A 48-Year-Old Obese Man with a 3 cm Liver Lesion and a History of Hemochromatosis and Lymphoma

A 41-year-old obese, but otherwise healthy man was found on routine blood testing to have a serum ferritin level of greater than 1000 ng/mL (normal = 20 to 380). A bone marrow biopsy was unremarkable. He was diagnosed with hemochromatosis and was treated with phlebotomy for several years. He was free of symptoms until the age of 46, when he noticed a “lump” in his chest. Chest X ray and a magnetic resonance imaging (MRI) revealed a sternal mass, which was biopsied and revealed a B-cell lymphoma. The patient underwent chemotherapy with a regimen of cyclophosphamide, hydroxydaunorubicin, Oncovin^®, and prednisone (CHOP), as well as Rituximab and radiation therapy. This resulted in marked shrinking of the sternal mass. He was followed with routine computed tomography (CT) and positron emission tomography (PET) scans. Six months after completing treatment, he had a repeat biopsy of his chest wall that was negative for malignancy.

On a subsequent routine follow-up CT scan about 8 months prior to his most recent admission, a 3 cm mass was noted in the right lobe of the liver along with several preexisting cystic structures (Fig. [1]). A PET scan 2 months later revealed increased uptake in the midportion of the right lobe of the liver abutting on the lateral chest wall. This lesion corresponded to the hyperdense lesion seen on CT scan, which was biopsied. Histological examination was reported to “favor malignant epithelial neoplasm.” Liver function tests and tumor markers (alpha fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9) were normal.

Figure 1 CT image showing a 3-cm hyperdense lesion in the periphery of the liver (arrow).

Following this diagnosis, he was referred for further work-up, including upper and lower endoscopies. Additional laboratory findings at that time showed a serum iron of 52 ug/dL (normal = 40 to 190), total iron-binding capacity of 305 ug/dL (normal = 250 to 440), transferrin saturation of 17% (normal = 15 to 50), ferritin of 67 ng/mL (normal = 20 to 380), serum transferrin of 227 mg/dL (normal = 188 to 341), prothrombin time of 13.3 seconds (normal = 11.5 to 14.5), and negative serological studies for hepatitis B and C. The patient was also found to be heterozygous for both the C282Y and H63D mutations of the hemochromatosis (HFE) gene.

A nonanatomic resection of the mass in the right lobe of liver was performed. There were two liver cysts, one in segment VII and one in the left lateral segment, which were not excised. Dense adhesions of the liver to the anterior chest wall and diaphragm were noted, likely because of prior radiation therapy.

