Evaluation of prognostic histological parameters proposed for pleural mesothelioma in diffuse malignant peritoneal mesothelioma. A short report

Our plain-English summary of Evaluation of prognostic histological parameters proposed for pleural mesothelioma in diffuse malignant peritoneal mesothelioma. A short report, by F. Pezzuto, L. Vimercati, F. Fortarezza, et al (Diagnostic Pathology, 2021).

The study

• Authors: F. Pezzuto, L. Vimercati, F. Fortarezza, A. Marzullo, A. Pennella, D. Cavone, A. Punzi, C. Caporusso, A. d'Amati, T. Lettini, G. Serio
• Journal: Diagnostic Pathology
• Published: 2021;16(1):64
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignant neoplasm with poor survival that shares some similarities with the best-known pleural variant, pleural mesothelioma. The recent European Reference Network on Rare Adult Cancers (EURACAN)/International Association for the Study of Lung Cancer (IASLC) proposals attempted to improve the histological diagnosis and patient risk stratification. Herein, we investigated whether the pathology recommendations and suggestions of the pleural proposals were applicable to diffuse malignant peritoneal mesothelioma.

Methods: Fifty multiple laparoscopic biopsies of DMPM were consecutively collected at the Pathology Unit of the University of Bari. A two-tier system, i.e., low, and high grade, was used to categorize 34 epithelioid DMPMs. Architectural patterns, cytological features and stromal changes were also reported. Immunohistochemistry was performed for BRCA1-associated protein 1 (BAP1), programmed death-ligand 1 (PD-L1), and Ki67, while fluorescence in situ hybridization (FISH) was performed for p16/cyclin-dependent kinase inhibitor 2A (CDKN2A).

Results: High-grade epithelioid mesothelioma, high Ki67, and p16/CDKN2A deletion were significantly associated with short survival (p = 0.004, p < 0.0001, and p = 0.002, respectively). BAP1 loss and PD-L1 negativity were the most common findings. Multivariate analysis revealed that the nuclear grading system and p16 deletion significantly correlated with survival (p = 0.003 each).

Conclusions: The present study examined the prognostic significance of several factors proposed for pleural mesothelioma in an extra pleural site. Notably, the introduction of a grading system may provide better risk stratification in epithelioid DMPM. Ki67, BAP1 and p16/CDKN2A should also be measured whenever possible. A detailed report with all supportive data would allow us to collect sufficient information for use in further studies on larger case series.

© 2021. The Author(s).

In plain English

This short report from Italy tested whether tissue features recommended for reporting pleural mesothelioma also relate to survival in diffuse malignant peritoneal mesothelioma. The authors examined biopsies from 50 patients collected at the University of Bari pathology unit between March 1990 and December 2017, in a retrospective design. None of the patients had cytoreductive surgery, intraperitoneal chemotherapy or immunotherapy after diagnosis, all had died by last follow-up, and median survival was 6 months. The article did not report on the patients' asbestos exposure. Of 34 epithelioid tumors, 15 were graded low and 19 high. Survival differed by tumor grade (p = 0.004), and survival was worst with a homozygous p16/CDKN2A deletion, found in 30 cases. When factors were analyzed together, only nuclear grading and p16/CDKN2A deletion remained significant predictors of survival (p = 0.003 each). BAP1 loss, found in 43 cases, was not statistically significantly linked to survival. The authors concluded that their findings support a standardized grading system for epithelioid peritoneal mesothelioma. They noted the retrospective design and the small sample size as limitations.

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: Retrospective study of consecutively collected biopsies (published as a short report), with tissue staining, genetic (FISH) testing and survival analysis
• Who was studied: 50 patients with diffuse malignant peritoneal mesothelioma (DMPM), whose laparoscopic biopsies were collected at the Pathology Unit of the University of Bari, Italy, between March 1990 and December 2017. 13 were female. None received cytoreductive surgical therapy, intraperitoneal chemotherapy or immunotherapy after diagnosis, and all had died at last follow-up.
• Main results:
  • Of the 50 tumors, 34 (68%) were epithelioid, 12 (24%) biphasic and 4 (8%) sarcomatoid.
  • Survival differed significantly by histological subtype, with the shortest survival in sarcomatoid tumors (p = 0.002).
  • Median survival for all 50 patients was 6 months.
  • Of the 34 epithelioid tumors, 15 were low grade and 19 high grade. Survival differed significantly by tumor grade (p = 0.004), with shorter survival in high-grade tumors.
  • A homozygous p16/CDKN2A deletion was found in 30 of 50 cases (60%) and was associated with the worst prognosis.
  • In multiple linear regression including Ki67, nuclear grading, necrosis and p16/CDKN2A deletion, only nuclear grading and p16/CDKN2A deletion were significant predictors of survival (p = 0.003 each).
  • BAP1 loss was found in 43 of 50 cases (86%). It was not statistically significantly associated with survival.
  • PD-L1 was positive in only one (2%) case, which was biphasic.
  • Women in this series had shorter survival than men, and the difference was statistically significant.
• The authors' conclusion: The authors concluded that the grading system proposed for pleural mesothelioma also correlated with survival in this peritoneal series. They said their findings support establishing a standardized grading system for better risk stratification in epithelioid DMPM.
• Limitations the authors state:
  • Retrospective study design
  • The relatively small sample size did not allow all morphological evaluations and statistical correlations
  • PD-L1 results were not available for all patients because the remaining tissue lacked tumor cells
  • BAP1 was retained in only 7 cases, which limited the power of the statistical tests
  • The shorter survival in women may be due to the limited number of female patients

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Peritoneal Mesothelioma, Neoplasm, Lung Cancer, IASLC, Pathology, Epithelioid, Immunohistochemistry.

Related studies

• Prognostic Value of Ki67 Percentage, WT-1 Expression and p16/CDKN2A Deletion in Diffuse Malignant Peritoneal Mesothelioma: A Single-Centre Cohort Study — F. Pezzuto, G. Serio, et al. (2020)
• Diffuse mesothelioma of the peritoneum: correlation between histological and clinical parameters and survival in 73 patients — S. Liu, P. Staats, et al. (2014)
• Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study — S. Valmary-Degano, P. Colpart, et al. (2017)
• 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)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• High Wilms' tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma — A. Scattone, G. Serio, et al. (2012)

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