BONE METASTASIS HEPATOCELLULAR CARCINOMA

*Latif A. and **Muzrekchi A.
Departments of *Medicine & **Radiology, Hamad Medical Corporation, Doha, Qatar

Abstract:

We report a case of hepatocellular carcinoma in a forty five year old man with Hepatitis C virus and liver cirrhosis. He presented with headache, double vision and left-sided facial numbness. MRI and a CT scan of his head revealed metastasis at the base of the skull

Introduction:

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is responsible for approximately one million deaths annually, most of them in the Far East and Sub-Saharan Africa(1).

Hepatitis C virus (HCV) is now recognized as a major risk factor for HCC, evidenced by serum serology of antibody to HCV (anti-HCV) and HCV RNA(2). Other risk factors include hepatitis B virus, alcohol consumption, aflatoxin-liver cirrhosis and metabolic disorders such as hemochromatosis. Hepatocellular carcinoma with extra-hepatic spreading is not uncommon(3). The most frequent site for spread of HCC tumor is invasion of the liver capsule followed by extravascular invasion, vascular invasion and finally intrahepatic metastasis(4).

Case Report:

A 45-year-old Yemeni male was admitted to hospital on 11th October 1998 with a history of passing black watery stools for the previous month. There was no history of abdominal pain or vomiting or dysphagia or heartburn. He had a poor appetite and had lost 15kg of weight over one month. He complained of generalized headache, double vision when looking to the left and a left side facial numbness for the preceding thirty days. He exhibited no speech disturbances and had no fits.

In 1960 he had been treated for urinary bilharziasis and malaria and on 23rd November 1997 he had been admitted to hospital with a transient loss of consciousness. At that time CT of his head and his EEG were reported to be normal.

The patient looked well and was not jaundiced or cyanosed. His blood pressure was 110/90mm Hg, temperature 36.7oC, heart sounds were normal and auscultation of the chest showed only normal vesicular breathing sounds. The spleen was palpable three fingers below the costal margin, there was no ascites and no stigmata of chronic liver disease. CNS examination revealed left lateral rectus palsy. No other physical abnormalities were found.

Laboratory tests showed Hb 12.9 g/dl, WBC 5.9 x 103 /cmm, platelets 93 x 103/cmm, blood indices were normal, PT 17.1/sec.,INR 1.4, PTT 36.4, blood glucose 5.4mmol/L, ALT 45u/L, AST 80u/L, alkaline phosphatase 217u/L, total protein 72g/L, serum albumin 24g/L, serum cholesterol 3.22mmol/L, triglycerides 0.99mmol/L. HbsAg negative, HCV positive, Schistosoma titer 1:128.

Microscopical examination of his urine showed 20-30 RBC/HPF. Tests on urine for ketones and protein were negative as was also urine culture. A chest x-ray was normal. a-Fetoprotein was 500.7 iu/ml (normal range 0-9iu/ml).

Esophago-gastroduodenoscopy showed grade III esophageal varices, fundal varices with congested gastropathy, a deep antral gastric ulcer and a normal duodenum. There was no active bleeding. The Clo test was negative. Gastric biopsy showed chronic gastritis of moderate activity with Helicobacter pylori present and a mild focal intestinal metaplasia. There was no evidence of malignant changes.

Abdominal sonography showed a well-defined focal lesion measuring 7.2 x 6.1cm in the right lobe of the liver extending towards the right kidney. The spleen measured 20 cm in length. Abdominal CT showed a cirrhotic liver with a primary hepatocellular carcinoma in the right lobe, extensive lymphadenopathy in the upper abdomen and retroperitoneum and an enlarged spleen secondary to portal hypertension (Figure 1). Liver biopsy under sonography confirmed hepatocellular carcinoma with established liver cirrhosis.

Figure 1: CT abdomen showing small cirrhotic liver, large ill-defined mass infiltrating the right hepatic lobe, extensive lymphadenopathy, moderate splenomegaly.

