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Granulomas Dr Manasa Shettisara Janney
- 1. GRANULOMAS Dr Manasa S J PG Resident, CHAFB
- 2. Granulomatous reaction pattern • Discrete collection of macrophages or its derivatives with variable number of admixed inflammatory cells • Response to insoluble, nondegradable, or slowly released antigens • Effectively “walls off” the offending agent
- 3. Formation of granulomas • Persistent T-cell responses to certain microbes • Immunemediated inflammatory diseases(Crohn disease) • Response to relatively inert foreign bodies (suture or splinter)
- 5. Imp. definitions • Histiocyte: Tissue macrophage, has a large, ovoid, pale nucleus(can be eccentric and indented) The nucleolus usually is distinct, small, and can be single or multiple • Cytoplasm may be abundant but is indistinct
- 6. Imp. definitions • Epithelioid histiocyte: Activated histiocyte with abundant eosinophilic granular cytoplasm and poorly defined cell borders
- 7. Imp. definitions • Multinucleated histiocyte: >1 nucleus • Langhans, Touton, and Foreign body
- 8. Imp. definitions • Tuberculoid granuloma : A well circumscribed collection of epithelioid histiocytes with a surrounding relatively dense infiltrate of lymphocytes. Necrosis variable • Sarcoidal granuloma : A well-circumscribed collection of epithelioid histiocytes with relatively few or no lymphocytes • Palisaded granuloma : Histiocytes arranged in a palisade or “like staves around a central focus” • Necrobiosis: Focal alteration or degeneration of collagen • Caseation necrosis: Identical to ischemic necrosis and coagulation necrosis. The necrotic tissue has lost its structure and appears amorphous, pale pink and somewhat granular
- 11. Epitheloid cell granuloma • Masses of epitheloid cells (Pale pink cells with indistinct margins and vesicular nuclei) • With cuff of lymphocytes- Tuberculoid • Without cuff of lymphocytes- Sarcoid
- 12. Macrophage cell granuloma • Masses of macrophages • Can be admixed with other inflammatory cells • Ex-LL, Xanthogranulomas
- 13. Palisading/Necrobiotic granuloma • Periphery-elongated or spindle-shaped nuclei that are palisaded;roughly parallel to each other and perpendicular to edge of central necrotic zone
- 14. Epitheloid Cell Macrophage Palisading Misc 1. Tuberculoid a) With necrosis-Cut TB, LMDF, Gumma b) Without necrosis Tuberculoid leprosy, Cut Leishmaniasis(CL), Late Syphilis, Sporotrichosis; FB granuloma, Rosacea 1. Diffuse macrophage infiltrations Cut Leishmaniasis, LL 1. Granuloma annulare 2. Necrobiosis lipoidica 3. Rheumatoid nodule 4. Palisading granulomatous neutrophilic dermatitis 5. Syphilis 6. FB 1. With Vasculitis 2. Elastolytic granuloma 3. Granulomatous MF 2. Sarcoid Syphilis, Fungal, Sarcoidosis, FB, few lymphomas 2. Suppurative/ Mixed cell Fungal, Atypical MB, CL, Botryomycosis, Cat scratch dis., LGV, Malakoplakia; Follicular occlusion, PG, FB(suture), Halogenodermas
- 15. 3. Xanthogranulomas LL; Juvenile, Necrobiotic, Reticulohistiocytic
- 16. Cutaneous TB (a) by direct inoculation into the skin ( primary chancre, tuberculosis verrucosa cutis (TVC), tuberculosis cutis orificialis lesions) (b)by hematogenous spread from an internal lesion (lupus vulgaris, miliary tuberculosis, and tuberculous gumma lesions) (c) by direct extension (scrofuloderma)
- 17. Acute nonspecific inflammation- bacilli multiply and cannot be phagocytosed by neutrophil polymorphs Macrophages then phagocytose the organisms Cytokines recruit and activate macrophages epithelioid cells. Some fuse to form giant cells. As delayed hypersensitivity increases caseation necrosis, mediated by TNF and macrophage proteases
- 18. Primary TB • Earliest phase-acute neutrophilic reaction, with areas of necrosis,numerous tubercle bacilli • After 2 wks, monocytes and macrophages predominate • 3 to 6 wks after onset, epithelioid cells, giant cell granulomas with caseation develop • In time, necrosis lessens, and number of tubercle bacilli decreases, PPD becomes positive • Draining lymph nodes- caseating granulomas
- 19. Primary TB
- 20. Scrofuloderma • Center- nonspecific changes • Deeper portions, periphery - tuberculoid granulomas with a considerable amount of necrosis and inflammatory reaction • AFB+ • PPD is typically strongly positive
- 21. Gumma • Caseation necrosis with a rim of epithelioid cells and giant cells • Acid-fast bacilli are scanty, but usually demonstrable on histologic sections
- 22. TVC • Pseudocarcinomatous squamous hyperplasia with marked hyperkeratosis and acanthosis • Mixed lymphohistiocytic infiltrate with an occasional sprinkling of neutrophils • Abscess, tuberculoid granulomas are usually present
