1.What is hepatic hemangioma? Histologically, hepatic hemangioma is divided into 4 types: cavernous hemangioma, sclerosing hemangioma, vascular endothelial cell tumor and capillary hemangioma. The cavernous hemangioma is the most common, accounting for about 95-98% of hepatic hemangiomas, and its autopsy detection rate is 0.4-7.3%. It can be seen in people of all ages, but it is more common in women aged 30-50. Hepatic cavernous hemangioma is the most common benign tumor of the liver and is a congenital benign vascular malrotation, not a true tumor, but a hepatic microarterial malformation. The exact cause is unknown, but most scholars believe that it is caused by abnormal vascular development during embryonic development, and its growth is characterized by progressive vascular expansion rather than hyperplasia or hypertrophy. In the thick-walled type, there are more collagen fibers and fibroblasts in the wall, and the lumen of the vessel is small or even slit-like. In the thin-walled type, there are only a few collagen fibers and fibroblasts in the wall, and the lumen of the vessel is large. Hemangiomas present as dark red, blue-purple cystic elevations in the liver. They are lobulated or nodular, soft, compressible, and mostly clearly demarcated from adjacent tissues. Most hepatic cavernous hemangiomas are solitary lesions, but about 10% of patients have multiple lesions. Clinically, they can be classified into 3 levels according to the size of the tumor: small cavernous hemangioma with a diameter of ≤4 cm; large cavernous hemangioma with a diameter of >4-10 cm; and giant cavernous hemangioma with a diameter of >10 cm. Most of the patients have no clinical symptoms and are found during physical examination or other reasons for ultrasound or CT examination. On ultrasound, the hemangioma appears as a focal hyperechoic area; on CT scan, the lesion appears as a hypointense area, and on contrast, it shows characteristic enhancement, i.e., peripheral to central enhancement within a few minutes; on MRIT2-weighted images, it appears as a high-signal “light bulb sign”. The diagnosis is usually made on the basis of the above imaging methods, and angiography is rarely used for diagnosis. Some of the larger tumors may show symptoms of upper abdominal discomfort, abdominal distension, abdominal pain and other pressure symptoms. Occasionally, abdominal mass can be palpated. Laboratory tests are mostly abnormal. 2.What are the causes of hepatic hemangioma? At present, the mainstream academic community believes that hepatic cavernous hemangioma is a congenital benign vascular malformation, not a true tumor, but a hepatic micro-arterial malformation. The exact cause is not clear, but most scholars believe that it is caused by abnormal vascular development during embryonic development, and its growth is characterized by progressive vascular dilatation rather than hyperplasia or enlargement. 3.Does hepatic hemangioma progress quickly? In most cases, the tumor grows slowly and the symptoms are mild; clinically, no special treatment is needed. Generally, the course of the disease is stable, but in some cases, the growth rate is fast, and the size of the tumor increases within 1 to 2 years or even 3 months. In clinical practice, it is observed that most CHL is found after the age of 40, mostly during physical examination or examination for other diseases. At this time, CHL is found to have begun to undergo degenerative changes. Only a very small number of CHLs are stimulated by some factor to proliferate too rapidly and thus produce symptoms. This kind of CHL is most often seen in young people before 35 years old, especially in women of childbearing age who have repeated pregnancies and long-term oral estrogenic contraceptives, and its mechanism is still unclear. 4.Can hepatic hemangioma become cancerous? The endothelial cells of CHL blood sinusoidal wall are mature endothelial cells without proliferative behavior, therefore, no malignant transformation of CHL has been reported so far. 5.Does hepatic hemangioma occur in young people? Hepatic hemangioma is a common vascular malformation in children, accounting for about 12% of liver tumors in children; it is most common in infants under 6 months of age, with equal incidence in both sexes and mostly multiple incidences. 6.Who are vulnerable to liver hemangioma? What are the conditions that need to be alerted? Hepatic cavernous hemangioma is most commonly seen in young women. It has been reported that hemangioma can increase rapidly in pregnancy or oral contraceptive use, but the mechanism is unclear, and it is difficult to determine whether hepatic hemangioma has female hormone dependence. The symptoms of hepatic hemangioma are not specific, and the cause is often difficult to define. It has been reported that 54% of symptomatic hepatic hemangiomas are not caused by the hemangioma itself, but by diseases of the gastrointestinal tract or biliary tract. Therefore, special attention should be paid to rule out the presence of other organic lesions in symptomatic hepatic hemangiomas. Most of them are found during abdominal imaging for other reasons, but they are also often found incidentally during dissection or autopsy. Small hemangiomas are asymptomatic, and even large hemangiomas are usually asymptomatic. However, if the tumor is large and pulls the liver envelope or compresses the adjacent tissues and organs such as gastrointestinal tract, there may be symptoms such as vague pain in the upper abdomen, postprandial fullness, nausea and vomiting. Most of the above symptoms will disappear naturally after 1 to 3 weeks, but a few of them may persist. If there is acute bleeding or thrombosis in the tumor or inflammatory reaction in the liver envelope, abdominal pain may be severe and may be accompanied by fever and abnormal liver function. Spontaneous rupture and bleeding of hepatic hemangioma or twisting of the tumor tip leading to acute abdominal manifestations are extremely rare. The disease may also be associated with thrombocytopenia or hypofibrinogenemia, known as Kasabach-Merritt syndrome. This is a rare complication of hepatic hemangioma, most commonly seen in children, and is related to the recent thrombosis within the giant hemangioma that consumes a large amount of coagulation factors. 