Pathological findings for Mesothelioma
Malignant Mesothelioma can be categorized as biphasic, epithelioid, or sarcomatoid based on tissue samples collected during biopsy. The pathological diagnosis is achieved with the help of immunohistochemistry to reveal the incidence of epithelial, mesothelial, or true sarcomatous differentiation in the malignant cells. Diagnostic yield obtained using CT guided biopsy have been reported to vary from 60% (single attempt) to 85% (multiple attempts). However, optimal yields are eventually obtained by initiating an open or thoracoscopic pleural biopsy.
For diagnosing malignant mesothelioma, there is currently no standalone immunohistochemical mesothelial marker that can facilitate high sensitivity and 100% specificity. Hence, a variety of epithelial and mesothelial markers have been developed. The first priority should be to distinguish between a malignant pleural process and an inflammatory one. Immunochemistry procedures have demonstrated that unlike benign pleural diseases, mesothelioma repeatedly shows immunoreactivity for epithelial membrane antigen (EMA), p53 and keratin.
However, making a distinction between malignant mesothelioma and other malignancies can prove more difficult since mesotheliomas, especially the epithelioid type, can have traits similar to various other tumors. Even in such a case, immunohistochemistry can help make an appropriate differentiation of mesothelioma. Markers that have been utilized for this purpose include thrombomodulin, WT-1, cytokeratin 5/6, mesothelin, and calretinin. For mesothelioma, markers that are the most sensitive and specific include cytokeratin 5/6, calretinin and mesothelin (in epithelioid mesothelioma). However, a recent review article has mentioned that mesothelin returns positive detections in 27% of squamous cell carcinomas. The article also reports that cytokeratin 5/6 and calretinin can be utilized for both squamous cell carcinoma of the lung and adenocarcinoma of the lungs as well as other affected body parts. Making the right diagnosis can prove difficult in such a situation and hence, a panel of two positive and two negative markers should be adequate to establish the presence of malignant mesothelioma.
Mesothelioma Diagnosis – Use of Serum Markers
Making an early detection in case of malignant mesothelioma is extremely difficult due to the huge time difference that usually exists between exposure and onset of the disease. Currently, the potential use of serum markers is being assessed for achieving an accurate diagnosis. An ideal serum marker would be one that offers multiple benefits such as:
- Early detection
- Accurate identification of all the different subtypes
- Ability to differentiate between malignant mesothelioma and benign pleural disease and other metastatic pleural malignancies
- Ability to track the patient’s response to administered therapy and predict survival chances.
Although no such ideal serum marker is currently available, medical studies have suggested using osteopontin, mesothelin or megakaryocyte as possible solutions.
A glycoprotein, Osteopontin is over-expressed in melanoma and in carcinomas of the lung, gastric, colorectal, breast and ovaries. Increased levels have displayed a positive correlation with metastases, tumor progression and invasion. Although, increased levels can also be due to other malignancies, recent data indicates that osteopontin can be utilized as an effective marker for mesothelioma. It has prognostic powers similar to Ca-125 that is utilized for diagnosing ovarian cancer. As per medical studies, a sensitivity of 77% and specificity of 85% has been suggested for mesothelioma.
A membrane bound glycoprotein, mesothelin is expressed by mesothelial cells and over-expressed when exposed to malignancies such as mesothelioma. Soluble mesothelin related proteins (SMRP) have been identified as serum proteins and are said to be released by the alternative splicing of the mesothelin protein, which prevents adherence to cell membranes. Since SMRP concentration levels increase in case of malignant mesothelioma, this protein has been identified as a potential serum marker for diagnosing the disease. However, identifying the subtypes of mesothelioma using this marker alone is difficult, especially the sarcomatoid type. This is because even when patients have increased levels of SMRP, displaying a sensitivity of between 80–83% and specificity of between 80–100%, the marker is still linked mostly with the epithelioid sub-type. Despite anomaly, an FDA-approved assay, MESOMARK (Fujirebio Diagnostics Inc, Malvern, PA) has been made commercially available for the purpose of disease monitoring in biphasic and epithelioid mesothelioma.
Megakaryocyte Potentiating Factor (MPF) is released by cells of varied mesothelioma cell lines. In recent medical trials involving mesothelioma patients, MPF had increased in 91% of patients, compared with controls. However, after surgery, the increased levels in peritoneal mesothelioma patients had returned to normal. This can make MPF useful for the purpose of monitoring treatment response in mesothelioma patients.
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