Lymph nodes & spleen, nonlymphoma

Lymph nodes-infectious / parasitic disorders

Mycobacteria-atypical / other than TB or leprosy

Editorial Board Members: Patricia Tsang, M.D., M.B.A., Anamarija M. Perry, M.D.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Ahmed Alrajjal, M.D.
Ali Gabali, M.D., Ph.D.

Last author update: 13 May 2024
Last staff update: 13 May 2024

Copyright: 2003-2024,, Inc.

PubMed Search: Atypical mycobacteria

Ahmed Alrajjal, M.D.
Ali Gabali, M.D., Ph.D.
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Cite this page: Alrajjal A, Gabali A. Mycobacteria-atypical / other than TB or leprosy. website. Accessed May 19th, 2024.
Definition / general
  • Common cause of granulomatous lymphadenitis in immunocompetent children (1 - 5 years) and immunocompromised adults (Pediatr Int 2018;60:1062)
  • Clinical definite diagnosis of nontuberculous (non-TB) mycobacterial lymphadenitis requires a positive mycobacterial culture or positive PCR test of the purulent discharge or fine needle aspirate (FNA; based on the International Pediatric Otolaryngology Group [IPOG] 2023 Consensus guidelines) (Int J Pediatr Otorhinolaryngol 2023;166:111469)
Essential features
  • Unilateral anterior neck lymph nodes in children (1 - 5 years) and immunocompromised adults (e.g., HIV+)
  • Granulomatous inflammation with or without necrosis or partial or total nodal effacement by sheets of foamy histiocytes
  • Diagnosis is by positive culture for atypical mycobacteria or by excluding Mycobacterium tuberculosis in the presence of suggestive histology (Adv Exp Med Biol 2017;944:19)
  • Diagnosis can be established by positive PCR on excisional tissue biopsy or FNA, although performing an FNA on a suspected lymph node to confirm MTB lymphadenitis is controversial due to possible complications (i.e., iatrogenic needle track fistula formation) (J Clin Tuberc Other Mycobact Dis 2021;24:100244)
  • Atypical mycobacterial lymphadenitis
  • Non-TB mycobacterial lymphadenitis (NTML)
ICD coding
  • ICD-10: A31.8 - other mycobacterial infections
  • Children ages 1 - 5 are most susceptible
  • Immunocompromised adults, HIV+
  • Head and neck, usually unilateral anterior cervical chain lymph nodes
  • Mycobacterial, intracellular organisms, replicate within macrophages
  • Macrophages antagonize bacterial growth via TNF dependent mechanisms
  • Mycobacteria induce infected macrophage apoptosis
  • Newly recruited macrophages engulf cellular debris, contributing to granuloma expansion
  • Newly infected macrophages can exit the primary granuloma and establish secondary granuloma in distal tissue (Cold Spring Harb Perspect Med 2014;5:a018499)
  • Most common causes are M. avium intracellulare complex, M. marinum, M. fortuitum, M. scrofulaceum, M. kansasii (Clin Infect Dis 1995;20:954)
Clinical features
  • Chronic, slow growing, painless, lymphadenopathy
  • Head and neck, unilateral
  • Culture: sensitivity 41%, specificity 100% (gold standard) (Int J Pediatr Otorhinolaryngol 2018;112:48)
  • PCR: sensitivity 71.6%, specificity 100%
  • Immunoassay: sensitivity 87.5 - 100%, specificity 81 - 100%
  • Skin tests (PPD-S): sensitivity 70%, specificity 94%
  • Higher sensitivity of skin test by using multiple species coverage (e.g., PPD-A and PPD-K) (Eur J Pediatr 2021;180:1279)
  • PCR can identify Mycobacterium tuberculosis and 6 dominant nontuberculous mycobacterial species with a sensitivity of ~40% and 98% specificity (Microbiol Spectr 2023;11:e0160623)
  • Nucleic acid amplification (NAAT) only for Mycobacterium tuberculosis complex; M. tuberculosis and M. bovis: 90% sensitivity
    • Good for diagnosis but not follow up; could detect RNA 6 months after starting therapy
Radiology description
  • Ultrasound: markedly decreased echogenicity, intranodal liquefactive / cystic necrosis, nodal matting and adjacent soft tissue edema (Pediatr Radiol 2006;36:1063)
Case reports
  • 19 month old girl with the first reported case of human infection with Mycobacterium stomatepiae (JMM Case Rep 2018;5:e005146)
  • 7 year old healthy girl with a rare case of Mycobacterium simiae cervical lymphadenitis (Aust J Otolaryngol 2022;5:31)
  • 44 year old HIV+ man with diffuse large B cell lymphoma stage IV and on chemotherapy treatment presented with mycobacterial pseudotumor showing as an FDG avid mass on interim PET / CT (IDCases 2023;32:e01757)
  • 46 year old man with necrotizing lymphadenitis during therapy for acute myeloid leukemia (Infect Chemother 2017;49:78)
  • 67 year old man without immunodeficiency with right axillary lymphadenitis and lung right upper lobe nodule (Respir Med Case Rep 2019;28:100947)
  • Complete excision: highest cure rate and highest risk of facial nerve palsy
  • Macrolides and rifampin for 6 months is the most commonly used regimen (Int J Pediatr Otorhinolaryngol 2023;166:111469)
  • Decision on excision versus longterm antibiotics versus no treatment should be based on location and number of lymph nodes (J Infect 2015;71:9)
  • Spontaneous regression may occur after 4 - 6 months
Clinical images

