(A) etiology
Etiology and asbestos exposure related to its incidence and exposure to very long intervals, often in more than 30 years. Early in the 20th century, 40 years, foreign scholars found the incidence of mesothelioma and asbestos exposure are closely related. Shipyard workers, pipeline workers, welders and paint, the incidence of construction workers 300 times higher than the average person. Close relationship between mesothelioma and asbestos exposure has been confirmed by the fact that more and more and recognized. At the same time, European and American scholars found that about 60% of patients had peritoneal mesothelioma, occupational history of asbestos exposure or asbestos lung tissue corpuscles, in the use of asbestos-induced pleural mesothelioma in experimental animals, also place a small number of animals peritoneal mesothelioma, indicating the occurrence of peritoneal mesothelioma and asbestos exposure there is a certain relationship. Different types of asbestos fibers disease risk as follows: crocidolite> amosite> chrysotile asbestos. 0.5 ~ 50μm in diameter is generally believed that long before the asbestos dust into the respiratory tract, and then by the diaphragmatic lymph or blood into the abdominal cavity and net deposition in the peritoneum, the formation of asbestos bodies, and sometimes asbestos bodies in the surrounding foreign body giant cell reaction can occur. Asbestos fiber intake by the digestive tract can reach the peritoneum via the intestinal wall. Mesothelioma from exposure to asbestos found that an average of 35 to 40 years, the incidence peaks in 45 years after exposure. The exact mechanism of asbestos-induced mesothelioma is also unclear. But about 30% of the mesothelioma patients no history of exposure to asbestos, asbestos fibers in contact with the quantitative and did not show a large number of asbestos fibers. Reported occurred with mesothelioma and other factors related to radiation therapy, history of exposure to thorium dioxide (often patients have received diagnostic tests related to history.) In addition, patients with a history of Hodgkin increased risk of mesothelioma.
Virus infection: the simian virus (simian virus 40, SV40), which is a DNA tumor virus. According to the literature, the United States about 50% of the mesothelioma patients with biopsy specimens there SV40, which induces telomerase activity in primary mesothelioma, but not fibroblasts. 72h after infection of wild-type SV40 telomerase activity can be measured after 1 week shows a clear DNA ladder. Telomerase activity in cell structure and is proportional to the number of SV40 T antigen, SV40 infected by mesothelial cells, telomerase activity increased, making difficult to apoptosis in mesothelial cells, easily understood form of mesothelioma.
Mesothelioma may also be to the following factors: exposure to fluorspar, tuberculosis scars, chronic inflammation, radioactive substances, such as genetic predisposition.
(B) of the pathogenesis
According to their biological behavior and tumor invasion and scope, can be divided into benign and malignant mesothelioma, localized and diffuse. Reported cases of mesothelioma in bulk, about 57.1% occurred in the pleura, peritoneum occurred in 39.5% and 1% occur in the pericardium, can involve multiple serosal surface, or even in the testis sheath.
1. Mesothelioma tissue that comes from both its early cells, the surface of the peritoneal mesothelial cells and connective tissue cells. Has recently been proved to be from a single cell, that mesothelial cells. Mesothelial cells and fibroblasts to the epithelial cells showed two forms of differentiation. Dardick (1984) found in sarcomatoid mesothelioma in the region does not show the ultrastructural features of fibroblasts, which show different stages of differentiation characteristics of epithelial cells. Blobel proved by immunohistochemistry cytokeratin polypeptide (cytokeratin polypeptide) in the fibrous mesothelioma, and expressed in all epithelial mesothelioma. The wavy fiber protein (fibrin), in the same or the same tumor cells also expressed the two-way display the expression characteristics of mesothelioma.
2. Peritoneal mesothelioma can be divided into low grade cystic mesothelioma, well-differentiated papillary mesothelioma and malignant mesothelioma.
(1) low grade cystic mesothelioma: is common in middle-aged women, often located in the pelvic extraperitoneal and can be invaded. Tumors larger envelope was not obvious, ill-defined, often in the structure of the surrounding pelvic adhesions. Section for multi-cystic, smooth wall, clear liquid or capsule containing thin mucus. Flat to low columnar wall covered mesothelial cells, mild to moderate abnormal, can be presented papillary hyperplasia and metaplasia. Cystic hyperplasia of fibrous stroma, in which no chronic inflammatory cell infiltration.
(2) well-differentiated papillary mesothelioma: not common, even in the operation found that occurs in women of childbearing age. Prognosis is usually good, even to the development of malignant mesothelioma. Visible over the pelvic peritoneum and omentum showed papillary or nodular lesions, solid, white, diameter <2cm. Tumors may also occur in the stomach, intestine and mesenteric peritoneum. Endoscopic papillary tumors of flat to cuboidal single-layer coating the surface of mesothelial cells, nuclear atypia, rare mitotic figures, cytoplasmic axis for the fibrous stroma. Visible tumors formed by the mesothelial cells in a small tube, branch-like cords or solid pieces, occasionally sand body.
