Research Article | | Peer-Reviewed

Mesonephric-Like Adenocarcinoma of the Endometrium Mimicking Advanced Tubo-Ovarian Cancer - A Literature Review Based on a Special Case

Received: 6 September 2023    Accepted: 28 September 2023    Published: 17 November 2023
Views:       Downloads:
Abstract

Mesonephric-like adenocarcinoma of the endometrium (ML-AC) is a rare variant of endometrial adenocarcinoma with aggressive clinical behavior and unusual metastatic spread. Because of its rarity, the diagnosis may be challenging but needs to be accurate due to the mostly poor prognostic outcome of these tumors. To aid in the understanding and recognition of this entity we present the detailed histopathological, immunohistochemical and molecular analysis of a case of ML-AC clinically mimicking advanced ovarian cancer in a 55-year-old woman and put it in the context of literature research on ovarian and endometrial carcinomas. In the present case the patient revealed abdominal distension, ascites and a moderately elevated CA-125 level (504.8 U/ml) with widespread peritoneal carcinomatosis and an endometrial lesion confined to the endometrium with the presence of free-floating tumor cells within the tubal lumen, suggesting transtubal peritoneal spread of the endometrial primary. All tumor sites shared various architectural patterns on histology with negative staining for p16, WT-1 and estrogen receptor and positivity for TTF-1. Matched pair molecular analysis revealed an identic clonal KRAS-mutation (p.G12C) within the endometrial, peritoneal and lymph node involvement as well as in the recurrent tumor. There was retained mismatch repair protein staining and p53 wild type pattern without any additional mutational alterations, including POLE. A hepatic recurrence was diagnosed after 11 months. Literature study confirms our findings and the suggestion of a morphomolecular diagnostic approach additional to the fact that KRAS-mutation may represent a targetable alteration within a specialized therapeutic approach for this entity.

Published in Cancer Research Journal (Volume 11, Issue 4)
DOI 10.11648/j.crj.20231104.12
Page(s) 127-135
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Endometrium, Cancer, Mesonephric, Adenocarcinoma, TTF-1, Prognosis, KRAS-Mutation, Ovarian

