Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma

Our plain-English summary of Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma, by K. Kadota, K. Suzuki, C.S. Sima, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: K. Kadota, K. Suzuki, C.S. Sima, V.W. Rusch, P.S. Adusumilli, W.D. Travis
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(5):896-904
• Cited by: 98 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This study reviewed slides from 232 patients with epithelioid diffuse malignant pleural mesothelioma diagnosed at Memorial Sloan-Kettering Cancer Center, New York, from 1989 to 2009. It did not examine asbestos exposure. Two pathologists sorted each tumor into five microscopic subtypes: trabecular, tubulopapillary, micropapillary, solid, or pleomorphic. A tumor counted as pleomorphic when at least 10% showed cells of very irregular size and appearance. Median overall survival after surgery was 16.2 months (95% CI 14.6–19.0) for all 232 patients. The 34 patients with pleomorphic tumors had the shortest median survival, 8.1 months (95% CI 4.9–17.0), compared with 24.9 months (22.9–39.9) for trabecular tumors. Pleomorphic tumors more often showed tumor in lymph vessels (68%) and veins (59%). After adjusting for age, side, stage and invasion, the pleomorphic subtype remained independently linked to shorter survival. Its survival did not differ significantly from that of biphasic or sarcomatoid mesothelioma. Among 159 patients with microscopic tumor at the surgical margins, pleomorphic tumors had the shortest median time to recurrence (13.7 months), significant only versus tubulopapillary and trabecular tumors. The authors proposed reclassifying pleomorphic tumors as biphasic or sarcomatoid.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective clinicopathological review of tumor slides and patient records from a single institution, with survival analysis
• Who was studied: 305 patients diagnosed with diffuse malignant pleural mesothelioma at Memorial Sloan-Kettering Cancer Center, New York, between 1989 and 2009. Of these, 232 had epithelioid, 47 biphasic and 26 sarcomatoid tumors. The 232 epithelioid patients had a median age of 64 and 72% were men.
• Exposure: The article does not report asbestos or any other exposure. The factor studied was the tumor's microscopic subtype: trabecular, tubulopapillary, micropapillary, solid or pleomorphic. Pleomorphic meant cellular pleomorphism in at least 10% of the tumor.
• Main results:
  • Among all 232 epithelioid patients, median overall survival, measured after surgery, was 16.2 months (95% CI 14.6–19.0). Two-year survival was 34% and five-year survival 11%.
  • The 34 patients (15%) with the pleomorphic subtype had the worst median overall survival, 8.1 months (95% CI 4.9–17.0). Median survival was 15.8 months for micropapillary, 17.9 months for tubulopapillary and 24.9 months (95% CI 22.9–39.9) for trabecular tumors. The micropapillary subtype's shorter survival was not significantly worse than that of the tubulopapillary or trabecular subtypes.
  • Tumor in lymph vessels was found in 44% of all cases. It was seen in 95% of micropapillary and 68% of pleomorphic tumors. Tumor in veins was found in 23% of all cases and in 59% of pleomorphic tumors.
  • After adjusting for age, laterality, stage, and lymphatic and vascular invasion, the pleomorphic subtype was an independent predictor of worse survival. Compared with pleomorphic tumors, the risk of death was 49% lower for trabecular, 50% lower for tubulopapillary, 58% lower for micropapillary and 33% lower for solid tumors. The hazard ratios were 0.51 (95% CI 0.29–0.91), 0.50 (0.30–0.85), 0.42 (0.22–0.78) and 0.67 (0.43–1.05). The solid-subtype result was not statistically significant (p = 0.077).
  • Median survival was 16.2 months for epithelioid, 7.0 months for biphasic (47 patients) and 3.8 months for sarcomatoid (26 patients) mesothelioma. The pleomorphic subtype's survival curve was near identical to biphasic, and it did not differ significantly from sarcomatoid.
  • Among 159 patients whose surgery left microscopic tumor at the margins (R1 resection), the 22 with pleomorphic tumors had the shortest median time to recurrence, 13.7 months. The difference was significant only compared with tubulopapillary (23.6 months) and trabecular (67.2 months) tumors.
• The authors' conclusion: The authors concluded that the pleomorphic subtype is associated with aggressive behavior. They proposed it be regarded as a sarcomatoid pattern rather than an epithelioid one, with such tumors reclassified as biphasic or sarcomatoid. They suggested this be considered in a future revision of the WHO classification.
• Limitations the authors state:
  • The authors found no link between survival and four cell features (microcystic, clear cell, deciduoid, small cell). They noted this negative finding could be due to the small number of cases.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleomorphic, Epithelioid, Pleural Mesothelioma, Biphasic Mesothelioma, Sarcomatoid, Mesothelioma, Trabecular, Tubulopapillary.

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