A 75-year-old man presented to our hospital with three-week history of anorexia, abdominal fullness, chills, and three-day history of jaundice. He was diagnosed with AV nodal reentry tachycardia (AVNRT) six months earlier which terminated with the Valsalva maneuver. His medication included Diltiazem and Aspirin. He had no further episodes of AVNRT and liver enzymes were normal at routine follow-up in the cardiology clinic two months before presentation. On admission he was afebrile and reported no abdominal pain, hematemesis, melena, or pale stools. Physical examination revealed a frail looking man with skin and scleral icterus, normal heart sounds, and blood pressure. Abdominal examination revealed epigastric tenderness without organomegaly or ascites. Laboratory tests were significant for total bilirubin 9 mg/dL, albumin 4.0 g/dL, alkaline phosphatase 383 U/L, gamma-glutamyl transferase 701 U/L, aspartate aminotransferase, 104 U/L, alanine aminotransferase 206 U/L, and lactate dehydrogenase 451 U/L. Carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) levels were normal and CA19-9 was 38.8 IU/mL. Human immunodeficiency virus (HIV) and hepatitis panel were negative. Chest X-ray was normal and ECG showed sinus tachycardia. Abdominal ultrasound scan was negative for cholelithiasis and cholecystitis. Contrast enhanced triple-phase computerized tomography scan of his abdomen showed a hepatic mass measuring 13 × 11 × 10 cm with small dilated bile ducts surrounding the mass (Figure
Computerized abdominal tomography scan showing the 13 × 11 × 10 cm hepatic mass with small dilated bile ducts surrounding the mass.
(a) Angiosarcoma: H&E section (600x magnification). (b) CD34 immunostain highlights tumor cells along with blood vessels (400x magnification).
Hepatic angiosarcoma (HAS) is a very rare and aggressive tumor that accounts for about 1.8–2% of all primary liver cancers. Epidemiologically, it is associated with exposure to polyvinyl chloride (PVC), thorium dioxide (thorothrast), arsenic, and inorganic copper [
Laboratory tests two months prior to presentation, at presentation, and at the time of patient’s death.
Laboratory tests | Normal range | 2 months prior to presentation | At presentation | Time of death |
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Liver function tests | ||||
Total bilirubin | 0.3–1.2 mg/dL | 0.9 | 9.8 | 27 |
Direct bilirubin | 0–0.3 mg/dL | 0.2 | 6.3 | 18.5 |
Alkaline phosphatase | 36–92 U/L | 81 | 383 | 1120 |
Gamma-glutamyl transferase | 0–30 U/L | 58 | 701 | 1200 |
Aspartate aminotransferase | 0–35 U/L | 25 | 104 | 5522 |
Alanine aminotransferase | 0–35 U/L | 21 | 206 | 2313 |
Prothrombin time | 11–13 sec | 14.1 | 14.8 | 43.2 |
Partial thromboplastin time | 25–35 sec | 27.5 | 34.6 | 69.9 |
International normalized ratio | 1.10 | 1.16 | 4.97 | |
Lactate dehydrogenase (LDH) | 60–100 U/L | 190 | 451 | 20000 |
Peripheral blood cell count | ||||
Hemoglobin, g/L | 12.6–16.8 | 14.4 | 14.1 | 5.5 |
White blood cell count, /L | 3.7–10.5 × 109 | 5.4 | 6.5 | 26 |
Platelet count, /L | 167–400 × 109 | 144 | 143 | 22 |
Blood chemistry | ||||
Sodium, mmol/L | 135–144 | 145 | 139 | 123 |
Potassium, mmol/L | 3.5–5 | 4.6 | 5.1 | 5.4 |
Chloride, mmol/L | 100–110 | 110 | 104 | 95 |
Bicarbonate, mmol/L | 23–31 | 24 | 24 | 10 |
Blood urea nitrogen, mmol/L (mg/dL) | 2.85–7.14 (7.98–20) | 15 | 20 | 80 |
Creatinine, mmol/L (mg/dL) | 53.0–123.7 (0.6–1.4) | 0.8 | 1.2 | 6.3 |
The presenting symptoms of hepatic angiosarcoma are nonspecific and may be confused with any other hepatobiliary disorder [
Differential diagnosis of a focal hepatic mass.
