Diffuse Hepatic Hemangiomatosis without Extrahepatic Involvement in an Adult Patient

A 33-year-old woman was admitted to our hospital with a two-month history of abdominal distension and edema. The patient had no prior history of drug usage, including oral contraceptives, and no relevant family medical history. Upon admission, the patient underwent a physical examination, which revealed diffuse hepatomegaly, pitting edema in both legs, however no abnormal cardiac murmur. The laboratory findings indicated abnormalities including a hemoglobin level of 7.5 g/dL, a platelet count of 18,000/mm³, as well as a slightly elevated serum alanine aminotransferase (50 U/I) and aspartate aminotransferase (56 U/I). Moreover, the hepatitis B virus antigen was negative, and the titer of the hepatitis B virus antibody and alpha-fetoprotein were normal. The clinical and radiological evaluation showed no evidence of Rendu-Osler-Weber disease or hemangiomas in the extrahepatic region.

An ultrasonography revealed a diffuse heterogeneous echoic infiltrative mass containing numerous and various-sized hypoechoic nodules involving the entire liver (Fig. 1A). A Doppler ultrasonography revealed no remarkable tumor vascularities except for the underlying hepatic parenchymal vascular flow (Fig. 1B). A hepatic dynamic CT was performed and demonstrated the multifocal enhancing hepatic nodules on both the arterial and portal phases, as well as an increased area of contrast enhancement with a centripetal filling pattern of nearly the entire hepatic tumor on a delayed phase CT (Fig. 1C-F). In addition, areas of capsular retraction were also noted. However, there was no remarkable tumor calcification or intervening normal hepatic parenchyma in either of the hepatic lobes. No intraabdominal metastasis or lymphadenopathy was observed. Subsequently, a 99mTc-labeled red blood cell scan was performed and the blood pool images were taken at five hours after inhomogeneous diffuse activity in the entire hepatic mass (Fig. 1G). However, no extrahepatic mass with abnormally increased radioactivity was observed on this 99mTc-labeled red blood cell scan. Our differential diagnoses included a diffuse hemangiomatosis, epithelioid hemangioendothelioma, and angiosarcoma. To rule out a hepatic angiosarcoma, an ultrasound-guided automated gun biopsy, using an 18-gauge core needle was performed in the right hepatic lobe. Before the biopsy, the patient's platelet count was 170,000/mm³ after infusion of fresh frozen plasma. No complications, including intrahepatic or intraperitoneal hemorrhage, were encountered following the biopsy. The patient's histology revealed prominent cavernous vascular proliferation and fibrosis without angiosarcomatous components (Fig. 1H). Further, the patient showed no hemangiomas in other regions of the body, including the skin. Hence, a final diagnosis of isolated diffuse hepatic hemangiomatosis was established. The patient continued to complain about continuous abdominal distension, which rapidly progressed to the deterioration of hepatic function. Ten days following admission, the patient expired due to hepatic failure.

Fig. 1
Diffuse hepatic hemangiomatosis in 33-year-old woman.

A. Ultrasonography indicates heterogeneous infiltrative hepatic tumor containing various-sized hypoechoic nodules.

B. No remarkable tumor vascularity is observed, except for hepatic parenchymal vessels.

C-F. Dynamic CT demonstrates early nodular contrast enhancement on arterial (D) and gradual centripetal pattern of contrast enhancement in diffuse infiltrating hepatic mass on portal (E) and delayed (F) phases. Neither intratumoral calcifications nor area of normalappearing intervening hepatic parenchymal vessels are visible.

G. 99mTc-labeled red blood cell scan reveals heterogeneous uptake of radiopharmaceuticals throughout hepatic mass, involving whole liver on blood pool images. Diffuse tumor uptake is still noted on delayed scan obtained five hours later.

H. Histological findings reveal endothelial cell proliferation and dilated blood channels (Hematoxylin & Eosin staining, × 200).

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A hemangioma is the most common benign tumor affecting the liver. It occurs in all age groups, although hepatic hemangiomatosis occurs predominantly in infants and may cause life threatening conditions (1). However, diffuse hepatic hemangiomatosis in adults is very rarely encountered and moreso when observed without any other organ involvement (2-4). Although several cases of long-term adult survival of diffuse neonatal hemangiomatosis have been reported (5, 6), the etiology and natural history of diffuse hepatic hemangiomatosis remains unclear.

The histological characteristics of hemangiomatosis includes the presence of large vascular channels in both the normal-appearing hepatic parenchyma and the cavernous tumor region (2). The histological findings of our ultrasound-guided biopsy specimen revealed prominently increased vascular proliferation and fibrosis with no sarcomatous change on staining (Fig. 1H), as well as vascular endothelial cells showing positive staining on immunochemical stains, which included Masson's trichrome stain and the Gomori reticulin stain.

As no reliable clinical or radiological findings have been reported for the differential diagnosis of hepatic hemangiomatosis from rare primary vascular hepatic tumors such as hepatic hemangioendothelioma or angiosarcoma, the diagnosis relies solely on the histological findings (7). Also, because it is so rare, only a few reports document the imaging findings of diffuse hepatic hemangiomatosis. However, these imaging findings are similar to those of other common hepatic hemangiomas, including variable echoic lesions on the ultrasound, vascular pooling of contrast material within the tumor on angiography, a centripetal enhancement pattern on dynamic enhancement studies, and bright tumor signal intensities on T2-weighted MR images (2, 3, 8). In our patient, the ultrasonography findings included a heterogeneous echoic infiltrative hepatic mass containing numerous hypoechoic nodules. Compared to the histological findings, the heterogeneous infiltrative echotexture may be caused by hemangiomatosis and parenchymal fibrosis. Our case showed a delayed centripetal contrast-enhancement pattern of the tumor on a dynamic CT and diffuse uptake on vascular pooling images from a 99mTc-labeled red blood cell scan. Because our case revealed imaging findings similar to hepatic hemangiomas, epithelioid hemangioendotheliomas, and angiosarcomas, diffuse hepatic hemangiomatosis should be considered in the differential diagnoses (7, 9).

Patients with diffuse hemangiomatosis showed symptoms of abdominal pain and a palpable abdominal mass. The natural history and underlying etiology of diffuse hepatic hemangiomatosis is uncertain. Although previous reports have cited the role of steroid medications in the development of hepatic cavernous hemangiomas (10) and the administration of metoclopramide medications in a patient with diffuse hepatic hemangiomatosis (8), no history of steroid or estrogen use was documented in the reported cases of diffuse hepatic hemangiomatosis, including our patient. The prognosis of diffuse hepatic hemangiomatosis without extrahepatic involvement is still unclear because it occurs so rarely and has variable clinical courses in affected patients. In the literature, various prognoses have been reported for diffuse hepatic hemangiomatosis without extrahepatic lesion in adults (2, 3, 8, 11). In our patient, hepatic function rapidly deteriorated following admission. The cause of the hepatic failure and the patient's death remains unclear. The possibility exists that a minimal amount of the remaining normal hepatic parenchyma with extensive hepatic hemangiomatosis involving the entire liver may have caused hepatic failure and subsequent patient death. More cases of diffuse hepatic hemangiomatosis are needed to establish their natural course and prognosis.

Despite its rarity, we concluded that the diagnosis of diffuse hepatic hemangiomatosis in adults can be suggested in patients with a diffusely involved hepatic tumor showing radiologic findings of hepatic hemangioma.