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

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.

Lurbinectedin in Refractory Diffuse Malignant Peritoneal Mesothelioma: Report of Two Cases

Mesothelioma is a malignancy of serosal membranes. Parietal pleura is the most common site, with peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. The prognosis is often very poor with median overall survival ranging from 6 to 18 months in patients who are not candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to non-resectable disease or comorbid conditions. For patients with resectable disease, CRS and HIPEC have become the standard of care. However, for patients with unresectable malignant mesothelioma there is unfortunately no effective systemic treatment beyond the first line. Based on the results of a recent phase II trial, lurbinectedin has clinical activity and acceptable toxicity in the second- and third-line treatment of malignant pleural mesothelioma. However, until present, no data have been available for patients with MPM and for patients who become refractory after multiple treatment lines. We report on two patients with metastatic MPM who achieved durable disease control of 10+ and 8 months with lurbinectedin in the fourth and fifth treatment line, respectively.

Prognostic Value of Ki67 Percentage, WT-1 Expression and p16/CDKN2A Deletion in Diffuse Malignant Peritoneal Mesothelioma: A Single-Centre Cohort Study

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignant neoplasm with a poor survival. Although some advances in knowledge have been obtained for the pleural form, much less is known about DMPM. Advantages in terms of prognosis are still limited and strong efforts need to be made. The aim of our study was to correlate several histological and molecular factors with survival in a large cohort of 45 DMPMs. We evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, desmoplastic reaction, Ki67 percentage, WT-1 expression, p16 protein by immunohistochemistry and CDKN2A deletion by FISH. Our results showed that epithelioid histotype, nuclear grade 2, mitotic count ≤5 x mm2, absence of desmoplasia and p16/CDKN2A deletion, low Ki67 value, and high WT-1 expression were correlated with the most prolonged survival (p = 0.0001). Moreover, p16 loss in immunohistochemistry reflected CDKN2A deletion detected with FISH, and both were correlated with the worst survival (p = 0.0001). At multivariate analysis, Ki67 value, WT-1 expression and p16/CDKN2A deletion emerged as independent prognostic factors (p = 0.01, p = 0.0001 and p = 0.01, respectively). These parameters are easy to analyse at the time of DMPM diagnosis and may support better patient stratification, prediction of treatment effectiveness and therapeutic optimization.