Why do we perform Fine Needle Aspiration Cytology (FNAC) if it can yield false negatives?

Why We Perform FNAC Despite Potential False Negatives

FNAC remains a valuable diagnostic tool because it provides critical information for clinical decision-making even when negative, and a negative result does not end the diagnostic pathway when clinical suspicion remains high.

Understanding FNAC's Diagnostic Value

FNAC serves multiple essential purposes beyond simply confirming malignancy:

• High specificity when positive: When FNAC is positive for malignancy, it has excellent correlation with final histology (97% in thyroid lesions, 96.8% in gallbladder carcinoma), allowing immediate treatment planning without more invasive procedures 1, 2

• Guides subsequent management: FNAC results determine the next diagnostic or therapeutic step rather than serving as a definitive endpoint 3

• Minimally invasive with low morbidity: The procedure is safe, rapid, and cost-effective compared to surgical biopsy, with no significant complications reported in large series 2, 4, 5

The Critical Concept: Negative FNAC ≠ Excluded Malignancy

A negative FNAC result should never be used to exclude malignancy when clinical suspicion remains high 3, 6:

• Poor negative predictive value: For biliary malignancies, the negative predictive value is only 34-47%, meaning many cancers will be missed 6

• Sensitivity limitations: FNAC sensitivity for biliary malignancies is 75-83%, and initial melanoma detection was only 20-40% (improved to 65-80% with refined techniques) 6, 7

• Sampling error: The needle may miss the malignant area, particularly in heterogeneous lesions, cystic degeneration, or technically challenging locations like the pancreatic uncinate process 3, 8

Algorithmic Approach When FNAC is Negative

Step 1: Assess Clinical and Radiological Suspicion

• High suspicion with negative FNAC: Proceed to repeat FNAC, core biopsy, or definitive surgery depending on the clinical scenario 3, 6

• Moderate suspicion: Repeat FNAC or obtain image-guided core biopsy 3

• Low suspicion: Consider observation with close follow-up 3

Step 2: Verify Adequacy of Sample

• Confirm lymphocytes were present in lymph node aspirates to ensure adequate sampling occurred 3

• Inadequacy rates vary by operator: Pathologists and radiologists achieve 9-11% inadequacy rates versus 20% for surgeons in salivary gland FNAC 5

• Repeat aspiration if inadequate: Studies show repeat EUS-guided FNA yields correct diagnosis in 61-84% of cases after initial failure 3

Step 3: Context-Specific Management

For pancreatic masses with negative FNAC 3:

• If resectable lesion + high suspicion + good surgical candidate → proceed to surgical resection
• If borderline resectability or marginal health status → repeat EUS-guided FNA in 2-4 months
• Avoid CT-guided biopsy due to needle tract seeding risk

For lymph nodes with negative FNAC 3:

• If clinical suspicion persists and lymphocytes were seen → perform open or core biopsy
• Ensure biopsy incision allows subsequent complete lymph node dissection without compromise

For gallbladder wall thickening with negative FNAC 6:

• Discuss at multidisciplinary tumor board
• Proceed to cholecystectomy if imaging strongly suggests malignancy despite negative cytology
• Do not delay surgery waiting for tissue diagnosis in resectable cases

For thyroid nodules with negative FNAC 9, 1:

• Repeat ultrasound-guided FNAC for nodules >1 cm with suspicious features
• Consider serum calcitonin for medullary carcinoma (higher sensitivity than FNAC)
• Cytology-histology discrepancy occurs in only 2% of cases with proper technique

Common Pitfalls to Avoid

• Never assume negative FNAC excludes cancer when clinical or radiological features suggest malignancy 6

• Do not delay definitive treatment in resectable cases waiting for positive cytology—this worsens outcomes if malignancy is present 6

• Avoid excessive repeat passes: Diagnostic yield plateaus after 7-8 passes, beyond which specimens become bloody and nondiagnostic 3

• Do not ignore inadequate samples: Confirm adequate cellularity before accepting a negative result 3

Enhancing FNAC Diagnostic Yield

• Onsite cytopathology presence: Increases diagnostic sensitivity from 32-53% to 77-97% and reduces inadequate samples from 13-20% to 0-1% 3

• Ancillary techniques: Cell block preparation, fluorescence in situ hybridization, and K-ras/p53 analysis improve yield in indeterminate cases 3, 8

• Image guidance: Ultrasound or EUS guidance significantly improves adequacy and accuracy 2, 1, 5

• Operator experience: Diagnostic sensitivity improves substantially with experience (from 30% to 80-90% in pancreatic masses) 3