The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis

Our plain-English summary of The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis, by S. Klebe, Y. Nakatani, K. Dobra, et al (Pathology, 2021).

The study

• Authors: S. Klebe, Y. Nakatani, K. Dobra, K.J. Butnor, A.C. Roden, A.G. Nicholson, A.M. Marchevsky, A.N. Husain, A. Segal, A.E. Walts, B. Weynand, C.W. Michael, S. Dacic, D. Godbolt, R. Attanoos, E. Santoni-Rugiu, F. Galateau-Salle, K. Hiroshima, A.L. Moreira, J. Burn, K. Nabeshima, A.R. Gibbs, A. Churg, L.A. Litzky, L. Brcic, M.S. Tsao, M. Mino-Kenudson, S.B. Rørvig, H.D. Tazelaar, T. Krausz, Y.Z. Zhang, L.R. Chirieac, M.B. Beasley, A. Hjerpe
• Journal: Pathology
• Published: 2021;53(4):446-453
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of 'malignant mesothelioma, cannot exclude MMIS' or 'atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS' could be used on cytology samples, adding 'no evidence of invasion in sample provided' for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS.

Copyright © 2021. Published by Elsevier B.V.

In plain English

This article combined an online survey of specialist pulmonary pathologists with the authors' critical appraisal of malignant mesothelioma in situ (MMIS), a proposed pre-invasive stage of mesothelioma. The survey covered 34 pathologists from 28 institutions in 11 countries, and asked how they diagnose mesothelioma from fluid (cytology) samples and how they handle MMIS. Of the respondents, 80% were comfortable diagnosing mesothelioma on cytology. 71% had made or suggested an MMIS diagnosis, and 82% required supporting immunohistochemistry or molecular results, but only 47% required the radiology result. 47% had seen patients receive active treatment, such as chemotherapy or surgery, after an MMIS diagnosis. 44% had seen in situ disease progress, and 35% had seen progression after more than 4 years. 12% said a known history of asbestos exposure would prompt extra tests on an effusion that did not look malignant. The authors concluded that treatment approaches vary widely and that collaborative work is needed. They suggested a low threshold for extra testing, and cytology report wording such as 'malignant mesothelioma, cannot exclude MMIS'.

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: International survey of pulmonary pathologists, presented together with the authors' critical appraisal of the MMIS concept (a 'Controversies in Pathology' article)
• Who was studied: 34 specialist pulmonary pathologists with a declared interest in mesothelioma diagnosis, from 28 institutions in 11 countries, who also co-authored the paper
• Main results:
  • 80% of the surveyed pathologists were comfortable diagnosing mesothelioma (not specifically MMIS) on cytology
  • 35% of the pathologists would diagnose mesothelioma on cytology from malignant morphology alone
  • 24% of the pathologists would diagnose mesothelioma on cytology from an abnormal BAP1, MTAP or molecular result alone, regardless of morphology or radiology
  • For an effusion that did not look malignant, 65% of the pathologists would order extra BAP1, MTAP or molecular studies if clinical suspicion was high, 35% if the effusion was recurrent, and 12% if they knew of a history of asbestos exposure
  • All the pathologists knew of MMIS as a diagnostic entity, and 71% had made or suggested the diagnosis
  • Only 10% of the pathologists had made or suggested an MMIS diagnosis on cytology
  • 82% of the pathologists required supporting immunohistochemistry or molecular marker results (CDKN2A loss, negative MTAP or BAP1) to diagnose MMIS
  • Only 47% of the pathologists required knowledge of the concurrent radiology result to diagnose MMIS
  • Individual pathologists had made the MMIS diagnosis between 0 and more than 20 times
  • MMIS as defined by the WHO was very rare: two cases in one database of 4677 specimens and seven cases in another database of 3214 cases
  • 47% of the pathologists had seen patients receive active treatment after an MMIS diagnosis
  • The treatments seen included intrapleural or systemic chemotherapy (15%), decortication (26%) and extrapleural pneumonectomy (6%)
  • 44% of the pathologists had observed progression of in situ disease
  • Time to progression varied: 15% of respondents had seen progression within 6 to 12 months, and 35% after more than 4 years
  • The authors found no consensus among experts on diagnostic criteria
  • The authors suggested a low threshold for ancillary testing on cytology and histology samples
  • The authors suggested that cytology samples meeting the criteria for mesothelioma, but lacking clinical and radiological correlation, could be reported as 'malignant mesothelioma, cannot exclude MMIS'
• The authors' conclusion: The authors concluded that treatment approaches for MMIS vary widely and that a concerted collaborative effort will be needed to gather data and inform future practice
• Limitations the authors state:
  • Clinical follow-up varied: some pathologists actively followed patients while others relied on clinical databases
  • Case records varied: some pathologists kept personal databases and others searched departmental records
  • The authors stated that understanding of MMIS is limited

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma in Situ, Cytology, Mesothelioma, Epithelioid, Atypical Mesothelial Proliferation.

Related studies

• MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma — D.B. Chapel, J.J. Schulte, et al. (2020)
• Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group — A.N. Husain, T.V. Colby, et al. (2018)
• Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group — A.N. Husain, T. Colby, et al. (2013)
• New Insights on Diagnostic Reproducibility of Biphasic Mesotheliomas: A Multi-Institutional Evaluation by the International Mesothelioma Panel From the MESOPATH Reference Center — F. Galateau Salle, N. Le Stang, et al. (2018)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)

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