REFERENCES

• 1 Bergquist A, Ekbom A, Olsson R et al.. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis.  J Hepatol. 2002;  36 321-327
• 2 Boberg K M, Bergquist A, Mitchell S et al.. Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation.  Scand J Gastroenterol. 2002;  37 1205-1211
• 3 Genetic haemochromatosis . Report of a meeting of physicians and scientists at the Royal Free Hospital School of Medicine.  Lancet. 1997;  349 1688-1693
• 4 Leggett B A, Halliday J W, Brown N N et al.. Prevelance of haemochromatosis amongst asymptomatic Australians.  Br J Haematol. 1990;  74 525-530
• 5 Feder J N, Gnirke A, Thomas W et al.. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.  Nat Genet. 1996;  13 399-408
• 6 Britto M R, Thomas L A, Balaratnam N, Griffiths A P, Duane P D. Hepatocellular carcinoma arising in non-cirrhotic liver in genetic haemochromatosis.  Scand J Gastroenterol. 2000;  35 889-893
• 7 Gelatti U, Donato F, Tagger A et al.. Etiology of hepatocllular carcinoma influences clinical and pathologic features but not patient survival.  Am J Gastroenterol. 2003;  98 907-914
• 8 Morcos M, Dubois S, Bralet M et al.. Primary liver carcinoma in genetic hemochromatosis reveals a broad histologic spectrum.  Am J Clin Pathol. 2001;  116 738-743
• 9 Cauza E, Peck-Radosavlijevic M, Ulrich-Pur H et al.. Mutations of the HFE gene in patients with hepatocellular carcinoma.  Am J Gastroenterol. 2003;  98 442-447
• 10 Orii T, Ohkohchi N, Sasaki K et al.. Cholangiocarcinoma arising from pre-existing biliary hamartoma of liver-report of a case.  Hepatogastroenterology. 2003;  50 333-336
• 11 Parkin D M, Ohshima H, Srivatanakul P, Vatanasapt V. Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention.  Cancer Epidemiol Biomarkers Prev. 1993;  2 537-544
• 12 Kurathong S, Lerdverasirikul P, Wongpaitoon V et al.. Opisthorchis viverrini infection and cholangiocarcinoma, a prospective, case-controlled study.  Gastroenterology. 1985;  89 151-156
• 13 Schwartz D A. Cholangiocarcinoma associated with liver fluke infection: a preventable source of morbidity in Asian immigrants.  Am J Gastroenterol. 1986;  81 76-79
• 14 Leung J W, Yu A S. Hepatolithiasis and biliary parasites.  Baillieres Clin Gastroenterol. 1997;  11 681-706
• 15 Chen M F, Jan Y Y, Jeng L B et al.. Intrahepatic cholangiocarcinoma in Taiwan.  J Hepatobiliary Pancreat Surg. 1999;  6 136-141
• 16 Lee C C, Wu C Y, Chen G H. What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma?.  J Gastroenterol Hepatol. 2002;  17 1015-1020
• 17 Chijiiwa K, Ohtani K, Noshiro H et al.. Cholangiocellular carcinoma depending on the kind of intrahepatic calculi in patients with hepatolithiasis.  Hepatogastroenterology. 2002;  49 96-99
• 18 Tocchi A, Mazzoni G, Liotta G et al.. Late development of bile duct cancer in patients who had biliary enteric drainage for benign disease: a follow-up study of more than 1,000 patients.  Ann Surg. 2001;  234 210-214
• 19 Chapman R W. Risk factors for biliary tract carcinogenesis.  Ann Oncol. 1999;  10(Suppl 4) 308-311
• 20 Lee F I, Tharakan J, Vasudev K S, Isaacs P E. Malignant hepatic tumours associated with previous exposure to Thorotrast: four cases.  Eur J Gastroenterol Hepatol. 1996;  8 1121-1124
• 21 Kuper H, Lagiou P, Mucci L A et al.. Risk factors for cholangiocarcinoma in a low risk Caucasian population.  Soz Praventivmed. 2001;  46 182-185
• 22 Temizkan M, Ouwendijk J T, Middelkoop M P et al.. A young female with a cholangiocarcinoma in the past: is pregnancy allowed?.  Acta Gastroenterol Latinoam. 1996;  26 31-34
• 23 Key T J, Appleby P N, Reeves G K et al.. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.  J Natl Cancer Inst. 2003;  95 1218-1226
• 24 Bastounis E A, Karayiannakis A J, Syrigos K et al.. Sex hormone changes in morbidly obese patients after vertical banded gastroplasty.  Eur Surg Res. 1998;  30 43-47
• 25 Sasaki M, Tsuneyama K, Ishikawa A, Nakanuma Y. Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte-macrophage colony-stimulating factor.  Hum Pathol. 2003;  34 1337-1344
• 26 Kuper H, Ye W, Broome U et al.. The risk of liver and bile duct cancer in patients with chronic viral hepatitis, alcoholism or cirrhosis.  Hepatology. 2001;  34 714-718
• 27 Donato F, Gelatti U, Tagger A et al.. Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy.  Cancer Causes Control. 2001;  12 959-964
• 28 Jaiswal M, Larusso N F, Burgart L J, Gores G J. Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism.  Cancer Res. 2000;  60 184-190
• 29 Terada T, Ashida K, Endo K et al.. c-erbB-2 protein is expressed in hepatolithiasis and cholangiocarcinoma.  Histopathology. 1998;  33 325-331
• 30 Ozaki S, Harad K, Sanzen T et al.. In situ nucleic acid detection of human teolmerase in intrahepatic cholangiocarcinoma and its preneoplastic lesion.  Hepatology. 1999;  30 914-919
• 31 Terada T, Ueyama J, Ukita Y, Ohta T. Protein expression of double-stranded RNA-activated protein kinase (PKR) in intrahepatic bile ducts in normal adult livers, fetal livers, primary biliary cirrhosis, heptolithiasis and intrahepatic cholangiocarcinoma.  Liver. 2000;  20 450-457
• 32 Lee K T, Liu T S. Expression of transforming growth factor betas and their signaling receptors in stone-containin intrahepatic bile ducts and cholangiocarcinoma.  World J Surg. 2003;  27 1143-1148
• 33 Sasaki M, Huang S F, Chen M F et al.. Decrease of deleted in malignant brain tumour-1 (DMBT-1) expression is a crucial late event in intrahepatic cholangiocarcinoa.  Histopathology. 2003;  43 340-346
• 34 Sasaki M, Tsuneyama K, Nakanuma Y. Aberrant expression of trefoil family 1 in biliary epithelium in hepatolithiasis and cholangiocarcinoma.  Lab Invest. 2003;  83 1403-1413
• 35 Orikasa H, Ohyama R, Tsuka N, Eyden B P, Yamazaki K. Lipid-rich clear-cell hepatocellular carcinoma arising in non-alcoholic steatohepatitis in a patient with diabetes mellitus.  J Submicrosc Cytol Pathol. 2001;  33 195-200
• 36 Tsuneyama K, Kaizaki Y, Doden K et al.. Combined hepatocellular and cholangiocarcinoma with marked squamous cell carcinoma components arising in non-cirrhotic liver.  Pathol Int. 2003;  53 90-97
• 37 Katoh M, Takeuchi K, Murahima N et al.. Hepatocellular carcinoma with splenic metastasis developing after 16 years of chemotherapy for chronic myelogenous leukemia: a case report.  Jpn J Clin Oncol. 1994;  24 111-115
• 38 Britto M R, Thomas L A, Balaratnam N, Griffiths A P, Duane P D. Hepatocellular carcinoma arising in non-cirrhotic liver in genetic haemochromatosis.  Scand J Gastroenterol. 2000;  35 889-893
• 39 Lau S K, Prakash S, Geller S A, Alsabeh R. Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma.  Hum Pathol. 2002;  33 1175-1181