(3) malignant mesothelioma: single or multiple tumors were dispersed growth, while involving the visceral and parietal peritoneum can be classified according to shape and limitations of diffuse type. Localized malignant mesothelioma, clear boundary, pedunculated or capsule, hard and tough, low degree of malignancy. Diffuse malignant mesothelioma, diffuse peritoneal thickening involved, the surface was papillary, plaque or nodular, highly malignant. In general see, widely distributed peritoneal surface tumor nodules of varying sizes, isolated, or was beaded cluster mass, from a few millimeters to several centimeters in diameter, yellowish white or gray, hard, like a rubber-like texture . Late thickened peritoneum, peritoneal tumor was covered by dense white, so that organ into a "frozen" (frozen) state. Tumor tissue and abdominal viscera, especially the digestive tract fused with each other sticky and difficult to separate, or organs in the abdominal cavity peritoneal surface showed multiple nodular masses of grape-like, or diffusely distributed in the abdominal peritoneal surface of the diaphragm, peritoneal surface, and after omentum, mesentery, small intestine and colon serosa or the liver, bladder surface. Sometimes multiple nodules fused into lumps.
Peritoneal mesothelial cells pathologic tumor peritoneal mesothelioma outlook general observation is similar to pleural mesothelioma, there are 2 types, namely, diffuse peritoneal mesothelioma and limitations of peritoneal mesothelioma, in general, diffuse 75% of malignant mesothelioma, and limitations of mesothelioma are mostly benign. The former showed a large number of tumor nodules or plaques covered in the parietal or visceral peritoneum with tumor development, the bulk of the thickening of the film was widely covered and in the parietal peritoneum, or abdominal organs on the surface, may be associated with ranging in size tumor or nodule. Mostly off-white tumor tissue, hard and tough, also was jelly, may have hemorrhage and necrosis. Tumor tissue, fibrous tissue hyperplasia, and even a glass-like change. Tumors can invade the liver or intestine, but rarely invade deep organs, omentum can be completely replaced by tumor tissue, intestinal adhesions can occur, there is intra-abdominal effusion, and even bloody ascites. Limitations of peritoneal mesothelial cells in the tumor, tumor tissue showed nodular or plaque in the parietal or visceral peritoneum, are pale, hard, circumscribed, rarely hemorrhage and necrosis (Figure 1).
3. Peritoneal mesothelioma peritoneal mesothelial cells were observed generally have three kinds of tumor histological type:
(1) fibrous mesothelioma: fibrous mesothelioma tumor cells composed of spindle cells, fusiform cells, accompanied by varying amounts of collagen fibers, the limitations of this type more common in mesothelioma. In fibrous mesothelioma cancer is sometimes difficult to distinguish with fibrous tissue, tumor cells were spindle-shaped cells of the surrounding collagen may have, or even a weave-like structure, focal calcification or ossification, when there are obvious interstitial fibrosis or hyaline degeneration, some people call it the ligament-like mesothelioma. Recently, some people will come from the subcutaneous connective tissue between the source of the tumor, called the peritoneal fibroma. Mesothelial cells from the surface before said fibrous mesothelioma. However, based solely on morphology, it is sometimes difficult to distinguish between the two (Figure 2).
(2) epithelioid mesothelioma: epithelial mesothelioma tumor cells were cuboidal or polygonal, often tubular or papillary structures clock. Found in most epithelial mesothelioma, diffuse mesothelioma, the tumor cells were different differentiation status, can form well-differentiated tubular or papillary structures, but also showed a massive piece of undifferentiated tumor tissue, tumor cells of different sizes, in solid, surrounded by connective tissue. Tubular form papillary structures adenoid tumor, tubular or cystic, lined by cubic or flat epithelial cells, the same size, vesicular nucleus, showing 1 to 2 nucleoli. Abundant cytoplasm, cell outlines clear. Also showed a fracture or tumor-like formation of cysts of varying sizes, lined by flattened epithelial cells, these fractures are sometimes seen within the papillae. Similar to the papillary adenocarcinoma. Some cases, the tumor cells arranged in solid, cords or nests, without adenoid or papillary structures. But sometimes may have mucus around the tumor material, forming a similar structure of mucus lake. More consistent cell morphology, nuclear sizes, when the cytoplasm vacuolization mucopolysaccharide containing material (Figure 3).
