Mycobacterium tuberculosis Lymphadenitis

Mycobacterium tuberculosis Lymphadenitis

Tariq Muzzafar, MBBS

Scanning electron micrograph of M. tuberculosis. The bacterium ranges from 2-4 µm long and 0.2-0.5 µm wide. (Courtesy J. Carr, CDC Public Health Image Library, #9997.)

Thin section transmission electron micrograph demonstrates M. tuberculosis bacilli. (CDC Public Health Image Library, #8433.)



  • Acid-fast bacilli (AFB)

  • Tuberculosis (TB)


  • Lymphadenitis caused by infection with Mycobacterium tuberculosis


Infectious Agents

  • Mycobacterium tuberculosis

Immunocompetent Patients

  • Reactivation of disease at site seeded during primary infection by hematogenous route

  • Infection of tonsils, adenoids, and Waldeyer ring

  • Abdominal involvement may occur via ingestion of milk or sputum infected with M. tuberculosis

Immunocompromised Patients

  • Human immunodeficiency virus (HIV) infection most common

  • Reactivation of latent infection

  • Part of generalized infection, miliary dissemination

    • Greater mycobacterial load than immunocompetent patients



  • Incidence

    • ˜ 40% of peripheral lymphadenopathy in developing world

    • Prevalence of TB lymphadenitis in children ≤ 14 years in rural India: 4.4/1,000

    • Lymphadenitis is most common form of extrapulmonary tuberculosis (5-10% of cases)

    • In developed countries, most cases occur in immigrants and travelers to endemic areas

      • Immigrant populations mostly originate from Southeast Asia and Africa

    • In USA, 20% of TB cases are extrapulmonary

      • ˜ 30% of these cases present with lymphadenitis

    • M. tuberculosis is common in HIV-positive individuals

      • Part of pulmonary or disseminated disease

      • Most extrapulmonary TB cases occur with CD4 counts ≤ 100 cells/µL

  • Age

    • Historically, common in children

    • At present, children affected predominantly in developing countries

    • Peak age in developed countries: 20-40 years

  • Gender

    • M:F ratio = 1:2

  • Ethnicity

    • Asian Pacific Islanders more susceptible


  • Characteristically, multiple lymph nodes (LNs) involved

  • 90% involve superficial LNs in head and neck region

    • Anterior and posterior cervical (most common)

    • Supraclavicular, submandibular, preauricular, submental also involved

  • Other LNs: Axillary, inguinal, mesenteric, mediastinal, and intramammary

  • Isolated intraabdominal LNs can be involved

    • Periportal, peripancreatic, and mesenteric

  • Generalized lymphadenopathy and hepatosplenomegaly in 5%

  • Painless progressive swelling in neck

  • Parabronchial and paratracheal involvement can lead to airway compromise

  • 5% of children develop lymphadenopathy within 6 months of infection

  • In adults, TB represents reactivation of previous infection

  • Up to 1/3 of patients report previous or family history of TB

  • LN on physical examination

    • Firm, rubbery, discrete, and nontender

    • May be swollen and tender due to secondary bacterial infection

  • Ulcer &/or sinus tract formation in 10%

Laboratory Tests

  • Tuberculin skin test (TST)

    • Positive in 90% of cases with TB lymphadenopathy

    • May be negative in HIV-positive patients with TB

  • Interferon-γ release assays

    • Measure in vitro T-cell interferon-γ release in response to 2 unique antigens

      • Sensitivity in active TB: 75-90%

      • Highly specific for M. tuberculosis

      • Negative in prior BCG vaccination and in sensitization to nontuberculous mycobacteria

      • Cannot distinguish between latent and active tuberculosis

    • 2 widely studied tests

      • Enzyme-linked immunospot (ELISpot) (T-SPOT.TB; Oxford Immunotec; Oxford, UK)

      • Enzyme-linked immunosorbent assay (ELISA) (QuantiFERON-TB Gold; Cellestis; Chadstone, VIC; Australia)

    • For diagnosis of latent infection

      • Sensitivity of ELISA similar to TST

      • ELISpot more sensitive

  • Direct staining

    • Carbolfuchsin stains (Ziehl-Neelsen stain; Kinyoun stain) highlight AFB

      • AFB are bright red against blue or green background, depending on counterstain

      • Must be scanned under oil-immersion

      • Time consuming due to limited size of field viewed at 1 time

    • Fluorochrome stain (auramine O, with or without rhodamine)

      • Scanning quicker since slides can be scanned at 25x objective

      • Confirmation may require 40x objective

      • Bacteria bright yellow (auramine) or orange-red (rhodamine) against dark background

  • Microbiological culture

    • Loewenstein-Jensen (L) medium

      • Less sensitive

      • Recommended only for chromogenic studies and biochemical tests

    • Middlebrook 7H10 and 7H11 agar medium used for isolation and susceptibility testing

    • Automated Radiometric Detection Systems: BACTEC 460 (BD Diagnostic Systems; Sparks, MD; USA)

    • Automated Nonradiometric Detection Systems

      • MGIT 960 (BD Diagnostic Systems)

      • MB/BacT System (BioMerieux; Durham, NC; USA)

      • BACTEC MYCO/F lytic blood culture bottle (BD Diagnostic Systems)

      • ESP Culture System II (TREK Diagnostic Systems, Inc.; Cleveland, OH; USA)

  • Gas-liquid and high-performance liquid chromatography

    • Useful in culture confirmation

  • Molecular diagnosis

    • Uses

      • Culture confirmation of isolates

      • Identification of isolates

      • Direct detection

      • DNA fingerprinting

      • Strain-typing

    • Quicker identification than by traditional methods

    • 2 amplification-based methods FDA approved in USA

      • Amplicor M. tuberculosis PCR assay (Roche Diagnostics; Indianapolis, IN; USA)

      • Amplified M. tuberculosis Direct Test (Gen-Probe Incorporated; San Diego, CA; USA)

    • Home-brew PCR, including real-time PCR assays, have been developed but need validation by individual laboratories

    • DNA sequencing can make rapid and accurate identification

    • Strain-typing has been used in detection of drug resistance


  • Surgical approaches

    • Needed in minority of patients

    • Indications: Failure of antimicrobial chemotherapy, pressure effect

    • Excisional biopsy preferred since incisional biopsy may result in sinus tract formation

  • Drugs

    • All patients treated with antituberculous agents

    • Treatment may be started prior to culture confirmation

      • Particularly when pathologic features suspicious or in high-risk subject

    • Adults: 6 months of isoniazid, rifampin, pyrazinamide, and ethambutol

    • Children: 2 months of isoniazid, rifampin, and pyrazinamide, plus 2 months of isoniazid and rifampin

    • Mediastinal lymph node involvement treated with same regimen as lung involvement


  • Antimicrobial therapy curative; relapse rates of up to 3.5%

  • In 30% of patients after beginning therapy

    • Paradoxical increase in LN size

    • New enlarged LNs may develop

    • Mechanism is immune response to mycobacterial killing

    • Must be differentiated from relapse

  • HIV-positive patients who begin HAART may develop immune reconstitution inflammatory syndrome with worsening lymphadenopathy

  • Residual palpable LNs after completion of therapy may be present in 5-30% of patients

  • Retreatment generally considered to be unnecessary if

    • Cultures are negative

    • Compliance with treatment is documented


General Features

  • Not definitively diagnostic of TB lymphadenitis

Radiographic Findings

  • 80% of children and 20% of adults show evidence of recent or active tuberculosis in lungs

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Mycobacterium tuberculosis Lymphadenitis
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