General pathology · Inflammation
Granulomatous inflammation: caseating vs non-caseating, the causes to know !
- Lesion
A granuloma is a tight ball of activated macrophages around something hard to kill; how it looks under the microscope points to the cause.
Updated 2026-11-01
What it is
Granulomatous inflammation is a special form of chronic inflammation in which activated macrophages turn into epithelioid cells and gather into nodules, often with multinucleated giant cells and a rim of lymphocytes. The pathologist's task is to find the cause: central caseous necrosis suggests tuberculosis or a fungus, polarised light may reveal foreign material, and special stains look for acid-fast bacilli or fungi. The immune mechanism is covered in Inmunología; this page covers morphology and causes.
Structure
- Epithelioid cells: activated macrophages with pale, elongated (slipper-shaped) nuclei and abundant pink cytoplasm, packed like an epithelium.
- Langhans giant cells have nuclei in a horseshoe at the periphery; foreign-body giant cells have scattered nuclei, often around visible material.
- Rim of lymphocytes (mostly CD4 T cells), sometimes plasma cells; older granulomas acquire a fibrous capsule and may calcify.
- Caseous necrosis: central, granular pink debris with no cell outlines; grossly white-yellow and cheese-like.
- Sarcoidosis: tight non-caseating granulomas; giant cells may hold asteroid or Schaumann bodies (not specific).
Causes of granulomas
| Cause | Type of granuloma | How it is confirmed |
|---|---|---|
| Tuberculosis | Caseating; Langhans giant cells | Ziehl-Neelsen stain (acid-fast bacilli), culture, molecular tests |
| Leprosy (tuberculoid form) | Non-caseating, along dermal nerves; few bacilli | Skin biopsy, Fite stain; the lepromatous form shows foamy macrophages full of bacilli instead |
| Histoplasmosis | Caseating or non-caseating; small yeasts inside macrophages | Silver (GMS) or PAS stain, antigen tests, culture |
| Paracoccidioidomycosis | Mixed suppurative and granulomatous; yeasts with multiple buds (‘ship's wheel’) | Silver stain, KOH preparation, culture |
| Tertiary syphilis | Gumma: necrotic centre with a rim rich in plasma cells | Serology; spirochetes are scarce |
| Cat-scratch disease (Bartonella henselae) | Stellate necrotising granulomas with central neutrophils in lymph nodes | Serology, PCR, Warthin-Starry stain |
| Sarcoidosis | Non-caseating, tight; many organs, hilar lymph nodes | Diagnosis of exclusion: negative stains and cultures |
| Crohn disease | Non-caseating, in the bowel wall | Biopsy with transmural inflammation and the clinical picture |
| Granulomatosis with polyangiitis | Necrotising granulomas with vasculitis | c-ANCA (anti-PR3), biopsy |
| Foreign body (sutures, talc, wood) | Foreign-body giant cells around the material | Polarised light may show birefringent material |
Markers
- Ziehl-Neelsen (acid-fast bacilli)
- Fite (M. leprae)
- GMS silver (fungi)
- PAS (fungi)
- Warthin-Starry (Bartonella, spirochetes)
- Polarised light (foreign material)
Clinical notes
- In Colombia and Latin America tuberculosis, leprosy, histoplasmosis and paracoccidioidomycosis are endemic, so a granuloma in a biopsy calls for stains and cultures before sarcoidosis is diagnosed.
- Leprosy is a spectrum: strong Th1 immunity gives few, well-formed granulomas (tuberculoid); weak immunity gives sheets of foamy macrophages full of bacilli (lepromatous).
- Caseation is not proof of tuberculosis: fungi can caseate too, and tuberculosis in people with advanced HIV may form poor granulomas.
Test yourself
Think of the answer, then tap the question to see it.
How do Langhans giant cells differ from foreign-body giant cells?
Langhans cells have nuclei in a horseshoe at the periphery (typical of tuberculosis); foreign-body giant cells have scattered nuclei, often around visible material.
Which stain looks for Mycobacterium tuberculosis in a granuloma?
The Ziehl-Neelsen (acid-fast) stain; culture and molecular tests add sensitivity.
A child scratched by a kitten has a lymph node with stellate necrotising granulomas and central neutrophils. What is the cause?
Cat-scratch disease, caused by Bartonella henselae.
Why is sarcoidosis a diagnosis of exclusion?
Its non-caseating granulomas are not specific; infections such as tuberculosis, fungi and leprosy must be ruled out with stains and cultures.
Related
- Chronic inflammation: causes, cells and features
- Patterns of necrosis: coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous
- Special stains in diagnosis: Congo red, Prussian blue, PAS, Ziehl–Neelsen, Gram
- Inflammation: the cardinal signs and its five steps
Related conditions
- Tuberculosis
- Pulmonary tuberculosis
- Sarcoidosis
- Crohn disease
- Leprosy (Hansen disease)
- Histoplasmosis
- Syphilis
- Paracoccidioidomycosis
- Bartonella infections (cat-scratch disease, Carrion disease)
- Schistosomiasis
- Granulomatosis with polyangiitis
- Giant cell arteritis
- Chronic granulomatous disease
- Hypersensitivity pneumonitis
- Spinal tuberculosis (Pott disease)
Elsewhere in DurgiPedia
- Granulomatous inflammation
- Type IV hypersensitivity (delayed, T cells)
- Monocyte and macrophage
- Interferon-γ
- TNF-α
- Microscopy and stains: H&E, PAS, trichrome, silver, immunohistochemistry
Microorganisms
- Mycobacterium tuberculosis
- Mycobacterium leprae
- Histoplasma capsulatum
- Paracoccidioides brasiliensis
- Treponema pallidum
- Bartonella
- Schistosoma mansoni / S. haematobium / S. japonicum
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Tuberculosis (World Health Organization (WHO), 2025); Leprosy (World Health Organization (WHO), 2026); Sarcoidosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); 17.5 Inflammation and Fever (OpenStax (Microbiology), 2016).
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Representative model, for educational purposes only.