PRACTICAL GASTROENTEROLOGY • MARCH 200368

INTRODUCTION

L iver hemangioma is the most common benigntumor of the liver (1–6). It is composed of cavitieslined with endothelial cells and filled with blood

(4). Giant liver hemangioma (GLH) is defined as a lesiongreater than 4 cm in diameter (1). Most cases with liverhemangioma are asymptomatic and discovered inciden-tally on a liver ultrasound or computed tomography scan(2–4). Most patients with liver hemangioma have normalliver function tests (1,3–6). Infrequently, patients maycomplain of abdominal pain. There are few reportedcases in the literature of patients with GLH who presentwith a triad of right upper quadrant abdominal pain,f e v e r, and abnormal liver enzymes (3–6). After carefulworkup, these cases had no evidence of infection, malig-n a n c y, or other causes of acute inflammation. Biochemi-cal and clinical manifestations disappeared after surg i c a lresection. We describe a patient with infarcted GLH pre-senting with the same triad of signs and symptoms, whichnormalized after surgical resection.

Infarcted Giant Liver HemangiomaPresenting with Signs of Acute Inflammation

A CASE TO REMEMBER

Sherif Saadeh, M.D. and Kevin D. Mullen, M.D.,Departments of Gastroenterology, Radiology, Pathol-ogy, and General Surgery, Cleveland Clinic Founda-tion, Cleveland, Ohio and Department of Gastroen-terology at MetroHealth Medical Center, Case West-ern Reserve University, Cleveland, Ohio. WilliamCarey, M.D., David Barnes, M.D., Mark Baker, M.D.,Terry Gramlich, M.D., David Vogt, M.D., Departmentsof Gastroenterology, Radiology, Pathology, and Gen-eral Surgery, Cleveland Clinic Foundation, Cleveland,Ohio.

Sherif Saadeh, Kevin D. Mullen, William Carey, David Barnes, Mark Baker, Terry Gramlich, and David Vogt

Liver hemangioma is generally benign and asymptomatic. In this case report, wedescribe a patient who presented with giant liver hemangioma (GLH) and signs ofacute inflammation. The patient had a 3-month history of right upper quadrant pain,fever, and abnormal liver enzymes. Imaging studies revealed GLH, and carefulworkup ruled out infectious etiology and malignancy. After surgical resection, thepatient’s symptoms disappeared and biochemical markers returned to normal. His-tological examination revealed GLH with extensive necrosis and thrombosis. Clini-cians should consider in their differential diagnosis that GLH, while usually silent,may present with acute inflammatory symptoms and abnormal liver enzymes. Surgi-cal resection is curative.

CASE REPORTA 47-year old male was referred to the Cleveland ClinicFoundation from outside hospital with 3-months historyof right upper quadrant pain, fever, and persistently ele-vated levels of alkaline phosphatase and γ- g l u t a m y l-transferase. During his previous hospitalization, alaparascopic cholecystectomy was performed but failedto resolve his symptoms; the intraoperative cholan-giogram was negative. Post-operatively, the patientremained febrile, and multiple repeated blood cultureswere negative for organisms. An endoscopic retrogradecholangiopancreatography (ERCP) revealed mild biliaryleak for which a stent was placed. Pathologic evaluationof surgical specimen was inconclusive and tissue fromgall bladder revealed candidal fungal growth. Intra-venous amphotericin was given for 18 days. In spite ofthe above management, the patient had persistent fluctu-ating fever, abdominal pain and elevated liver enzymelevels. At this point, he was transferred to the ClevelandClinic.

On admission, the patient had a temperature of 38°Cand the liver was palpable at the right costal margin. Oth-erwise, he had no stigmata of chronic liver disease. Lab-oratory workup revealed a normal white blood cellcount, hemoglobin level, platelet count, kidney function,prothrombin time, α-fetoprotein level, and serum biliru-bin. Serum alkaline phosphatase was 2–11 times and γ-glutamyltransferase 2–7 times the upper limit of normal.Bacterial, fungal, and amebic cultures were all negative.

Computed tomography (CT) of the abdomen (Fig.1) showed low attenuated large mass (14.1 × 12.1 × 1 2cm) with peripheral irregular nodular enhancementoccupying the left lateral segment of the liver. Magneticresonance imaging (MRI) of the abdomen showed acomplex heterogenous mass in the left hepatic lobe, withmixed areas of decreased and slightly increased signalintensity on T1 weighted images (Fig. 2), and increasedsignal intensity on T2 weighted images (Fig. 3). Fine-needle aspiration of the central complex part of the masswas consistent with infarcted cavernous hemangioma. Aleft lateral segmentectomy of the liver was performed.The weight of the removed liver was 570 grams. Histo-logical examination showed cavernous hemangioma(Fig. 4) with areas of extensive necrosis and infarction(Fig. 5). Biopsy specimens from the unaffected liverwere consistent with mild steatosis and negative for

m a l i g n a n c y. The patient had a smooth post-operativecourse. Biochemical and clinical symptoms normalizedsoon after the surg e r y. An ERCP was repeated in two

PRACTICAL GASTROENTEROLOGY • MARCH 2003 69

A CASE TO REMEMBER

Infarcted Giant Liver Hemangioma

Figure 1. Computed tomographic scan (CT) of the abdomendisplaying left lobe liver mass with peripheral enhancement nottypical of a cavernous hemangioma.

Figure 2. T1 weighted magnetic resonance imaging (MRI) ofthe left lobe liver mass after enhancement showing heteroge-nous peripheral enhancement not typical of a cavernoushemangioma. Delayed scans did not demonstrate any centrale n h a n c e m e n t .

