Reproducibility of Malignant Pleural Mesothelioma Histopathologic Subtyping

Our plain-English summary of Reproducibility of Malignant Pleural Mesothelioma Histopathologic Subtyping, by L. Brcic, G. Vlacic, F. Quehenberger, et al (Archives of Pathology & Laboratory Medicine, 2018).

The study

• Authors: L. Brcic, G. Vlacic, F. Quehenberger, I. Kern
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2018;142(6):747-752
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: - Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis. Several studies have analyzed potential prognostic markers, but histologic type remains the single most important prognostic factor. Histologic subtypes of epithelioid MPM seem to have prognostic and therapeutic implications. Interobserver agreement in histologic pattern classification should be high.

Objective: - To assess interobserver and intraobserver reproducibility in histologic differentiation between the main types of MPMs, and in further subtyping of epithelioid-type mesothelioma.

Design: - One representative hematoxylin-eosin-stained slide was selected from the archive for each of 200 patients with MPM. They were reviewed independently by 3 pathologists and classified according to the current World Health Organization classification of pleural tumors. After the first round of evaluations, a consensus meeting was organized where problems were addressed and representative images for each histologic category were selected. Two months later, cases were reevaluated by all 3 pathologists.

Results: - After the first round, overall interobserver agreement for histologic subtyping of mesothelioma was fair (κ, 0.36). The agreement was increased to substantial (κ, 0.63) in the second round. Improvement was found in interobserver agreement for all types of MPM and for most epithelioid subtypes.

Conclusions: - Moderate to substantial agreement in histologic typing and subtyping of MPM can be achieved. However, training with additional clarification of diagnostic criteria, their strict application, and help from consensus-based illustrative images is needed.

In plain English

This study tested how consistently pathologists classify malignant pleural mesothelioma under the microscope. One representative stained slide from each of 200 patients, from archives in Croatia and Slovenia, was digitized and reviewed independently by 3 pathologists with 20, 5 and 1 years of experience. They sorted cases into epithelioid, sarcomatoid or biphasic types under the 2015 World Health Organization criteria and subtyped epithelioid cases by their predominant pattern. After a consensus meeting that agreed on criteria and reference images, all cases were reviewed again 2 months later. Overall agreement, measured with the kappa statistic, was fair in the first round (0.36) and substantial in the second (0.63). In the second round, kappa was 0.90 for sarcomatoid, 0.74 for epithelioid and 0.64 for biphasic type. Agreement for the acinar pattern stayed low (0.32). Each pathologist's agreement with their own earlier readings was moderate (0.56, 0.56 and 0.50). In 24 needle-biopsy samples, second-round agreement was 0.56. The authors concluded that moderate to substantial agreement can be achieved, but that diagnostic criteria need further clarification.

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: Interobserver and intraobserver reproducibility study of archived pathology slides, with two rounds of review separated by a consensus meeting
• Who was studied: 200 consecutive archived samples from patients diagnosed with malignant pleural mesothelioma: 100 from Zagreb, Croatia and 100 from Golnik, Slovenia. Of these, 137 were video-assisted thoracoscopic biopsies, 39 pleurectomies and 24 percutaneous pleural needle core biopsies. The slides were reviewed by 3 pathologists. Years of collection are not given.
• Exposure: Not studied. The study examined how pathologists classified slides, not asbestos or other exposure.
• Main results:
  • First round, overall agreement among the 3 pathologists: kappa 0.36 (fair). Kappa between pairs of pathologists was 0.34, 0.35 and 0.38.
  • First round, by main type: sarcomatoid 0.60, epithelioid 0.50, biphasic 0.28.
  • Second round, after the consensus meeting, overall agreement: kappa 0.63 (substantial). Kappa between pairs of pathologists was 0.56, 0.64 and 0.70.
  • Main types, first round to second round: epithelioid 0.50 to 0.74, sarcomatoid 0.60 to 0.90, biphasic 0.28 to 0.64.
  • Epithelioid subtypes: the largest improvements were for micropapillary (0.07 to 0.42), deciduoid (0.12 to 0.44) and solid (0.27 to 0.58) patterns. Agreement for the acinar pattern stayed low, at 0.29 and then 0.32.
  • Each pathologist's agreement with their own first-round readings was moderate: kappa 0.56, 0.56 and 0.50. The lowest value was for the least experienced pathologist.
  • In the 24 needle-biopsy samples, agreement was 0.33 in the first round and 0.56 (moderate) in the second, lower than the 0.63 for the whole group.
• The authors' conclusion: The authors concluded that moderate to substantial agreement in typing and subtyping can be achieved. They found that sample size seems to limit agreement and that consensus-based images help. They noted that excellent agreement was not reached for most types and subtypes, so diagnostic criteria need further clarification.
• Limitations the authors state:
  • Because only hematoxylin-eosin-stained slides were used, the authors could not tell whether a spindle-cell component was reactive stroma or a genuine sarcomatoid component.
  • The needle-biopsy subanalysis included only 24 samples.
  • The authors raised differences in the pathologists' experience as a possible limitation. Based on the intraobserver results, they concluded that it was not in fact a limitation.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Histological Subtype, Epithelioid, Mesothelioma.

Related studies

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• Reproducibility of histological subtyping of malignant pleural mesothelioma — L. Brčić, M. Jakopović, et al. (2014)
• 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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