Spectrum of appearances on CT and MRI of hepatic epithelioid hemangioendothelioma

HEHE is a rare, low-grade malignant vascular tumor. The risk factors are currently unknown. It may be related to the use of oral contraceptive pills, chronic hepatitis B, excessive drinking and past history of chloroethylene exposure [1, 6]. The tumor is usually found in adults and shows a slight female predominance (male-to-female ratio, 2:3). The peak age of diagnosis is 30–40 years old [1, 3, 7]. HEHE can be divided into solitary lesion and multiple lesions in the liver. It has been reported that most of HEHE cases are characterized by multiple lesions, solitary lesion only accounts for 13 % – 18 % [1, 2]. All patients in the study were characterized by multiple lesions in the liver. Metastases have been reported in 27 %–37 % of patients, usually in the lung, and other common sites including regional lymph nodes, peritoneum, omentum, mesentery and bone. However, no metastases or ascites were found in the study.

Pathologically, HEHE tumor cells in our study demonstrated presence of intracytoplasmic lumina and erythrocytes with positive CD34 which were consistent with the findings obtained from previous reports,

Lesions of HEHE are more frequently subcapsular [8, 9], and 74.3 % of the lesions were subcapsular in our study. According to previous reports, there are two patterns of growth in the gross appearance of HEHE: the nodular type and the diffuse type [10]. However, three types were identified in our study, including nodular type, coalescent type and mixed type, in HEHE, in which the coalescent type has seldom been reported in previous reports. Nodular type (45.5 %) and mixed type (45.5 %) accounted for the vast majority of HEHE in the study. The simple coalescent type presented in only one case, however there were six cases (54.5 %) with coalescent growth. We consider that mild mass effect of coalescent type is a characteristic manifestation of HEHE. In other tumors the pattern of coalescent growth was rarely found, hence this pattern may be an important implication to the diagnosis of HEHE.

All lesions were hypodense on unenhanced CT. Calcification is considered as one of the common features seen in approximately 15 %–25 % of patients as suggested by previous reports, however, our findings showed inconsistent data. This may be due to the relatively small sample size (11) in our study. All lesions observed demonstrated low signal intensity on T1 weighted images and high heterogeneous signal intensity on T2 weighted images compared to the normal liver parenchyma.

Miller et al [11] reported capsular retraction as an important finding of HEHE. The pathological basis is hepatic fibrosis caused by the lesion and compensatory hypertrophy of unaffected hepatic segments [12–14]. In our study, six cases showed capsular retraction in lesions larger than 2.0 cm. This may be explained by that larger tumors are more likely to be located in the hepatic subcapsule or to cause local hepatic fibrosis. However, capsular retraction may also be one of the features seen in other benign or malignant liver lesions, such as cholangiocarcinoma and metastatic carcinoma. Therefore, capsular retraction remains an important finding but not a specific sign of HEHE.

Another important finding of HEHE is the “lollipop sign” as reported by Alomari et al in 2006 [15], who thought that “lollipop sign” was a characteristic finding of HEHE. Six cases showed “lollipop sign” in the study. “Lollipop sign” rarely occurs in most benign and malignant hepatic tumors, hence it can be considered as more characteristic finding of HEHE.

Dynamic contrast-enhanced scanning plays an important role in the diagnosis of HEHE. In general, as a vascular tumor, HEHE shows delayed enhancement in dynamic enhanced scanning. In this study, we found that the lesions showed three patterns of contrast enhancement, including mild homogeneous enhancement, ring-like enhancement and heterogeneous delayed enhancement. We also found that the patterns of contrast enhancement were closely related to the size of lesions. Smaller lesions (<2.0 cm) mostly showed mild homogeneous enhancement. With the enlargement of the lesions, HEHE could be characterized by multiple enhanced patterns. Lager lesions (>3.0 cm) mostly showed heterogeneous delayed enhancement. We consider that different patterns of contrast enhancement are related to pathological basis. Pathologically, the tumor tissues include epithelial and dendritic cells in variable proportions [1, 3, 16]. Larger tumor cells typically demonstrate presence of intracytoplasmic lumina containing erythrocytes, which resembles signet ring-like structures [17]. The peripheral tumor cells grow along preexisting sinusoids and terminal hepatic venules. Atrophic hepatocytes are obliterated. These may lead to heterogeneous enhancement of HEHE [1]. The presence of peripheral rich cellular zone and tissue edema may contribute to high density during enhanced scanning. The presence of abundant mucinous and stroma may contribute to the lack of central unenhanced areas [10, 18].

Based on our findings, HEHE could be discriminated from its differential diagnosis such as hepatic metastatic carcinoma, cholangiocarcinoma, and other liver vascular tumors like hepatic angiosarcoma or cavernous hemangioma.

The image features of hepatic metastatic carcinoma are more complicated. Similar to HEHE, this disease shows ring-like enhancement or nonspecific enhancement. However, the following tips could be applied in distinguishing hepatic metastatic carcinoma from HEHE: a known history of a primary malignancy; most commonly seen as peripheral enhancement lesions together with less common features such as delayed enhancement and invading blood vessels. Further more, HEHE lesions mostly demonstrate mild to moderate FDG uptake, while hepatic metastatic carcinoma commonly demonstrate intense FDG uptake. PET-CT could be used to detect the presence of metastatic tumor affecting distant organs to provide accurate staging.

For cholangiocarcinoma, it usually grows along the bile ducts. The adjacent bile ducts are nearly always dilated or are embedded by tumors. Invaded blood vessels are also shown. Cancer antigen 19-9 is usually elevated.

Other hepatic vascular tumors can be discriminated from HEHE, Hepatic cavernous hemangioma usually demonstrate more regular and obvious enhancement with similar appearances to arteries during arterial phase. On the other hand, hepatic angiosarcoma, a high-grade malignant vascular tumor, is often characterized by its irregular enhancement during arterial phase with enhanced nodular edge during portal vein phase or in delayed phase. Capsular retraction are usually not seen in hepatic vascular tumors.