Comparative analysis of prognostic histopathologic parameters in subtypes of epithelioid pleural mesothelioma.

AIMS: Malignant pleural mesothelioma (MPM) is a rare malignancy with dismal prognosis. While the epithelioid type is associated with more favorable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. METHODS AND RESULTS: Tumor specimens of 192 patients with epithelioid MPM from five European centers were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival. Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histologic subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer overall survival than the solid/trabecular group (732 vs. 397 days, p=0.0013). Pleomorphic tumors had the shortest overall survival (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis-necrosis score. The mitosis-necrosis score was a robust and independent prognostic factor in our patient cohort. The prognostic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumors showed a greater improvement in overall survival after receiving multimodal therapy than those with solid or trabecular tumors. CONCLUSIONS: Histologic subtypes of epithelioid MPM have a prognostic impact and might help to select patients for intensive multimodal treatment approaches.