Abstract 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.
