Pathology of mesothelioma


The incidence of mesothelioma has been gradually increasing in Japan, and the underlie factor for this is considered to be the increase in the sum of asbestos imported into Japan between 1960 and 1975. Mesothelioma can be roughly divided into localized and diffuse types, but the early is highly rare. In making a diagnosis of mesothelioma, it is important to confirm the localization of tumor and the specific gross findings before histological examen. Mesothelioma can be categorized histologically as epithelioid character, sarcomatoid type, biphasic type, desmoplastic type, among others. It can take many forms ; consequently, there are many diseases to be differentiated when the diagnosis of mesothelioma is based on histological analyses. Immunohistochemical stains are utilitarian for making a diagnosis, but the discipline combination of antibodies as positivist or negative markers should be selected and a comprehensive judgment of the stain results is necessary. The accuracy of the pathological diagnosis is very authoritative to the patients because they can be receive official compensation or relief when the diagnosis of mesothelioma is confirmed. Under award conditions, both clinicians and pathologists must make a concert attempt to improve the accuracy of the diagnosis of mesothelioma. Keywords:

Antibody, Diagnostic accuracy, Differential diagnosis, Immunohistochemistry, Mesothelioma

Incidence of mesothelioma

Mesothelioma is a malignant tumor that originates in the pleura, peritoneum, pericardium and tunic vaginalis, all locations where a lining of normal mesothelial cell is salute. According to the official data of Ministry of Health, Labor and Welfare in Japan, the number of end due to mesothelioma was 500 in 1995, increasing gradually to 953 in 2004. This increase appears to parallel the increase of the measure of asbestos imported into Japan between 1960 and 1975, given that the latent menstruation from the beginning of exposure to asbestos and an initial diagnosis of mesothelioma is approximately 40 years. More detail examination of the 878 patients who officially died from mesothelioma in 2003 reveals that the male : female ratio was about 3:1 and that the peak of age of patients was 60+ in males and 70+ in females. The placement of the mesothelioma was in the pleura in 84 % of the cases, in the peritoneum in 12 % and in the pericardium in 1 % ; there were not cases of mesothelioma in the tunic vaginalis. A larger proportion of females had mesothelioma in the peritoneum and pericardium than in the pleura [ 1 ] .

General findings on mesothelioma

Mesothelioma can be approximately classified into localized and diffuse types, with the incidence of the latter being much higher than that of the former [ 2 ]. The localized form of mesothelioma was more frequently diagnosed in the past ; however, most of the localize forms are presently diagnosed as a lone hempen tumor [ 3 ], which is a discriminate entity from mesothelioma based on immunohistochemical phenotyping ( positive for CD34, a marker of primitive endothelial cell ) and has no relation to asbestos exposure [ 4 ]. At the early stage of pleural mesothelioma, little nodules are found in the parietal pleura ( not in the intuitive pleura ) that finally extend along the pleural coat. finally, parietal and visceral pleura show adhesiveness, and the tumor encloses the entire lung parenchyma. very few cases of peritoneal mesothelioma have been reported at the early phase and, consequently, little is known in terms of pathology and disease progression during the early degree [ 5 ]. Most of peritoneal mesothelioma is found as a diffusely extensive tumor involving intestinal serous membrane or a big tumor located at the omentum or mesentery. Following the initial diagnosis of mesothelioma, it is significant to confirm the placement of the tumor and its crying findings before histological examen. In the case of a pleural mesothelioma, a tumor in the lung parenchyma suggests lung cancer with a pleural extension. In females with peritoneal extension, the ovary should be cautiously examined as the primary web site of the tumor because the differential gear diagnosis between ovarian cancer and peritoneal mesothelioma is unmanageable and can only be made on the basis of histological analyses .

Differential diagnosis

It is important to remember that there are many diseases to be differentiated when making a pathological diagnosis and that the tissue to be differentiated varies in terms of histological type ( Table ). Epithelioid types must be differentiated from lung adenocarcinoma for pleural mesothelioma [ 12 ], ovarian serous papillary adenocarcinoma or peritoneal serous carcinoma for peritoneal mesothelioma [ 13 ]. In terms of sarcomatoid types, sarcoma originating in the chest wall, lung, pleura, abdominal wall, peritoneum and intestine must be excluded. Sarcomatoid carcinoma ( spindle cell sarcoma or pleomorphic carcinoma ) of the lung is very unmanageable to differentiate from sarcomatoid pleural mesothelioma [ 14 ]. In terms of the biphasic type, carcinosarcoma or pneumonic blastoma of the lung, biphasic synovial sarcoma [ 15 ] of the pleural mesothelioma and carcinosarcoma of the female genital organs must be differentiated from their peritoneal counterpart. The desmoplastic type has a like histology to fibrous pleuritis [ 16 ], and the differential diagnosis is very unmanageable, peculiarly if entirely a little biopsy specimen is available. reactive mesothelial hyperplasia associated with pleuritis or other lung or pleural disease must be differentiated from early-stage epithelioid mesothelioma [ 17 ] .

