Diagnostic Approach for Extrapulmonary Tuberculosis (EPTB)
Obtain appropriate specimens from the suspected site of involvement for comprehensive microbiological testing including microscopy, WHO-recommended rapid molecular tests (such as Xpert MTB/RIF), culture with species identification, drug susceptibility testing, and histopathological examination in quality-assured laboratories. 1
Core Diagnostic Algorithm
Step 1: Specimen Procurement
- Obtain tissue or fluid samples from the suspected extrapulmonary site using biopsy, fine needle aspiration, or fluid aspiration as clinically appropriate 1
- For surgical specimens, save biological material in normal saline for microbiological/molecular testing AND in formalin for histopathology 1
- The pauci-bacillary nature of EPTB makes adequate specimen collection critical—every effort must be made to obtain bacteriological confirmation 1
Step 2: Initial Laboratory Testing
Microbiological Testing (Priority):
- Rapid molecular testing (NAAT/Xpert MTB/RIF) should be performed on all specimens—this is now standard of care, not optional 1
- Mycobacterial culture with species identification and drug susceptibility testing on every specimen 1
- Smear microscopy (though sensitivity is limited in EPTB) 1
Histopathological Examination:
- Perform histological examination on tissue specimens—sensitivity ranges 60-100% depending on site, though specificity is limited as granulomas occur in other conditions 1
- Both positive and negative histology results require clinical context interpretation due to frequent false results 1
Step 3: Adjunctive Testing for Fluid Specimens
Cell Counts and Chemistries:
- Perform on pleural, cerebrospinal, ascitic, and joint fluids 1
- While sensitivity/specificity data are limited, these provide rapid information to guide further testing 1
Adenosine Deaminase (ADA) Levels:
- Measure ADA in pleural, cerebrospinal, peritoneal, and pericardial fluid 1
- For TB meningitis: sensitivity 79-93% and specificity 80-96% depending on threshold used (4 U/L vs 8 U/L) 1
- A positive ADA result supports the diagnosis, though thresholds must be interpreted carefully 1
Step 4: Imaging Studies
Site-Appropriate Imaging:
- Use radiology, ultrasound, CT, MRI, or PET-CT to complement microbiological testing and guide specimen procurement 1
- Imaging helps localize lesions, map disease extent, and identify optimal biopsy sites 1
- Critical caveat: Imaging findings are not specific and can mimic many diseases—never diagnose EPTB on imaging alone 1
Interpretation Framework
When Microbiological Tests Are Positive:
- NAAT positive: Use as evidence of EPTB to guide treatment decisions—false positives are unlikely 1
- Culture positive: Definitive diagnosis; proceed with drug susceptibility testing 1
When Microbiological Tests Are Negative:
- NAAT negative: Cannot exclude TB—false negatives are exceedingly common in EPTB 1
- Consider clinical context, histopathology, ADA levels, and imaging findings together 1
- In seriously ill patients, immunocompromised patients, or those with HIV, expedite evaluation and consider empiric treatment if clinical evidence strongly suggests TB 1
Critical Pitfalls to Avoid
Avoid fluoroquinolones during diagnostic workup—they are active against M. tuberculosis and may cause transient improvement, confounding diagnosis 1
Do not rely on single test modality: The pauci-bacillary nature of EPTB means no single test has adequate sensitivity 2, 3, 4
Do not delay treatment in high-risk patients: For seriously ill, HIV-positive, or immunocompromised patients with strong clinical suspicion, initiate treatment while awaiting confirmatory results 1
Ensure quality-assured laboratory testing: All microbiological testing must occur in laboratories meeting quality standards 1
Special Populations
Children with suspected EPTB:
- Obtain specimens from suspected sites for microscopy, rapid molecular tests, species identification, DST with culture, and histopathology 1
- Bacteriological confirmation is essential but more challenging in pediatric cases 1
HIV-coinfected patients: