Malignant Mesothelioma Diagnosis

Our plain-English summary of Malignant Mesothelioma Diagnosis, by Q. Arif, A.N. Husain (Archives of Pathology & Laboratory Medicine, 2015).

The study

• Authors: Q. Arif, A.N. Husain
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2015;139(8):978-80
• Type of article: Review
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: Malignant mesothelioma is a relatively rare pleural tumor that may mimic benign mesothelial lesions and various other tumors including carcinomas and sarcomas. This makes the diagnosis challenging for the pathologist.

Objective: To provide a brief but useful update on the immunohistochemical, cytogenetic, and molecular markers that are currently available for the diagnosis of malignant mesothelioma.

Data Sources: Reference materials including peer-reviewed publications, text books, and consensus opinion reports among pathologists.

Conclusions: It is important to correlate histologic findings on adequate biopsy samples with clinical and radiologic features. Useful diagnostic mesothelial markers include calretinin, WT-1, cytokeratin 5/6, and D2-40 (podoplanin). It is recommended that at least 2 mesothelial and 2 carcinoma markers with greater than 80% sensitivity and specificity be used for the diagnosis of mesothelioma when all clinical, radiologic, and histologic features are concordant. p16 deletion is reported in up to 70% of primary epithelioid and 90% to 100% of sarcomatoid pleural mesotheliomas. Presence of this homozygous gene deletion is so far the best indicator of mesothelioma. To date, this deletion has not been reported in any benign mesothelial lesion. The impact of various histologic patterns on the clinical and prognostic aspects of mesothelioma is addressed. The pleomorphic pattern, when present in more than 10% of tumor, translates into a highly aggressive behavior and is associated with poor survival. Recent studies have shown that the high-grade subgroup of deciduoid mesothelioma with pleomorphic histologic pattern also has a more aggressive clinical course. Nuclear grade (combination of nuclear atypia and mitotic count) may also prove to be an independent prognostic factor.

In plain English

This short review summarized published studies, textbooks and consensus reports on how pathologists diagnose malignant mesothelioma, mostly of the pleura. It reported no new patient data and did not discuss asbestos. The authors wrote that biopsy findings must be matched with clinical and imaging findings, and that invasion of existing tissue, especially fat, remains the key sign of malignancy. Citing other studies, they reported that p16/CDKN2A deletions were found in up to 70% of primary epithelioid and 90% to 100% of sarcomatoid pleural mesotheliomas. They wrote that this homozygous deletion has not been reported so far in any benign mesothelial lesion. They called it the best marker of malignancy in a mesothelial lesion, but noted that 9p deletions alone cannot separate mesothelioma from other tumors. When clinical, imaging and tissue findings agree, they recommended testing at least 2 mesothelial and 2 carcinoma markers with greater than 80% sensitivity and specificity. Studies they reviewed linked a pleomorphic pattern in more than 10% of a tumor, and high-grade deciduoid mesothelioma, with more aggressive disease. A proposed nuclear grading system still needs validation.

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: Brief narrative review summarizing recent literature and consensus guidance on the pathologic diagnosis of malignant mesothelioma
• Who was studied: Not a study of patients. The review drew on peer-reviewed publications, textbooks and consensus opinion reports among pathologists.
• Main results:
  • From cited studies: GLUT-1 showed focal positivity in 67% of mesotheliomas and in 3% of reactive lesions. IMP3 showed diffuse positivity in 73% of mesotheliomas and was negative in reactive lesions.
  • p16/CDKN2A deletions are reported in up to 70% of primary epithelioid and 90% to 100% of sarcomatoid pleural mesotheliomas.
  • Homozygous 9p21 deletion was described as the best marker of malignancy in a mesothelial lesion, because it has not been reported so far in any benign mesothelial lesion.
  • Immunohistochemistry for loss of p16 protein is not recommended as a substitute for detecting p16 deletion.
  • 9p deletions also occur in other tumors, such as non-small cell carcinomas and sarcomas of the lung, so 9p deletions alone cannot distinguish these tumors from mesothelioma.
  • Two cited studies found that a pleomorphic pattern in more than 10% of an epithelioid tumor carried highly aggressive behavior and poor survival, similar to that of sarcomatoid mesotheliomas.
  • A cited study of 21 deciduoid mesotheliomas found that the high-grade subgroup had a much more aggressive clinical course than the low-grade tumors.
  • The authors recommended using at least 2 mesothelial and 2 carcinoma markers with greater than 80% sensitivity and specificity when clinical, radiologic and histologic features are concordant.
  • The most useful mesothelial markers named were calretinin, WT-1, cytokeratin 5/6 and D2-40 (podoplanin).
  • The most useful general carcinoma markers named were MOC31, BG8, carcinoembryonic antigen and BerEp4.
• The authors' conclusion: The authors concluded that histologic findings on an adequate biopsy must be correlated with clinical and radiologic features, and that invasion of preexisting tissue, particularly adipose tissue, remains the key indicator of malignancy.
• Limitations the authors state:
  • The proposed 3-tier nuclear grading system for epithelioid mesothelioma, which came from a single-institution study of 232 patients, needs further studies to validate it.
  • Laboratories still vary widely in which antibodies they select for testing.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Carcinoma, Sarcoma, Biopsy, Calretinin, Wilms Tumor 1 (WT-1), Cytokeratin 5/6, Podoplanin (D2-40).

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 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)
• 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)
• PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma — D.B. Chapel, A.N. Husain, et al. (2017)
• BAP1 Immunostain and CDKN2A (p16) FISH Analysis: Clinical Applicability for the Diagnosis of Malignant Mesothelioma in Effusions — A.E. Walts, K. Hiroshima, et al. (2016)
• The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis — S. Klebe, Y. Nakatani, et al. (2021)

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