A 57-year-old man comes to the office due to anorexia, a 4.5 kg (9.9 lb) weight loss, and generalized weakness. Other medical conditions include psoriasis and cervical spondylosis. Two years ago, the patient emigrated from Taiwan, where he worked for many years on a maize (corn) farm. He does not use tobacco, alcohol, or recreational drugs. Vital signs are within normal limits. BMI is 23 kg/m2. The patient appears cachectic. Examination shows a mass in the liver. There is no splenomegaly or ascites. Laboratory results are as follows:
| Total bilirubin | 1.8 mg/dL |
| Alanine aminotransferase (SGPT) | 70 U/L |
| Aspartate aminotransferase (SGOT) | 105 U/L |
| Alkaline phosphatase | 280 U/L |
| Anti–hepatitis C virus antibodies | negative |
| Hepatitis B surface antigen | negative |
| Antibody to hepatitis B core antigen | negative |
| Antibody to hepatitis B surface antigen | positive |
Abdominal ultrasound shows a 6-cm mass in the right lobe of the liver; the remainder of the liver appears normal. Biopsy of the mass shows plates of abnormal cells that are smaller than normal hepatocytes with a high nuclear/cytoplasmic ratio and nuclear pleomorphism. Which of the following is most likely responsible for this patient's current condition?
This patient with weight loss, weakness, and abnormal laboratory studies (eg, hyperbilirubinemia, elevated liver enzymes) has a liver mass with histopathologic features of hepatocellular carcinoma (HCC). Common risk factors include viral hepatitis, alcohol use, congenital metabolic disorders, and environmental toxins. Given this patient's former job on a corn farm, aflatoxin B1 exposure likely contributed to tumor development.
Aflatoxin B1 is a carcinogenic metabolite produced as a by-product by certain strains of Aspergillus that contaminate grains and nuts (eg, corn, peanuts), particularly in hot, humid environments (eg, Southeast Asia, sub-Saharan Africa). Ingestion contributes to pathogenesis by inducing specific mutations in p53 that impair the protein's tumor-suppressor function, leading to unregulated hepatocyte proliferation and accumulation of further genetic abnormalities. In addition, chronic exposure can act with other risk factors (eg, hepatitis B virus [HBV] infection) to significantly increase the risk for HCC.
Patients with HCC are often asymptomatic or have mild abdominal pain with nonspecific symptoms (eg, weight loss, malaise). Those with underlying chronic liver disease may show signs of worsening cirrhosis (eg, ascites, variceal bleeding). Microscopically, HCC typically shows thickened plates of malignant hepatocytes that resemble normal hepatocytes but are often smaller and have variable cytologic atypia (eg, pleomorphism, high nuclear/cytoplasmic ratio).
(Choice A) Chronic HBV infection is a common risk factor for HCC, but this patient's serology studies are consistent with prior vaccination, not chronic infection.
(Choice B) Vinyl chloride exposure is a risk factor for hepatic angiosarcoma, a malignant vascular tumor. Weight loss and weakness may occur, but histopathology typically shows infiltrative vascular structures lined by atypical (eg, pleomorphic, hyperchromatic) endothelial cells.
(Choice D) Clonorchis sinensis (liver fluke) infection is a risk factor for cholangiocarcinoma, a malignant tumor derived from bile duct epithelium. Although C sinensis is endemic in east Asia, histopathology of cholangiocarcinoma typically shows infiltrative glands lined by atypical epithelial cells.
(Choice E) Nonalcoholic fatty liver disease is a risk factor for HCC but is usually associated with metabolic syndrome (eg, obesity, hypertension); liver ultrasonography typically reveals evidence of fatty infiltration.
(Choice F) This patient has psoriasis, a chronic inflammatory skin disorder that causes well-circumscribed, erythematous plaques with silver-white scales. Psoriasis is not thought to have a direct role in HCC pathogenesis.
Educational objective:
Aflatoxin B1 is a carcinogen produced by Aspergillus that contaminates food (eg, corn) in hot, humid environments (eg, Southeast Asia). Chronic aflatoxin B1 ingestion is associated with inactivating p53 mutations that increases the risk for hepatocellular carcinoma.