Advances in pathological diagnosis of mesothelioma: what pulmonologists should know

Our plain-English summary of Advances in pathological diagnosis of mesothelioma: what pulmonologists should know, by A. Louw, A. Badiei, J. Creaney, et al (Current Opinion in Pulmonary Medicine, 2019).

The study

• Authors: A. Louw, A. Badiei, J. Creaney, M.S. Chai, Y.C.G. Lee
• Journal: Current Opinion in Pulmonary Medicine
• Published: 2019;25(4):354-361
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose Of Review: Malignant pleural mesothelioma (MPM) is a universally fatal illness with a rising incidence, particularly in developing countries. The diagnosis can be challenging and require repeated investigations with implications for the patient and healthcare system.

Recent Findings: Distinguishing between benign/reactive and malignant mesothelial proliferations can be challenging. Cytological diagnosis of MPM from pleural fluid is as reliable as histological analysis of tissue biopsies in epithelioid MPM - an approach endorsed by the International Academy of Cytology. Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway. The prognostic values of these molecules are being investigated. Clinicians should be aware of the recently described BAP1 tumor predisposition syndrome and offer genetic investigations in potential patients. Routine use of prophylactic radiotherapy in MPM patients after pleural interventions has been disproved in a randomized trial.

Summary: Diagnosis of epithelioid MPM can be established on pleural fluid analysis in most patients. The use of BAP1 immunostaining and CDKN2A/p16 fluorescence in-situ hybridization are particularly useful in distinguishing benign from malignant mesothelial proliferations. Clinicians should ensure these investigations are available in the pathological assessment of cases to minimize invasive investigations and the associated risks.

In plain English

This article was a review by authors in Perth, Western Australia, of recent advances in diagnosing malignant pleural mesothelioma. It was written for lung specialists and did not study new patients. It reported that consensus guidelines now accept diagnosis of epithelioid mesothelioma from pleural fluid cytology. In support, it cited a 20-year audit by Segal et al. in which all but two of 379 cytology-diagnosed cases were confirmed. It described the SMART trial, which randomized 203 patients: those given preventive radiotherapy after pleural procedures had a lower risk of tract metastases (odds ratio 0.51). The authors judged that the low rate of symptomatic tract metastases (3.9%) did not justify radiotherapy for all patients. Citing published studies, the review reported that loss of BAP1 and homozygous deletion of CDKN2A/p16 have not been reported in benign mesothelial proliferations. It added that negative results for both do not exclude mesothelioma. The authors concluded that, with adequate expertise, many patients can be diagnosed from pleural fluid, and that BAP1 and CDKN2A/p16 testing helps separate mesothelioma from benign conditions.

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: narrative review of published studies, guidelines and trials on the diagnosis of malignant pleural mesothelioma
• Who was studied: No new patients; the review covered published literature on the diagnosis of malignant pleural mesothelioma (MPM)
• Main results:
  • Cited SMART trial (203 MPM patients randomized): patients given prophylactic radiotherapy after pleural procedures had a lower risk of tract metastases (odds ratio 0.51). The authors said this did not justify radiotherapy for all patients, given the low incidence (3.9%) of symptomatic tract metastases.
  • Cited 20-year audit by Segal et al.: all but two of 379 mesothelioma cases diagnosed by pleural fluid cytology were confirmed correct by later tissue biopsy, electron microscopy or autopsy
  • Across cited studies, BAP1 loss was reported in 56 to 68% of MPM. It was more common in epithelioid (63–81%) than biphasic (39–60%) or sarcomatoid (0–22%) subtypes.
  • No report of BAP1 loss in benign mesothelial proliferations to date
  • Homozygous deletion of CDKN2A/p16 had a specificity of 100% in distinguishing MPM from benign mesothelial proliferations in cited studies. Intact CDKN2A/p16 does not exclude malignancy.
  • Combining BAP1 IHC and CDKN2A/p16 FISH improved sensitivity to 78–93%, especially in epithelioid MPM. Negative results for both do not exclude mesothelioma.
  • Germline BAP1 mutations in mesothelioma cases were estimated to be at most 1–2% in Europeans
  • Homozygous deletion of CDKN2A/p16 by FISH correlated with poorer prognosis in cited studies. Whether somatic BAP1 loss predicts prognosis was unclear because results conflicted.
• The authors' conclusion: The authors concluded that, with adequate expertise, MPM can be diagnosed from pleural fluid cytology in many patients, avoiding tissue biopsies and the risk of needle tract metastases. They also concluded that BAP1 IHC and CDKN2A/p16 FISH are particularly useful in distinguishing MPM from benign mesothelial proliferations.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Epithelioid, Cytology, BAP1, CDKN2A, BAP1 Tumor Predisposition Syndrome.

Related studies

• Pathology of the pleura: what the pulmonologists need to know — P.T. Cagle, T.C. Allen (2011)
• Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, M. Hamasaki, et al. (2021)
• A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, T. Hida, et al. (2018)
• Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens — K.B. Berg, A.M. Churg, et al. (2020)
• Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma — D. Wu, K. Hiroshima, et al. (2017)
• Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know — I. Opitz, R. Bueno, et al. (2014)

Browse more research in Current Opinion in Pulmonary Medicine, or return to medical research.