benign reactive mesothelial hyperplasia
Wednesday 26 September 2012
BRMH; benign mesothelial hyperplasia; reactive mesothelial hyperplasia; Reactive pleuritis with mesothelial hyperplasia; reactive mesothelial proliferation
pleural reactive mesothelial hyperplasia
pericardial reactive mesothelial hyperplasia
peritoneal reactive mesothelial hyperplasia
mesothelial cell hyperplasia
orthogonal configuration of the penetrating thin-walled vessels in relation to the pleural surface.
Yet despite the advent of immunohistochemistry as an essential adjunct to the pathological diagnosis of MM, consistent and reliable diagnosis continues to be problematical in some cases, especially for small biopsies.
Many anatomical pathologists emphasise the identiﬁcation of neoplastic invasion as the deﬁnitive criterion for deﬁnitive diagnosis of malignant mesothelioma as opposed to reactive mesothelial hyperplasia.
Accordingly, Churg and Galateau-Sallé stated in 2012 that, after allowance for pseudoinvasive ﬁndings such as en face sections and benign entrapment of mesothelioma as a consequence of ﬁbro-inﬂammatory processes: ‘… invasion of the stroma continues to be by far the most reliable criterion for separating benign from malignant mesothelial proliferations. Fat is the stroma most frequently encountered and the ﬁnding of mesothelial cells in fat makes the proliferation malignant unless there is an extraordinarily good reason to believe otherwise. The same comment applies [even more so] to invasion of muscle or invasion of lung or another organ.’
- According to Attanoos and colleagues, the muscle filament protein desmin is strongly expressed in 34/40 (85%) of reactive mesothelial hyperplasia but in only 6/60 (10%) of neoplastic mesothelium.
- According to Attanoos and colleagues, epithelial membrane antigen (EMA), a glycosylated membrane protein antigen, is strongly expressed by only 8/40 (20%) of reactive mesothelial cells and by 48/60 (80%) of malignant mesothelium.
- Others have also demonstrated preferential EMA expression by malignant mesothelium ranging from 58% to 100%, with reactive mesothelial cells expressing EMA in 0% to 33% of cases.
- Cury and coworkers noted that EMA staining in malignant mesothelium is generally both strong and diffuse, as opposed to weak and patchy expression by reactive mesothelial cells.
- Nuclear overexpression of p53, a nuclear phosphoprotein involved in cellular differentiation and turnover, has been linked with neoplasia due to gene mutation on chromosome 17.
- p53 was exclusively expressed by neoplastic epithelium in 40% of cases (27/60) but not by reactive mesothelial cells (0/40) in the Attanoos study.
- However, the range of p53 expression in other studies has been highly variable ranging from 25% to 97% in malignant mesothelium and 45% to 60% in reactive mesothelium.
- Expression of Bcl-2, a 26-kDa protein that interferes with normal programmed cell death, is limited to disorders with high apoptotic rates.
- It has been consistently expressed in less than 10% of malignant mesotheliomas but has not been reproducibly detected in reactive mesothelium, indicating its low sensitivity but high specificity for mesothelial neoplasia.
- Burstein and colleagues recently reported preliminary results that positive immunostaining for XIAP can reliably distinguish benign reactive mesothelial hyperplasia from malignant mesothelioma in a high percentage of cases (USCAP Meeting, 2006).
- The putative role of XIAP immunostaining requires further confirmation.
In summary, the immunoprofile EMA+ (strong), p53+, Bcl-2+, and desmin negative may be interpreted with caution to support a diagnosis of mesothelial malignancy. It must be concluded that there is currently no reproducibly accurate immunohistochemical test that can distinguish benign reactive mesothelial hyperplasia (BRMH) from malignant mesothelioma.