- 23. Lupus vulgaris • Tuberculoid granulomas- epithelioid cells and giant cells(LC,FB) • Caseation necrosis-slight or absent • Associated infiltrate of lymphocytes (prominent in TVC-like lesions) • Granulomas cause destruction of appendages,fibrosis • 2 changes in epidermis common
- 24. Tuberculids • Papulonecrotic- Wedge shaped necrosis, Vasculitic picture, granuloma formation-poor
- 26. Leprosy • Spectrum of manifestations • Hallmark- Involvement of appendages, nerve, arrector pilorum • Granulomas
- 27. Indeterminate leprosy • Mild lymphocytic and macrophage accumulation around NVB, supfcl and deep dermal vessels, sweat glands, and arrector pilori muscle • Focal lymphocytic invasion into the lower epidermis and into dermal nerves may be observed • No formed epithelioid cell granulomas • Schwann cell hyperplasia+/-
- 28. TT • Large epithelioid cells arranged in compact granulomas along neurovascular bundles, with dense peripheral lymphocyte accumulation • Langhans giant cells are typically absent • Dermal nerves may be absent (obliterated) or surrounded and eroded by dense lymphocyte cuffs. • AFB rarely found, even in nerves
- 29. BT • Granulomas with peripheral lymphocytes follow the NVB and infiltrate appendages • Langhans giant cells are variable in number and are not large in size
- 30. BB • Diffuse epitheloid cell granuloma • Lymphocytes are scanty • No Langhans giant cells • BI ranges from 3 to 4 • Dermal edema is prominent between inflammatory cells
- 31. BL • Lymphocytes more prominent and tendency for some activation of macrophages to form poorly to moderately defined granulomas • Perineural fibroblast proliferation, forming an “onion skin” in cross section, is typical • Foamy cells not prominent and globi do not usually accumulate • BI ranges from 4 to 5
- 32. Lepromatous leprosy • Grenz zone + • Mild-to-moderate, superficial and deep, perivascular and periadnexal infiltrate of foamy histiocytes • Infiltrate may cause destruction of cutaneous appendages and extends into subcutaneous fat • No macrophage activation to form epithelioid cell granulomas • Nerves well preserved
- 33. Type 1 reaction • Edema within and about granulomas and proliferation of fibrocytes in dermis • In upgrading reactions, granuloma becomes more epithelioid and activated, and Langhans giant cells are larger • May have fibrinoid necrosis within granulomas and dermal nerves • In downgrading reactions, necrosis is much less common, and over time the density of bacilli increases
- 34. ENL • Foci of acute inflam. superimposed on chronic multibacillary leprosy • Polymorph neutrophils + • Foamy macrophages containing fragmented bacilli are usual • Necrotizing vasculitis affecting arterioles, venules, and capillaries occurs in some cases of ENL
- 35. Lucio reaction • Vascular changes are critical • Endothelial proliferation leading to luminal obliteration • Thrombosis in the medium- sized vessels of dermis and subcutis • Sparse, largely mononuclear infiltrate • AFB in endothelium • Ischemic necrosis, leads to hemorrhagic infarcts and results in crusted erosions or frank ulcers
- 36. Leishmaniasis • Dense mixed dermal inflam. infiltrate histiocytes, lymphocytes, and plasma cells • Giant cells and eosinophils+/- • Neutrophils noted once ulceration has occurred • Parasitized histiocytes+ • Early lesions-acanthosis or atrophy • Later lesions-ulceration and pseudoepitheliomatous hyperplasia
- 37. Sporotrichosis • Early lesions-nonspecific inflammatory infiltrate composed of neutrophils, lymphoid cells, plasma cells, and histiocytes • Long standing lesions- hyperplastic epidermis with small, intraepidermal, and dermal lymphoplasmacytic infiltrate with small abscesses, eosinophils, giant cells, small granulomas often associated with asteroid bodies • Later, through coalescence, a characteristic arrangement of the -central “suppurative” zone,“tuberculoid” zone,“round cell” zone
- 38. Sporotrichosis • Early lesions-nonspecific inflammatory infiltrate • Long standing lesions- hyperplastic epidermis with dermal lymphoplasmacytic infiltrate with abscesses, eosinophils, giant cells, small granulomas often associated with asteroid bodies • Later, through coalescence, a characteristic arrangement of the -central “suppurative” zone,“tuberculoid” zone,“round cell” zone
- 39. Cryptococcosis • Two types of histologic reaction-gelatinous and granulomatous • Gelatinous – numerous organisms, very little tissue reaction • Granulomatous- pronounced tissue reaction-histiocytes, giant cells, lymphoid cells and fibroblasts • Areas of necrosis+/-
