Skip to main content

Advertisement

SpringerLink
Log in

Histological classification of mucinous ovarian tumors: inter-observer reproducibility, clinical relevance, and role of genetic biomarkers

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The morphological distinction between the various types of mucinous ovarian tumors has major prognostic implications but may be challenging. The aims of our study were to describe inter-observer reproducibility in the morphological diagnosis of mucinous ovarian tumors, to evaluate the clinical relevance of possible diagnostic discrepancies, and to identify molecular abnormalities correlated with the histological type. Seventy-nine ovarian mucinous borderline tumors (MOB) and either expansile or infiltrative carcinomas (MOC) were independently reviewed by two gynecological pathologists. Molecular analysis was performed in 32 cases. Concordance between the two pathologists was reached in 67 cases (k: 0.78). The main discrepancies (8/12) were the evaluation of nuclear grade 3 or that of microfoci (< 5 mm) of infiltrative-type carcinoma in an otherwise typical expansile MOC. Our follow-up analysis showed that infiltrative MOC had a lower overall survival (OS) (p < 0.0024) and progression-free survival (PFS) (p = 0.0060) as compared with MOB and expansile MOC. The presence of nuclear grade 3 or microfoci (< 5 mm) of infiltrative-type pattern of invasion in an otherwise typical expansile MOC did not alter the prognosis as compared with expansile MOC without these features, in terms of OS (p < 0.0028) and PFS (p = 0.0074). KRAS mutations were more frequent in MOB (71%), than in expansile (50%) and infiltrative MOC (14%). In contrast, the prevalence of TP53 mutation was lower in MOB (43%), than in expansile (58%) and infiltrative MOC (71%). Our results confirm that in MOC, the expansile pattern of invasion is associated with a better prognosis than extensive (> 5 mm) infiltrative-type pattern of invasion. No specific or sensitive molecular profile might help in the differential diagnosis of mucinous ovarian tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Kurman RJ, International Agency for Research on Cancer, World Health Organization (eds) (2014) WHO classification of tumours of female reproductive organs, 4th edn. Lyon, International Agency for Research on Cancer

    Google Scholar 

  2. Dube V, Roy M, Plante M et al (2005) Mucinous ovarian tumors of Mullerian-type: an analysis of 17 cases including borderline tumors and intraepithelial, microinvasive, and invasive carcinomas. Int J Gynecol Pathol 24:138–146

    Article  Google Scholar 

  3. Riopel MA, Ronnett BM, Kurman RJ (1999) Evaluation of diagnostic criteria and behavior of ovarian intestinal-type mucinous tumors: atypical proliferative (borderline) tumors and intraepithelial, microinvasive, invasive, and metastatic carcinomas. Am J Surg Pathol 23:617–635

    Article  CAS  Google Scholar 

  4. Colombo N, Sessa C, du Bois A, Ledermann J, McCluggage WG, McNeish I, Morice P, Pignata S, Ray-Coquard I, Vergote I, Baert T, Belaroussi I, Dashora A, Olbrecht S, Planchamp F, Querleu D, Baert T, Banerjee S, Belaroussi I, Blecharz P, Bruchim I, Cibula D, Colombo N, Concin N, Davidson B, Dashora A, Devouassoux-Shisheboran M, du Bois A, Ferrero A, Glasspool R, González-Martin A, Heinzelmann-Schwarz V, Joly F, Kim JW, Kridelka F, Ledermann J, Lorusso D, Mahner S, McCluggage WG, McNeish I, Mikami M, Mirza MR, Morice P, Nicum S, Olbrecht S, O’Donnell DM, Pautier P, Planchamp F, Pignata S, Querleu D, Ray-Coquard I, Rodolakis A, Sehouli J, Selcukbiricik F, Sessa C, Singh N, Tan DSP, Timmerman D, Tognon G, van der Velden J, Vergote I, Witteveen PO, Zeimet AG, ESMO-ESGO Ovarian Cancer Consensus Conference Working Group (2019) ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease†. Ann Oncol 30(5):672–705

