What are the causes of elevated Carcinoembryonic Antigen (CEA) levels when a Positron Emission Tomography (PET) scan is normal?

Causes of Elevated CEA with Normal PET Scan

Elevated CEA levels with normal PET scan findings are most commonly due to non-malignant conditions including liver disease, inflammatory bowel disease, smoking, and benign gastrointestinal disorders, rather than occult malignancy. 1

Common Non-Malignant Causes

Liver Disorders

• Alcoholic liver disease - Can cause CEA elevations typically <10 ng/mL 1
• Viral hepatitis - Both acute and chronic forms
• Cirrhosis (all types) - Approximately 50% of patients with severe benign hepatic disease have elevated CEA 1
• Biliary obstruction - Especially when accompanied by cholangitis

Inflammatory Conditions

• Inflammatory bowel disease - Particularly active ulcerative colitis, with levels correlating with disease severity 1
• Pancreatitis - Both acute and chronic forms
• Diverticulitis - Can cause transient CEA elevation
• Gastritis and peptic ulcer disease 2

Pulmonary Conditions

• Chronic obstructive pulmonary disease 2
• Smoking - A significant contributor to mild CEA elevation 1

Other Conditions

• Diabetes 2
• Colonic polyps - Can cause mild elevations 1
• Any acute or chronic inflammatory state 2

Occult Malignancy Considerations

Despite normal PET scan findings, certain malignancies may still be present but undetected:

• Medullary thyroid carcinoma - Can cause persistent CEA elevation with initially negative workup 3
• Small or early colorectal cancer recurrence - Below detection threshold of imaging
• Slow-growing tumors with low metabolic activity

Diagnostic Algorithm

1. Confirm elevation with repeat testing - Single elevated CEA levels often normalize on repeat testing 4

2. Assess for common benign causes:

   • Liver function tests to rule out hepatic disorders
   • Evaluate smoking status
   • Screen for inflammatory conditions

3. If CEA continues to rise despite negative PET:

   • Consider specialized testing for medullary thyroid carcinoma (serum calcitonin) 3
   • Consider contrast-enhanced MRI for better soft tissue definition 2
   • Consider repeat fine needle aspiration of any suspicious lesions, even if initially negative 3

4. Monitoring strategy:

   • For stable, mildly elevated levels (<10 ng/mL) without clinical evidence of disease: monitor CEA every 3-6 months 4
   • For rising levels: shorten interval between imaging studies 2

Clinical Pearls and Pitfalls

• Pitfall: Relying solely on a single elevated CEA measurement - up to 57% of unexplained elevations return to normal range on follow-up 4

• Pitfall: Assuming PET scan negativity excludes all malignancy - some cancers like medullary thyroid carcinoma may be missed 3

• Pearl: The liver is essential for CEA metabolism and excretion - liver workup is necessary for any patient with elevated CEA 1

• Pearl: Smoking may contribute to elevated CEA levels, particularly in patients with concurrent alcoholic liver disease or pancreatitis 1

• Pearl: CEA levels >25 ng/mL are highly suggestive of metastatic cancer (particularly hepatic metastasis) even with negative imaging and warrant more aggressive investigation 5