Pleomorphic Epithelioid Diffuse Malignant Pleural Mesothelioma A Clinicopathological Review and Conceptual Proposal to Reclassify as Biphasic or Sarcomatoid Mesothelioma

Introduction: In patients with epithelioid diffuse malignant pleural mesothelioma (DMPM), clinical stage is the current primary prognostic factor. We sought to investigate whether histologic subtyping can prognostically stratify patients with epithelioid DMPM. Methods: Hematoxylin and eosin-stained slides of 232 patients with epithelioid DMPM (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed. We classified the tumors into five subtypes, according to the predominant histological pattern: trabecular, tubulopapillary, micropapillary, solid, and pleomorphic (>= 10% of tumor). Results: Median overall survival (OS) of all patients with epithelioid DMPM was 16.2 months. Patients with pleomorphic subtype (n = 34) had the worst median OS (8.1 months), followed by solid (n = 89, 13.7 months), micropapillary (n = 20, 15.8 months), tubulopapillary (n = 51, 17.9 months), and trabecular (n = 38, 24.9 months). The pleomorphic subtype was associated with lymphatic and vascular invasion (p < 0.001). The micropapillary subtype was associated with lymphatic invasion (p < 0.001). In univariate analyses, pleomorphic subtype was significantly associated with poor OS (p = 0.003). The pleomorphic subtype showed no significant difference on OS compared with biphasic and sarcomatoid DMPM. In a multivariate analysis, the pleomorphic subtype was an independent predictor of poor OS (p = 0.031). In patients who underwent R1 resection, pleomorphic subtype had the shortest median time to recurrence (13.7 months). Conclusion: Our finding that the pleomorphic subtype is a predictor of aggressive behavior in epithelioid DMPM with no survival difference from biphasic or sarcomatoid DMPM suggests that it may be best regarded as a sarcomatoid pattern rather than a subtype of epithelioid DMPM.