Elevated AFP in Men: Causes and Diagnostic Approach

Introduction to Elevated AFP

The American College of Physicians and other medical organizations acknowledge that benign liver disease, including hepatitis, hepatic toxicity from chemotherapy, and other liver disorders, is the most common non-malignant cause of elevated AFP in adult men 1
The National Comprehensive Cancer Network notes that intrahepatic cholangiocarcinoma can produce elevated AFP levels 2
The American Society of Clinical Oncology recognizes that metastatic colon cancer to the liver may elevate AFP 2
Lymphoma, small-cell lung cancer, Ewing sarcoma, and osteogenic sarcoma can all cause AFP elevation, as stated by the Journal of Clinical Oncology 1

When evaluating elevated AFP in a man without known testicular cancer or HCC, the European Society for Medical Oncology recommends measuring concurrent β-hCG and LDH to evaluate for occult germ cell tumor 3
The American College of Radiology suggests obtaining testicular ultrasound even if physical examination is normal, as occult testicular tumors can present with only marker elevation 3
The National Institute of Health advises performing CT chest, abdomen, and pelvis to identify retroperitoneal or mediastinal primary tumors 3
The American Association for the Study of Liver Diseases recommends checking liver function tests (ALT, AST, bilirubin) and hepatitis B/C serologies to assess for benign liver disease 3
The American Society of Clinical Oncology notes that obtaining serial AFP measurements over 2-4 weeks can help distinguish between cancer-associated AFP and constitutively elevated AFP 1, 3

The American Cancer Society states that pure seminoma never produces AFP; if a patient with "pure seminoma" histology has elevated AFP, assume undetected nonseminomatous elements are present 1, 4
The European Association for the Study of the Liver notes that AFP elevation is only present in 40-60% of HCC cases, so normal AFP does not exclude HCC 2
The College of American Pathologists advises that laboratory artifact from hemolysis does not typically affect AFP (unlike LDH), but should be considered if results are inconsistent 1
The American Medical Association states that the upper limit of normal for AFP is 9 ng/mL if <40 years old and 13 ng/mL if ≥40 years old 3