How to interpret ascitic fluid cytology?

How to Interpret Ascitic Fluid Cytology

Ascitic fluid cytology should be ordered selectively based on clinical suspicion of malignancy, not routinely, as it has variable sensitivity (0-96.7%) depending on tumor type and is primarily useful for diagnosing peritoneal carcinomatosis. 1

When to Order Cytology

• Order cytology only when there is high pretest probability of peritoneal carcinomatosis based on clinical context, imaging findings, or low SAAG (<1.1 g/dL) suggesting non-portal hypertensive causes 2
• Do not order cytology routinely for all ascitic fluid samples, as it is not indicated for diagnosing infectious peritonitis (use PMN count instead) 2
• Consider cytology in patients with known malignancy, unexplained ascites with low SAAG, or imaging suggesting peritoneal involvement 1

Interpreting Cytology Results

Positive Cytology

• Positive cytology is highly specific for peritoneal carcinomatosis with sensitivity of 82.8% on first sample, 93.3% with two samples, and 96.7% with three samples 2
• In patients with peritoneal carcinomatosis without massive liver metastases, cytology is uniformly positive (96.7% sensitivity) 3
• Positive cytology confirms malignant ascites and indicates peritoneal involvement requiring oncologic management 3

Negative Cytology

• Negative cytology does NOT exclude malignancy, particularly in certain clinical scenarios 3:
  • Massive liver metastases without peritoneal involvement (uniformly negative cytology) 3
  • Hepatocellular carcinoma superimposed on cirrhosis (negative cytology; use ascitic fluid alpha-fetoprotein instead, with 87% sensitivity) 4
  • Chylous ascites from lymphatic obstruction (negative cytology; look for milky appearance and triglycerides >200 mg/dL) 3

Optimizing Cytology Yield

• Submit 50 mL of fresh warm ascitic fluid hand-carried to the laboratory for immediate processing to maximize sensitivity 2
• Consider repeat paracentesis if initial cytology is negative but clinical suspicion remains high (sensitivity increases to 93.3% with second sample) 2
• Combine cytology with tumor markers to increase positive predictive value: CEA, EpCAM, CA 15-3, and CA 19-9 are useful 1
• Do NOT use CA 125 as it is elevated in ascites from any cause and has no discriminatory value 1

Critical Pitfall: Elevated PMN Count in Malignancy

• 18-30% of patients with malignancy-related ascites have PMN ≥250 cells/mm³, mimicking spontaneous bacterial peritonitis 5
• In peritoneal carcinomatosis or massive liver metastases, 30% have PMN ≥250 cells/mm³ and 19% have PMN ≥500 cells/mm³ 5
• Distinguish malignancy from SBP using these features 5:
  • Ascitic fluid RBC ≥10,000 cells/mm³ suggests hepatocellular carcinoma
  • Ratio of RBC to total leukocyte count ≥100 suggests hepatocellular carcinoma
  • PMN to total leukocyte ratio ≤75% suggests malignancy rather than SBP
  • SAAG <1.1 g/dL suggests peritoneal carcinomatosis

Alternative Diagnostic Approaches

• For suspected hepatocellular carcinoma with cirrhosis: Measure ascitic fluid alpha-fetoprotein (87% sensitivity, 95% specificity) rather than relying on cytology 4
• For suspected tuberculous peritonitis: Use adenosine deaminase (ADA) >32-40 U/L (100% sensitivity in non-cirrhotics; use >27 U/L cutoff in cirrhotics) rather than AFB smear (0-86% sensitivity) or culture (20-83% sensitivity) 2, 1
• Consider flow cytometry to detect aneuploidy in cases where traditional cytology is negative but malignancy is strongly suspected 6

Algorithmic Approach to Cytology Interpretation

1. First, calculate SAAG to determine if portal hypertension is present 7
2. If SAAG ≥1.1 g/dL (portal hypertension): Cytology rarely helpful unless hepatocellular carcinoma suspected (then order ascitic AFP) 4
3. If SAAG <1.1 g/dL (non-portal hypertensive): Order cytology if malignancy suspected 1
4. If PMN elevated: Rule out SBP first with culture; if culture negative and clinical features suggest malignancy (RBC count, PMN ratio), proceed with cytology 5
5. If initial cytology negative but suspicion high: Repeat paracentesis and consider tumor markers or flow cytometry 2, 6