Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma
Abstract
Despite recent advances in the treatment of pleural mesothelioma, it remains a challenging and heterogeneous disease, with limited options for patients. Survival rates have only marginally improved in the past years, highlighting the need for a better biological understanding of the disease for the translation into clinical practice. Although recent years have seen substantial progress in genomics and molecular pathology, much of the existing literature has focused on morphology-correlated changes, with molecular, immunohistochemical, clinical, and blood biomarkers largely studied in a correlative framework. Despite these efforts, TNM classification remains the most powerful predictor of survival and one of the most important parameters to guide therapy in clinical practice. However, emerging evidence reveals that histology alone fails to capture the full heterogeneity of the disease, leading to suboptimal diagnostic, prognostic, and therapeutic approaches. This review summarizes recent major molecular findings relating not only to histology but also ploidy, tumor microenvironment, and methylation-which together offer a more comprehensive understanding of interpatient heterogeneity. In light of these results, we discuss the potential for a new morpho-molecular classification based on these molecular findings to overcome the current clinical challenges. Future directions for the field are also proposed, including the potential for emerging technologies such as single-cell, spatial omics, and artificial intelligence to fill in the gaps of bulk studies and unveil clinically relevant information about pleural mesothelioma tumor heterogeneity.
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BibTeX
@article{drevet2026moving,
title = {{Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma}},
author = {Gabrielle Drevet and Lipika Kalson and Laurane Mangé and Francoise Galateau-Salle and Arnaud Scherpereel and Lara Chalabreysse and Julien Mazières and Luka Brcic and Nicolas Alcala and Jean-Michel Maury and Lynnette Fernandez-Cuesta and Matthieu Foll},
journal = {Journal of Thoracic Oncology},
year = {2026},
month = oct,
doi = {10.1016/j.jtho.2026.01.003},
url = {https://hal.science/hal-05842062v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma
AU - Gabrielle Drevet
AU - Lipika Kalson
AU - Laurane Mangé
AU - Francoise Galateau-Salle
AU - Arnaud Scherpereel
AU - Lara Chalabreysse
AU - Julien Mazières
AU - Luka Brcic
AU - Nicolas Alcala
AU - Jean-Michel Maury
AU - Lynnette Fernandez-Cuesta
AU - Matthieu Foll
PY - 2026
DA - 2026/10/28
JO - Journal of Thoracic Oncology
DO - 10.1016/j.jtho.2026.01.003
UR - https://hal.science/hal-05842062v1
AB - Despite recent advances in the treatment of pleural mesothelioma, it remains a challenging and heterogeneous disease, with limited options for patients. Survival rates have only marginally improved in the past years, highlighting the need for a better biological understanding of the disease for the translation into clinical practice. Although recent years have seen substantial progress in genomics and molecular pathology, much of the existing literature has focused on morphology-correlated changes, with molecular, immunohistochemical, clinical, and blood biomarkers largely studied in a correlative framework. Despite these efforts, TNM classification remains the most powerful predictor of survival and one of the most important parameters to guide therapy in clinical practice. However, emerging evidence reveals that histology alone fails to capture the full heterogeneity of the disease, leading to suboptimal diagnostic, prognostic, and therapeutic approaches. This review summarizes recent major molecular findings relating not only to histology but also ploidy, tumor microenvironment, and methylation-which together offer a more comprehensive understanding of interpatient heterogeneity. In light of these results, we discuss the potential for a new morpho-molecular classification based on these molecular findings to overcome the current clinical challenges. Future directions for the field are also proposed, including the potential for emerging technologies such as single-cell, spatial omics, and artificial intelligence to fill in the gaps of bulk studies and unveil clinically relevant information about pleural mesothelioma tumor heterogeneity.
SN - 1556-0864
SN - 1556-1380
ER -