    Article  CAS  Google Scholar 

  5. Morice P, Gouy S, Leary A (2019) Mucinous ovarian carcinoma. N Engl J Med 380:1256–1266

    Article  CAS  Google Scholar 

  6. Gouy S, Saidani M, Maulard A et al (2018) Characteristics and prognosis of stage I ovarian mucinous tumors according to expansile or infiltrative type. Int J Gynecol Cancer 28:493–499

    Article  Google Scholar 

  7. Chiannilkulchai N, Pautier P, Genestie C, Bats AS, Vacher-Lavenu MC, Devouassoux-Shisheboran M et al (2017) Networking for ovarian rare tumors: a significant breakthrough improving disease management. Ann Oncol 28:1274–1279

  8. Mayr D, Hirschmann A, Lohrs U, Diebold J (2006) KRAS and BRAF mutations in ovarian tumors: a comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants. Gynecol Oncol 103:883–887

    Article  CAS  Google Scholar 

  9. Cuatrecasas M, Villanueva A, Matias-Guiu X, Prat J (1997) K-ras mutations in mucinous ovarian tumors: a clinicopathologic and molecular study of 95 cases. Cancer 79:1581–1586

    Article  CAS  Google Scholar 

  10. Anglesio MS, Kommoss S, Tolcher MC, Clarke B, Galletta L, Porter H, Damaraju S, Fereday S, Winterhoff BJ, Kalloger SE, Senz J, Yang W, Steed H, Allo G, Ferguson S, Shaw P, Teoman A, Garcia JJ, Schoolmeester JK, Bakkum-Gamez J, Tinker AV, Bowtell DD, Huntsman DG, Gilks CB, McAlpine JN (2013) Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas. J Pathol 229:111–120

    Article  CAS  Google Scholar 

  11. Köbel M, Piskorz AM, Lee S, Lui S, LePage MF, Rosenfeld N, Mes Masson AM, Brenton JD (2016) Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma. J Pathol Clin Res 2:247–258

    Article  Google Scholar 

  12. Rodríguez IM, Prat J (2002) Mucinous tumors of the ovary: a clinicopathologic analysis of 75 borderline tumors (of intestinal type) and carcinomas. Am J Surg Pathol 26:139–152

    Article  Google Scholar 

  13. Lee KR, Scully RE (2000) Mucinous tumors of the ovary: a clinicopathologic study of 196 borderline tumors (of intestinal type) and carcinomas, including an evaluation of 11 cases with ‘pseudomyxoma peritonei’. Am J Surg Pathol 24:1447–1464

    Article  CAS  Google Scholar 

  14. Gilks CB, Ionescu DN, Kalloger SE, Köbel M, Irving J, Clarke B, Santos J, Le N, Moravan V, Swenerton K, Cheryl Brown Ovarian Cancer Outcomes Unit of the British Columbia Cancer Agency (2008) Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol 39:1239–1251

    Article  CAS  Google Scholar 

  15. McCluggage WG, Judge MJ, Clarke BA, Davidson B, Gilks CB, Hollema H, Ledermann JA, Matias-Guiu X, Mikami Y, Stewart CJ, Vang R, Hirschowitz L, International Collaboration on Cancer Reporting (2015) Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Mod Pathol 28:1101–1122

    Article  Google Scholar 

  16. Lee YJ, Lee MY, Ruan A, Chen CK, Liu HP, Wang CJ, Chao WR, Han CP (2016) Multipoint Kras oncogene mutations potentially indicate mucinous carcinoma on the entire spectrum of mucinous ovarian neoplasms. Oncotarget. 7:82097–82103

    Article  Google Scholar 

  17. Ryland GL et al (2015) Mutational landscape of mucinous ovarian carcinoma and its neoplastic precursors. Genome Med 7(1):87