(3) mixed mesothelioma: differentiation of mesothelioma, also known as two-way, in the same fiber and epithelial tumor associated with 2 components. Zllzllki (1980) reported 210 cases of diffuse malignant mesothelioma, the epithelial-like 67%, mixed 26%, 7% fibrosis, the latter most commonly within the limitations of mesothelioma. Mixed mesothelioma tumor cells and epithelioid sarcoma by the kind of composition, morphology similar to synovial sarcoma. Sarcomatoid component composed of spindle cells, it is often a transitional form of epithelial components, which can be displayed, mesothelioma is a cell from a single source, and asbestos-related mesothelioma in common to this form. Mucinous adenocarcinoma and mesothelioma, staining on the identification of a help, but low differentiation adenocarcinoma, mucus staining can also be negative. The tumor cells Alcianblue mesothelioma can also be displayed positive staining, but these are also found in the extracellular mucous stroma. Reticular fiber staining tumor cells is rich in reticular fibers, and help distinguish it from adenocarcinoma. When the tumor was found asbestos bodies (asbestosbody) when there is help in the diagnosis of mesothelioma, especially in pleural mesothelioma. As asbestos and the occurrence of lung cancer have relationships, so that only the reference value of asbestos bodies (Figure 4).
4. Peritoneal mesothelioma ultrastructural electron microscopy, especially transmission electron microscopy, the diagnosis of mesothelial tumors have a high value. Ultrastructural features are: mesothelioma tumor cells have numerous, slender, brush-like microvilli appear on the surface of tumor cells, but can also appear in the cytoplasm. However, in adenocarcinoma of the microvilli, the number of small, short stick. Mesothelioma has a huge nucleus of cells, prominent nucleoli, moderate amount of mitochondria is the rough endoplasmic reticulum surrounding the common glycogen granules, bundles of fiber tension and intracellular vacuoles. Smooth endoplasmic reticulum is not well developed. Cells outside the substrate, but most do not complete. Connections between cells, can also be found desmosomes. These ultrastructural features were mainly observed in epithelial cells of mesothelioma in mesothelioma or mixed. The fibrous mesothelioma, ultrastructure similar to fibroblasts, the tumor cells in the spindle, is rich in rough endoplasmic reticulum, occasional small cavities between cells and microvilli (Fig. 5).
5. Peritoneal mesothelioma immunohistochemistry Immunohistochemical differential diagnosis of mesothelioma and adenocarcinoma have some help. Cytokeratin (cytokeratin) showed positive in mesothelioma, but CEA was negative or weakly positive; adenocarcinoma positive for CEA are mostly strong, and keratin (keratin) often focal positive or negative. However, due to various reasons, the literature in the immunohistochemical identification of mesothelioma and adenocarcinoma of the reports, each with different results. So simple and so can not make a final conclusion, other technologies must be integrated to make an objective diagnosis. Some mesothelioma patients, accompanied by metabolic disorders, such as blood glucose less psychosis. Occasional limitations of peritoneal mesothelioma can be presented multiple cystic, lined with simple cuboidal or flat epithelium, capsule containing a transparent liquid.
Mesothelioma cell electron microscopy and enzyme histochemical characteristics: mainly by epithelioid mesothelioma cells (epithelioid cell, EC), fibroblast-like cells (fibroblast-like cell, FLC), intermediate cells (interim cell, IC) and primitive mesenchymal cells (primary mesenchymal cell, PMC) 4 kinds of cells formed. EC to enrich characterized by microvilli, cell surface microvilli are slender, its length and width and diameter ratio of 10:1 ~ 15:1, which is far greater than the proportion of other cancer, several tumor cells around showed a sinus-like gap, within which there are many intertwined slender microvilli, FLC in the rough endoplasmic reticulum more. EC dehydrogenase and oxidase activity were higher, and lower hydrolytic activity. FLC cell activity and the EC is the opposite. This may be related to two different types of activity related to cell function.
Immunohistochemical Features of mesothelioma: Since the original mesenchymal cells directly or through intermediate cells to epithelial cells, may also be differentiated into fiber-type cells, which immunohistochemical staining of mesothelioma complex types The immunohistochemical characteristics of mesothelioma cells in Table 1.
As can be seen from the table, mesothelioma, a variety of immunohistochemical expression of different, positive expression and negative results were not 100%. Therefore, certain abdominal tumors, particularly ovarian serous cystadenocarcinoma and tubular epithelial mesothelioma, papillary structures difficult to identify. The former only 2% of CEA expression, whereas epithelial membrane antigen and human milk fat globulin expression there is a higher percentage, so the use of the immunohistochemistry is difficult to distinguish between the two. Recent application of Ber-Ep4 antibody can be identified malignant mesothelioma and adenocarcinoma, Ber-Ep4 and retroperitoneal abdominal peritoneal metastatic adenocarcinoma, and adenocarcinoma of the positive rate was 100%, while only 115 cases of mesothelioma expression in 1 case (accounting for 0.87%). Therefore, the use of comprehensive analysis of immunohistochemical staining, can make the correct pathologic diagnosis of mesothelioma, electron microscopy if the conditions are even more perfect.
