Single nodular hepatic epithelioid hemangioendothelioma: a rare form of presentation

A 22-year-old female, presented to our Institution following the incidental discovery of a liver nodule on non-contrast-enhanced CT. At the time of evaluation, the patient was asymptomatic and physical examination was unremarkable. There was no history of liver disease. Laboratory studies were normal. Viral serologies and tumour markers were negative.

Non-contrast-enhanced CT revealed a 2.5cm hypodense, non-calcified nodule located at the periphery of segment III (Fig.1).

On T2-WI MR images, a solitary lesion displaying a target appearance, with a central core of high signal and a peripheral halo of intermediate intensity, was seen (Fig.2). This target appearance was also evident on T1-WI (Fig.3) and on DWI, where a peripheral halo of restriction surrounded a central non-restrictive core (Fig.4). After contrast injection, there was discrete peripheral enhancement on the arterial phase (Fig.5) with centripetal progression on portal and delayed phases (Fig.6). On hepatobiliary phase, a heterogeneously hypointense lesion (Fig.7) was seen in association with a thrombosed portal branch, giving rise to the “lollipop sign” (Fig.8).

Left hepatectomy was performed and histopathological analysis revealed a sparsely cellular neoplasm made up by large epithelioid cells and fibrotic stroma (Figs.9,10). Foci of spontaneous necrosis (Fig.11) and venous and perineural involvement were documented. Immunohistochemistry studies demonstrated vascular differentiation and lack of epithelial markers expression (Fig.12).

Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumour with an estimated incidence of <0.1/100000.[1] Adult females are more commonly affected, with a female-to-male ratio of 3:2 and a mean age of 41.7 years at diagnosis.[2]

The pathogenesis of HEH is still unknown, but unlike other primary liver tumours, it is not associated with chronic liver disease. Possible etiologic factors include oral contraceptives, alcohol, and viral hepatitis, but their exact role remains debatable.[2]

Clinical manifestations of HEH are non-specific and up to 25% of patients are asymptomatic upon diagnosis. Among symptomatic patients, right-upper quadrant pain is the most frequent complaint, followed by hepatomegaly and weight loss.[1,2] Laboratory studies are normal or show non-specific elevations of liver enzymes. Tumour markers are usually within the normal range.[2]

HEH has three forms of presentation: single-nodular, multifocal-nodular and diffuse disease[4,5].  The majority of cases initially present with multiple subcapsular lesions (multifocal-nodular), that over time coalesce into large liver masses (diffuse)[3]. Single-nodular HEH (SN-HEH) is the rarest (13-17% of cases) and earliest form of disease presentation.[4]

On CT, SN-HEH appears as a solitary hypodense subcapsular lesion, more commonly located on the right lobe[4,6]. After contrast administration, peripheral arterial enhancement followed by gradual centripetal progression is usually noted.[4]

On MRI, the lesion typically has low T1 signal intensity. On T2-WI, a characteristic target appearance with a central core of high signal (necrotic tissue) surrounded by a halo of intermediate signal (viable tumour) is usually observed.[7] The “target sign” can also be appreciated on DWI, where a peripheral halo of restriction surrounds a central non-restrictive area.[1] This DWI appearance can resemble that of intrahepatic cholangiocarcinomas, and often leads to misdiagnosis of HEH. The enhancement pattern is similar to the one observed on CT. A hypointense linear structure ending at the periphery of the lesion may be seen, corresponding to a thrombosed portal branch, and giving rise to the typical “lollipop sign”^.[7]

HEH is a low- to intermediate-grade malignancy. Nonetheless, its clinical outcome is unpredictable.[3]

Treatment options for HEH have not yet been standardized, and include chemotherapy, percutaneous ablation, surgical resection and liver transplantation[1]. In multifocal-nodular and diffuse HEH,  surgical resection and ablation are often unsuccessful due to the multicentricity of the disease, therefore, liver transplantation is frequently the best treatment choice for these patients[6]. For SN-HEH treatment strategies include surgical resection and transcatheter-arterial-chemoembolization[6]. Nevertheless, close imaging follow-up should always be maintained, since progression into multifocal or diffuse disease can occur, even after successful treatment.[4]

Teaching Points

• SN-HEH is the rarest and earliest form of disease presentation;
• When a subcapsular lesion is found on a non-cirrhotic liver, particularly if associated with the target and lollipop signs, the diagnosis of SN-HEH should be considered.