Saturday 2 July 2016
Ideally, pathologists should play an advisory role in determining the approach to the pleural biopsy, as they will be faced with the challenge of interpretation. The optimal biopsy techniques when MM is a serious diagnostic consideration are either a video-assisted thoracoscopic biopsy or open pleural biopsy.
The attending surgeon’s evaluation of the pleura should be sought whenever the biopsy interpretation is in doubt. The gross appearance of a pleural surface diffusely studded by tumor and showing infiltration into soft tissues is virtually diagnostic of malignancy and favors diffuse MM. An experienced surgeon will often suggest the diagnosis. In addition, the surgeon’s assessment that the pleural process is likely benign argues against the diagnosis of malignant mesothelioma.
The number of biopsy samples required to establish the diagnosis of mesothelioma is entirely dependent on the adequacy of sampling. Multiple biopsies from the most suspicious areas should be harvested, and these should be sufficiently deep to include the endofascial soft tissues of the chest wall. The number of biopsies is sufficient only when the pathologist can either establish or exclude the diagnosis of malignant mesothelioma with confidence. Unless clinical contraindications exist, the underlying lung should be sampled, as this can yield information concerning microscopic intrapulmonary extension of MM and the concomitant presence of benign fibroinflammatory disease attributable to asbestos exposure.
In practice, repeated biopsies may be necessary, in order to establish an unequivocal diagnosis of diffuse MM.
When MM is suspected but the morphological features are insufficient to establish the diagnosis beyond doubt, the biopsy report should be crafted to let the clinician know that continued monitoring and repeat biopsies may be indicated.
For example, an indeterminate biopsy showing severely atypical mesothelial hyperplasia, in the background of occupational exposure to asbestos, clinical, radiographic, or gross findings compatible with MM, should prompt the surgical pathologist to phrase the final diagnosis as “atypical mesothelial hyperplasia without diagnostic features of malignancy, however, mesothelioma cannot be excluded with confidence.” This leads the clinician to consider what, if any, diagnostic tests must be done next.
Adequate sampling is the best way to avoid this awkward situation for the surgeon, pathologist, and most importantly, the patient, who may not understand why an invasive procedure did not yield a definitive diagnosis. But unfortunately, even under the best of circumstances, the definitive diagnosis of MM can be elusive.
- 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.
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Malignancies in the lung and pleura mimicking benign processes. Colby TV. Semin Diagn Pathol. 1995 Feb;12(1):30-44. PMID: 7770673
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