References
[1] Kolin DL, Costigan DC, Dong F, Nucci MR, Howitt BE. A Combined Morphologic and Molecular Approach to Retrospectively Identify KRAS-Mutated Mesonephric-like Adenocarcinomas of the Endometrium. Am J Surg Pathol. 2019 Mar; 43 (3): 389-398.
[2] Pors J, Cheng A, Leo JM, Kinloch MA, Gilks B, Hoang L. A Comparison of GATA3, TTF1, CD10, and Calretinin in Identifying Mesonephric and Mesonephric-like Carcinomas of the Gynecologic Tract. Am J Surg Pathol. 2018 Dec; 42 (12): 1596-1606.
[3] Ma T, Chai M, Shou H, Ru G, Zhao M. Mesonephric-Like Adenocarcinoma of Uterine Corpus: A Clinicopathological and Targeted Genomic Profiling Study in a Single Institution. Front Oncol. 2022 Jul 5; 12: 911695.
[4] Deolet E, Van Dorpe J, Van de Vijver K. Mesonephric-Like Adenocarcinoma of the Endometrium: Diagnostic Advances to Spot This Wolf in Sheep's Clothing. A Review of the Literature. J Clin Med. 2021 Feb 11; 10 (4): 698.
[5] Pors J, Ho J, Prentice L, Thompson E, Cochrane D, Gibbard E, Huntsman D, Gilks B, Hoang LN. c-KIT Analysis and Targeted Molecular Sequencing of Mesonephric Carcinomas of the Female Genital Tract. Am J Surg Pathol. 2020 Apr; 44 (4): 495-502.
[6] Kim HG, Kim H, Yeo MK, Won KY, Kim YS, Han GH, Kim HS, Na K. Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Analyses of Clinicopathological, Molecular, and Prognostic Characteristics With Retrospective Review of 237 Endometrial Carcinoma Cases. Cancer Genomics Proteomics. 2022 Jul-Aug; 19 (4): 526-539.
[7] Kim H, Na K, Bae GE, Kim HS. Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors. Diagnostics (Basel). 2021 Nov 4; 11 (11): 2042.
[8] 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. Targeted Genomic Profiling Reveals Recurrent KRAS Mutations in Mesonephric-like Adenocarcinomas of the Female Genital Tract. Am J Surg Pathol. 2018 Feb; 42 (2): 227-233.
[9] Al Nabhani S, Doyle A, Kennedy S, McVey R, Crown J, Gibbons D. Endometrial Mesonephric-like Adenocarcinoma Presenting as an Ocular Lesion: A Case Report. Int J Gynecol Pathol. 2022 Mar 1; 41 (2): 161-167.
[10] Euscher ED, Bassett R, Duose DY, Lan C, Wistuba I, Ramondetta L, Ramalingam P, Malpica A. Mesonephric-like Carcinoma of the Endometrium: A Subset of Endometrial Carcinoma With an Aggressive Behavior. Am J Surg Pathol. 2020 Apr; 44 (4): 429-443.
[11] Mills AM, Jenkins TM, Howitt BE, Fan J, Ring KL, Cook I. Mesonephric-like Endometrial Carcinoma: Results From Immunohistochemical Screening of 300 Endometrial Carcinomas and Carcinosarcomas for This Often Overlooked and Potentially Aggressive Entity. Am J Surg Pathol. 2022 Jul 1; 46 (7): 921-932.
[12] da Silva EM, Fix DJ, Sebastiao APM, Selenica P, Ferrando L, Kim SH, Stylianou A, Da Cruz Paula A, Pareja F, Smith ES, Zehir A, Konner JA, Cadoo K, Reis-Filho JS, Abu-Rustum NR, Mueller JJ, Weigelt B, Park KJ. Mesonephric and mesonephric-like carcinomas of the female genital tract: molecular characterization including cases with mixed histology and matched metastases. Mod Pathol. 2021 Aug; 34 (8): 1570-1587.
[13] Momeni-Boroujeni A, Nguyen B, Vanderbilt CM, Ladanyi M, Abu-Rustum NR, Aghajanian C, Ellenson LH, Weigelt B, Soslow RA. Genomic landscape of endometrial carcinomas of no specific molecular profile. Mod Pathol. 2022 Sep; 35 (9): 1269-1278.
[14] Horn LC, Höhn AK, Krücken I, Stiller M, Obeck U, Brambs CE. 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. J Cancer Res Clin Oncol. 2020 Apr; 146 (4): 971-983.
[15] Sorosky JI. Endometrial cancer. Obstet Gynecol. 2008 Feb; 111 (2 Pt 1): 436-47.
