The separation of benign and malignant mesothelial proliferations

Our plain-English summary of The separation of benign and malignant mesothelial proliferations, by A. Churg, F. Galateau-Salle (Archives of Pathology & Laboratory Medicine, 2012).

The study

• Authors: A. Churg, F. Galateau-Salle
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2012;136(10):1217-26
• Type of article: Review
• Cited by: 75 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: The separation of benign from malignant mesothelial proliferations is crucial to patient management but is often a difficult problem for the pathologist.

Objective: To review the pathologic features that allow separation of benign from malignant mesothelioma proliferations, with an emphasis on new findings.

Data Sources: Literature review and experience of the authors.

Conclusions: Invasion is still the most reliable indicator of malignancy. The distribution and amount of proliferating mesothelial cells are important in separating benignity from malignancy, and keratin stains can be valuable because they highlight the distribution of mesothelial cells. Hematoxylin-eosin examination remains the gold standard, and the role of immunochemistry is extremely controversial; we believe that at present there is no reliable immunohistochemical marker of malignancy in this setting. Mesothelioma in situ is a diagnosis that currently cannot be accurately made by any type of histologic examination. Desmoplastic mesotheliomas are characterized by downward growth of keratin-positive spindled cells between S100-positive fat cells; some cases of organizing pleuritis can mimic involvement of fat, but these fat-like spaces are really S100-negative artifacts aligned parallel to the pleural surface. Fluorescence in situ hybridization on tissue sections to look for homozygous p16 gene deletions is occasionally useful, but many mesotheliomas do not show homozygous p16 deletions. Equivocal biopsy specimens should be diagnosed as atypical mesothelial hyperplasia and another biopsy requested if the clinicians believe the process is malignant.

In plain English

This article was a review, based on the published literature and the authors' own experience, of how pathologists can tell benign (non-cancerous) growths of mesothelial cells from malignant mesothelioma under the microscope. Mesothelial cells line the chest, abdomen, heart sac and hydrocele sacs. The review did not study asbestos exposure; asbestos appeared only as a cause of benign effusions. The authors stated that invasion of surrounding tissue, such as fat, remained by far the most reliable sign of malignancy, and that keratin stains helped show where mesothelial cells were. Using French Group Mesopath data on 55 patients followed for 5 years, they reported that desmin staining gave no predictive value. Epithelial membrane antigen and p53 staining gave statistically significant survival differences that the authors judged of little practical use. Three-year survival was about 60% in 67 cases diagnosed as atypical mesothelial hyperplasia and approximately 15% in 640 mesothelioma cases. The authors concluded that no immunostain reliably separated benign from malignant growths, and that better markers of malignancy were needed.

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 (literature review plus the authors' experience), including some unpublished survival data from Group Mesopath
• Who was studied: Benign and malignant mesothelial proliferations of the pleura, pericardium, peritoneum and hydrocele sacs. The review includes Group Mesopath (French panel) survival data on 55 patients followed for 5 years, and on 67 patients diagnosed with atypical mesothelial hyperplasia compared with 640 diagnosed with mesothelioma.
• Exposure: Not an exposure study. Asbestos is mentioned only as a cause of benign asbestos effusions, which can be hemorrhagic.
• Main results:
  • The authors stated that invasion of the stroma (most often fat, but also muscle, lung or another organ) remains the most reliable criterion for malignancy.
  • Pankeratin (keratin) stains help show the distribution of mesothelial cells, including subtle invasion of fat.
  • Group Mesopath: of 97 problem cases circulated to the whole panel, there was disagreement in 47% on whether the process was benign or malignant.
  • Group Mesopath patients followed for 5 years (55 patients), using a 10% staining cutoff: desmin staining gave no predictive value.
  • Same group: 5-year survival was about 70% with less than 10% epithelial membrane antigen staining versus 35% with more than 10% staining, a statistically significant difference.
  • Same group: for p53, 5-year survival was 75% versus 30%. The authors described this as a statistical difference with little practical application.
  • Group Mesopath: 3-year survival was about 60% in the 67 atypical mesothelial hyperplasia cases versus approximately 15% in the 640 mesothelioma cases.
  • In organizing pleuritis, fat-like spaces ('fake fat') are artifacts. S100 staining can separate true fat from these spaces.
  • The authors stated that only a proportion of mesotheliomas show homozygous p16 gene loss on FISH, so the presence of p16 does not rule out malignancy.
  • The authors advised against diagnosing mesothelioma in situ and suggested such cases be reported as atypical mesothelial hyperplasia.
• The authors' conclusion: The authors concluded that immunohistochemical staining has not yet provided a marker that reliably separates benign from malignant mesothelial proliferations, and that better markers of malignancy are needed.
• Limitations the authors state:
  • The authors noted there is very little published on what a diagnosis of atypical mesothelial hyperplasia means for patient outcome.
  • The authors stated that the literature on GLUT-1, X-linked inhibitor of apoptosis and IMP-3 is too scanty to recommend these markers for general use.
  • The authors said the significance of mesothelial cells crossing the elastic layer of the pleura needs further study.
  • The authors described technical limits of p16 FISH: section thickness can make genes appear lost, and single cells are hard to pick out.

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, Mesothelial Cells, Mesothelioma in Situ, Desmoplastic Mesothelioma, Fluorescence In Situ Hybridization (FISH), Mesothelioma, Biopsy, Atypical Mesothelial Proliferation.

Related studies

• 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)
• CD146 immunohistochemical staining for the separation of benign from malignant mesothelial proliferations — T. Salisbury, A. Churg (2021)
• New Markers for Separating Benign From Malignant Mesothelial Proliferations: Are We There Yet? — A. Churg, B.S. Sheffield, et al. (2016)
• BAP1 immunohistochemistry and p16 FISH to separate benign from malignant mesothelial proliferations — B.S. Sheffield, H.C. Hwang, et al. (2015)
• IMP3 and GLUT-1 immunohistochemistry for distinguishing benign from malignant mesothelial proliferations — A.F. Lee, A.M. Gown, et al. (2013)
• Immunohistochemistry for NF2, LATS1/2, and YAP/TAZ Fails to Separate Benign From Malignant Mesothelial Proliferations — B.S. Sheffield, J. Lorette, et al. (2016)

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