CB, McAlpine JN (2015) A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 113(2):299–310CrossRefGoogle Scholar
  29. Wani Y, Notohara K, Tsukayama C (2008) Mesonephric adenocarcinoma of the uterine corpus: a case report and review of the literature. Int J Gynecol Pathol 27(3):346–352CrossRefGoogle Scholar
  30. Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih IEM, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG (2010) ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 363(16):1532–1543CrossRefGoogle Scholar
  31. Wu H, Zhang L, Cao W, Hu Y, Liu Y (2014) Mesonephric adenocarcinoma of the uterine corpus. Int J Clin Exp Pathol 7(10):7012–7019 (eCollection 2014) PubMedPubMedCentralGoogle Scholar
  32. Yamamoto S, Sakai Y (2019) Pulmonary metastasis of mesonephric-like adenocarcinoma arising from the uterine body: a striking mimicry of follicular thyroid carcinoma. Histopathology 74(4):651–653CrossRefGoogle Scholar
  33. Yamamoto Y, Akagi A, Izumi K, Kishi Y (1995) Carcinosarcoma of the uterine body of mesonephric origin. Pathol Int 45(4):303–309CrossRefGoogle Scholar
  34. Yano M, Shintani D, Katoh T, Hamada M, Ito K, Kozawa E, Hasegawa K, Yasuda M (2019) Coexistence of endometrial mesonephric-like adenocarcinoma and endometrioid carcinoma suggests a Müllerian duct lineage: a case report. Diagn Pathol 14(1):54CrossRefGoogle Scholar
  35. Zhang L, Cai Z, Ambelil M, Conyers J, Zhu H (2019) Mesonephric adenocarcinoma of the uterine corpus: report of 2 cases and review of the literature. Int J Gynecol Pathol 38(3):224–229CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Division of Gynecologic, Breast and Perinatal Pathology, Institute of PathologyUniversity Hospital LeipzigLeipzigGermany
  2. 2.Division Molecular Pathology, Institute of PathologyUniversity Hospital LeipzigLeipzigGermany
  3. 3.Department of Obstetrics and GynecologyTechnical University MunichMunichGermany

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