Angiosarcoma

　　First, etiology

　　Hepatic angiosarcoma is an interstitial tumor with a very high degree of malignancy. The etiology of most patients is unknown. Folk et al. investigated 168 cases, of which 75% had an unknown cause. In recent years, some hepatic angiosarcomas related to chemical substances have been reported abroad, which has attracted people's attention. It is believed to be related to exposure to vinyl chloride. Among 1183 workers in a vinyl chloride factory in the United States, 7 cases of hepatic angiosarcoma occurred, with an average latency period of 17 years. A few can also occur after taking synthetic steroids, estrogens, and contraceptives, with a latency period of more than 10 years.

　　Vinyl chloride is a gas produced during the manufacturing process of polyvinyl chloride. Under the action of endoplasmic reticulum enzymes, vinyl chloride is converted into mutagenic and carcinogenic metabolites, which then bind covalently to DNA. Experimental studies have shown that long-term exposure to vinyl chloride can induce hepatic angiosarcoma in rats or humans. The drinking water containing inorganic arsenic, the use of inorganic arsenic and copper sulfate as pesticides in vineyards, and long-term exposure can lead to hepatic angiosarcoma. There were 1 case of angiosarcoma each 36 years after the Hiroshima atomic bomb explosion and 3 years after external radiation therapy with radium rods for breast cancer. The disease also occurs in patients with psoriasis treated with potassium arsenite for a long time. Other substances that can cause hepatic angiosarcoma include radium, inorganic copper, and monoamine oxidase inhibitors. There are also reports of idiopathic hemochromatosis associated with angiosarcoma. Factors related to the incidence of human hepatic angiosarcoma.

　　Second, pathogenesis

　　The evolution process of hepatic angiosarcoma may have the following 5 main pathways: ① The sinusoidal endothelial cells of the liver lobule from atypical hyperplasia to anaplastic cell hyperplasia; ② The initial hyperplasia of liver cells, followed by atrophy and disappearance; ③ Perisinusoidal fibrous tissue hyperplasia; ④ Progressive sinus expansion to hematoma formation; ⑤ Transformation of sinus wall cells and portal area capillary endothelial cells into sarcoma cells.

　　1. Gross examination:Angiosarcoma often occurs in a multicentric pattern, mainly involving two lobes of the liver. Its gross appearance is characterized by numerous cysts filled with blood, with diameters ranging from 1 to 15 cm, and those with a diameter of 5 cm are more common. The tumors are mostly solitary and circular, with varying sizes of solid tumors, a surface with multiple nodules, clear boundaries, but without a capsule. Larger masses are spongy, with the largest weighing up to 3 kg, and can be accompanied by thrombosis and secondary necrosis. The cut surface shows grayish or brown jelly-like shiny tissue interlaced with hemorrhage and necrotic foci, with large cavities filled with non-clotting blood visible within the tumor. In cases exposed to thorium dioxide or polyvinyl chloride, there is often reticular fibrosis, splenomegaly, but it is rare to be associated with liver cirrhosis.

　　2, Pathological and histological examination:The tumor is composed of spindle-shaped or irregularly shaped malignant endothelial cells with unclear boundaries. The cytoplasm is eosinophilic, and the nuclei are deeply stained, with a narrow and elongated or irregular shape. The nucleoli in the nuclei can be large or small and similarly eosinophilic. Large and atypical nuclei as well as multinucleated cells can also be seen, and nuclear division is common. Thin-walled veins are scattered within the tumor, and about half of the cases show hematopoietic cell foci. Immunohistochemical examination can show the presence of factor VIII-related antigen in tumor cells. Tumor cells proliferate along the pre-existing vascular lumen, and the terminal hepatic venules and portal vein branches also show proliferation. The proliferation of tumor cells within the liver sinusoids can lead to the atrophy of hepatic cells, the breakage of liver plates, and the enlargement of vascular lumens to form cavities of varying sizes. The walls of the cavities are rough and uneven, and the inner walls are lined with tumor tissue cells, which are sometimes polypoid or papillary protrusions. The cavities are filled with thrombi and tumor fragments. The invasion of tumor into the terminal hepatic venules and portal vein branches can lead to the obstruction of these vessels, which can explain why tumors are often prone to bleeding, infarction, and necrosis. Sometimes, tumor cells aggregate into small nodular solid masses, similar to fibrosarcoma.

　　Immunohistochemical techniques can be used to detect the presence of factor VIII-related antigen in tumor cells.

　　In most cases, the tumor can invade the portal vein or central vein, which often occurs within the tumor nodules, but may also occur in distant liver lobules, and extramedullary hematopoietic foci are common. Secondary hemosiderosis may occur due to microangiopathic hemolytic anemia. In hepatic angiosarcoma induced by胶质二氧化钍, it is easy to see the deposition of胶质二氧化钍 within the reticuloendothelial cells or freely in the sinusoids, Glisson sheath, or walls of the terminal hepatic venules. The deposits are colorless and refractive, and the deposits stained with HE usually appear pink and brownish yellow. Radioautography can show the α-rays emitted by thorium, which appear as short streaks. Energy-dispersive X-ray microanalysis can also detect the presence of thorium elements. Angiosarcomas caused by thorium dioxide, arsenic, or vinyl chloride often have liver cirrhosis and fibrosis in non-tumor tissue. About 1/3 of patients have idiopathic cirrhosis, and there is no morphological difference between tumors caused by specific etiological factors and idiopathic tumors.

