Disease Introduction
Hepatic hemangioma is a relatively common benign tumor of the liver, clinically spongy hemangioma is the most common, the detection rate of natural population autopsy is 0.35-7.3%, accounting for 5-20% of benign liver tumors. In recent years, with increased awareness of health checkups and advances in various diagnostic imaging techniques, the detection rate of asymptomatic small hemangiomas has increased significantly. Most cases are clinically asymptomatic or mildly symptomatic, with a long course, slow growth and good prognosis.
There are not many basic and clinical studies on this disease, and there is a lack of mature and strict diagnostic and treatment criteria, and there are many ambiguities and even misconceptions about the definition of treatment protocols and indications. The treatment plan has not yet formed a more unified clinical pathway for doctors and patients to choose.
Causes
The exact cause of hepatic hemangioma is still unclear, but there are several theories.
(1) Congenital abnormal development theory: Most scholars believe that the occurrence of hemangioma is caused by congenital malformation of the terminal blood vessels of the liver;
(2) Hormonal stimulation theory: Some scholars have observed that the growth of hemangioma can be accelerated during female puberty, pregnancy and oral contraceptive pills, etc. They believe that female hormones may also be one of the pathogenic mechanisms of hemangioma;
(3)Others: such as deformation of capillary tissue after infection, resulting in capillary dilation, vascular expansion after local necrosis of liver tissue to form a vacuole, and congestion and expansion of its surrounding blood vessels; regional blood circulation stagnation in the liver, resulting in the formation of spongy expansion of blood vessels.
Disease classification
Hepatic hemangiomas can be pathologically classified into 4 types according to the amount of fibrous tissue.
(1) Spongiotic hemangioma, which is the most common type;
(2) Sclerosing hemangioma;
(3) Vascular endothelial cell tumors;
(4) capillary hemangioma, which is rare. At present, they are mostly classified by diameter: <5cm (small hemangioma); 5-10cm (hemangioma); 10cm-15cm (giant hemangioma); >15cm (very large hemangioma), which may have some significance in guiding the treatment plan of patients with hepatic hemangioma and providing effective reference for the diagnosis and treatment of hepatic hemangioma.
Disease hazards
Hepatic hemangioma can develop in any age group, and it is more common in 30-50 years old, and the literature reports that there are more women than men, and the ratio of men to women is about 1:3-6. However, our analysis of 53859 cases of healthy population physical examination data showed that the incidence of hepatic hemangioma was 3,11%, and the incidence rate of men and women was comparable (3,36% vs. 2,88%, P>0,05), and this phenomenon is different from the literature report This phenomenon differs from the results reported in the literature and may be related to the fact that previous literature reports analyzed outpatient or inpatient exposed cases rather than large population-based censuses;
Most small hemangiomas were not included in the statistics. An in-depth analysis of the size composition of hemangiomas in males and females in our census showed that the proportion of hepatic hemangiomas >5 cm of all cases was 2.56 times higher in females than in males (2.90% vs. 1.26%, P>0.05), a result that supports our hypothesis.
Further analysis of the relationship between age and prevalence showed an increase in prevalence with increasing age, with a peak at 40-60 years of age and a subsequent decrease. This phenomenon may be explained by the fact that as age increases, the incidence of occult hemangiomas, which are initially difficult to detect, increases as they grow and are detected; after 40-60 years of age, some of the hemangiomas stop growing and some of them even recede, resulting in a decrease in incidence.
This phenomenon was verified in our analysis of 131 cases followed for more than 5 years, where the proportion of cases with enlarged hemangiomas decreased significantly with age, and the extent of the increase in the maximum diameter of hemangiomas also decreased significantly. In the analysis of the relationship between sex, age and hemangioma size, we found that female hemangiomas were larger than male hemangiomas in all age groups, and the size of hemangiomas increased significantly with age, reaching a peak at the age of 40-60 years, and then slightly decreased thereafter.
From the above data, we can easily conclude that the development of hemangioma may be influenced by changes in hormone levels, and the influence of estrogen may be more obvious, which may also explain why the incidence of hepatic hemangioma >5 cm in diameter is much higher in women than in men.
Disease symptoms
Most hepatic hemangiomas have no obvious discomfort and are usually detected during routine ultrasound examinations or abdominal surgery. When hemangiomas increase in size to more than 5 cm, non-specific abdominal symptoms may
These include.
(1) abdominal mass: the mass is cystic in nature, no pressure pain, smooth or non-smooth surface, and sometimes a conduction vascular murmur can be heard on auscultation in the mass;
(2) Gastrointestinal symptoms: vague pain and discomfort in the right upper abdomen, as well as loss of appetite, nausea, vomiting, belching, post-food distension and dyspepsia;
(3) Compression symptoms: Huge hemangioma can push and compress the surrounding tissues and organs. Compression of the lower esophagus may cause dysphagia; compression of the extrahepatic bile duct may cause obstructive jaundice and gallbladder effusion; compression of the portal vein system may cause splenomegaly and ascites; compression of the lungs may cause dyspnea and pulmonary atelectasis; compression of the stomach and duodenum may cause digestive symptoms;
(4) Rupture and bleeding of hepatic hemangioma may cause severe pain in the upper abdomen, as well as bleeding and shock symptoms, which is one of the most serious complications, mostly for larger hepatic hemangiomas growing below the rib cage that rupture and bleed due to external force;
(5) Kasabach-Merritt syndrome, which is a coagulation abnormality caused by hemangioma accompanied by thrombocytopenia and massive coagulation factor depletion. The pathogenesis of Kasabach-Merritt syndrome is the retention of blood in a giant hemangioma with massive depletion of red blood cells, platelets, coagulation factors II, V, VI, and fibrinogen, causing abnormal coagulation mechanisms that can further develop into DIC;
(6) Others: When a tipped hemangioma growing outside the liver is twisted, necrosis may occur, resulting in severe abdominal pain, fever and deficiency. There are also individual patients with arteriovenous fistula formation due to huge hemangioma, resulting in increased return blood volume and increased heart burden, leading to heart failure and death. There are also rare cases of biliary hemorrhage.
