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

Our plain-English summary of 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, by D.B. Chapel, J.J. Schulte, G. Absenger, et al (Modern Pathology, 2021).

The study

• Authors: D.B. Chapel, J.J. Schulte, G. Absenger, R. Attanoos, L. Brcic, K.J. Butnor, L. Chirieac, A. Churg, F. Galateau-Sallé, K. Hiroshima, Y.P. Hung, H. Kindler, T. Krausz, A. Marchevsky, M. Mino-Kenudson, J. Mueller, K. Nabeshima, K. Turaga, A.E. Walts, A.N. Husain
• Journal: Modern Pathology
• Published: 2021;34(2):380-395
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant peritoneal mesothelioma historically carried a grim prognosis, but outcomes have improved substantially in recent decades. The prognostic significance of clinical, morphologic, and immunophenotypic features remains ill-defined. This multi-institutional cohort comprises 225 malignant peritoneal mesotheliomas, which were assessed for 21 clinical, morphologic, and immunohistochemical parameters. For epithelioid mesotheliomas, combining nuclear pleomorphism and mitotic index yielded a composite nuclear grade, using a previously standardized grading system. Correlation of clinical, morphologic, and immunohistochemical parameters with overall and disease-free survival was examined by univariate and multivariate analyses. On univariate analysis, longer overall survival was significantly associated with diagnosis after 2000 (P = 0.0001), age <60 years (P = 0.0001), ECOG performance status 0 or 1 (P = 0.01), absence of radiographic lymph-node metastasis (P = 0.04), cytoreduction surgery (P < 0.0001), hyperthermic intraperitoneal chemotherapy (P = 0.0001), peritoneal carcinomatosis index <27 (P = 0.01), absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001). Among epithelioid malignant mesotheliomas only, longer overall survival was further associated with female sex (P = 0.03), tubulopapillary architecture (P = 0.005), low nuclear pleomorphism (P < 0.0001), low mitotic index (P = 0.0007), and low composite nuclear grade (P < 0.0001). On multivariate analyses, the low composite nuclear grade was independently associated with longer overall and disease-free survival (P < 0.0001). Our data further clarify the interactions of clinical and pathologic features in peritoneal mesothelioma prognosis and validate the prognostic significance of a standardized nuclear-grading system in epithelioid malignant mesothelioma of the peritoneum.

In plain English

This retrospective cohort study gathered 225 cases of malignant peritoneal mesothelioma (mesothelioma of the abdominal lining) from 11 institutions in 6 countries: 186 diagnosed after 2000 and 39 between 1970 and 1996. The authors compared 21 clinical, tissue and staining features with survival. Asbestos exposure data were requested but too sparse to analyze. Patients diagnosed after 2000 lived longer, even among those given neither tumor-removal surgery nor heated abdominal chemotherapy (median 21 versus 7 months). Among epithelioid tumors diagnosed after 2000, a nuclear grade combining nuclear abnormality and how often cells divided was linked to survival: median 58 months for grade I (86 patients; 95% confidence interval 38 to 87), 32 months for grade II (62 patients; 22 to 51) and 7 months for grade III (13 patients; 3 to 12). In multivariate analysis, grade remained independently associated with overall and disease-free survival. BAP1 protein loss on staining was not associated with overall survival. The authors concluded that this grading system has prognostic value in epithelioid peritoneal mesothelioma, while noting that pathologists agree only fairly on its features.

