Lung

Infectious

Bacterial

Tuberculosis



Last author update: 4 October 2022
Last staff update: 4 October 2022

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PubMed search: Pulmonary tuberculosis

Hui-Hua Li, M.D., Ph.D.
Jefree J. Schulte, M.D.
Page views in 2021: 17,359
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Cite this page: Li H, Schulte JJ. Tuberculosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungnontumorTB.html. Accessed December 9th, 2022.
Definition / general
  • Infectious disease caused by Mycobacterium tuberculosis
  • Disease can be manifested as primary, secondary and miliary tuberculosis
Essential features
  • Infectious disease caused by M. tuberculosis
  • Hallmark is necrotizing granulomatous inflammation, composed of central necrotic zone surrounded by epithelioid histiocytes and Langhans type giant cells
  • Presence of M. tuberculosis should be confirmed by microbiologic cultures or nucleic acid amplification testing (NAAT)
Terminology
  • TB
  • Mycobacterium tuberculosis (MTB)
ICD coding
  • ICD-10: A15.0 - tuberculosis of lung
  • ICD-11: 1B10 - tuberculosis of the respiratory system
Epidemiology
Sites
  • Most commonly affects the respiratory system but other systems can be involved in disseminated disease (gastrointestinal [GI] system, lymphoreticular system, skin, central nervous system, musculoskeletal system, reproductive system and liver) (J Family Community Med 2019;26:83)
Pathophysiology
  • Infection begins when M. tuberculosis enters lungs via inhalation, reaches the alveolar space and encounters resident alveolar macrophages
  • If alveolar macrophages do not eliminate the bacteria, M. tuberculosis invades the lung interstitial tissue, either by direct infection of alveolar epithelium or as a result of the infected alveolar macrophage migrating to the interstitium
  • Dendritic or other inflammatory cells transport M. tuberculosis to pulmonary lymph nodes for T cell priming; this yields recruitment of immune cells to form a granuloma
  • Granuloma may contain infection (latent TB)
  • Bacteria replicate within the growing granuloma; if the granuloma fails to contain the infection, bacteria may disseminate to other organs and can enter the bloodstream, leading to reentry and release into the respiratory tract; the infected host is now infectious and symptomatic (active TB disease)
  • Primary TB is defined as an infection caused by MTB in a previously uninfected host; secondary TB usually occurs due to reactivation of latent TB after initial primary infection; miliary TB is the disseminated form with hematogenous spread of MTB to the lungs and other organs
  • Selected reviews on the pathophysiology of M. tuberculosis infection: Nat Rev Dis Primers 2016;2:16076, FEMS Microbiol Rev 2019;43:341
Etiology
Diagrams / tables

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Mycobacterium tuberculosis infection

Clinical features
  • Chronic and persistent cough (often productive), weight loss, fever, night sweats and hemoptysis (J Biomed Sci 2020 Jun;27:74)
  • History of latent TB or exposure to infected individual may be identified
Diagnosis
  • Based on a combination of exposure history, clinical symptoms, radiologic and laboratory findings (Nat Rev Dis Primers 2016;2:16076)
  • Diagnosis can be made with lung or lymph node biopsy, surgical resection specimen, cytology specimen and autopsy specimen, although lung biopsy does not have a routine role in diagnosis
Laboratory
  • Active TB disease
    • Imaging techniques (chest Xrays and PET CT)
    • Sputum smears (AFB or Ziehl-Neelsen staining)
    • Cultures
    • Molecular tests (nuclear amplification and gene based tests)
  • Latent TB infection
    • Tuberculin skin testing (Mantoux test with purified protein derivative [PPD])
    • Interferon release assays (IGRA)
  • Selected references with discussions on diagnostic techniques: Nat Rev Dis Primers 2016;2:16076, J Biomed Sci 2020 Jun;27:74, N Engl J Med 2021;385:2271
Radiology description
  • Often identified on chest Xray or CT
  • Commonly presents as cavitary lesion in upper lobe in infected immunocompetent hosts
  • Immunocompromised patients can show lower lobe disease with adenopathy and pleural effusion
  • Review of radiographic findings: Insights Imaging 2022;13:3
Radiology images

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Chest Xray and high resolution CT of active tuberculosis

Prognostic factors
Case reports
Treatment
Gross description
  • Cavitary disease
  • Tuberculomas: localized conglomerates of necrotizing granulomatous infection
  • Classically described findings:
    • Ghon focus: subpleural, often upper lobe nodule
    • Ghon complex: Ghon focus plus lymphatic or hilar lymph node involvement
    • Caseous necrosis (cheese-like, tan to white grumous material)
  • Can cause empyema (chronic or active infection of the pleural space), resulting in pus accumulation in pleural cavity
  • Bronchiectasis (irreversible dilatation of the bronchi and bronchioles)
  • References: Semin Diagn Pathol 2017;34:518, StatPearls: Ghon Complex [Accessed 23 May 2022]
Gross images

Contributed by Sajna V.M. Kutty, M.D.
65 year old male chronic smoker with 3 cm lung mass