[16] Reijnen C, Visser NC, Kasius JC, Boll D, Geomini PM, Ngo H, Van Hamont D, Pijlman BM, Vos MC, Bulten J, Snijders MP, Massuger LF, Pijnenborg JM. Improved preoperative risk stratification with CA-125 in low-grade endometrial cancer: a multicenter prospective cohort study. J Gynecol Oncol. 2019 Sep; 30 (5): e70.
[17] Koh HH, Park E, Kim HS. Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics. Diagnostics (Basel). 2022 Jan 27; 12 (2): 326.
[18] Han Y, Liu C. Clinicopathological characteristics and prognosis of uterine serous carcinoma: A SEER program analysis of 1016 cases. J Obstet Gynaecol Res. 2021 Jul; 47 (7): 2460-2472.
[19] Åkesson Å, Adok C, Dahm-Kähler P. Recurrence and survival in endometrioid endometrial cancer - a population-based cohort study. Gynecol Oncol. 2023 Jan; 168: 127-134.
[20] Seay K, Akanbi T, Bustamante B, Chaudhary S, Goldberg GL. Mesonephric-like adenocarcinoma of the ovary with co-existent endometriosis: A case report and review of the literature. Gynecol Oncol Rep. 2020 Oct 4; 34: 100657.
[21] McCluggage WG, Vosmikova H, Laco J. Ovarian Combined Low-grade Serous and Mesonephric-like Adenocarcinoma: Further Evidence for A Mullerian Origin of Mesonephric-like Adenocarcinoma. Int J Gynecol Pathol. 2020 Jan; 39 (1): 84-92.
[22] Nilforoushan N, Liu L, Finkelman BS, Andersen J, Liu Y, James J, Hung CF, Wu TC, Vang R, Xing D. Ovarian Combined Serous Borderline Tumor/Low-grade Serous Carcinoma and Mesonephric-like Lesion: Report of 2 Cases With New Observations. Int J Gynecol Pathol. 2023 Mar 1; 42 (2): 182-191.
[23] Chen Q, Shen Y, Xie C. Mesonephric-like adenocarcinoma of the ovary: A case report and a review of the literature. Medicine (Baltimore). 2020 Nov 25; 99 (48): e23450.
[24] Howitt BE, Nucci MR. Mesonephric proliferations of the female genital tract. Pathology. 2018 Feb; 50 (2): 141-150.
[25] McCluggage WG. Mesonephric-like Adenocarcinoma of the Female Genital Tract: From Morphologic Observations to a Well-characterized Carcinoma With Aggressive Clinical Behavior. Adv Anat Pathol. 2022 Jul 1; 29 (4): 208-216.
[26] Park S, Park E, Kim HS. Mesonephric-like Carcinosarcoma of the Uterine Corpus: Clinicopathological, Molecular and Prognostic Characteristics in Comparison With Uterine Mesonephric-like Adenocarcinoma and Conventional Endometrial Carcinosarcoma. Cancer Genomics Proteomics. 2022 Nov-Dec; 19 (6): 747-760.
[27] Soslow RA, Tornos C, Park KJ, Malpica A, Matias-Guiu X, Oliva E, Parkash V, Carlson J, McCluggage WG, Gilks CB. 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. 2019 Jan; 38 Suppl 1(Iss 1 Suppl 1): S64-S74.
[28] Loukovaara M, Pasanen A, Bützow R. Molecular classification of endometrial carcinoma: a clinically oriented review. J Clin Pathol. 2022 May 30: jclinpath-2022-208345.
[29] Labi FL, Evangelista S, Di Miscia A, Stentella P. FIGO Stage I endometrial carcinoma: evaluation of lung metastases and follow-up. Eur J Gynaecol Oncol. 2008; 29 (1): 65-6.
[30] Mao W, Wei S, Yang H, Yu Q, Xu M, Guo J, Gao L. Clinicopathological study of organ metastasis in endometrial cancer. Future Oncol. 2020 Apr; 16 (10): 525-540.
[31] Huvila J, Pors J, Thompson EF, Gilks CB. Endometrial carcinoma: molecular subtypes, precursors and the role of pathology in early diagnosis. J Pathol. 2021 Apr; 253 (4): 355-365.
[32] Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 Jun 24; 384 (25): 2371-2381.
[33] Fakih MG, Kopetz S, Kuboki Y, Kim TW, Munster PN, Krauss JC, Falchook GS, Han SW, Heinemann V, Muro K, Strickler JH, Hong DS, Denlinger CS, Girotto G, Lee MA, Henary H, Tran Q, Park JK, Ngarmchamnanrith G, Prenen H, Price TJ. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. 2022 Jan; 23 (1): 115-124.
Cite This Article
  • APA Style