- 40. Cryptococcosis • Two types of histologic reaction-gelatinous and granulomatous • Gelatinous – numerous organisms, very little tissue reaction • Granulomatous- pronounced tissue reaction-histiocytes, giant cells, lymphoid cells and fibroblasts • Areas of necrosis+/-
- 41. Mycetoma • Extensive granulation tissue-abscesses sinuses • Early phase-tissue surrounding abscess- lymphoid cells, plasma cells, histiocytes and fibroblasts • Late phase-fibroblasts predominate • “Sulfur granules”
- 42. Juvenile xanthogranuloma • Macrophages with a variety of cellular features • Early lesions- large accumulations of vacuolated cells without significant lipid infiltration intermingled with only a few lymphocytes and eosinophils • Mature lesions- granulomatous infiltrate- foamy cells, foreign-body giant cells, and Touton giant cells, lymphocytes, and eosinophils • Regressing lesions-fibrosis
- 43. Sarcoidosis • Circumscribed collection of epithelioid granulomas without caseation and peripheral rim of lymphocytes • Asteroid bodies-Star shaped eosinophilic bodies(trapped collagen within cells) • Schaumann bodies- Calcified oval laminated bodies derived from lysosomes • Non specific- Berylliosis, FB granuloma, Necrobiotic XG
- 44. Granuloma annulare • Epidermis- Normal/ Parakeratosis • Dermis- Ring shaped areas of necrobiosis (pale), surrounded by palisading histiocytes • Eosinophils in large numbers • Histiocytes- interstitial pattern • Increased mucin - hallmark • Changes limited to upper and mid dermis
- 45. Rheumatoid nodule • Subcutis & deep dermis • Fibrinoid degeneration of collagen surrounded by histiocytes • Nuclear fragments and basophilic material are often present • Mucin is almost always minimal or absent • FB giant cells + • Proliferation of blood vessels associated with fibrosis.
- 46. Necrobiosis lipoidica • Epidermis- normal, atrophic or hyperkeratotic • Horizontal shelf like areas of necrobiosis • Infiltrate-Histiocytes, plasma cells, lymphocytes, FB giant cells(Granuloma disciformis of Meissner) • Infiltrate extending to subcutis • Vasculitis+/- • Sclerosis+ • Granulomas-Common in diabetic form • Florid palisading, Cholesterol clefts+ diabetic form
- 47. Foreign body granuloma • Histiocytes, FB giant cells, lymphocytes surrounding foreign body • Foreign material within macrophages and giant cells • Silk,nylon sutures,wood, talc, surgical glove starch powder and sea urchin spines • Doubly refractile on polarizing examination
- 48. Cheilitis granulomatosa(Miescher Melkersson-Rosenthal syndrome) • Recurrent labial edema, relapsing facial paralysis, fissured tongue • Edema, lymphangiectasia and perivascular lymphoplasmacytic infiltrate/Noncaseating poorly circumscribed epithelioid histiocytes, +/- lymphocytes • Affected lymph nodes may show granulomatous inflammation
- 49. SUMMARY- LEPROSY
- 50. Feature Indeterminate TT BT BL LL Grenz zone + Absent + + + Infiltrate PN, PA PN.PA PN,PA Diffuse Diffuse Granuloma Poorly formed No epitheloid cells Tuberculoid Tuberculoid Macrophage Macrophage Giant cells - Langhan’s FB FB - Lymphocytes Many Plenty Many Few Very few Plasma cells, Foam cells Few Many Nerves Mild thickening Thickened Thickened Thickened Onion peeling Bacilli Occ - Occ Many Numerous, Globi
- 52. Feature Tuberculoid Leprosy Lupus Vulgaris Sarcoidosis Cut. Leishmaniasis Epidermal changes Normal Always+ Atrophy, Hypertrophy Normal Normal/Thinning Location of granuloma Mid & lower dermis Upper dermis Upper & mid dermis Upper & mid dermis Spcl features Involvement of nerves Caseation Naked granulomas Tuberculoid granuloma rare Clues Thickened nerve, Oval large granuloma Destruction of elastic fibres Asteroid & Schaumann bodies Plasma cells, necrosis Organism AFB(L) AFB(TB) - LD bodies Stain Fite Faraco ZN - Giemsa
- 54. Feature Granuloma annulare Necrobiosis lipoidica Rheumatoid nodule Epidermis Normal Thinned/Ulcerated Normal Necrobiosis Ring shaped, discrete foci Plate like, diffuse Large, sharply defined areas Location Supfcl/mid dermis Extensive Deep Infiltration Single filing Alternates with necrobiosis Surrounding necrobiosis Type of cells Palisading histiocytes Histiocytes, giant cells, tuberculoid Histiocytes, giant cells, eosinophils Appearance of collagen Pale, bluish, incomplete degeneration Pale Eosinophillic Vasculitis Uncommon Common Common Fibrosis Rare Common Common Deposited material Mucin Lipid Fibrinoid
- 60. THANK YOU… Langerhans cells, Pancreatic islets Langhans giant cells