Table 2

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Usefulness of immunohistochemistry in an accurate diagnosis

The histochemical stain of hyarulonic acid and electron microscopic studies have been widely used in the past for making a differential diagnosis between mesothelioma and other tumors. however, immunohistochemical stains are presently the method of choice because of the simplicity and ease of these techniques. many antibodies have been detected for function in immunohistochemical staining techniques aimed at diagnosing mesothelioma, but as so far there is no antibody that is completely specific for mesothelioma and on which a diseased diagnosis of mesothelioma can be singly based. Therefore, the combination of a number of antibodies as positive or veto markers is important, and an judgment of the results in a comprehensive examination manner is necessary ( Table ) .

Table 3

Type of mesothelioma Positive markers Negative markers
Epithelioid type Calretinin CEA
Thrombomodulin Napsin A
Mesothelin Surfactant apoprotein
D2-40 Ber EP4
Sarcomatoid type AE1/AE3 Myo D1, Myoglobin
CAM5.2 Desmin, h-calredesmon
S-100p, KP-1

Open in a separate window In the subject of epithelioid mesothelioma, calretinin, WT1, thrombomodulin, mesothelin and D2-40 can be applied as a mesothelial cell marker [ 18 – 22 ]. CEA, TTF-1, Napsin A and wetting agent apoprotein are used as markers for lung adenocarcinoma. In the event of ovarian serous papillary adenocarcinoma, we recommend CEA, Ber-EP4, MOC-31 and ER ( estrogen sense organ ) as positive markers [ 23 ]. The antibodies chosen for sarcomatoid mesothelioma are very unlike from those used for epithelioid mesothelioma. In the shell of sarcomatoid mesothelioma, cytokeratin ( AE1/AE3 or CAM5.2 as antibodies ) exhibits a high gear specificity and is the most utilitarian [ 24 ]. On the other hand, because the diagnosis for true sarcoma is based on the specific specialization of tumor cells, mesothelioma is eliminated by making its differentiation clear. For model, the take after antibodies are known to be utilitarian : MyoD1, desmin and myoglobin for rhabdomyosarcoma ; desmin, α-SMA and h-caldesmon for leiomyosarcoma ; S-100p for malignant nerve sheath tumor ; KP-1 for malignant hempen histiocytoma [ 25 ]. The most unmanageable tumor to be differentiated from sarcomatoid mesothelioma of pleura is sarcomatoid carcinoma ( spindle cellular telephone carcinoma, pleomorphic carcinoma ) of the lung. When immunohistochemical stainings are used, both respond positively to cytokeratin [ 24 ]. In this encase, consequently, the crude finding or the clinical diagnosis by imaging is identical authoritative, as already mentioned. Immunohistochemical stains may be utilitarian in differentiating between fibrous pleuritis and desmoplastic mesothelioma. Desmin is incontrovertible for spike cells of the fibrous pleuritis, while desmin is minus for tumor cells of the sarcomatoid mesothelioma [ 26 ]. The combination of EMA, desmin and p53 is useful for differentiating between reactive mesothelial hyperplasia and early-stage epithelioid mesothelioma. reactive mesothelial cells are positive for desmin and negative for EMA and p53 [ 27 ] .

Compensation or relief of patients

In the recompense system for occupational exposures to asbestos and in the modern law for non-occupational exposure to asbestos, if the diagnosis of mesothelioma is certain, it can about always be presumed to be related to asbestos vulnerability and the patients can receive compensation or respite. therefore, the accuracy of the diseased diagnosis as mesothelioma is very significant. however, a rough estimate is that approximately 10–15 % of mesothelioma patients receive an inadequate diagnosis. In the committee for the sagacity of patients ’ relief, 30 % of applicants are judged as not having mesothelioma or the decision is deferred until extra evidence is provided. It is consequently essential that japanese clinicians and pathologists make an campaign to improve the accuracy of the diagnosis as mesothelioma. In detail, the pathologists must improve the accuracy of the pathological diagnosis using adequate immunohistochemical stains .



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