Diagnostic Approach for Extrapulmonary Tuberculosis (EPTB)

Core Diagnostic Algorithm

The European Respiratory Society recommends obtaining tissue or fluid samples from the suspected extrapulmonary site using biopsy, fine needle aspiration, or fluid aspiration as clinically appropriate 1, 4
For surgical specimens, the European Respiratory Society suggests saving biological material in normal saline for microbiological/molecular testing and in formalin for histopathology 1, 4
The World Health Organization recommends rapid molecular testing (NAAT/Xpert MTB/RIF) on all specimens, which is now standard of care, not optional 1, 2, 5, 3
The European Respiratory Society recommends mycobacterial culture with species identification and drug susceptibility testing on every specimen 1, 2, 3
Smear microscopy is recommended, though sensitivity is limited in EPTB 2, 3

The Clinical Infectious Diseases society recommends performing histological examination on tissue specimens, with sensitivity ranging from 60-100% depending on the site 6
Cell counts and chemistries should be performed on pleural, cerebrospinal, ascitic, and joint fluids, providing rapid information to guide further testing 7, 8
Measuring Adenosine Deaminase (ADA) levels in pleural, cerebrospinal, peritoneal, and pericardial fluid is recommended, with sensitivity and specificity depending on the threshold used 7

The European Respiratory Society recommends using radiology, ultrasound, CT, MRI, or PET-CT to complement microbiological testing and guide specimen procurement 1, 4, 5
Imaging helps localize lesions, map disease extent, and identify optimal biopsy sites, but findings are not specific and can mimic many diseases 1, 4

A positive NAAT result is considered evidence of EPTB to guide treatment decisions, with false positives being unlikely 6
A culture positive result is a definitive diagnosis, and drug susceptibility testing should be performed 1, 2
When microbiological tests are negative, clinical context, histopathology, ADA levels, and imaging findings should be considered together 7, 8, 6

For children with suspected EPTB, the European Respiratory Society recommends obtaining specimens from suspected sites for microscopy, rapid molecular tests, species identification, DST with culture, and histopathology 1, 4
For HIV-coinfected patients, expedited diagnostic evaluation and a low threshold for empiric treatment are recommended 1, 4