    Article  Google Scholar 

  18. Cheasley D, Wakefield MJ, Ryland GL, Allan PE, Alsop K, Amarasinghe KC, Ananda S, Anglesio MS, Au-Yeung G, Böhm M, Bowtell DDL, Brand A, Chenevix-Trench G, Christie M, Chiew YE, Churchman M, DeFazio A, Demeo R, Dudley R, Fairweather N, Fedele CG, Fereday S, Fox SB, Gilks CB, Gourley C, Hacker NF, Hadley AM, Hendley J, Ho GY, Hughes S, Hunstman DG, Hunter SM, Jobling TW, Kalli KR, Kaufmann SH, Kennedy CJ, Köbel M, le Page C, Li J, Lupat R, McNally OM, McAlpine JN, Mes-Masson AM, Mileshkin L, Provencher DM, Pyman J, Rahimi K, Rowley SM, Salazar C, Samimi G, Saunders H, Semple T, Sharma R, Sharpe AJ, Stephens AN, Thio N, Torres MC, Traficante N, Xing Z, Zethoven M, Antill YC, Scott CL, Campbell IG, Gorringe KL (2019) The molecular origin and taxonomy of mucinous ovarian carcinoma. Nat Commun 10:3935

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Gustave Roussy, Villejuif, France

    Catherine Genestie, Miriam Al Battal & Jean-Yves Scoazec

  2. INSERM 981, Gustave Roussy Cancer Campus, Villejuif, France

    Catherine Genestie, Aurélie Auguste & Alexandra Leary

  3. Faculté de Médecine de Bicêtre, Université Paris Saclay, Le Kremlin-Bicêtre, France

    Jean-Yves Scoazec & Philippe Morice

  4. Department of Surgery, Gustave Roussy, Villejuif, France

    Sébastien Gouy & Philippe Morice

  5. Department of Tumor Genetics, Gustave Roussy, Villejuif, France

    Ludovic Lacroix

  6. Department of Medicine, Gustave Roussy, Villejuif, France

    Patricia Pautier & Alexandra Leary

  7. Department of Pathology, Université Claude Bernard Lyon 1, Villeurbanne, France

    Mojgan Devouassoux-Shisheboran

  8. Department of Pathology, Centre Hospitalier Lyon Sud, 165 Chemin du Grand Revoyet, 69495, Pierre Bénite Cedex, France

    Mojgan Devouassoux-Shisheboran

Authors
  1. Catherine Genestie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aurélie Auguste
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miriam Al Battal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jean-Yves Scoazec
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sébastien Gouy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ludovic Lacroix
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Philippe Morice
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Patricia Pautier
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alexandra Leary
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mojgan Devouassoux-Shisheboran
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Catherine Genestie: pathological review of all cases, design of the study, writing of the article

Aurélie Auguste: molecular study, writing of the article (molecular study)

Miriam Al Battal: molecular study

Jean-Yves Scoazec: critical review of the article and English review

Sébastien Gouy, Philippe Morice, and Patricia Pautier: provided clinical data and consent of patients

Ludovic Lacroix: molecular study

Alexandra Leary: design of the molecular study, writing of the article (molecular study), and English writing

Mojgan Devouassoux-Shisheboran: design of the pathological study, pathological review of the cases, writing of the article (pathological study)

Corresponding author

Correspondence to Mojgan Devouassoux-Shisheboran.

Ethics declarations

The study was approved by the Ethics Committee of the Medical Board (Institut Gustave Roussy). This study was conducted in accordance with the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Genestie, C., Auguste, A., Al Battal, M. et al. Histological classification of mucinous ovarian tumors: inter-observer reproducibility, clinical relevance, and role of genetic biomarkers. Virchows Arch 478, 885–891 (2021). https://doi.org/10.1007/s00428-020-02939-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-020-02939-w

Keywords

Search

Navigation