Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study

Our plain-English summary of Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study, by N. Benzerdjeb, P. Dartigues, V. Kepenekian, et al (Virchows Archiv, 2021).

The study

• Authors: N. Benzerdjeb, P. Dartigues, V. Kepenekian, S. Valmary-Degano, E. Mery, G. Averous, A. Chevallier, M.H. Laverriere, I. Villa, F.G. Sallé, L. Villeneuve, O. Glehen, S. Isaac, J. Hommell-Fontaine, RENAPE Network
• Journal: Virchows Archiv
• Published: 2021;479(5):927-936
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. A recently described nuclear-grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The present study was undertaken to validate this grading system in epithelioid malignant peritoneal mesothelioma (EMPM) and to compare to combined grade, including nuclear atypia, mitotic count, and tumor necrosis. Cases of EMPM, from 1995 to 2018, were analyzed from 7 French institutions from RENAPE network. Solid growth, tumor necrosis, nuclear atypia, and mitotic count were evaluated by at least 3 pathologists from the RENAPATH group. The predictions in terms of OS and PFS of nuclear grade and combined grade were analyzed. Nuclear grade was computed combining nuclear atypia score and mitotic count into a grade of I-III. Another system combining nuclear atypia score, mitotic score, and tumor necrosis was evaluated and defined as a combined grade I-III. A total of 138 cases were identified. The median follow-up was 38.9 months (range: 1.1-196.6). Nuclear and combined grades III were independently associated with a shorter OS (p < 0.05), and a shorter PFS (p < 0.05). Patients with combined grade I tumors had the best overall and progression-free survivals, in comparison to nuclear grade I. In this large multicentric study, combined grade and nuclear grade were the best independent predictors of OS and PFS in EMPM. These systems should be easily described by pathologists involved into the management of malignant peritoneal mesothelioma, because of their potential therapeutic implications.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

In plain English

This retrospective study examined 138 patients from 7 French institutions, diagnosed between 1995 and 2018 with epithelioid malignant peritoneal mesothelioma, a cancer of the abdominal lining. It did not study asbestos or any other cause of the disease. Pathologists scored tumor slides for nuclear atypia (how abnormal the cell nuclei looked), mitotic count (how many cells were dividing) and tumor necrosis (dead tumor tissue). The 'nuclear grade' combined nuclear atypia and mitotic count, and the 'combined grade' also added tumor necrosis. Both ran from I to III. Median follow-up was 38.9 months. The analysis was adjusted for age, sex and treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Compared with grade I, combined grade III was associated with shorter overall survival (hazard ratio 50.06, 95% confidence interval 6.11 to 410.10), and so was nuclear grade III (10.70, 3.47 to 32.99). Both grade III categories were also associated with shorter progression-free survival. The authors concluded that the two grades were the best independent predictors of survival in this disease. They noted that patients differed in chemotherapy and institution.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Multi-institutional retrospective study of tumor pathology and patient survival (prognostic study)
• Who was studied: 138 patients with epithelioid malignant peritoneal mesothelioma (EMPM) diagnosed 1995 to 2018 at 7 French institutions in the RENAPE network. Follow-up data were available for 138 patients for overall survival and 134 for progression-free survival.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The factors examined were tumor features seen under the microscope (nuclear atypia, mitotic count, tumor necrosis, solid growth) and two grading systems built from them. Nuclear grade combined nuclear atypia and mitotic scores. Combined grade added tumor necrosis to those two scores.
• Main results:
  • Median follow-up was 38.9 months (range 1.1 to 196.6).
  • In univariate analysis, lower overall and progression-free survival was associated with nuclear atypia score 3, mitotic count of 5 or more per 10 high-power fields, presence of tumor necrosis, solid-predominant growth, nuclear grade III and combined grade III (p less than 0.05).
  • Multivariate analysis was adjusted for age, sex and treatment by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.
  • In multivariate analysis, shorter overall survival was associated with combined grade III (HR 50.06, 95% CI 6.11 to 410.10).
  • In multivariate analysis, shorter overall survival was also associated with nuclear grade III (HR 10.70, 95% CI 3.47 to 32.99).
  • In multivariate analysis, lower progression-free survival was associated with combined grade III (HR 11.34, 95% CI 2.86 to 44.87) and with nuclear grade III (HR 9.64, 95% CI 3.20 to 29.04).
  • The authors reported that patients with combined grade I tumors had a lower risk of recurrence and longer survival than those with nuclear grade I.
• The authors' conclusion: The authors concluded that combined grade and nuclear grade were the best independent predictors of overall and progression-free survival in epithelioid malignant peritoneal mesothelioma.
• Limitations the authors state:
  • The patient group was heterogeneous in chemotherapy drugs, number of chemotherapy lines, whether specimens were taken after chemotherapy, and institution.
  • The study was not designed to assess whether the grades perform differently by specimen type (resection or biopsy) or by prior chemotherapy.
  • Institutions differed significantly in patient age, use of post-operative chemotherapy and residual tumor.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Nuclear Grade, Prognosis, Epithelioid, Peritoneal Mesothelioma, Mesothelioma, Pleural Mesothelioma, Nuclear Atypia, Mitotic Count.

Related studies

• Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study — L.E. Rosen, T. Karrison, et al. (2018)
• Tertiary lymphoid structures in epithelioid malignant peritoneal mesothelioma are associated with neoadjuvant chemotherapy, but not with prognosis — N. Benzerdjeb, P. Dartigues, et al. (2021)
• Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases — D.B. Chapel, J.J. Schulte, et al. (2021)
• A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma — K. Kadota, K. Suzuki, et al. (2012)
• Reproducibility for histologic parameters in peritoneal mesothelioma — D.J. Hartman, A. Borczuk, et al. (2017)
• Deciduoid mesothelioma: report of 21 cases with review of the literature — N.G. Ordóñez (2012)

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