What does an elevated Alpha-Fetoprotein (AFP) level, normal Carbohydrate Antigen 19-9 (CA19.9), slightly elevated Carcinoembryonic Antigen (CEA), colon wall thickening on Positron Emission Tomography-Computed Tomography (PET-CT) scan but normal Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scans, and a biopsy showing moderately differentiated adenocarcinoma deposits mean?

Interpretation of Elevated AFP with Moderately Differentiated Adenocarcinoma

The findings strongly suggest primary hepatocellular carcinoma (HCC) or cholangiocarcinoma, with the significantly elevated AFP (1700) and biopsy showing moderately differentiated adenocarcinoma being the most concerning features requiring urgent hepatobiliary specialist evaluation.

Clinical Significance of the Findings

• The markedly elevated AFP level of 1700 is highly suspicious for primary liver malignancy, particularly hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCCA), as AFP is a key tumor marker used in the diagnostic workup of liver malignancies 1, 2
• The slightly elevated CEA (6.1) with normal CA19-9 suggests a possible colorectal origin, though this pattern can also be seen in primary hepatobiliary malignancies 1, 3
• The discrepancy between imaging modalities (positive PET-CT showing colon wall thickening but normal MRI and CT) is significant, as PET-CT is more sensitive for metabolically active lesions but less specific than MRI for characterizing liver lesions 1
• The biopsy finding of "moderately differentiated adenocarcinoma" without specifying the primary site is consistent with either metastatic disease or primary hepatobiliary malignancy 1, 4

Diagnostic Algorithm

1. Hepatobiliary evaluation should be prioritized:

   • Complete liver function tests including AST, ALT, alkaline phosphatase, and bilirubin 1
   • Hepatocyte-specific contrast-enhanced MRI of the liver (if not already performed) to better characterize any liver lesions 1
   • Consider MRCP (magnetic resonance cholangiopancreatography) to evaluate the biliary tree 1

2. Additional tumor marker assessment:

   • Serial AFP measurements to track trends (rising values suggest active malignancy) 2, 3
   • Consider additional markers like PIVKA-II (also known as DCP) which can help differentiate HCC from other causes of elevated AFP 2

3. Pathology review:

   • Immunohistochemical staining of the biopsy specimen for:
     • Hepatocyte markers (HepPar-1, Arginase-1, glypican-3) 1
     • Biliary markers (CK7, CK19, CRP) 1
     • Colorectal markers (CK20, CDX2, SATB2) 1
   • Consider molecular profiling for treatment planning 1

4. Colonoscopy evaluation:

   • Complete colonoscopy to evaluate the colon wall thickening seen on PET-CT 1
   • Targeted biopsies of any suspicious areas 1

Interpretation of Specific Findings

• Elevated AFP (1700): This level is significantly above normal and strongly suggests:

  • Primary hepatocellular carcinoma as the most likely diagnosis 2, 3
  • Possible intrahepatic cholangiocarcinoma (iCCA), particularly the small-duct subtype which can produce AFP 1, 4
  • Less likely but possible: germ cell tumor with hepatic involvement 1

• Elevated CEA (6.1): Mildly elevated CEA has limited specificity but:

  • Can be seen in both primary colorectal cancer and hepatobiliary malignancies 1, 5
  • Should be monitored serially as a potential marker of disease progression 3, 5

• Normal CA19-9: While often elevated in pancreaticobiliary malignancies:

  • Does not rule out cholangiocarcinoma or pancreatic cancer 1, 6
  • The combination of elevated AFP with normal CA19-9 favors HCC over typical cholangiocarcinoma 1, 4

• PET-CT finding of colon wall thickening: This finding requires careful interpretation:

  • May represent a primary colorectal lesion or inflammatory changes 1
  • The discrepancy with normal CT and MRI suggests possible false positive on PET-CT 1
  • Colonoscopy with biopsy is essential for definitive evaluation 1

• Biopsy showing moderately differentiated adenocarcinoma: This finding is nonspecific and requires:

  • Immunohistochemical characterization to determine tissue of origin 1
  • Correlation with imaging and tumor marker findings 1, 3

Clinical Implications and Next Steps

• The constellation of findings most strongly suggests primary hepatobiliary malignancy, particularly HCC or a variant of cholangiocarcinoma 1, 2
• Urgent referral to a hepatobiliary specialist and multidisciplinary tumor board is warranted 1
• Treatment planning should be deferred until a definitive diagnosis of the primary site is established 1
• If hepatocellular carcinoma is confirmed, staging should include assessment for cirrhosis, portal hypertension, and vascular invasion 1, 2

Common Pitfalls to Avoid

• Focusing exclusively on the colon findings without adequately investigating the liver as the primary site given the markedly elevated AFP 2, 3
• Assuming normal CT/MRI rules out hepatobiliary malignancy - dedicated hepatocyte-specific contrast MRI may reveal lesions not seen on standard imaging 1
• Treating as metastatic colorectal cancer without definitive evidence, as primary hepatobiliary malignancies have different treatment approaches 1
• Failing to consider rare entities like combined hepatocellular-cholangiocarcinoma which can present with mixed features 1, 4