7.What tests are needed to confirm the diagnosis of hepatic hemangioma? The diagnosis of hepatic hemangioma depends on a series of tests such as liver function, tumor markers, B-mode ultrasound, nuclear scan, CT, MRI, or even hepatic arteriography. Liver function tests are generally within the normal range, except for rapid tumor enlargement compressing the bile ducts or thrombosis. Occasionally, moderate or even severe anemia, thrombocytopenia or hypofibrinogenemia may occur in a few cases of giant hemangioma complicated by thrombosis. None of the tumor marker tests are abnormally elevated. B-mode ultrasound can detect hemangiomas larger than 2 cm in diameter, which typically present as a well-defined hypoechoic occupancy with less pronounced posterior echogenic enhancement due to less attenuation of the ultrasound transmission through the blood of the cavernous sinus. However, most small hemangiomas are strongly echogenic, while larger hemangiomas exhibit internal echogenic disarray and uneven intensity, which is due to intra-tumor fibrous degeneration, thrombosis or necrosis. The CT picture is characteristic, with low-density occupancy on plain scan, well-defined and lobulated, and in about 10% of cases, calcification secondary to fibrosis or thrombosis can be seen. CT is highly sensitive and specific for the diagnosis of hepatic hemangioma, but it is sometimes difficult to distinguish small lesions from metastatic liver cancer with multiple blood supplies. Isotope-labeled erythrocyte liver scan is highly specific for the diagnosis of hemangioma, typically showing a filling defect at an early stage and a centripetal filling after a delay of 30-50 min, with a diagnostic sensitivity of 85,7%, specificity of 100%, and positive predictive value of 100%,. MRI has special diagnostic significance for this disease and does not miss small lesions. MRI has a sensitivity of 73%-100% and a specificity of 83%-97%, and should be the main method of examination after B-mode ultrasound. Arteriography can also be used to diagnose the disease. Most of the procedures chosen are hemangioma excision, which is a temporary blockage of the hepatic hemangioma, typically with a “cotton wool”-like change in the thick nutrient artery and a large area of retained contrast. This test is performed only as a preoperative procedure to understand the anatomical relationship between the hemangioma and the hepatic vessels and is not routinely performed. Some people believe that it is safer to perform needle biopsy of hemangiomas under B-type ultrasound guidance by percutaneous needle puncture to the center of the tumor or percutaneously through normal liver tissue to reach the lesion site, but there are reports of fatal bleeding, especially when the hemangioma is located on the surface of the liver or under the peritoneum, where the risk of bleeding is greater. Therefore, percutaneous hepatic aspiration biopsy should be contraindicated for lesions with suspected hemangioma. In addition, needle biopsy of hemangiomas has a significant false-negative rate, which is another reason not to perform this test. However, direct laparoscopic biopsy may be helpful in confirming the diagnosis of this disease. Clinical symptoms and laboratory tests are not specific for the diagnosis of hepatic cavernous hemangioma. The diagnosis of hepatic hemangioma is confirmed by the typical presentation of two or more of the above imaging studies, and no further investigations are required. B-type ultrasound is preferred for imaging diagnosis, followed by MRI, multi-phase spiral CT or isotope-labeled erythrocyte scan, and the diagnosis can be confirmed in most cases. 8.How can ultrasound and CTMRI diagnose hepatic hemangioma? The diagnosis of hemangioma mainly relies on imaging examination: ultrasound examination of small hemangioma is mostly hyperechoic, while those with hypoechogenicity are mostly reticulated, mostly round and irregular in shape, with clear borders. There is no obvious compression of the surrounding liver parenchyma and blood vessels, and there is usually no blood flow signal on Doppler. Large hemangiomas can be lobulated in cross-section, and the internal echogenicity is still predominantly enhanced. They may appear as a tubular network, or irregular nodular or lumpy hypoechoic areas, and sometimes calcified hyperechoic and posterior acoustic images, which are caused by thrombus formation, mechanization or calcification in the lumen of the vessel. Larger hemangiomas (>5 cm) may have significant deformation on compression when they are below the rib margin, whereas other parenchymal occupancies often do not have this feature. Doppler shows predominantly low-velocity venous flow within large angiomas, with little if any arterial spectrum, and even occasionally a low flow resistance index (RI). In CT scan, small hemangiomas are typically uniformly hypointense and well-defined, while larger hemangiomas have more hypointense areas in the center of the lesion, mostly irregular in shape, and their frequency increases with increasing tumor diameter. Zhongshan Hospital of Fudan University has counted 89 hemangiomas in 60 cases, and those with diameters below 4 cm did not show this, while those with diameters of 4-5 or 9 cm showed 57.1%, 6-7 or 9 cm 80%, and those with diameters above 8 cm up to 100%. In contrast to the surgical pathology, lower density areas represent thrombosis, scar tissue or hemorrhagic