MRI of the head showed an irregular mass on the left of the base of the skull with intra- and extra-cranial extension eroding and destroying the bony floor of the middle cranial fossa. The mass infiltrated the left side of the sphenoid sinus, the antero-medial aspect of the left temporal lobe and was beginning to erode the intratemporal fossa and infiltrate the extra-cranial muscles. It also extended to, but had not infiltrated, the anterior part of the nasopharynx abutting the hard palate (Figure 2). With CT guidance, five needle aspiration biopsies were taken from the mass at the base of the skull. These confirmed metastatic hepatocellular carcinoma.

Figure 2: MRI T1 showed a large mass mainly present at left infro-temperol fossa extended upward into base of left middle cranial fossa and also into left sphenoid sinus eroding the apex of petrous bone.

The patient started a course of adriamycin (50 mg/m2 = 100 mg IV) but his general condition deteriorated rapidly and he died two months after diagnosis.

Discussion:

Hepatocellular carcinoma is relatively rare in the United States and Europe where the annual incidence is less than four cases per 100,000 while it is one of the four most common malignant tumors of adults in China, Taiwan, Korea and sub-Saharan Africa with an annual incidence as high as 150 cases per one million of population(5).

Hepatocellular carcinoma spreads locally and metastasizes distally by hematogenous and lymphatic routes. Autopsy series have reported 30% to 70% of patients with hepatoma having metastases at the time of death. These usually involve lymph nodes (42%), lungs (18%) and the adrenal gland. Other less common sites include the brain, skull and heart(6).

The diagnosis of bone metastasis in our patient was made at the time of the diagnosis of HCC. His diplopia and numbness of the face was caused by the cerebral and extra-cranial muscle invasion. In addition to the metastasis in the skull there was extensive abdominal lymphadenopathy.

The prognosis for HCC depends upon the stage of development of the tumor but is generally very poor. Metastases occur late in the disease and bone metastasis as the initial manifestation of HCC is rare. A Medline search for HCC with bone metastases revealed 40 cases in the last five years. The incidence of HCC with bone metastasis at the time of initial diagnosis was around five per cent, varying slightly from series to series. Vertebrae, ribs, the skull and the long bones were the predominant metastatic localizations. In 1986 Kuhlman reviewed a series of 300 patients with HCC and found 22 cases of skeletal metastases involving most frequently the spine, ribs and long bones. Skull involvement was rare. In all cases the plain appearance of the metastases was osteolytic(7).

In conclusion, bone metastases from HCC are fairly rare and it is even more rare to find bone metastases as the first overt manifestation of HCC.

References:

1. Szmunes W: Hepatocellular Carcinoma and the Hepatitis B virus: Evidenc e of a causal association. Prog med virol 24: 40-69, 1978.

2. Di-Bisceglie-AM, Hepatitis C and Hepatocellular Carcinoma. Hepatology: 1977 Sept; 26 (3 suppl 1): 345-385.

3. Yen-FS: Wo-JC: Lai-CR: Sheng-Wr: Kuo-BI: Chen-TZ: Tsay -SII: Lee-SD, Clinical and Radiological pictures of Hepatocellular Carcinoma with intracranial metastasis. J. Gastroenterol-Hepatol. 1995 Jul-Aug: 10(4): 413-8.

4. Mitsunobu-M: Tovosaka-A: Oriyama-T: Okamoto-E: Nakao-N. Clin-Exp-Metastasis. 1996 Nov: 14(6): 520-9.

5. London WT: Primary Hepatocellular Carcinoma-Etiology, Pathogenesis, and Prevention. Hum pathol 12: 1086-1097, 1981.

6. W.T. Yang, W. Yeo, S.F. Leung & Co. MRI and CT of metastatic Hepatocellular Carcinoma Causing Spinal Cord Compression. Clinical Radiology (1977) 52, 755-760.

7. Kuhlman JE, Fishman EK, Leichner PK, et al. Skeletal metastases from hepatoma: Frequency, distribution, and radiology features. Radiology 1986; 160: 175-8.