Can gallbladder cancer with elevated Carbohydrate Antigen 19-9 (CA 19-9) levels and imaging findings from a Contrast-Enhanced Computed Tomography (CECT) abdomen and pelvis be differentiated from tuberculosis (TB)?

Gallbladder Malignancy is More Likely Than Tuberculosis in This Case

Based on the imaging findings of gallbladder wall thickening with direct invasion into adjacent organs (liver, colon, duodenum), fistula formation, and CA 19-9 elevation to 320 U/mL, this presentation is highly suspicious for gallbladder carcinoma rather than tuberculosis, and tissue diagnosis should be urgently pursued. 1, 2

Why Malignancy is the Primary Concern

Imaging Features Favor Malignancy

• Diffuse circumferential GB wall thickening with direct invasion into segment V of liver, hepatic flexure of colon, and second part of duodenum represents locally advanced disease characteristic of gallbladder carcinoma 3
• Multiple peripherally enhancing hypodense liver lesions (largest 17 × 15 mm) are concerning for metastatic disease rather than tuberculous abscesses 3
• Necrotic lymphadenopathy (periportal, pericaval, superior mesenteric) can occur in both conditions, but when combined with the above findings, strongly suggests malignancy 3

CA 19-9 Elevation Interpretation

• CA 19-9 of 320 U/mL exceeds the 100 U/mL threshold that has 75% sensitivity and 80% specificity for biliary tract malignancy 3, 1
• While CA 19-9 can be elevated in benign biliary obstruction and cholangitis, persistently elevated levels after biliary decompression suggest malignancy 3, 1
• In gallbladder carcinoma specifically, mean CA 19-9 levels of 625 U/mL have been reported, with values >252 U/mL having 100% sensitivity and 98.9% specificity for malignancy 2
• The mild hyperbilirubinemia (2.1 mg/dL) could contribute to CA 19-9 elevation, but the degree of elevation is disproportionate to the bilirubin level 1, 4

Why Tuberculosis is Less Likely

TB Would Present Differently

• Peritoneal TB typically causes ascites, peritoneal nodules, and omental thickening—none of which are present in this case 1
• Hepatobiliary TB usually manifests as multiple small hepatic granulomas or miliary nodules, not peripherally enhancing hypodense lesions suggestive of metastases 3
• TB cholecystitis is extremely rare and would not typically cause the degree of local invasion seen here (direct extension into liver, colon, and duodenum with fistula formation) 5

Clinical Context Matters

• The presence of a large 32 mm gallstone with wall dehiscence suggests chronic cholecystitis as the underlying process, which is a known risk factor for gallbladder carcinoma 6, 5
• Pneumobilia and fistula formation in this context are more consistent with complicated gallstone disease with superimposed malignancy than TB 4

Critical Diagnostic Algorithm

Immediate Next Steps

1. Obtain tissue diagnosis via image-guided biopsy of liver lesions or lymph nodes—this is essential and cannot be deferred 3
2. Check CEA and CA-125 as additional tumor markers (CEA elevated in 30% of biliary malignancies, CA-125 in 40-50%) to strengthen diagnostic certainty 3, 1
3. Assess Lewis antigen status if considering CA 19-9 reliability, as 5-10% of population cannot produce CA 19-9 1, 7

If Biopsy Shows Malignancy

• Proceed with staging CT chest and consideration for palliative vs. surgical management based on resectability 3
• The presence of liver lesions and extensive local invasion suggests unresectable disease 3

If Biopsy is Non-Diagnostic or Shows Inflammation

• Consider TB workup including AFB culture, GeneXpert, and TB PCR from biopsy tissue 1
• Empiric anti-TB therapy could be considered if strong clinical suspicion exists (endemic area, constitutional symptoms, negative malignancy workup) 1
• Re-measure CA 19-9 after biliary decompression if obstruction is relieved—normalization would favor benign disease 3, 1

Important Caveats

Rare Benign Mimics Exist

• Xanthogranulomatous cholecystitis (XGC) can mimic gallbladder cancer radiologically and cause extreme CA 19-9 elevation (reported up to 5,791 U/mL) 6, 5
• However, XGC typically does not show the multiple liver lesions seen in this case 6, 5
• In one series, 54% of XGC cases had elevated tumor markers, with 45.95% having elevated CA 19-9 5

Do Not Delay Based on CA 19-9 Alone

• Even CA 19-9 levels in the thousands can occur in benign disease (choledocholithiasis with cholangitis reported at 98,628 U/mL) 4
• However, the combination of imaging findings, CA 19-9 elevation, and clinical presentation makes malignancy far more likely 1, 2
• Tissue diagnosis remains mandatory regardless of tumor marker levels 3, 1

Mortality Considerations

• Gallbladder carcinoma with liver involvement and fistula formation represents advanced disease with poor prognosis (5-year survival <5%) 8
• Delayed diagnosis due to consideration of benign etiologies worsens outcomes 2, 8
• Lymph node metastasis and CA 242 levels are independent prognostic factors in gallbladder cancer 8