Abstract / Summary
Extrapulmonary tuberculosis (EPTB) accounts for approximately 16% of notified tuberculosis (TB) cases worldwide and disproportionately affects children and immunocompromised populations. Paucibacillary disease, anatomically diverse sites, and nonspecific presentations make EPTB one of the most persistent diagnostic challenges in TB control. This review integrates microbiological, molecular, sequencing-based, and histopathological approaches to EPTB diagnosis within the context of site-specific immunopathology, including granuloma biology and the microenvironment of caseous necrosis. Comparative evidence is synthesized across osteoarticular, lymph node, pleural, central nervous system, and disseminated EPTB, focusing on Xpert MTB/RIF and Ultra, targeted and metagenomic next-generation sequencing (mNGS), and emerging host-response biomarkers and AI-assisted histopathology. Pragmatic, tiered diagnostic algorithms are proposed for resource-limited settings, where most EPTB occurs, and unresolved gaps in current international guidance are identified. Aligning diagnostic modality choice with anatomical site, specimen quality, pathological subtype, and laboratory capacity can shorten the time to EPTB diagnosis and inform host-directed diagnostic strategies.