65 year old male chronic smoker with 3 cm lung mass



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Lung with cavity

Lung with cavity and caseous necrosis

Histomorphological patterns

Histomorphologic
patterns of
postprimary
tuberculosis

Microscopic (histologic) description
  • Hallmark is necrotizing granulomatous inflammation, composed of central necrotic zone surrounded by epithelioid histiocytes with varied number of multinucleated giant cells and lymphocytes
  • Multinucleated giant cells may contain Langhans type giant cells (nuclei arranged in a horseshoe shaped pattern at the periphery of the cell) but Langhans type giant cells are not specific for TB infection
  • Organisms are usually present within the central zone of necrosis, seen on special stains (in some cases)
  • Nonnecrotizing granulomas can be present as well
  • References: Semin Diagn Pathol 2017;34:518
Microscopic (histologic) images

Contributed by Hui-Hua Li, M.D., Ph.D., Jefree J. Schulte, M.D. and Aliya N. Husain, M.D.
Necrotizing granuloma core biopsy

Necrotizing granuloma core biopsy

Giant cells

Giant cells

Large necrotizing granuloma

Large necrotizing granuloma

Necrotizing granuloma

Necrotizing granuloma

Positive AFB stain

Positive AFB stain



Contributed by @AnaPath10 on Twitter
Tuberculosis Tuberculosis Tuberculosis

Tuberculosis

Virtual slides

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Necrotizing granulomatous inflammation

Miliary TB, H&E

Miliary TB, AFB

Cytology description
  • Epithelioid granulomas, Langhans type giant cells, necrosis and acute or chronic inflammation
  • Sources of sampling: aspirates from transbronchial lung biopsy, mediastinal lymph nodes and other smears
Cytology images

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Lymph node tuberculosis

Lymph node tuberculosis

Positive stains
Videos

Case of pulmonary tuberculosis with granulomas

Histopathology of pulmonary tuberculosis

Sample pathology report
  • Left lung, transbronchial biopsy:
    • Necrotizing granulomatous inflammation with AFB positive bacilli (see comment)
    • Comment: AFB histochemical stain highlights occasional AFB positive bacilli within necrotizing granulomas. GMS histochemical stain is negative for fungal elements. Correlation with microbial cultures is needed.
  • Station 7 lymph node, fine needle aspiration:
    • Necrotizing granulomatous inflammation with AFB positive bacilli (see comment)
    • Comment: AFB histochemical stain highlights occasional AFB positive bacilli within necrotizing granulomas. GMS histochemical stain is negative for fungal elements. Correlation with microbial cultures is needed.
Differential diagnosis
  • Nontuberculous mycobacterial disease / atypical mycobacterial infection:
    • Including M. avium complex (MAC), M. kansasii, M. xenopi and M. abscessus
    • Cannot be distinguished from tuberculosis based on gross or microscopic appearance
    • Positive identification of the organism by culture or polymerase chain reaction (PCR) techniques is necessary for precise speciation
  • Granulomatous fungal infections:
    • Including histoplasmosis, blastomycosis, cryptococcosis and coccidioidomycosis
    • Often presents as asymptomatic solitary pulmonary nodules
    • Combination of necrotizing and nonnecrotizing granulomas with overlapping histologic features making it difficult to predict a specific pathogen based on the histologic findings alone
  • Sarcoidosis:
    • Noncaseating granuloma composed of epithelioid cells, giant cells and lymphocytes
    • Well formed granulomas tend to be distributed along lymphatic pathways and may coalesce to form macroscopic nodules (nodular sarcoidosis)
  • Granulomatosis with polyangiitis (Wegener):
    • Combination of necrotizing granulomatous inflammation and necrotizing vasculitis targeting small to medium size vessels
Board review style question #1

A 72 year old woman who is HIV positive and has a significant medical history of diabetes mellitus presents to the ED with persistent cough, hemoptysis and chest pain. Imaging findings are concerning for infectious disease. A nodular lesion in the lung is biopsied (see image above). Special stains reveal AFB positive bacilli. Which of the following statements is true?

  1. Correlation with microbial cultures or PCR is required for definitive diagnosis
  2. Granulomatous changes would be expected to be observed near the lymphatics of the lung (lymphatic or lymphangitic distribution)
  3. These findings are consistent with sarcoidosis
  4. These findings are diagnostic of Mycobacterium tuberculosis
Board review style answer #1
A. Correlation with microbial cultures or PCR is required for definitive diagnosis

Comment Here

Reference: Tuberculosis
Board review style question #2
A 63 year old man is diagnosed with Mycobacterium tuberculosis infection following bronchoscopy, with smears showing acid fast bacilli and culture growing M. tuberculosis. Which of the following statements is true?

  1. If alveolar macrophages fail to eradicate M. tuberculosis, the resultant inflammatory response is typically characterized by eosinophil infiltration
  2. M. tuberculosis cannot grow outside of the lung parenchyma
  3. M. tuberculosis first infects type 1 pneumocytes and replicates within the cytoplasm of the pneumocyte
  4. Resident macrophages within the lungs are the primary cell that is infected, upon initial infection by M. tuberculosis
Board review style answer #2
D. Resident macrophages within the lungs are the primary cell that is infected, upon initial infection by M. tuberculosis

Comment Here

Reference: Tuberculosis
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