Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2-tier nuclear grade

Our plain-English summary of Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2-tier nuclear grade, by Y.Z. Zhang, C. Brambilla, P.L. Molyneaux, et al (Histopathology, 2020).

The study

• Authors: Y.Z. Zhang, C. Brambilla, P.L. Molyneaux, A. Rice, J.L. Robertus, S. Jordan, E. Lim, L. Lang-Lazdunski, S. Begum, M. Dusmet, V. Anikin, E. Beddow, J. Finch, N. Asadi, S. Popat, J.L. Quesne, A.N. Husain, W.O.C.M. Cookson, M.F. Moffatt, A.G. Nicholson
• Journal: Histopathology
• Published: 2020;77(3):423-436
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Nuclear grade has been recently validated as a powerful prognostic tool in epithelioid malignant pleural mesothelioma (E-MPM). In other studies histological parameters including pleomorphic features and growth patterns were also shown to exert prognostic impact. The primary aims of our study are (i) externally validate the prognostic role of pleomorphic features in E-MPM and (ii) investigate if evaluating growth pattern in addition to 2-tier nuclear grade improves prognostication.

Methods And Results: 614 consecutive cases of E-MPM from our institution over a period of 15 years were retrospectively reviewed, of which 51 showed pleomorphic features. E-MPM with pleomorphic features showed significantly worse overall survival compared to those without (5.4 versus 14.7 months). Tumours with predominantly micropapillary pattern showed the worst survival (6.2 months) followed by solid (10.5 months), microcystic (15.3 months), discohesive (16.1 months), trabecular (17.6 months) and tubulo-papillary (18.6 months). Sub-classification of growth patterns into high grade (solid, micropapillary) and low grade (all others) led to good separation of overall survival (10.5 versus 18.0 months) but did not predict survival independent of 2-tier nuclear grade. A composite score comprised of growth pattern and 2-tier nuclear grade did not improve prognostication compared with nuclear grade alone. Intra-tumoural heterogeneity in growth patterns is ubiquitous.

Conclusions: Our findings support the incorporation of E-MPM with pleomorphic features in the epithelioid subtype as a highly aggressive variant distinct from 2-tier nuclear grade. E-MPM demonstrates extensive heterogeneity in growth pattern but its evaluation does not offer additional prognostic utility to 2-tier nuclear grade.

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

In plain English

This retrospective study reviewed 614 consecutive epithelioid malignant pleural mesothelioma cases at the authors' institution, 2003 to 2017. Most (87.0%) had a biopsy only. Asbestos exposure was not studied. One pathologist, blinded to outcomes, examined slides for 'pleomorphic features' and growth patterns. Pleomorphic features, meaning severely abnormal nuclei in at least 10% of tumour cells, were found in 51 of 614 cases (8.3%). These patients had median overall survival of 5.4 months, versus 14.7 months without them. Pleomorphic features remained linked to survival after accounting for nuclear grade and other factors. Among the 563 cases without pleomorphic features, median survival was 10.5 months when the predominant growth pattern was high grade (solid or micropapillary) and 18.0 months when it was low grade. However, a score combining growth pattern with nuclear grade predicted no better than nuclear grade alone. Most tumours contained several patterns. The authors concluded that pleomorphic features mark a highly aggressive epithelioid variant, and that growth pattern adds no prognostic value beyond 2-tier nuclear grade. They noted the study was retrospective and could not assess treatment.

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 review of tumour tissue from a hospital cohort, with survival analysis (univariate and multivariate)
• Who was studied: 614 consecutive patients with histologically confirmed epithelioid malignant pleural mesothelioma at the authors' institution, 2003 to 2017. Median age was 70 years and 75.6% were male. Growth-pattern analyses used 563 cases after the 51 with pleomorphic features were excluded.
• Exposure: Not an exposure study. Asbestos exposure was not reported. The factors studied were tumour features seen under the microscope: pleomorphic features, growth patterns (solid, tubulo-papillary, trabecular, micropapillary, microcystic, discohesive, cribriform, WDPM-like) and 2-tier nuclear grade.
• Main results:
  • Pleomorphic features were present in 8.3% (51/614) of cases.
  • Patients whose tumours had pleomorphic features had significantly worse median overall survival than those without (5.4 versus 14.7 months).
  • In multivariate analysis that included 2-tier nuclear grade, pleomorphic features remained independently linked to survival: hazard ratio 3.01 versus low nuclear grade (P less than 0.001) and 1.47 versus high nuclear grade (P = 0.029).
  • Among the 563 cases without pleomorphic features, tumours with a high grade predominant growth pattern (predominant solid or micropapillary) had worse median overall survival than those with a low grade predominant pattern (10.5 versus 18.0 months, P less than 0.001).
  • A composite score combining growth pattern and 2-tier nuclear grade did not improve prognosis prediction compared with nuclear grade alone. In multivariate analysis its hazard ratio (1.65, score 2 versus 0) was lower than that of 2-tier nuclear grade (2.02, high versus low grade). The 2.02 figure is cited from the authors' earlier study.
  • Most tumours showed more than one growth pattern. Only 9.6% (54/563) had a single pure pattern.
  • Among tubulo-papillary-predominant tumours, 11 of 269 (4.1%) showed WDPM-like features. These patients had longer median overall survival than those without (78.7 versus 18.0 months, P = 0.001). There were too few cases for multivariate analysis.
• The authors' conclusion: The authors concluded that tumours with pleomorphic features should be grouped within the epithelioid subtype as a highly aggressive variant, distinct from 2-tier nuclear grade. They also concluded that evaluating growth pattern offers no additional prognostic value beyond 2-tier nuclear grade.
• Limitations the authors state:
  • The study was retrospective and could not examine other factors linked to pleomorphic features, such as metabolic uptake.
  • The authors could not evaluate response to treatment, including surgery and chemotherapy.
  • Staging, metabolic uptake and treatment information were not included because they were incompletely recorded.
  • The surgically resected group was small and statistically underpowered.
  • Sampling error could not be fully excluded, because most pleomorphic cases did not have resection or autopsy.

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, Nuclear Grade, Overall Survival, Micropapillary, Trabecular, Tubulopapillary.

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• Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma — K. Kadota, K. Suzuki, et al. (2011)
• Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases — D.B. Chapel, J.J. Schulte, et al. (2021)
• Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival — J. Paajanen, S. Laaksonen, et al. (2020)

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