When the Diagnosis of Mesothelioma Challenges Textbooks and Guidelines

Our plain-English summary of When the Diagnosis of Mesothelioma Challenges Textbooks and Guidelines, by G. Rossi, F. Davoli, V. Poletti, et al (Journal of Clinical Medicine, 2021).

The study

• Authors: G. Rossi, F. Davoli, V. Poletti, A. Cavazza, F. Lococo
• Journal: Journal of Clinical Medicine
• Published: 2021;10(11)
• Type of article: Review
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The diagnosis of malignant mesothelioma (MPM) does not pose difficulties when presenting with usual clinico-radiologic features and morphology. Pathology textbooks and national/international guidelines generally describe the findings of classic MPM, underlining common clinical presentation, the gold standard of sampling techniques, usual morphologic variants, immunohistochemical results of several positive and negative primary antibodies in the differential diagnosis, and the role of novel molecular markers. Nevertheless, MPM often does not follow the golden rules in routine practice, while the literature generally does not sufficiently emphasize unusual features of its manifestation. This gap may potentially create problems for patients in sustaining a difficult diagnosis of MPM in clinical practice and during legal disputes. Indeed, the guidelines accidentally tend to favor the job of lawyers and pathologists defending asbestos-producing industries against patients suffering from MPM characterized by uncommon features. The current review is aimed at underlining the wide spectrum of clinical and radiological presentation of MPM, the possibility to consistently use cytology for diagnostic intent, the aberrant immunohistochemical expression using so-called specific negative and positive primary antibodies, and finally proposing some alternative and more unbiased approaches to the diagnosis of MPM.

In plain English

This narrative review by pathologists and clinicians based mainly in Italy was prompted by their routine practice, consultations and medico-legal disputes. It reported no new data; its figures showed individual cases. The authors argued that textbooks and guidelines describe classic malignant pleural mesothelioma (MPM) but give too little attention to unusual presentations. They gathered published reports of MPM appearing as a solitary lung nodule, interstitial lung disease, pneumothorax or a mediastinal mass. They cited studies finding 'mesothelial' stains in lung cancers, and one in which a TTF-1 antibody clone stained 8 of 19 sarcomatoid mesotheliomas. They discussed diagnosis on fluid (cytology) samples, stating that loss of BAP1 staining in mesothelial cells indicates malignancy. Cited studies reported that biopsy had labelled 45 of 103 non-epithelioid tumors as epithelioid, and that expert second opinion differed from original diagnoses in 53% of cases. The authors concluded that all MPM are potentially medicolegal cases. They also concluded that MPM with an epithelioid component may be diagnosed on cytology or cell blocks if clinical and imaging findings, cellular atypia, evidence of mesothelial differentiation and possibly genetic changes are carefully correlated.

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 the literature, illustrated with figures from individual patients; no original study data
• Who was studied: Published literature on malignant pleural mesothelioma, drawn on because of the authors' own experience in routine practice, external consultations and medico-legal disputes; individual patient cases shown in figures
• Exposure: Not an exposure study. The review deals with how mesothelioma is diagnosed. It notes that other, non-regulated mineral fibers such as erionite or antigorite may cause asbestosis and MPM, and that MPM may occur after chest radiotherapy.
• Main results:
  • The review described published reports of MPM with unusual imaging appearances, mimicking lung cancer, interstitial lung disease, pneumothorax or an anterior mediastinal mass.
  • Citing Miettinen and Sarlomo-Rikala's study of 596 lung carcinomas, the review reported calretinin (a 'mesothelial' marker) expression in 67% of giant cell carcinomas, 49% of small cell carcinomas and 38% of large cell carcinomas.
  • Citing Klebe et al., the review reported that the TTF-1 SP141 antibody clone stained the nuclei of 8 of 19 (42%) sarcomatoid mesotheliomas, while the 8G7G3/1 clone did not.
  • For sarcomatoid MPM, which often lacks mesothelial markers, the authors argued that results for non-mesothelial markers (e.g., claudin-4 and CEA) carry more weight than positive mesothelial stains.
  • On cytology, the review stated that loss of BAP1 staining in mesothelial cells indicates malignancy.
  • The authors stated that a cytology or cell-block diagnosis of MPM with an epithelioid component requires careful correlation of clinical and imaging findings, cellular atypia, demonstration of mesothelial cell differentiation and possibly genetic alterations (e.g., CDKN2A or BAP1 loss).
  • Citing Bueno et al., the review reported that 45 of 103 (44%) patients with non-epithelioid MPM on the surgical specimen had originally been diagnosed as epithelioid type on pleural biopsy.
  • Citing van der Bij et al., the review reported that 6% (97 of 1498) of MPM patients had no pathologic diagnosis. Citing Klebe et al., it reported that expert second opinion differed significantly from the original diagnosis in 53% of cases.
• The authors' conclusion: The authors concluded that all MPM are potentially medicolegal cases, and that pathologists and lawyers should consider unusual presentations. They also concluded that MPM with an epithelioid component may be diagnosed on cytology or cell blocks and should not be rejected for lack of a biopsy. Such a diagnosis requires careful correlation of clinical and imaging findings, cellular atypia, mesothelial differentiation and possibly genetic alterations. Finally, they concluded that tumor heterogeneity is an under-recognized issue.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Pathology, Differential Diagnosis, Cytology.

Related studies

• Pleural mesothelioma: When echo-endoscopy (EUS-B-FNA) leads to diagnosis in a minimally invasive way — R. Piro, M. Fontana, et al. (2021)
• 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)
• Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up — P. Baas, D. Fennell, et al. (2015)
• Peritoneal mesothelioma: PSOGI/EURACAN clinical practice guidelines for diagnosis, treatment and follow-up — S. Kusamura, V. Kepenekian, et al. (2021)
• Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up — R.A. Stahel, W. Weder, et al. (2010)

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