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 cohort study with central pathology review and univariate and multivariate survival analyses
• Who was studied: 225 malignant peritoneal mesotheliomas from 11 institutions in 6 countries: 186 diagnosed after 2000 and 39 diagnosed before 2000 (1970 to 1996). Well-differentiated papillary mesothelioma, benign multicystic mesothelioma and paratesticular mesotheliomas were excluded.
• Exposure: Asbestos exposure was not analyzed. Data on it, including fiber type and dose, were requested but were available in too few cases. The study examined treatments (cytoreductive surgery, hyperthermic intraperitoneal chemotherapy) and tumor features as predictors of survival.
• Main results:
  • Among tumors diagnosed after 2000, 94% were epithelioid. Of these epithelioid tumors, 53% were grade I, 39% grade II and 8% grade III.
  • Median overall survival for epithelioid tumors diagnosed after 2000 (n = 168) was 39 months (95% confidence interval 32 to 51). For biphasic tumors diagnosed after 2000 (n = 17) it was 14 months (4 to 71). For epithelioid tumors diagnosed before 2000 (n = 21) it was 12 months (7 to 14).
  • Among patients who had neither cytoreduction nor hyperthermic intraperitoneal chemotherapy, overall survival was 21 months for those diagnosed after 2000 versus 7 months for those diagnosed before 2000 (P = 0.0006).
  • Among all tumors diagnosed after 2000, univariate analysis linked longer overall survival with several factors: younger age, better performance status, no lymph node metastasis on imaging, cytoreduction surgery, hyperthermic intraperitoneal chemotherapy, peritoneal carcinomatosis index below 27, absence of necrosis, and epithelioid histotype.
  • In the multivariate model for all tumors diagnosed after 2000, longer overall survival was independently associated with cytoreduction surgery, non-sarcomatoid histotype and absence of necrosis.
  • Among epithelioid tumors diagnosed after 2000, median overall survival differed by composite nuclear grade: grade I (n = 86) 58 months (38 to 87), grade II (n = 62) 32 months (22 to 51), grade III (n = 13) 7 months (3 to 12). The univariate hazard ratio for grade III versus grade I was 8.1 (4.0 to 16.4).
  • In the multivariate model for epithelioid tumors diagnosed after 2000 (n = 125), longer overall survival was independently associated with cytoreduction surgery, lower composite nuclear grade, and tubulopapillary architecture. The hazard ratio for grade III versus grade I was 7.6 (3.1 to 18.5).
  • Necrosis was not independently associated with overall survival among epithelioid tumors.
  • When the model was plotted by histotype and grade, survival curves for grade III epithelioid and biphasic mesothelioma essentially overlapped.
  • For disease-free survival after cytoreduction among epithelioid tumors (multivariate, n = 55), low composite nuclear grade and low Ki67 index were independently associated with longer disease-free survival. The hazard ratio for grade III versus grade I was 6.8 (1.6 to 29.4). Among all cytoreduced tumors, only low Ki67 index was independent.
  • Overall survival was virtually identical for patients with BAP1 loss (34 months) and without BAP1 loss (36 months).
  • Pleural involvement had no adverse impact on survival.
• The authors' conclusion: The authors concluded that the composite nuclear-grading system, originally developed for pleural mesothelioma, is validated for use in peritoneal mesothelioma. Of the 21 parameters evaluated, it was the only variable independently associated with both overall and disease-free survival.
• Limitations the authors state:
  • The authors used an existing pleural grading system. A peritoneal-specific system might differ and should be studied.
  • Because clinical data were collected retrospectively, peritoneal carcinomatosis index and ECOG performance status could not be included in multivariate models.
  • The tissue analyses used pre-treatment specimens only and are not validated for post-treatment material.
  • Agreement between pathologists on architecture, nuclear pleomorphism and mitotic index is fair at best, which may limit use of nuclear grading.
  • Rare histotypes were poorly represented. Only one tumor diagnosed after 2000 was purely sarcomatoid.
  • Paratesticular mesotheliomas were excluded.
  • Ki67 index was obtained in only a subset of cases, and the Ki67 findings were mixed.
  • Germline BAP1 sequencing was not available.
  • Other reported prognostic immunomarkers were not analyzed.

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: Peritoneal Mesothelioma, Multi-Institutional Series, Prognosis, Epithelioid, Mesothelioma, Nuclear Pleomorphism, Mitotic Count, Nuclear Grade.

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)
• Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study — N. Benzerdjeb, P. Dartigues, 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)
• A Histomorphologic Grading System That Predicts Overall Survival in Diffuse Malignant Peritoneal Mesothelioma With Epithelioid Subtype — K. Valente, A.U. Blackham, et al. (2016)
• Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — D. Baratti, M. Vaira, et al. (2010)
• Reproducibility for histologic parameters in peritoneal mesothelioma — D.J. Hartman, A. Borczuk, et al. (2017)

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