Images hosted on other servers:

Submandibular lymphadenopathy

Gross description
  • Enlarged rubbery lymph node, tan glistening surface with multifocal irregular necrotic soft tissue
Gross images

Images hosted on other servers:

Central caseation
in node involved
by M. avium

Frozen section description
  • Identical to microscopic
Microscopic (histologic) description
  • Granulomatous inflammation with or without necrosis, the presence of microabscesses, ill defined granulomas, noncaseating granulomas and a small number of giant cells favor nontuberculous mycobacteria over tuberculosis (Histopathology 1999;35:534)
  • Can present as bland appearing foamy histiocytes in sinuses or diffuse sheets occupying part or entire lymph node (mycobacterial pseudotumor) (IDCases 2023;32:e01757)
Microscopic (histologic) images

Contributed by Ahmed Alrajjal, M.D.

Sheets of foamy histiocytes

Nonnecrotizing granuloma

Reactive histiocytes

Sheets of histiocytes

Lymph node, AFB stain

Cytology description
  • Suppurative granulomas
  • Necrotizing granulomas are typical in M. tuberculosis infection but are also seen in atypical mycobacterial infection
  • Granulomas without necrosis can be suggestive of sarcoidosis
  • Multiple passes for cultures or PCR testing are recommended
  • Reference: BMC Infect Dis 2020;20:224
Cytology images

Contributed by Ahmed Alrajjal, M.D.

Touch imprint, lymph node granuloma

Images hosted on other servers:

Mycobacterium avium complex (MAC), Ziehl-Neelsen stain

Positive stains
  • Ziehl-Neelsen
    • Acid fast bacteria are red
    • Growth only (hot stain [i.e., requires dry heat for fixation])
    • Identifies TB and all non-TB mycobacteria
  • Kinyoun stain
    • Acid fast bacteria are red
    • Growth and susceptibility (cold stain [i.e., no dry heat fixation required])
    • Limited non-TB identification
  • Fite stain
    • Acid fast bacteria are red
  • Auramine O
    • Bright yellow luminous rods against a dark background with fluorescent microscope
    • Identifies TB and all non-TB mycobacteria
    • Increased sensitivity
  • References: Ann Clin Lab Sci Spring 2014;44:131, J Clin Tuberc Other Mycobact Dis 2021;24:100244
Negative stains
Molecular / cytogenetics description
Molecular / cytogenetics images

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PCR for 7 different strains

Sample pathology report
  • Lymph node, left neck, excision:
    • Nonnecrotizing granulomatous lymphadenitis (see comment)
    • Comment: The lymph node architecture is partially affected by sheets of foamy histiocytes and multifocal granulomas. The granulomas are ill defined and composed of epithelioid histiocytes, lymphocytes and occasional plasma cells. No evidence of necrosis is noted. Acid fast bacteria (AFB) Fite special stain is positive for mycobacterial organisms. Paraffin embedded block was sent for PCR analysis for strain identification and subspeciation and the results will be reported in an addendum.
Differential diagnosis
  • Tuberculous mycobacterial infection:
    • Usually necrotizing granulomas
    • Few organisms seen by AFB stain
    • Nucleic acid amplification and culture are positive for Mycobacterium tuberculosis
  • Fungal infection:
    • Acute: suppurative inflammation; neutrophils, eosinophils and histiocytes
    • Chronic: granulomatous inflammation; can be necrotizing
    • Negative for AFB stain and positive for GMS or PAS
  • Foreign body reaction:
    • Polarizable material may be present in tissue
  • Sarcoidosis:
    • Diagnosis of exclusion by definition
    • Negative for cultures and stains
    • Naked type granuloma with very few lymphocytes
Board review style question #1
What is the most common histologic finding in immunocompromised patients with nontuberculous mycobacterial lymphadenitis caused by Mycobacterium avium complex (MAC) infection?

  1. Follicular hyperplasia
  2. Necrotizing granulomatous inflammation
  3. Nonnecrotizing granulomatous inflammation with sheets of foamy histiocytes
  4. Parafollicular hyperplasia
  5. Suppurative inflammation
Board review style answer #1
C. Nonnecrotizing granulomatous inflammation with sheets of foamy histiocytes is the correct answer because atypical mycobacterial infection typically shows nonnecrotizing granuloma. Sheets of foamy histocytes morphology is also not uncommon, especially in MAC infection. Answer A is incorrect because this morphology is typical of other bacterial and some viral infections. Answer B is incorrect because necrotizing granuloma is seen in typical mycobacterial tuberculosis. Answer D is incorrect because parafollicular hyperplasia is associated with viral lymphadenitis. Answer E is incorrect because suppurative lymphadenitis is associated with bacterial infection.

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Reference: Mycobacteria-atypical / other than TB or leprosy
Board review style question #2

An HIV positive 34 year old man has an enlarged painless lymph node. Nucleic acid amplification and culture are negative for M. tuberculosis organisms. What is the most common mycobacterial infection in immunocompromised patients such as this one?

  1. M. aortuitum
  2. M. avium intracellulare
  3. M. gordonae
  4. M. scrufulaceum
Board review style answer #2
B. M. avium intracellulare is the most common nontuberculous mycobacterial infection in immunocompromised patients. Answers A, C and D are incorrect because they are isolated less frequently compared to M. avium intracellulare. Those organisms can be seen in immunocompetent children.

Comment Here

Reference: Mycobacteria-atypical / other than TB or leprosy
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