　　About 25% of patients with this disease have liver cirrhosis. Tumor rupture can lead to abdominal hemorrhage. Hepatic angiosarcoma is prone to intraperitoneal and gastrointestinal bleeding, and may also develop congestive heart failure due to the presence of分流 within the tumor. Patients with hepatic angiosarcoma often have thrombocytopenia and coagulation abnormalities due to the accumulation of platelets within the tumor. The excessive consumption of platelets within the tumor can cause disseminated intravascular coagulation with secondary fibrinolysis and microangiopathic hemolytic anemia caused by the rupture of red blood cells in the tumor blood circulation.

　　In daily life and diet, many specific precautions should be taken, as follows:

　　1. Avoid smoking and drinking;

　　2. Avoid overeating and greasy foods;

　　3. Avoid salted, smoked, roasted, and fried foods, especially charred and carbonized foods;

　　4. Avoid spicy and刺激性 foods such as scallions, garlic, Sichuan pepper, chili, and cassia;

　　5. Avoid moldy and pickled foods, such as moldy peanuts, moldy soybeans, salted fish, pickled vegetables, etc.; avoid foods with many bones, rough and hard, sticky and difficult to digest, and foods containing rough fibers;

　　6. Avoid heavy flavors, overly sour, overly sweet, overly salty, and cold foods. There are these taboos in the diet of hepatic hemangiomas.

　　7. Pay attention to physical exercise in daily life. If symptoms such as abdominal masses, weight loss, fatigue, and weakness are seen, early examination and timely treatment should be sought.

　　1. Blood tests:Anemia, microangiopathic hemolytic anemia, leukocytosis (65%) or leukopenia (25%), thrombocytopenia (62%), and decreased platelets may occur.

　　2. Liver function tests: Approximately 2/3 of the patients have liver function abnormalities: in a group of cases, 100% of those with sodium bromophenolate retention test (BSP) positivity, 85% with elevated ALP, 60% with hyperbilirubinemia, and some patients with elevated ALT. About 50% of patients have mild to moderate elevation of transaminases.

　　3. Disseminated intravascular coagulation: It is a rare complication of the disease, with a prolonged prothrombin time accounting for 72%.

　　4. p53 gene: Smith reported that mutations in the p53 tumor suppressor gene product could be detected in the serum of 225 patients with hepatic angiosarcoma who had long-term exposure to vinyl chloride, thereby proposing that the p53 gene could be one of the monitoring indicators for high-risk populations of hepatic angiosarcoma.

　　5. X-ray examination:Partial chest X-ray films may show elevation of the diaphragm or other rare signs, such as pleural effusion on the right side, atelectasis, or pleural mass. In cases related to thorium dioxide, abdominal plain films may reveal opacities of the liver, spleen, and abdominal lymph nodes.

　　6. CT Scan: Most cases of liver CT scans show abnormalities, such as inhomogeneous low-density mass lesions and tumor rupture images, with significant calcification visible after enhancement.

　　7. Hepatic Angiography: Hepatic angiography can provide valuable information for the diagnosis of the disease, showing abnormal vascular morphology, persistent staining around the tumor, and central radiating light areas, all highly suggesting hepatic angiosarcoma.

　　1. Avoid smoking and drinking;

　　2. Avoid overeating and greasy foods;

　　3. Avoid salted, smoked, roasted, and fried foods, especially charred and carbonized foods;

　　4. Avoid spicy and刺激性 foods such as scallions, garlic, Sichuan pepper, chili, and cassia;

　　5. Avoid moldy and pickled foods, such as moldy peanuts, moldy soybeans, salted fish, pickled vegetables, etc.; avoid foods with many bones, rough and hard, sticky and difficult to digest, and foods containing rough fibers;

　　6. Avoid heavy flavors, overly sour, overly sweet, overly salty, and cold foods. There are these taboos in the diet of hepatic hemangiomas.

　　7. Pay attention to physical exercise in daily life. If symptoms such as abdominal masses, weight loss, fatigue, and weakness are seen, early examination and timely treatment should be sought.

　　1. Treatment

　　For patients with limited nodules without liver cirrhosis, strive for early detection and early surgical resection, and postoperative chemotherapy and/or radiotherapy. The treatment of hepatic angiosarcoma is not satisfactory, as patients often seek medical attention in the late stage and cannot undergo surgical treatment. Treatment can include fluorouracil (5-Fu), vincristine, cyclophosphamide, methotrexate, doxorubicin (adriamycin) for chemotherapy and/or radiotherapy, which can extend the survival period. If tumor rupture and bleeding occur, selective hepatic artery embolization or surgical hemostasis may be considered. Platelet transfusion or cold agglutinate and other treatments may be administered if thrombocytopenia occurs. Liver transplantation can be performed if conditions permit.

　　2. Prognosis

　　Hepatic angiosarcoma grows rapidly, has a high degree of malignancy, develops quickly, has few opportunities for tumor resection, 50% of patients can have distant metastasis, the prognosis is poor, and most untreated patients die within 6 to 12 months, the cause of death is often cachexia or liver failure, and they can also die from tumor rupture.

　　Due to the difficulty of early diagnosis, even after surgery, the survival period is generally only 1 to 3 years.