Recent Advances in the Diagnosis of Malignant Mesothelioma: Focus on Approach in Challenging Cases and in Limited Tissue and Cytologic Samples

Our plain-English summary of Recent Advances in the Diagnosis of Malignant Mesothelioma: Focus on Approach in Challenging Cases and in Limited Tissue and Cytologic Samples, by S. Monaco, M. Mehrad, S. Dacic (Advances in Anatomic Pathology, 2018).

The study

• Authors: S. Monaco, M. Mehrad, S. Dacic
• Journal: Advances in Anatomic Pathology
• Published: 2018;25(1):24-30
• Type of article: Review
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelial proliferations can be diagnostically challenging in small specimens, such as body fluid cytology and small tissue biopsies. A great morphologic challenge for pathologists is the separation of benign reactive mesothelial proliferations from malignant mesotheliomas. Reactive mesothelial proliferations may have histologic features that resemble malignancy including increased cellularity, cytologic atypia, and mitoses. Recent advances in mesothelioma genetics resulted in identification of BAP1 mutations and p16 deletions as features of malignant mesotheliomas. Hence, BAP1 immunohistochemistry and fluorescence in situ hybridization for p16 emerged as 2 most common diagnostically helpful ancillary studies used on limited samples when the question is whether the proliferation is malignant or benign. In contrast, separation of mesothelioma from other malignancies is relatively straight forward using morphology and immunohistochemical stains. The choice of antibody panel to be applied in an individual case is driven by morphology, either epithelioid or sarcomatoid. This brief review will focus on morphology and ancillary testing of mainly pleural mesothelial proliferations.

In plain English

This article was a short review by pathologists of how malignant mesothelioma, mainly of the pleura, is diagnosed from small samples such as body fluid (effusion) cytology and small tissue biopsies. It did not study new patients or asbestos exposure. The authors stated that a history of asbestos exposure should not influence how biopsy or fluid samples are interpreted. The review covered two problems: telling benign reactive mesothelial cells apart from mesothelioma, and telling mesothelioma apart from other cancers. Citing earlier studies, it reported two markers. The first was loss of the BAP1 protein. The second was deletion of the p16/CDKN2A gene, found with a lab test called FISH. Both were reported as features of mesothelioma and not of reactive cells. The review cited p16 deletion in up to 80% of pleural and 25% of peritoneal mesotheliomas. The authors proposed testing BAP1 first, then p16 if BAP1 is intact. They cited a study in which only 44% of mesotheliomas were adequately subtyped on CT-guided biopsy and about 74% on VATS biopsy. The authors concluded that these markers have let pathologists do more with less.

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 article (no new data collected)
• Who was studied: No patients were studied. The review covered published work on pathologic diagnosis of mainly pleural mesothelial proliferations in effusion cytology and small biopsies.
• Exposure: Asbestos exposure was not studied. The authors stated that a history of asbestos exposure should not influence diagnostic interpretation of biopsy or effusion specimens.
• Main results:
  • Earlier studies reviewed by the authors reported that BAP1 loss detected by immunohistochemistry is a feature of malignant mesotheliomas and is not observed in benign reactive mesothelial cells.
  • According to studies cited in the review, deletion of p16/CDKN2A can be found in up to 80% of pleural mesotheliomas and only 25% of peritoneal mesotheliomas, and occurs in malignant mesothelioma only, not in reactive mesothelial cells.
  • Other proposed immunostain markers (p53, desmin, EMA, GLUT-1, IMP3) showed statistically significant differences between benign and malignant proliferations in earlier studies. The authors said their expression varies too much to be applied reliably in an individual case.
  • The authors proposed a workup: BAP1 immunohistochemistry first, with loss of BAP1 supporting mesothelioma. If BAP1 is intact, FISH for p16 deletion should be considered.
  • A survey by Paintal et al, cited in the review, included 55 laboratories. Of these, 65% stated they diagnose malignant mesothelioma in effusion material.
  • A cited study found that only 44% of malignant mesotheliomas were adequately subclassified on CT-guided biopsy and about 74% on VATS biopsy.
  • For separating mesothelioma from other cancers, the review states that the 2015 WHO and the guideline it prints as 'IMP' recommend 2 positive and 2 negative mesothelial markers.
  • For sarcomatoid mesothelioma, the authors described D2-40 and calretinin as the 2 most helpful markers.
• The authors' conclusion: The authors concluded that high-performing antibodies, together with BAP1 loss and p16 deletion by FISH, have allowed pathologists to do more with less. They added that, despite limitations, diagnosing mesothelioma on small biopsies can help patient care and treatment decisions.

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: Malignant Mesothelioma, Fluid Cytology, Mesothelioma, BAP1, Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), Epithelioid, Sarcomatoid.

Related studies

• Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies — F. Roberts, C.M. Harper, et al. (2001)
• Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of p16 — K. Hiroshima, D. Wu, et al. (2016)
• Differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells using the cell proliferation markers minichromosome maintenance protein 7, geminin, topoisomerase II alpha and Ki-67 — F. Kimura, I. Okayasu, et al. (2013)
• HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion — K. Hiroshima, D. Wu, et al. (2021)
• BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma — S.M. McGregor, J. McElherne, et al. (2017)
• Integrative approach to cytologic and molecular diagnosis of malignant pleural mesothelioma — A. Hjerpe, S. Abd Own, et al. (2020)

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