Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group

Our plain-English summary of Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group, by A.N. Husain, T.V. Colby, N.G. Ordóñez, et al (Archives of Pathology & Laboratory Medicine, 2018).

The study

• Authors: A.N. Husain, T.V. Colby, N.G. Ordóñez, T.C. Allen, R.L. Attanoos, M.B. Beasley, K.J. Butnor, L.R. Chirieac, A.M. Churg, S. Dacic, F. Galateau-Sallé, A. Gibbs, A.M. Gown, T. Krausz, L.A. Litzky, A. Marchevsky, A.G. Nicholson, V.L. Roggli, A.K. Sharma, W.D. Travis, A.E. Walts, M.R. Wick
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2018;142(1):89-108
• Type of article: Guideline
• Cited by: 442 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 and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks.

Conclusions: - There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (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 employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should 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 and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.

In plain English

This article was a review: a 2017 update of the International Mesothelioma Interest Group's consensus guidelines for diagnosing malignant mesothelioma, based on published literature and textbooks. The authors advised basing diagnosis on an adequate biopsy (less commonly, cytology), on both tissue appearance and immunohistochemical staining, and on clinical, radiologic and surgical findings. They stated that pathologists should not take asbestos exposure history into consideration when confirming or excluding the disease. They considered two techniques very useful for separating benign from malignant mesothelial growths: homozygous p16 deletion by FISH and loss of BAP1 staining. They noted these findings occur only in mesotheliomas but not in all of them, and that the techniques perform differently at different sites. For an initial staining workup they suggested 2 mesothelial markers and 2 markers for the other suspected tumor, and treating weak or focal staining of fewer than 10% of cells as negative. They described cytology, histochemical stains and electron microscopy as of limited usefulness. They concluded that histologic subtype is still the best pathologic predictor of prognosis. They noted the article was not meant as a comprehensive literature review.

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: Review article presenting updated consensus diagnostic guidelines (2017 update of the International Mesothelioma Interest Group consensus statement); no new patient data
• Who was studied: No study population. Contributors were pathologists in the International Mesothelioma Interest Group and others with expertise in the field. The source material was published literature and textbooks.
• Exposure: No exposure was studied. The guidelines address diagnostic methods: histology, immunohistochemistry, cytology, molecular tests and electron microscopy. On asbestos, the authors stated that exposure history should not be used by the pathologist in confirming or excluding mesothelioma.
• Main results:
  • Guideline: the diagnosis should be based on an adequate biopsy (less commonly, exfoliative or fine-needle aspiration cytology), interpreted with clinical, radiologic and surgical findings.
  • Guideline: the histologic diagnosis should rest on both appropriate morphology and appropriate immunohistochemical findings.
  • The authors considered two techniques very useful for separating benign from malignant mesothelial proliferations: homozygous deletion of p16 by FISH, and loss of BAP1 by immunohistochemistry. The two can be used together.
  • Homozygous p16 deletion by FISH and BAP1 loss were described as found only in mesotheliomas, but not in all mesotheliomas.
  • The two techniques work differently at different tumor sites. For example, most peritoneal epithelial mesotheliomas do not show p16 loss by FISH, and BAP1 loss is very uncommon in sarcomatous and desmoplastic mesotheliomas.
  • Suggested initial staining workup: 2 mesothelial markers and 2 markers for the other tumor under consideration.
  • Where possible, antibodies should have a sensitivity or specificity of at least 80%.
  • The authors suggested that weak or focal staining of fewer than 10% of cells be considered a negative result.
  • In the authors' view, markers such as epithelial membrane antigen, p53, IMP-3, CD146 or glucose transporter 1 should not be used to diagnose individual patients.
  • Immunohistochemical staining for p16 protein should not replace detection of p16 gene deletion.
  • Cytology, histochemical stains and electron microscopy were described as of limited usefulness.
• The authors' conclusion: The authors concluded that histologic subtype is still the best pathologic predictor of prognosis. They also said pathologists should consider clinical, radiologic and pathologic features together and get an expert second opinion in difficult cases.
• Limitations the authors state:
  • The authors stated the article is a practical reference, not a mandate or a comprehensive, in-depth literature review.
  • Because staining varies among antibody clones and laboratories, no specific antibody panel was recommended.

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: 2012 update of the consensus statement from the International Mesothelioma Interest Group — A.N. Husain, T. Colby, et al. (2013)
• 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)
• Recommendations for uniform definitions of surgical techniques for malignant pleural mesothelioma: a consensus report of the international association for the study of lung cancer international staging committee and the international mesothelioma interest group — D. Rice, V. Rusch, et al. (2011)

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