foci.The typical presentation in CT dynamic enhancement scans is nodular hyperenhancement at the edge of the lesion in the early stage, with the enhancement area gradually advancing toward the center of the lesion and decreasing in intensity over time, and finally filling the entire lesion with a gradual decrease in density to isointense filling in the delayed phase. The time required for the entire enhancement process is related to the size of the lesion, and the larger the lesion, the longer the time required, usually more than 3 min, usually 7-15 min, and in some cases up to 20-60 min. The central hypointense area seen on plain scan is never filled during the enhancement process. If the contrast injection method, dose, speed and scanning technique are reasonable, most of the 3-4 cm hemangiomas have the above typical performance. For those with a diameter of <3 cm, the enhancement performance can be diversified, but the delayed phase is isointense filling, which can be distinguished by combining with other imaging examinations. In MRI, T1-weighted hemangioma has low signal and T2-weighted hemangioma has high signal with uniform intensity and clear margins, and it is contrasted with the surrounding liver, which is described as "light bulb sign". The enhancement pattern of MRI dynamic scan is the same as that of CT, and the thrombus and mechanized foci in hemangioma are lower in T1-weighted and T2-weighted signal. Compared with nuclear imaging, both have comparable specificity, but MRI is more sensitive for small hemangiomas and lesions close to the heart and liver hilum. Angiography is recognized as the most sensitive and reliable method for diagnosing hemangiomas. The typical presentation is the appearance of dense cotton ball-like staining at the perimeter of the tumor seconds after continuous contrast injection, but it is slow to clear and persists into the venous phase, and then slowly decreases. However, because it is an invasive test, it is rarely used after the popularity of non-invasive tests such as CT and MRI. Hepatic cavernous hemangioma must often be differentiated from other hepatic occupying lesions, especially malignant lesions, especially in atypical cases. It is common for inexperienced patients to easily make a diagnosis based on ultrasound or CT scan alone without further examination, resulting in misdiagnosis of malignant lesions as hemangioma or missing malignant tumors that coexist with hemangioma, leading to delayed treatment with serious consequences. In order to avoid unfortunate events, in addition to standardized and comprehensive examination of each item, at least two or more combined imaging examinations should be routinely done for first-time patients, and only those with typical hemangioma features should be diagnosed, and even those diagnosed by comprehensive examination should be followed up carefully on a regular basis, and once suspicion is found, further comprehensive examination, differentiation and active treatment should be carried out. 9.How to distinguish hepatic hemangioma from liver cancer? Liver function, tumor markers, B-mode ultrasound, nuclear scan, CT, MRI, even hepatic arteriography, and liver biopsy can be used to differentiate them. How to determine whether the diagnosis of hepatic hemangioma is misdiagnosed: (1) The diagnosis must be confirmed by enhanced CT, and if CT still confirms the diagnosis of hemangioma, then the following diagnosis can be made. (2) If the patient also has cirrhosis, hepatitis B and AFP positive, then it is more likely to be hepatocellular carcinoma and must be closely monitored. (3) Most hepatocellular carcinomas grow rapidly and can grow exponentially or even several times within a month, even the very few slow growers can grow more than 30% within a month, while hepatic hemangiomas grow slowly and most of them do not grow in size within a year. Therefore, after the patient is diagnosed with hepatic hemangioma, he should still be actively reviewed within one year. Generally, the review can be arranged as follows (ultrasound can be used for the review): the first review should be done after 30 days, and there should be no change in the hemangioma; if there is any one of cirrhosis, hepatitis B or AFP positive, the review should be done once in 20 days; the review should be done only after three consecutive normal reviews. After 60 days of the first review, the second review should be conducted, and there should be no change in the hemangioma; then the review should be conducted once every three months for three times, and if there is still no change in the hemangioma, the review should be conducted once a year. 10.What should I do if I am diagnosed with hepatic hemangioma? Hepatic hemangioma is a benign lesion, and there is still no effective drug for hepatic hemangioma, so if the hemangioma is less than 5cm, there is no need to seek medical help everywhere, and regular follow-up is sufficient. If the tumor is >5cm and there are symptoms, you should go to the hospital and follow the medical advice. Most hepatic hemangiomas are asymptomatic and will not increase significantly with long-term follow-up, nor will they become cancerous or produce complications, so no treatment is needed. If there are obvious symptoms such as huge hemangioma pressing on adjacent organs such as stomach and intestine, causing upper abdominal discomfort, bloating, belching, abdominal pain, loss of appetite, nausea and other symptoms, and these symptoms are clinically confirmed to be caused by hemangioma, then surgery may be considered. A few hemangiomas may be complicated by coagulation dysfunction, such as depletion of clotting factors and platelets, in which case surgical removal is required. There are also patients whose diagnosis of hemangioma is not certain and cannot exclude other malignant tumors that require surgical resection.