Cytology Criteria for Diagnosing Peritonitis

Primary Diagnostic Criterion for Bacterial Peritonitis

• The American Association for the Study of Liver Diseases recommends that the diagnosis of spontaneous bacterial peritonitis (SBP) is established when the ascitic fluid PMN count is ≥250 cells/mm³, regardless of culture results 1, 2, 3
• A PMN count ≥250 cells/mm³ is diagnostic of SBP, even with negative cultures, with a strength of evidence based on multiple citations 1, 2, 3

Key Diagnostic Parameters

• The diagnosis of SBP is supported by a culture-negative neutrocytic ascites, which occurs in approximately 50% of SBP cases when older culture methods are used, but up to 80% are positive when fluid is inoculated into blood culture bottles at bedside, as recommended by the American Association for the Study of Liver Diseases 1, 4
• Bacterascites is defined as a positive culture with PMN <250 cells/mm³, and treatment is only recommended if the patient is symptomatic, according to the European Association for the Study of the Liver 3

When Cytology IS Indicated

• Cytologic examination should only be ordered when there is a high pretest probability of peritoneal carcinomatosis, not for diagnosing infectious peritonitis, as stated by the American Association for the Study of Liver Diseases 1, 4, 5

Cytology for Malignant Peritonitis

• The sensitivity of cytology for malignant peritonitis is 82.8% on the first sample, 93.3% with two samples, and 96.7% with three samples, according to the American Association for the Study of Liver Diseases 1, 4
• The optimal specimen for cytology is 50 mL of fresh warm ascitic fluid hand-carried to the laboratory for immediate processing, as recommended by the European Association for the Study of the Liver 1, 4

Distinguishing Secondary from Spontaneous Bacterial Peritonitis

• Secondary peritonitis can be differentiated from SBP by the presence of at least two of the following criteria: total protein >1 g/dL, lactate dehydrogenase (LDH) > upper limit of normal for serum, and glucose <50 mg/dL, as stated by the American Association for the Study of Liver Diseases 2, 6, 7
• The presence of multiple organisms on Gram stain/culture, including fungi and enterococcus, suggests secondary peritonitis, according to the Infectious Diseases Society of America 2, 6

Specialized Cytologic Findings for Other Conditions

• Tuberculous peritonitis is characterized by lymphocytosis in ascitic fluid, with a sensitivity of 0-86% for acid-fast bacilli (AFB) smear, and 20-83% for culture, as stated by the American Thoracic Society 7, 8
• Adenosine deaminase (ADA) levels >32-40 U/L have 100% sensitivity in non-cirrhotic patients, and >27 U/L in cirrhotic patients, for the diagnosis of tuberculous peritonitis, according to the European Association for the Study of the Liver 7, 8
• Pancreatic ascites is characterized by amylase levels >1,000 mg/dL, and chylous ascites is characterized by triglycerides >200 mg/dL, often >1,000 mg/dL, with a white milky appearance, as stated by the American Association for the Study of Liver Diseases 7

Ascitic Fluid Cytology Interpretation

Introduction to 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 9

Diagnostic Approach

• Consider cytology in patients with known malignancy, unexplained ascites with low SAAG, or imaging suggesting peritoneal involvement 9, 10
• Combine cytology with tumor markers to increase positive predictive value: CEA, EpCAM, CA 15-3, and CA 19-9 are useful 9, 10
• Do NOT use CA 125 as it is elevated in ascites from any cause and has no discriminatory value 9, 10

Distinguishing Malignancy from Infection

• Distinguish malignancy from SBP using features such as PMN to total leukocyte ratio ≤75% suggests malignancy rather than SBP 9

Alternative Diagnostic Approaches

• 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) 11

Diagnosis of Peritoneal Tuberculosis Using Ascitic Fluid Analysis

Initial Fluid Evaluation

• Ascitic fluid total‑cell count and differential should be performed; peritoneal TB typically shows lymphocytosis > 50 % of cells. 12
• Measure ascitic albumin to calculate the serum‑ascites albumin gradient (SAAG). 12
• Total protein concentration > 2.5 g/dL is common in TB peritonitis. 12

Adenosine Deaminase (ADA) Testing

• ADA measurement is the most accurate single test for TB peritonitis. In patients without cirrhosis, a cut‑off of ≥ 32–40 U/L yields 100 % sensitivity and 96.6–100 % specificity. [12][13]
• In patients with cirrhosis, a lower cut‑off of ≥ 27 U/L provides 100 % sensitivity and 93.3 % specificity. [12][13]
• ADA ≥ 32–40 U/L (or ≥ 27 U/L in cirrhosis) strongly supports a TB diagnosis and can be used to initiate empirical therapy after other causes are excluded. [12][13]

Microbiological Tests (Low Sensitivity)

• Acid‑fast (BTA) staining has very low sensitivity (0–86 %) and a negative result does not rule out TB; therefore it is not recommended as a primary diagnostic test. 12
• Mycobacterial culture sensitivity ranges from 20–83 %, requires 4–8 weeks, but remains useful for definitive confirmation and drug‑susceptibility testing. 12
• PCR for Mycobacterium is the fastest and most accurate molecular method and should be performed when available. 12

Diagnostic Algorithm Highlights

• Perform diagnostic paracentesis in every patient with new‑onset or worsening ascites. [12][13]
• If lymphocytes > 50 % and polymorphonuclear cells < 250 cells/mm³, consider TB peritonitis or malignancy. 12
• Conduct ADA testing on all ascitic samples showing lymphocytosis. [12][13]
• When ADA results are equivocal or unavailable, proceed to laparoscopy with peritoneal biopsy (gold standard) – sensitivity ≈ 95.5 %. Histology reveals caseating granulomas in 84–97 % of TB cases. 12

Special Considerations in Cirrhosis

• Cirrhotic patients may have false‑negative ADA because of low ascitic protein; applying the lower cut‑off (≥ 27 U/L) mitigates this risk. [12][13]
• Do not exclude TB solely on a low ADA value in cirrhosis. 12

When to Reserve Acid‑Fast Stain or Culture

• Routine BTA staining or culture is not indicated unless the patient has high TB risk (e.g., immigration from endemic regions, HIV infection, known TB exposure). 14
• These tests are costly and have limited sensitivity. [12][14]

Additional Tests to Exclude Other Causes

• Secondary bacterial peritonitis is suggested by ascitic glucose < 50 mg/dL and ascitic LDH > serum LDH. 12
• For suspected malignancy, cytology has a sensitivity of 82.8 % on the first sample and 96.7 % after three samples; send ≥ 50 mL of fresh warm fluid promptly to the laboratory. 14
• CA‑125 measurement is not useful because it rises in all types of ascites. 13

Practical Recommendation for Endemic Areas

• In TB‑endemic settings, the combination of ascitic lymphocytosis and ADA ≥ 32–40 U/L (or ≥ 27 U/L in cirrhosis) is sufficient to start empirical anti‑TB therapy after excluding malignancy, uremia, and bacterial peritonitis. Peritoneal biopsy is reserved for cases where ADA is unavailable or yields ambiguous results. 12