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

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.

Patterns in the incidence, mortality and survival of malignant pleural and peritoneal mesothelioma, New South Wales, 1972–2009

“…In a recent review of controversies in the diagnosis of malignant mesothelioma, 47 54 We also found differences in survival by age group, gender and histological subgroup, such that survival was greater for younger people, women and people with epithelioid histological subtype. These findings are consistent with previously published data.…”

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

“…The use of BAP1 immunostain can be particularly useful in the differential diagnosis between mesothelioma and reactive mesothelial proliferations that can be challenging in several instances [9][10][11]61 and especially on small tissue samples where stromal invasion cannot be properly evaluated. In this differential scenario, the role of immunohistochemistry is very controversial, as the results obtained using several markers (e.g., desmin, epithelial membrane antigen, p53, IMP3, GLUT-1, CD146, CD147, p16) were poorly reproducible among studies, with marked variability in sensitivity and specificity.…”

Diagnosis and Treatment of Malignant Pleural Mesothelioma

“…45 In recent years, gene expression in mesothelioma has been the object of intensive research, 46 and the expression of certain proteins has been targeted, including aquaporin-1, associated with selective water transport through the membrane and with cell proliferation. 47 Of special interest is the work on micro-RNA (miRNA) in mesothelioma. These are short, non-protein coding RNAs (17-22 nucleotides) that regulate gene expression and play an important role in oncogenesis.…”