Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group

Our plain-English summary of Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group, by A.N. Husain, T. Colby, N. Ordonez, et al (Archives of Pathology & Laboratory Medicine, 2013).

The study

• Authors: A.N. Husain, T. Colby, N. Ordonez, T. Krausz, R. Attanoos, M.B. Beasley, A.C. Borczuk, K. Butnor, P.T. Cagle, L.R. Chirieac, A. Churg, S. Dacic, A. Fraire, F. Galateau-Salle, A. Gibbs, A. Gown, S. Hammar, L. Litzky, A.M. Marchevsky, A.G. Nicholson, V. Roggli, W.D. Travis, M. Wick, International Mesothelioma Interest Group
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2013;137(5):647-67
• Type of article: Consensus statement, Guideline
• Cited by: 332 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.

Objective: To provide updated practical guidelines for the pathologic diagnosis of MM.

Data Sources: Pathologists involved in the International Mesothelioma Interest Group and others with an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks.

Conclusions: There was consensus opinion regarding (1) distinction of benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiation of epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. It is recommended that immunohistochemical markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

In plain English

This article is a consensus guideline, not an original study. It updated the International Mesothelioma Interest Group's 2009 guidance on the pathologic diagnosis of malignant mesothelioma. It drew on a 2006 Chicago workshop, contributing pathologists, and published literature and textbooks. The authors called it a practical reference, not a mandate or a literature review. It recommended basing diagnosis on an adequate biopsy (less commonly cytology), interpreted alongside clinical, radiologic and surgical findings. It said the pathologist should not consider a history of asbestos exposure, or its absence, in making the diagnosis, and added that attribution of cause is a separate issue. It said no fixed number of antibodies suits every case and that panels depend on the differential diagnosis. For telling epithelioid pleural mesothelioma from carcinoma, it recommended at least 2 mesothelial and 2 carcinoma markers plus cytokeratin. It suggested treating weak or focal staining of fewer than 10% of cells as negative. It cited recent studies showing that homozygous p16 gene deletion rules out a reactive lesion, but said the test cannot tell mesothelioma from adenocarcinoma.

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: Consensus statement and practical diagnostic guideline (published as a review article), updating a 2009 guideline; not an original study of patients
• Who was studied: No patients were studied. Contributors were pathologists involved in the International Mesothelioma Interest Group and others. The guideline grew out of a pathology workshop at the group's October 2006 meeting in Chicago.
• Exposure: No exposure was studied. The article discussed asbestos only to say that exposure history is not useful in making the pathologic diagnosis.
• Main results:
  • Recommendation: diagnosis of malignant mesothelioma should be based on an adequate biopsy (less commonly on cytology, exfoliative and fine-needle aspiration), read in the context of clinical, radiologic and surgical findings.
  • Recommendation: the pathologist should not take asbestos exposure history into account when diagnosing mesothelioma. The authors stated that attribution of cause is a separate issue.
  • Showing invasion into stroma or fat was described as a key feature in diagnosing malignant mesothelioma.
  • The article stated that no absolute number of antibodies can be recommended for every case, and that workup can be done in stages.
  • For distinguishing epithelioid pleural mesothelioma from carcinoma, the IMIG recommended at least 2 mesothelial and 2 carcinoma markers in addition to cytokeratin.
  • Recommendation: where possible, use antibodies with a sensitivity or specificity of at least 80%.
  • Suggestion: weak or focal staining of fewer than 10% of cells should be treated as negative when interpreting a panel of stains.
  • Citing recent published studies, the article stated that homozygous deletion of p16 rules out a reactive lesion.
  • The article stated that p16 deletion testing is not useful for distinguishing malignant mesothelioma from adenocarcinoma.
• The authors' conclusion: The authors concluded that the pathologist should always consider clinical, radiologic and pathologic features together and get an expert second opinion in difficult cases when necessary. They also noted that cytology, histochemical stains and electron microscopy are of limited usefulness.
• Limitations the authors state:
  • The authors stated that the guidelines are a practical reference, not a mandate or a review of the literature.
  • The authors stated that no specific antibody panel is recommended, because staining varies between antibody clones and between laboratories.
  • The authors noted that immunohistochemical procedures are not standardized across studies, which can produce conflicting sensitivity and specificity results.

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, Mesothelioma, Epithelioid, Spindle Cell, Differential Diagnosis, Carcinoma, Adenocarcinoma, Squamous Cell.

Related studies

• 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 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)
• 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 proposal to be applauded and promoted but which requires updating — M. Sheaff (2020)
• Highlights of the 14th international mesothelioma interest group meeting: Pathologic separation of benign from malignant mesothelial proliferations and histologic/molecular analysis of malignant mesothelioma subtypes — A. Churg, K. Nabeshima, et al. (2018)
• The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: evidence-based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center — A.M. Marchevsky, N. LeStang, et al. (2017)

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