Diagnosis | Clinical features | Radiographic appearance |
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Hemangioma | Most often asymptomatic, but can present with right upper quadrant pain and fullness. |
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Focal nodular hyperplasia | Largely benign symptomatology. |
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Hepatic cystadenoma | RUQ discomfort and pain; anorexia. |
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Hepatic abscess | Fever, abdominal pain, nausea, vomiting, and anorexia. |
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Hepatic adenoma | Episodic abdominal pain. |
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Hepatic cystadenocarcinoma | Jaundice, abdominal pain, weight loss, and ascites due to portal vein compression. |
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Hepatocellular carcinoma | RUQ pain, weight loss, decompensated liver disease; paraneoplastic phenomena such as erythrocytosis, hypercalcemia, and watery diarrhea. |
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Metastases | Abdominal pain, RUQ tenderness, jaundice, fever, weight loss, anorexia, hepatomegaly, and ascites. |
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Cholangiocarcinoma | Painless jaundice, pruritus, abdominal pain, weight loss, fever, clay-colored stools, and dark urine. |
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Hemangioendothelioma | Frequently asymptomatic. |
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Primary hepatic lymphoma | Hepatomegaly, splenomegaly; fever, night sweats, weight loss, and lymphadenopathy. |
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Hemangioblastoma | Extremely rare liver lesion. Seen in the setting of von Hippel-Lindau syndrome. |
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(1) Schwartz and Kruskal [
Histopathologic features in the differential diagnosis of hepatic angiosarcoma.
Tumor | Gross characteristics | Microscopy/histologic features | Immunohistochemistry |
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Angiosarcoma | Ill-defined, diffusely infiltrative spongy nodules with hemorrhage. Extensive and diffuse involvement of liver. | The tumor consists of malignant endothelial cells which grow along preexisting vascular channels and hepatic sinusoids. It shows solid and pseudopapillary patterns. Necrosis and hemorrhage present. Plump spindle cells with large pleomorphic nuclei. | Positive for CD31, CD34, factor VIII |
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Epithelioid hemangioendothelioma | Multiple, tan-gray, firm, circumscribed and focally confluent nodules up to 12 cm with infiltrative borders. It may show central calcification or ossification. | Tumor exhibits zonal pattern, with central sclerosis or hyalinization and tumor cells at the periphery in a sinusoidal proliferation. Tumor forms papillary tufting and glomeruloid structures within portal vein branches. Eosinophilic epithelioid tumor cells typically show vacuolated signet-ring-like features representing intracytoplasmic lumina sometimes containing erythrocytes. | Positive for factor VIII, CD31, CD34, cytokeratin (50%) |
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Hepatocellular carcinoma (HCC) | Solitary, multinodular or diffusely infiltrative soft, yellow-green or reddish mass in a background of cirrhosis. Smaller satellite nodules around large mass. High propensity of tumor to invade into the portal veins. Hemorrhage and necrosis are common. | Major histologic patterns are trabecular (plate-like), pseudoglandular (acinar) and compact (solid) types. Cells are polygonal with distinct cell membranes, abundant granular eosinophilic cytoplasm, higher nucleocytoplasmic ratio than normal, round nuclei with coarse chromatin and may have prominent nucleoli. Presence of sinusoidal vessels surrounding tumor cells is an important diagnostic feature. Intranuclear inclusions including eosinophilic hyaline bodies, Mallory hyaline, and fat droplets may be present. | Positive for HepPar1 (90% of all HCCs) and glypican-3, canalicular pattern of staining with polyclonal CEA, AFP (25%). |
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Kaposi sarcoma |
Hemorrhagic multifocal spongy nodules 5–7 cm. | Lesions centered on portal tracts with poorly vasoformative spindle-cell proliferation accompanied by red blood cell extravasation and focal deposition of hemosiderin. Cytoplasmic eosinophilic hyaline globules are a typical finding. | Positive for membranous/cytoplasmic CD31 and CD34 and nuclear HHV8. |
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Undifferentiated sarcoma |
Well-demarcated, solitary, unencapsulated lesion. Cut surface is variegated with solid and cystic/gelatinous areas, with necrosis and hemorrhage. | Tumor consists of loosely arranged, spindle-pleomorphic cells embedded in an abundant mucopolysaccharide-rich myxoid matrix. Dilated bile ducts and PAS-positive diastase-resistant globules found within the tumor cells; tumor not particularly vascular. | Positive for Vimentin, focally positive for Keratin; |
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Peliosis hepatis |
Honeycombed liver with multiple round, red-purple, blood filled spaces, range from 1mm to several cm. | Lesion consists of blood-filled spaces surrounded by a pseudocapsule of fibrin and early collagen. Rarely endothelial lining visible. |
Positive for Warthin-Starry stain ( |
(1) Gattuso et al. [
(2) Rosai [
Fulminant liver failure (FHF) due to HAS is very rare and the mechanism of liver failure is multifactorial. There have been six cases of FHF secondary to HAS reported in the literature to date and the available evidence suggests that a combination of hepatic ischemia leading to parenchymal infarction, vascular occlusion of portal vein flow by tumor, thrombi, and nonocclusive infarction of the liver due to shock from secondary causes such as sepsis or cardiac dysfunction may play a role [
Treatment of the tumor to date is empirical [
The authors declare that there is no conflict of interests regarding the publication of this paper.
Teddy Bader, M.D., is highly acknowledged for reviewing an earlier version of this paper.