Epithelioid hemangioendothelioma (EHE) is a rare low-to-intermediate grade vascular malignancy of the liver. Incidence is <0.1/million per year. More common in women (F:M = 3:2). Presents as multiple peripherally located nodules. The 'target sign' on T2 (central hypo, peripheral hyperintensity) and the 'lollipop sign' (vein termination at tumor) are pathognomonic findings. Capsular retraction is common. Prognosis is better than angiosarcoma — 5-year survival is 40-80%.
Age Range
20-60
Peak Age
40
Gender
Female predominant
Prevalence
Rare
EHE is a neoplasm originating from vascular endothelial cells. WWTR1-CAMTA1 fusion gene (>90%) or YAP1-TFE3 fusion gene are characteristic genetic alterations. Tumor cells grow within vascular lumens and infiltrate vascular structures — this forms the pathophysiological basis of the 'lollipop sign' (vein termination). Peripheral distribution is explained by tumor growth at terminal points of portal and hepatic vein branches. Central fibrosis/hyalinized stroma and peripheral active tumor cells form the basis of the 'target sign'. Capsular retraction results from peripheral lesions pulling on the capsule (desmoplastic reaction). OCP use has been reported as a risk factor but definitive evidence is weak.
The combination of the target sign on T2 (central hypointense fibrosis + peripheral hyperintense active tumor rim) with the lollipop sign (hepatic/portal vein branch terminating at tumor nodule) is the dual pathognomonic finding of epithelioid hemangioendothelioma. These two findings together are not seen in any other liver tumor. Peripheral/subcapsular distribution and capsular retraction are additional supportive findings.
Target sign on T2: central hypointense area (fibrosis/hyalinized stroma) + peripheral hyperintense rim (active tumor cells + edema). This pattern is the most diagnostic MRI finding of EHE.
Report Sentence
Target sign (central hypointensity + peripheral hyperintense rim) is seen in the liver lesions on T2-weighted sequences, suggesting epithelioid hemangioendothelioma.
Hepatic vein or portal vein branch abruptly terminating at the tumor nodule — 'lollipop sign'. The vein branch forms the stick, the tumor nodule forms the candy. Pathognomonic finding for EHE.
Report Sentence
Hepatic/portal vein branch termination at the tumor nodule ('lollipop sign') is seen, pathognomonic for epithelioid hemangioendothelioma.
Multiple peripherally located hypodense nodules on non-contrast CT. Subcapsular distribution is characteristic. Some lesions may show peripheral calcification or capsular retraction.
Report Sentence
Multiple peripheral/subcapsular hypodense nodules are seen in the liver with accompanying capsular retraction.
Peripheral delayed enhancement — active tumor periphery enhances slowly while fibrotic center does not enhance. CT counterpart of the target sign. Some lesions may show delayed fill-in throughout the entire lesion.
Report Sentence
The lesions demonstrate peripheral delayed enhancement with non-enhancing fibrotic center.
Hypointense lesions on T1. Capsular retraction is prominent in peripheral lesions — inward indentation of liver contour is seen.
Report Sentence
Hypointense peripheral lesions are seen on T1-weighted sequences with adjacent capsular retraction.
Multiple peripherally located hypoechoic nodules on US. Target appearance (hypoechoic center + echogenic peripheral rim) may be seen in some lesions. Capsular retraction is difficult to evaluate on US.
Report Sentence
Multiple peripheral hypoechoic nodules are seen in the liver.
Criteria
Low mitotic activity, minimal atypia. Slow growth — may remain stable for years.
Distinct Features
Good prognosis (5-year survival >80%). Follow-up acceptable for small lesions. Target sign prominent. Metastasis rare.
Criteria
High mitotic activity (>3/50 HPF), marked atypia, necrosis areas. Aggressive course.
Distinct Features
Poor prognosis (5-year survival <50%). Heterogeneous imaging — may overlap with angiosarcoma. Risk of lung and bone metastasis.
Criteria
Multiple nodules coalesce to form large confluent masses. Represents advanced disease.
Distinct Features
Coalescent lesions may lose the target pattern. Diffuse involvement may be a liver transplant indication. EHE liver transplant outcomes are better than other malignancies (5-year >50%).
Distinguishing Feature
Angiosarcoma is much more aggressive: heterogeneous, contains hemorrhage, grows rapidly. EHE is more homogeneous, shows target sign, grows slowly. Angiosarcoma may have thorotrast/vinyl chloride history. Capsular retraction common in EHE, rare in angiosarcoma.
Distinguishing Feature
ICC also shows capsular retraction and peripheral enhancement but lacks lollipop sign and target sign. Biliary dilatation is expected in ICC — not expected in EHE. ICC is usually solitary while EHE is mostly multifocal.
Distinguishing Feature
Hemangioma is very bright on T2 (light bulb sign) with peripheral nodular enhancement + centripetal fill-in. EHE has target sign, lollipop sign, and capsular retraction — hemangioma does not. Hemangioma is benign, EHE is low-grade malignant.
Urgency
routineManagement
surgicalBiopsy
NeededFollow-up
6-monthBiopsy is recommended for diagnostic confirmation in EHE — definitive diagnosis is made with WWTR1-CAMTA1 fusion gene testing. Surgery is the primary treatment for resectable lesions. Liver transplantation should be considered in diffuse multifocal disease — transplant outcomes in EHE are significantly better than other hepatic malignancies (5-year survival >50%). Observation is acceptable for low-grade, small, stable lesions. Chemotherapy and radiotherapy response is limited. Antiangiogenic agents (sorafenib, bevacizumab) and mTOR inhibitors (sirolimus) are used experimentally. 6-month CT/MRI follow-up is recommended.
Carries low-to-intermediate malignant potential. Treatment options include surgical resection and liver transplantation. Transplantation may be considered in cases with extensive multifocality. Response to chemotherapy is limited. Prognosis is significantly better than angiosarcoma.