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

Our plain-English summary of Comparative analysis of prognostic histopathologic parameters in subtypes of epithelioid pleural mesothelioma, by A. Bilecz, P. Stockhammer, D. Theegarten, et al (Histopathology, 2020).

The study

• Authors: A. Bilecz, P. Stockhammer, D. Theegarten, I. Kern, M. Jakopovic, M. Samarzija, T. Klikovits, M.A. Hoda, B. Döme, F. Oberndorfer, L. Muellauer, J. Fillinger, I. Kovács, C. Pirker, M. Schuler, T. Plönes, C. Aigner, W. Klepetko, W. Berger, L. Brcic, V. Laszlo, B. Hegedus
• Journal: Histopathology
• Published: 2020;77(1):55-66
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable 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: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (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 tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours.

Conclusions: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.

© 2020 The Authors. Histopathology published by John Wiley & Sons Ltd.

In plain English

This retrospective study re-examined tumour samples from 192 patients with epithelioid malignant pleural mesothelioma diagnosed from 1994 to 2018 at five European centres. It did not study asbestos exposure. The authors classified each tumour by its main growth pattern, or as pleomorphic if at least 10% consisted of anaplastic or giant cells. They scored nuclear grade and a mitosis-necrosis score and compared these with overall survival. Solid was the most common pattern (100 of 192). Patients with tubulopapillary or microcystic tumours had a median survival of 732 days, versus 397 days for solid or trabecular tumours. Pleomorphic tumours had the shortest median survival, 173 days. In a combined analysis, the mitosis-necrosis score was an independent predictor of survival, while tumour pattern did not reach statistical significance. In 55 separate cases from The Cancer Genome Atlas, the pattern difference appeared again (795 versus 406 days). Among patients given multimodal therapy, tubulopapillary or microcystic tumours showed a trend toward longer survival that was not statistically significant. The authors concluded that subtypes might help risk-stratify patients before treatment decisions, and said this needs further confirmation.

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 multicentre study of archived tumour specimens (histological re-classification correlated with overall survival), with an external validation set of digital slides
• Who was studied: 192 patients with epithelioid malignant pleural mesothelioma diagnosed between 1994 and 2018 at five European centres (Vienna n = 54, Budapest n = 30, Golnik n = 67, Zagreb n = 9, Essen n = 32); 143 were male. A validation set of 55 epithelioid cases from The Cancer Genome Atlas was also analysed.
• Exposure: Not reported: the article does not address asbestos or any other exposure. It studied tumour features (histological subtype, nuclear grade, mitosis-necrosis score) as predictors of survival.
• Main results:
  • Tumours were classified by predominant growth pattern and by pleomorphic features. A sample was assigned pleomorphic if at least 10% of the tumour area consisted of anaplastic or giant tumour cells.
  • The main tumour pattern in the 192 cases was solid in 100, tubulopapillary in 55, trabecular in 20, microcystic in 9, pleomorphic in 6 and micropapillary in 2.
  • Median overall survival by subtype was 727 days for tubulopapillary, 936 days for microcystic, 397 days for solid and 394 days for trabecular tumours. The two micropapillary cases were excluded from survival analysis.
  • With subtypes grouped, tubulopapillary/microcystic tumours had a median overall survival of 732 days, versus 397 days for solid/trabecular tumours (P = 0.003 in the main text).
  • Pleomorphic tumours had a median overall survival of 173 days, versus 397 days for solid/trabecular tumours (P = 0.039).
  • Higher mitosis-necrosis scores were associated with shorter survival. The main text gives 720 days, 386 days and 165 days by score group.
  • There was no significant survival difference between nuclear grades 1 and 2. Patients with nuclear grade 3 had a median of 123 days, versus 486 days for grade 2 (P = 0.0002).
  • In multivariate analysis, the mitosis-necrosis score was an independent prognostic factor (HR 1.56, 95% CI 1.13 to 2.16, P = 0.007). Histological subtype did not reach significance (P = 0.095).
  • Solid/trabecular tumours were associated with higher mitosis-necrosis scores (P less than 0.0001) and higher nuclear grades (P = 0.007) than tubulopapillary/microcystic tumours.
  • In the 55-case Cancer Genome Atlas validation set, solid/trabecular tumours had a median overall survival of 406 days, versus 795 days for tubulopapillary/microcystic tumours (P = 0.01).
  • Treatment information was available for 109 patients, of whom 44 received multimodal therapy. Among those 44, tubulopapillary/microcystic tumours showed a trend toward longer survival than solid/trabecular tumours (1068 versus 580 days; HR 2.29, 95% CI 0.95 to 5.12, P = 0.066). Among patients not receiving multimodal therapy, there was no significant difference (HR 1.16, 95% CI 0.65 to 2.07, P = 0.617).
• The authors' conclusion: The authors concluded that histological subtypes of epithelioid pleural mesothelioma have prognostic impact. They said subtypes might be useful to risk-stratify patients before therapeutic decisions in multimodal treatment settings, but that this observation needs further independent and prospective confirmation.
• Limitations the authors state:
  • Samples were not pre-selected by size and included percutaneous core needle biopsies. The authors call this partly a limitation, linked to sampling heterogeneity.
  • The small Cancer Genome Atlas validation cohort (n = 55) limited the feasibility of a multivariate analysis.
  • The finding on subtypes and multimodal therapy needs further independent confirmation and prospective validation.

Topics

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

Medical terms in this study, explained in our Lexicon: Epithelioid, Pleural Mesothelioma, Prognosis, Nuclear Grading, Necrosis, Overall Survival, Histological Subtype, Tubulopapillary.

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