Reproducibility of histological subtyping of malignant pleural mesothelioma

Our plain-English summary of Reproducibility of histological subtyping of malignant pleural mesothelioma, by L. Brčić, M. Jakopović, I. Brčić, et al (Virchows Archiv, 2014).

The study

• Authors: L. Brčić, M. Jakopović, I. Brčić, V. Klarić, M. Milošević, A. Sepac, M. Samaržija, S. Seiwerth
• Journal: Virchows Archiv
• Published: 2014;465(6):679-85
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) has a very poor prognosis. Although clinical stage is currently the only reliable prognostic factor, histologic subtyping reportedly also affects prognosis. Some studies propose reclassification of pleomorphic epithelioid as biphasic or sarcomatoid MPM. This study assessed prognostic significance and interobserver agreement in MPM subtyping of small biopsy specimens. We analyzed biopsy specimens, and clinical and survival data from records of 108 patients who were diagnosed between 2000 and 2010 at the Institute of Pathology University of Zagreb School of Medicine, of whom 98 had epithelioid MPM, six biphasic MPM, and four sarcomatoid MPM. Among epithelioid subtypes, 44 (44.9 %) were solid, 19 (19.4 %) tubulopapillary, 18 (18.4 %) acinar, six (6.1 %) adenomatoid, five (5.1 %) pleomorphic, four (4.1 %) trabecular, and two (2.0 %) micropapillary subtype. Interobserver reliability for histological diagnosis was found to be κ = 0.72 (P < 0.001). Median overall survival for epithelioid MPM was 10.5 months with an interquartile range (IQR) of 5.8-28.0 months but significantly shorter for the pleomorphic subtype (3 [IQR 3.0-8.0] months; P = 0.034), but not significantly different from biphasic (6.5 [IQR 3.5-15.3] months) and sarcomatoid mesothelioma (4.0 [IQR 1.3-6.8] months; P = 0.270). We found strong reproducibility of MPM subtyping with good interobserver agreement. Furthermore, our results indicate that pleomorphic subtype to be a predictor of poor prognosis and support classifying it with sarcomatoid or biphasic MPM, as patients with the pleomorphic, biphasic, or sarcomatoid subtype show similarly poor overall survival.

In plain English

This study re-examined archived biopsy specimens and records of 108 patients with malignant pleural mesothelioma. The patients were diagnosed between 2000 and 2010 at the Institute of Pathology, University of Zagreb School of Medicine, Croatia. Two pathologists independently classified the slides by tissue type and subtype, and the authors compared survival between groups. Of the 108 tumors, 98 were epithelioid, 6 biphasic and 4 sarcomatoid. The pathologists agreed with a kappa value of 0.72 (P less than 0.001). Median overall survival was 10.5 months for the epithelioid type and 3 months for its pleomorphic subtype (P=0.034). Survival for the pleomorphic subtype did not differ significantly from biphasic or sarcomatoid tumors (P=0.270). Of the patients, 41 of 108 had a history of occupational asbestos exposure, but these data were not available for all patients. Asbestos exposure showed no prognostic significance in the analyses. The authors noted that some subtype groups were very small. They concluded that the pleomorphic subtype should be reclassified as sarcomatoid or biphasic, based on overall survival.

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 archived biopsy specimens and patient records. Two pathologists classified the slides independently, and the authors analysed agreement between them and survival by subtype.
• Who was studied: 135 patients were identified as diagnosed with malignant pleural mesothelioma between 2000 and 2010 at the Institute of Pathology, University of Zagreb School of Medicine, Croatia. The 108 with a microscopically confirmed diagnosis and complete clinical information were included. Of these, 93 of 108 were male and the median age was 63 years.
• Exposure: Not an exposure study. Asbestos exposure was recorded as a patient characteristic: 41 of 108 had a history of occupational exposure to asbestos, and data were not available for all patients (the table lists 48 as unknown). No fiber types are given.
• Main results:
  • Of the 108 specimens, 98 (90.7%) were epithelioid, 6 (5.6%) biphasic and 4 (3.7%) sarcomatoid mesothelioma. Among the 98 epithelioid specimens, 5 (5.1%) were the pleomorphic subtype.
  • Agreement between the two pathologists had a kappa value of 0.72 (P less than 0.001).
  • Median overall survival for the epithelioid type was 10.5 months (interquartile range 5.8 to 28.0 months). For the pleomorphic subtype it was significantly shorter, at 3 months (interquartile range 3.0 to 8.0; P=0.034).
  • Overall survival in the pleomorphic subtype did not differ significantly from the biphasic type (median 6.5 months) or the sarcomatoid type (median 4.0 months), P=0.270.
  • Median overall survival by epithelioid subtype was: adenomatoid and tubulopapillary 25.5 months each; acinar 13 months; trabecular and micropapillary 11 months each; solid 8.5 months.
  • In bivariate and multivariate analyses, asbestos exposure, age, sex, pleural effusion, side of disease, surgery type and myxoid stroma had no prognostic significance.
• The authors' conclusion: The authors concluded that subtyping can be done on small biopsy samples with strong agreement between pathologists. They supported reclassifying the pleomorphic subtype of epithelioid mesothelioma as sarcomatoid or biphasic, based on overall survival, while cautioning that some subtype groups were small.
• Limitations the authors state:
  • Some subtype groups were very small; for example, the micropapillary group had only two patients.
  • The specimens were small biopsies, which occasionally made subtyping difficult.
  • The hazard ratios for subtypes other than pleomorphic indicate tendencies only; much larger groups would be needed for more definitive results.
  • Asbestos exposure data were not available for all patients.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Pleomorphic, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Biopsy, Pathology.

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• Interobserver Agreement in Histopathological Subtyping of Malignant Pleural Mesotheliomas — M. Mlika, F. Mezni (2021)
• The histopathological diagnosis of malignant mesothelioma v. pulmonary adenocarcinoma: reproducibility of the histopathological diagnosis — B.G. Skov, A.F. Lauritzen, et al. (1994)
• Accuracy and reproducibility of pleural effusion cytology — A. Fassina, U. Fedeli, et al. (2008)
• Pleural plaques in asbestos-exposed workers: reproducibility of a new high-resolution CT visual semiquantitative measurement method — G.S. Meirelles, J.I. Kavakama, et al. (2006)

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