Ancillary tests
Imaging (e.g., ultrasound, CT, MRI) is the main method to diagnose hepatic hemangioma. Comprehensive literature reports suggest that the diagnosis rate of hepatic hemangioma is 57.0%-90.5% for ultrasound, 94% for ultrasonography, 73.0%-92.2% for CT, 84.0-92.7% for MRI, and 62.5% for hepatic arteriography.
Ultrasound
Ultrasound examination is cheap, easy to perform, with high prevalence, non-invasive and painful, safe and reliable, and can repeatedly observe lesion changes for a short period of time and obtain more information, which is inferior to CT and MRI. Ultrasound of hepatic hemangioma is mostly hyperechoic, and those with hypoechogenicity have reticular structure, uniform density, regular shape and clear boundary.
Larger hemangiomas can be lobulated in cross-section, and the internal echogenicity is still dominated by enhancement, which can be in the form of a tubular network, or irregular nodular or lumpy hypoechoic areas, and sometimes calcified hyperechoic and posterior acoustic shadows, which are caused by thrombus formation, mechanization or calcification in the lumen of blood vessels.
Contrast ultrasound
In recent years, the role of contrast ultrasound in the differential diagnosis of hepatic occlusions has been gradually recognized by a wide range of physicians. Selective use of contrast ultrasound of the liver may be considered in cases of hepatic hemangioma with atypical imaging presentation.
The typical hemangioma ultrasonography shows nodular or ring-like enhancement in the periphery during the arterial phase, and then gradually expands to the center with time. This “slow-in, slow-out” enhancement feature is similar to that of spiral-enhanced CT. The sensitivity, specificity and accuracy of contrast ultrasound for small hepatic hemangiomas have been reported to be 100%, 87% and 94%.
Spiral-enhanced CT
CT scan shows well-defined round or round-like hypodense lesions in the liver parenchyma, a few of which may be irregular in shape, with a CT value of about 30HU. Dynamic CT or spiral CT multi-phase contrast-enhanced scan most specific typical performance: within 20-30s after rapid contrast injection, nodular enhancement appears at the edge of the early arterial lesion, and the enhancement density is higher than that of normal liver; with the extension of time, 50-60s after contrast injection, it enters the portal phase enhancement, and the contrast-enhanced foci fuse with each other;
After a few minutes of delayed scanning, the whole tumor was uniformly enhanced and the enhancement density continued to decrease, which was higher than or equal to the enhancement density of the surrounding normal liver parenchyma, and the whole contrast enhancement process had the characteristic of “early out and late in”. In some cavernous hemangiomas, there may be irregular hypointense areas without enhancement in the center of the tumor on delayed scans, but the peripheral part of the tumor still shows this “early exit and late return” feature.
MRI
MRI shows low signal in T1-weighted and high signal in T2-weighted, with uniform intensity and clear margins, and contrast with the surrounding liver, which is described as the “light bulb sign”. When the characteristic signs of CT and MRI are clearly diagnosed, there is no need for other expensive or invasive tests, and liver aspiration biopsy should be avoided.
Other
Hepatic arteriography is an invasive test and is not necessary. In recent years, whole-body positron emission computed tomography (PET/CT) has become available and is valuable in ruling out metabolically active malignancies.
Differential diagnosis
The main differential diagnoses of hepatic hemangioma are
Primary or metastatic hepatocellular carcinoma
Primary hepatocellular carcinoma often has a history of chronic hepatitis B, cirrhosis, abnormal liver function and elevated AFP; metastatic hepatocellular carcinoma, mostly multiple, often has a primary lesion in the digestive system;
Hepatic echinococcosis
Patients with a history of pastoral life, sheep and dog contact, positive intracutaneous test for hepatic encystment (Casoni test), and elevated eosinophil count ;
Non-parasitic hepatic cysts
Isolated solitary hepatic cysts are easily distinguished from hepatic hemangiomas, and only a few polycystic livers may sometimes be confused with hepatic hemangiomas. More than 50% of polycystic liver is combined with polycystic kidney, the lesions are multiple since the beginning, mostly all over the liver, ultrasound and CT examination show lesions as cystic cavities of different sizes with smooth and complete borders, there may be family genetic factors;
Others
Hepatic adenoma and hepatic hemangioendothelial cell sarcoma are rare. The former develops slowly, but the mass is hard and rubber-like; the latter develops faster and has malignant tumor characteristics, mostly seen in adolescents.
The theory is based on the fact that hepatic hemangioma is mainly supplied by hepatic artery, and thrombus can be formed in the tumor after embolization of artery. However, it is still controversial to treat hepatic hemangioma with TAE because of the poor long-term effect of large hemangioma and the difficulty of shrinking and mechanizing the tumor.
Moreover, while embolizing the hemangioma during embolization, the embolization agent often involves the normal blood supply to the hilar region and intrahepatic bile ducts, which can cause some serious complications, such as biliary tumor, hepatocellular necrosis, liver abscess, biliary cirrhosis, biliary ischemic stenosis and biliary artery fistula. Meanwhile, although the side effects of vascular sclerosing agent Pingyangmycin are few, the side effects of causing pulmonary fibrosis and damaging the arterial intima when used intra-arterially in large doses should not be underestimated.