    Hiller, G. G. R., Höhn, A. K., Krücken, I., Hagert-Winkler, A., Martin, M., et al. (2023). Mesonephric-Like Adenocarcinoma of the Endometrium Mimicking Advanced Tubo-Ovarian Cancer - A Literature Review Based on a Special Case. Cancer Research Journal, 11(4), 127-135. https://doi.org/10.11648/j.crj.20231104.12

    Copy | Download

    ACS Style

    Hiller, G. G. R.; Höhn, A. K.; Krücken, I.; Hagert-Winkler, A.; Martin, M., et al. Mesonephric-Like Adenocarcinoma of the Endometrium Mimicking Advanced Tubo-Ovarian Cancer - A Literature Review Based on a Special Case. Cancer Res. J. 2023, 11(4), 127-135. doi: 10.11648/j.crj.20231104.12

    Copy | Download

    AMA Style

    Hiller GGR, Höhn AK, Krücken I, Hagert-Winkler A, Martin M, et al. Mesonephric-Like Adenocarcinoma of the Endometrium Mimicking Advanced Tubo-Ovarian Cancer - A Literature Review Based on a Special Case. Cancer Res J. 2023;11(4):127-135. doi: 10.11648/j.crj.20231104.12

    Copy | Download

  • @article{10.11648/j.crj.20231104.12,
      author = {Grit Gesine Ruth Hiller and Anne Kathrin Höhn and Irene Krücken and Anne Hagert-Winkler and Mireille Martin and Adrian Pilny and Helmut Plett and Christine Elisabeth Brambs and Lars-Christian Horn},
      title = {Mesonephric-Like Adenocarcinoma of the Endometrium Mimicking Advanced Tubo-Ovarian Cancer - A Literature Review Based on a Special Case},
      journal = {Cancer Research Journal},
      volume = {11},
      number = {4},
      pages = {127-135},
      doi = {10.11648/j.crj.20231104.12},
      url = {https://doi.org/10.11648/j.crj.20231104.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20231104.12},
      abstract = {Mesonephric-like adenocarcinoma of the endometrium (ML-AC) is a rare variant of endometrial adenocarcinoma with aggressive clinical behavior and unusual metastatic spread. Because of its rarity, the diagnosis may be challenging but needs to be accurate due to the mostly poor prognostic outcome of these tumors. To aid in the understanding and recognition of this entity we present the detailed histopathological, immunohistochemical and molecular analysis of a case of ML-AC clinically mimicking advanced ovarian cancer in a 55-year-old woman and put it in the context of literature research on ovarian and endometrial carcinomas. In the present case the patient revealed abdominal distension, ascites and a moderately elevated CA-125 level (504.8 U/ml) with widespread peritoneal carcinomatosis and an endometrial lesion confined to the endometrium with the presence of free-floating tumor cells within the tubal lumen, suggesting transtubal peritoneal spread of the endometrial primary. All tumor sites shared various architectural patterns on histology with negative staining for p16, WT-1 and estrogen receptor and positivity for TTF-1. Matched pair molecular analysis revealed an identic clonal KRAS-mutation (p.G12C) within the endometrial, peritoneal and lymph node involvement as well as in the recurrent tumor. There was retained mismatch repair protein staining and p53 wild type pattern without any additional mutational alterations, including POLE. A hepatic recurrence was diagnosed after 11 months. Literature study confirms our findings and the suggestion of a morphomolecular diagnostic approach additional to the fact that KRAS-mutation may represent a targetable alteration within a specialized therapeutic approach for this entity.
    },
     year = {2023}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Mesonephric-Like Adenocarcinoma of the Endometrium Mimicking Advanced Tubo-Ovarian Cancer - A Literature Review Based on a Special Case
    AU  - Grit Gesine Ruth Hiller
    AU  - Anne Kathrin Höhn
    AU  - Irene Krücken
    AU  - Anne Hagert-Winkler
    AU  - Mireille Martin
    AU  - Adrian Pilny
    AU  - Helmut Plett
    AU  - Christine Elisabeth Brambs
    AU  - Lars-Christian Horn
    Y1  - 2023/11/17
    PY  - 2023
    N1  - https://doi.org/10.11648/j.crj.20231104.12
    DO  - 10.11648/j.crj.20231104.12
    T2  - Cancer Research Journal
    JF  - Cancer Research Journal
    JO  - Cancer Research Journal
    SP  - 127
    EP  - 135
    PB  - Science Publishing Group
    SN  - 2330-8214
    UR  - https://doi.org/10.11648/j.crj.20231104.12
    AB  - Mesonephric-like adenocarcinoma of the endometrium (ML-AC) is a rare variant of endometrial adenocarcinoma with aggressive clinical behavior and unusual metastatic spread. Because of its rarity, the diagnosis may be challenging but needs to be accurate due to the mostly poor prognostic outcome of these tumors. To aid in the understanding and recognition of this entity we present the detailed histopathological, immunohistochemical and molecular analysis of a case of ML-AC clinically mimicking advanced ovarian cancer in a 55-year-old woman and put it in the context of literature research on ovarian and endometrial carcinomas. In the present case the patient revealed abdominal distension, ascites and a moderately elevated CA-125 level (504.8 U/ml) with widespread peritoneal carcinomatosis and an endometrial lesion confined to the endometrium with the presence of free-floating tumor cells within the tubal lumen, suggesting transtubal peritoneal spread of the endometrial primary. All tumor sites shared various architectural patterns on histology with negative staining for p16, WT-1 and estrogen receptor and positivity for TTF-1. Matched pair molecular analysis revealed an identic clonal KRAS-mutation (p.G12C) within the endometrial, peritoneal and lymph node involvement as well as in the recurrent tumor. There was retained mismatch repair protein staining and p53 wild type pattern without any additional mutational alterations, including POLE. A hepatic recurrence was diagnosed after 11 months. Literature study confirms our findings and the suggestion of a morphomolecular diagnostic approach additional to the fact that KRAS-mutation may represent a targetable alteration within a specialized therapeutic approach for this entity.
    
    VL  - 11
    IS  - 4
    ER  - 

    Copy | Download

Author Information
  • Department of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany

  • Department of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany

  • Department of Molecular Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany

  • Department of Diagnostic Radiology, University Hospital Leipzig, Leipzig, Germany

  • Department of Diagnostic Radiology, University Hospital Leipzig, Leipzig, Germany

  • Department of Obstetrics and Gynecology, University Hospital Leipzig, Leipzig, Germany

  • Department of Obstetrics and Gynecology, University Hospital Leipzig, Leipzig, Germany

  • Department of Obstetrics and Gynecology, Cantonal Hospital Lucerne, Lucerne, Switzerland

  • Department of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany

  • Sections