Diagnosis of tuberculous lymphadenitis by molecular and immunological tools

Tuberculous lymphadenitis (TBL) represents the prevailing presentation of extrapulmonary tuberculosis (EPTB) that comprises ∼35% of EPTB cases, respectively, and mainly occurs at cervical lymph nodes. Diagnostic challenge in TBL is primarily due to paucibacillary nature of specimens, and most common laboratory tests produced inconclusive findings. We evaluated the literature on current diagnostic methods for TBL. Smear microscopy, culture, tuberculin skin testing, interferon-γ release assay, biochemical assessments, imaging, histopathological, and cytological examination, etc. are various conventional methods used to diagnose TBL but these are insufficient. Further, nucleic acid amplification tests (NAATs) such as loop-mediated isothermal amplification (LAMP), PCR/multiplex-PCR, nested-PCR, real-time PCR, and GeneXpert®MTB/RIF utilized for TBL diagnosis but they have their own merits and demerits. Presently, several tools have been employed for detection of circulating Mtb cell-free DNA (cfDNA) through NAATs, aptamer-linked immobilized sorbent assay, and immuno-PCR (I-PCR), etc. Currently, there is no single accessible test available for effective diagnosis of TBL. In this review, we summarized all detailed conventional methodologies along with additional tools such as ALISA, I-PCR, and cfDNA for detection of Mtb biomarkers that have been utilized for diagnosis of pulmonary TB (PTB) and various forms of EPTB that may also be investigated for diagnosis of TBL. Early diagnosis and treatment would help in reducing the severe complications associated with TBL such as fistula, ulceration, or abscess formation in lymph nodes. • Mtb is the primary causative agent of TBL. • TBL represents the most prevalent form of EPTB. • TBL diagnosis is challenging primarily due to atypical clinical manifestations. • NAATs revealed good diagnostic yield but they showed variable sensitivities and specificity. • Various applications suggest the potential for exploration in diagnosing TBL.