Granulomatous inflammation

Background

• A histological finding on biopsy with a wide differential

Etiologies By Histologic Pattern

Pattern	Etiologies
Foreign body	talc, starch, sutures, injectable fillers including hyaluronic acid
Necrotizing granuloma	Infectious: TB, NTM, coccidiomycosis, cryptococcosis, histoplasmosis, blastomycosis, aspergillosis, mucor, brucellosis, nocardiosis, yersiniosis, cat-scratch disease, pneumocystosis, echinococcosis Autoimmune: rheumatoid nodules, granuloma annulare, necrobiosis lipoidica, granulomatosis with polyangiitis
Non-necrotizing granuloma	Infectious: hepatosplenic candidiasis, coccidiomycosis, Q fever, CMV, TB, NTM, schistosomiasis, toxoplasmosis, rickettsioses, salmonellosis, HAV, HCV Autoimmune: sarcoidosis, eGPA, GCA, SLE, Crohn disease, PBC, orofacial granulomatosis, rosacea, granuloma annulare Toxic: actinic granuloma, berylliosis, zirconium, hot tub lung Dugs: BCG, NSAIDs, methotrexate Other: lymphoid interstitial pneumonia, hypersensitivity pneumonitis, chronic lymphocytic leukemia
Suppurative granuloma	Infectious: actinomycosis, Dirofilaria, Acanthamoeba, Balamuthia mandrillaris, cat-scratch disease, blastomycosis, brucellosis, lymphogranuloma venereum, dematiaceous molds, chromoblastomycosis, phaeohyphomycosis, NTM, tularemia, protothecosis, sporotrichosis, paracoccidiomycosis, yersiniosis, pinworm
Histiocytic response without granuloma	Infectious: Whipple disease, listeriosis, NTM (including Hansen disease), histoplasmosis, leishmaniasis, Rhodococcus Other: Langerhans cell histiocytosis, granulomatous mycosis fungoides, juvenile xanthogranuloma, reticulohistiocytoma, Rosai-Dorfman syndrome, pineal germinoma, seminoma, dysgerminoma, dendritic cell sarcoma, Erdheim-Chester disease, HLH, histiocytic sarcoma, interdigitating cell sarcoma, Langerhans cell sarcoma

Etiologies By System

• Lung
  • Infectious
    • Bacterial: actinomycosis, brucellosis, TB, Mycoplasma pneumoniae, nocardiosis, NTM, Rhodococcus
    • Fungal: aspergillosis, blastomycosis, coccidiomycosis, cryptococcosis, histoplasmosis, mucor
    • Other: Acanthamoeba, Balamuthia mandrillaris, CMV, Dirofilaria, toxoplasmosis
  • Non-infectious
    • Autoimmune: eGPA, GPA, lymphoid interstitial pneumonia, sarcoidosis
    • Neopalstic: Hodgkin lymphoma, Langerhans cell histiocytosis, metastasis, Rosai-Dorfman syndrome
    • Other: CGD, chronic pneumonia, drug toxicity, foreign body reactio, pneumoconiosis
• Skin
  • Infectious
    • Bacterial: actinomycosis, cat-scratch disease, lymphogranuloma venereum, malakoplakia, TB, NTM
    • Fungal: aspergillosis, blastomycosis, coccidiomycosis, cryptococcosis, histoplasmosis, mucor, chromoblastomycosis, sporotrichosis
    • Other: Acanthamoeba, Balamuthia mandrillaris, CMV, Dirofilaria, leishmaniasis, protothecosis
  • Non-infectious
    • Autoimmune: eGPA, Crohn disease, GPA, granuloma annulare, orofacial granulomatosis, rheumatoid nodule, sarcoidosis, SLE
    • Neoplastic: Granulomatous mycosis fungoides, Hodgkin lymphoma, juvenile xanthogranuloma, Langerhans cell histiocytosis, metastasis, reticulohistiocytoma, Rosai-Dorfman syndrome
    • Other: actinic granuloma, CGD, drugs, foreign body reaction, necrobiosis lipoidica, rosacea
• Kidney
• Liver
  • Infectious
    • Bacterial: actinomycosis, cat-scratch disease, brucellosis, lymphogranuloma venereum, Q fever, tularemia, listeriosis, malakoplakia, tuberculosis, NTM, rickettsioses, enteric fever, yersiniosis
    • Fungal: aspergillosis, blastomycosis, candidiasis, coccidiomycosis, histoplasmosis, mucor
    • Other: CMV, EBV, leishmaniasis, toxoplasmosis, echinococcosis, pinworm, HAV, HCV, schistosomiasis
  • Non-infectious
    • Autoimmune: GPA, Crohn disease, PBC, sarcoidosis
    • Neoplastic: HLH, Hodgkin lymphoma, metastasis, Rosai-Dorfman disease
    • Other: foreign body reaction, berylliosis, drug toxicities
• Lymph nodes
  • Infectious
    • Bacterial: actinomycosis, cat-scratch disease, brucellosis, lymphogranuloma venereum, Q fever, tularemia, listeriosis, malakoplakia, tuberculosis, NTM, Yersinia granulomatosis
    • Fungal: aspergillosis, blastomycosis, coccidiomycosis, cryptococcosis, histoplasmosis, mucor, sporotrichosis
    • Other: CMV, EBV, leishmaniasis, toxoplasmosis
  • Non-infectious
    • Autoimmune: eGPA, GPA, sarcoidosis
    • Neoplastic: dendritic cell sarcoma, Erdheim-Chester disease, HLH, histiocytic sarcoma, Hodgkin lymphoma, interdigitating cell sarcoma, Langerhans cell sarcoma, Langerhans cell histiocytosis, metastasis, Rosai-Dorfman disease
    • Other: foreign body reaction

Further Reading

• Histopathologic review of granulomatous inflammation. J Clin Tuberc Other Mycobact Dis. 2017 Feb 10;7:1-12. doi: 10.1016/j.jctube.2017.02.001. PMID: 31723695; PMCID: PMC6850266.