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A CASE TO REMEMBER

Infarcted Giant Liver Hemangioma

months after surgical resection of the giant hemangioma,and the stent was removed with no evidence of biliaryleak.

DISCUSSIONAlthough GLH is most often asymptomatic, there havebeen few case reports of GLH associated with inflam-matory manifestations (3–7). Bornman, et al (3)described two cases with GLH who experienced a triadof acute inflammatory process (fever, chills, right upperquadrant tenderness), a normal white blood cell count,and normal liver function tests. Pateron, et al (4)described two similar cases, but with associated abnor-mal liver tests. Pol, et al (5) reported three cases withinflammatory process complicating GLH. Smyrniotis, etal (6) reported one case of GLH associated with clinicaland laboratory manifestations of an underlying inflam-matory process (elevated fibrinogen, erythrocyte sedi-mentation rate (ESR), C-reactive protein (CRP), tumornecrosis factor (TNF), and interleukin-6).

The underlying pathophysiology of the inflamma-tory process in patients with GLH is not fully understood(3–6). One theory suggests that cytokines released fromhepatic macrophages and endothelial cells are responsi-

ble for the inflammatory process (6,9). Others considerthe key mediators to be interleukin-1 and -6 (9). Themost likely explanation for the pain and increased ESR,CRP and fibrinogen is thrombosis within the tumor(6,8). The elevated levels of alkaline phosphatase andγ-glutamyltransferase could be the result of compressionof bile ducts (Fig. 6), secondary to either the growingGLH itself, or to the rigid thrombosis and fibrosis thatoccur within the structure of the GLH (6–8). From an

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Figure 3. T2 weighted magnetic resonance imaging (MRI) ofthe left lobe liver mass shows heterogenous increased signalnot typical for a cavernous hemangioma.

Figure 4. (H&E stain ×200). Cavernous hemangioma consist-ing of dilated vascular channels lined by flat endothelial cells.

Figure 5. (H&E stain ×100). Area within the hemangioma (cen-tral part) shows ischemic necrosis (infarct).

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A CASE TO REMEMBER

Infarcted Giant Liver Hemangioma

imaging standpoint, it is well known that GLH does notdemonstrate the classic findings on either CT or MRI(4,10–12). Typically on CT, hemangiomas are low-den-sity on pre-contrast CT and during enhancement demon-strate discontinuous, peripheral, nodular enhancement.On delayed scanning, the enhancement slowly fills in acentripetal fashion (11,12). On MRI, without contrastenhancement, these lesions are low signal on T1weighted images and demonstrate very high signal,equal to cerebrospinal fluid or the gallbladder on T2weighted pulse sequences. They are sharply defined rel-ative to the adjacent liver and may demonstrate thin,internal septi. The enhancement after Gadolinium-DTPAis the same as on CT (12). The mass in this case as withother giant liver hemangiomas was atypical. Theenhancement peripherally was very continuous, espe-cially laterally, indicating a more neoplastic or inflam-matory process.

CONCLUSIONOur patient had a giant liver hemangioma that presentedwith an unusual combination of signs and symptoms:right upper quadrant abdominal pain, fever, elevatedserum alkaline phosphatase and γ- g l u t a m y l t r a n s f e r a s e ,and normal white blood cell count. Careful studyexcluded all other sources of inflammation except for theGLH. Clinical and biochemical abnormalities resolved

after surgical resection of the tumor. Histologic exami-nation confirmed the presence of giant cavernous liverhemangioma with extensive necrosis and infarction.GLH should be considered in the differential diagnosisof a liver mass that presents with signs and symptoms ofinflammation, even though it is rare in this context.

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hemangiomas of the liver: resect or observe? Am J Surg, 1983;145:49-53.

3. Bornman PC, Terblanche J, Blumgart RL, et al. Giant hepatichemangiomas: Diagnostic and therapeutic dilemmas. Surgery,1987;101:445-449.

4. Pateron D, Babany G, Belghiti J, et al. Giant hemangioma of theliver with pain, fever and abnormal liver tests. Report of twocases. Dig Dis Sci, 1991;36:524-527.

5. Pol B, Disdier P, Le Treut YP, et al. Inflammatory process com-plicating giant hemangioma of the liver: Report of three cases.Liver Transplant Surg, 1998;4(3):204-207.

6. Smyrniotis V, Kehagias D, Arkadopoulos N, et al. Liver heman-gioma with systemic inflammatory manifestations: Letter to theeditor. Am J Gastroenterol, 2000;95 (3):830-832.

7. Farges O, Daradkeh S, Bismuth H. Cavernous hemangiomas ofthe liver: Are there any indications for resection? World J Surg,1995;19:19-24.

8. Egea AM, Del Pozo Rodriguez M, Cantero MV, et al. Indicationsfor surgery in the treatment of hepatic hemangioma. Hepatogas -troenterology, 1996;43:422-426.

9. Feder LS, Tdaro JA, Laskin DL. Characterization of interleukin-1 and interleukin-6 production by hepatic endothelial cells andmacrophages. J Leucocyt Biol, 1993;53:126-132.

10. Takayasu K, Moriyama N, Shima Y, et al. Atypical radiographicfindings in hepatic cavernous hemangioma: correlation with his-tologic features. AJR, 1986;146:1149-1153.

11. Scatarige JC, Kenny JM, Fishman EK, et al. CT of giant cav-ernous hemangioma. AJR, 1987;149:83-85.

12. Choi BI, Han MC, Park JH, et al. Giant cavernous hemangiomaof the liver: CT and MR imaging in 10 cases. AJR, 1989;152:1221-1226.

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Figure 6. (H&E stain ×100). The hemangioma (left) entrapsportal structure (right) including bile ducts. Non-tumoroushepatocytes contain lipid vacuoles at the periphery (right).