Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA

Our plain-English summary of Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA, by D.W. Henderson, G. Reid, S.C. Kao, et al (Journal of Clinical Pathology, 2013).

The study

• Authors: D.W. Henderson, G. Reid, S.C. Kao, N. van Zandwijk, S. Klebe
• Journal: Journal of Clinical Pathology
• Published: 2013;66(10):854-61
• Type of article: Review
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pleural malignant mesothelioma (MM) includes several unusual and even rare but distinctive histological subtypes, in addition to the usual subdivision into epithelioid, biphasic and sarcomatoid MM. Criteria for discrimination between fibrous pleuritis versus desmoplastic mesothelioma include evidence of neoplastic invasion for diagnosis of desmoplastic MM, but this histological assessment is complicated by the recently-described 'fake fat phenomenon' in cases of fibrous pleuritis. The distinction between biphasic and monophasic synovial sarcoma of the pleura versus biphasic and sarcomatoid MM can be problematical and is most cogently based upon molecular detection of the t(X;18) translocation, whereas a clear diagnosis of MM for a pleural tumour histologically resembling synovial sarcoma is favoured by a negative result for this translocation and, probably, microRNA evidence supportive of a diagnosis of MM. Aquaporin-1 (AQP1) is a molecule involved in the growth of MM cells, and yet is a factor reported to correlate with improved survival rates for MM with an epithelioid component, in comparison to AQP1-poor MM, as assessed from AQP1 expression by epithelioid MM cells only (apart from co-expression by stromal endothelial cells in addition to the tumour cells). Recent reports have also focused upon germline mutations in the BRCA1-associated protein 1 (BAP1), not only in cases of familial mesothelioma, but also BAP1 deletion in sporadic MM. Prognostic factors for MM include not only the histological subtypes, but other independent variables that include (among others), AQP1 expression by mesothelioma cells, the clinical status of the patient, the serum neutrophil:lymphocyte ratio and blood thrombocytosis.

In plain English

This article was a review, Part 2 of a series, that summarised other researchers' published work on diagnosing malignant mesothelioma. It did not present a new patient study, though it included illustrative cases from the authors' own experience. It described rare subtypes, including desmoplastic mesothelioma, which must be told apart from benign fibrous pleuritis. Churg and colleagues had described a 'fake fat phenomenon' that can complicate that distinction. In one cited study (Weinbreck et al), none of 28 sarcomatoid mesotheliomas showed the t(X;18) translocation that defines synovial sarcoma. The review covered BAP1 gene mutations, including inherited mutations in two US families with mesothelioma but no identifiable asbestos or erionite exposure (Testa et al). In Kao et al's study of two patient cohorts, aquaporin-1 labelling of more than 50% of epithelioid mesothelioma cells was associated with significantly better survival than labelling of less than 50%. The review also covered microRNA as possible diagnostic markers and prognostic factors such as the blood neutrophil-to-lymphocyte ratio. The authors concluded that pathology reports can include prognostic markers, and that BAP1 and microRNA findings need further research.

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 (Part 2 of a two-part review) of published research on mesothelioma diagnosis, molecular features and prognosis, illustrated with cases from the authors' own experience
• Who was studied: No new patient study; the review drew on published studies, mainly of pleural malignant mesothelioma, and included illustrative cases from the authors' own experience
• Exposure: Asbestos exposure was not the subject of the review. One figure legend described a patient with pleural desmoplastic mesothelioma who had a history of non-occupational asbestos exposure
• Main results:
  • Citing earlier sources, the review stated that epithelioid, sarcomatoid and biphasic mesothelioma make up about 50–60%, 10–20% and 25–35% of all malignant mesotheliomas, respectively
  • Churg et al described a 'fake fat phenomenon' in fibrous pleuritis that can look like tumour invasion, complicating the diagnosis of desmoplastic mesothelioma
  • In a study by Weinbreck et al of 28 cases of sarcomatoid mesothelioma, none showed the t(X;18) translocation characteristic of synovial sarcoma
  • Testa et al reported inherited (germline) BAP1 mutations in two US families with a high incidence of mesothelioma but without identifiable asbestos or erionite exposure
  • Testa et al found BAP1 mutations in 4 of 18 (22%) sporadic mesotheliomas
  • Testa et al suggested that people with BAP1 mutations have enhanced susceptibility to the mesothelioma-causing effects of asbestos
  • In Kao et al's two cohorts of mesothelioma patients, aquaporin-1 labelling of more than 50% of the tumour cells, assessed in epithelioid mesothelioma cells, was associated with significantly better survival than labelling of less than 50%
  • In the study by Gee et al, miR-200c expression had positive and negative predictive values of 85% and 100% for mesothelioma versus lung cancer
  • In the study by Kirschner et al, increased miR-625-3p in blood distinguished mesothelioma patients from controls with an accuracy of 82%
  • In the German mesothelioma register, 5% of mesothelioma patients survived more than 3 years
  • Elevated blood neutrophil-to-lymphocyte ratio has been associated with poor prognosis in several independent cohorts of mesothelioma patients
  • According to the authors, the only molecular prognostic marker validated in independent patient series is a four-gene expression ratio test
• The authors' conclusion: The authors concluded that pathology reports on mesothelioma can include prognostic markers such as histological subtype, neutrophil-to-lymphocyte ratio and aquaporin-1 expression. They considered further investigation of BAP1 mutations clearly required, and judged microRNA biomarker research to still be in its infancy and in need of prospective studies.
• Limitations the authors state:
  • The authors did not revisit chromosomal and molecular changes in mesothelioma that had been reviewed elsewhere
  • The authors stated that detailed discussion of clinical prognostic markers was outside the scope of the review

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, Synovial Sarcoma, Mesothelioma, BAP1, Histological Subtype, Epithelioid, Biphasic Mesothelioma, Sarcomatoid.

Related studies

• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers — D.W. Henderson, G. Reid, et al. (2013)
• Pleural malignant mesothelioma versus pleuropulmonary synovial sarcoma: a clinicopathological study of 22 cases with molecular analysis and survival data — S. Klebe, S. Prabhakaran, et al. (2018)
• NY-ESO-1 expression in synovial sarcoma and other mesenchymal tumors: significance for NY-ESO-1-based targeted therapy and differential diagnosis — J.P. Lai, P.F. Robbins, et al. (2012)
• Pericardial synovial sarcoma, a potential for misdiagnosis: clinicopathologic and molecular cytogenetic analysis of three cases with literature review — Y. Cheng, W. Sheng, et al. (2012)
• The diagnostic utility of reduced immunohistochemical expression of SMARCB1 in synovial sarcomas: a validation study — J. Ito, N. Asano, et al. (2016)
• Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma — M. Miettinen, J. Limon, et al. (2001)

Browse more research in Journal of Clinical Pathology, or return to medical research.