1. Granulomas are collections of macrophages that form in response to insoluble antigens to wall them off. They consist of epithelioid histiocytes, multinucleated giant cells, and a variable inflammatory infiltrate. 2. The document classified and described the histopathology of different types of granulomas including epithelioid cell granulomas, macrophage granulomas, mixed cell granulomas, and palisading granulomas. Common causes of granulomas like tuberculosis, leprosy, and sarcoidosis were explained. 3. The approach to diagnosing granulomas involves classifying them as epithelioid, macrophage, or palisading granulo

1. GRANULOMAS IN
DERMATOLOGY
Presenter - Dr. Maria Ansari
Moderator - Dr. Girish P. N.

2. INTRODUCTION
CLASSIFICATION
HISTOPATHOLOGY OF EACH TYPE
APPROACH TO GRANULOMAS
CONCLUSION

3. 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.

4. COMPONENTS OF A GRANULOMA

5. 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. • Epithelioid histiocyte:
Activated histiocyte with abundant
eosinophilic granular cytoplasm and
poorly defined cell borders

7. • Multinucleated histiocyte: >1 nucleus
• Langhans,Touton,and Foreign body

9. ● Masses of epithelioid cells (Pale pink
cells with indistinct margins and
vesicular nuclei)
● Langhans giant cells
● With cuff of
lymphocytes-Tuberculoid
● Without cuff of
lymphocytes-Sarcoidal
Epitheloid cell granuloma

10. Mixed Cell Granulomas
Mixed cell infiltrate of lymphocytes, plasma cells, eosinophils,
macrophages, giant cells and polymorphs.

11. XANTHOGRANULOMA
● Foam cells mixed infiltrate of plasma cells, lymphocytes,
eosinophils.
● Touton Giant cells

12. Palisading(necrobiotic) Granulomas
Palisaded (“necrobiotic”) granulomas – comprised of epithelioid histiocytes
aligned as a rim around a central area of degenerated collagen
("necrobiosis").

13. EPITHELIOID CELL
1. Tuberculoid
a) With necrosis-Cut. TB, Lupus Miliaris Disseminatus et Faciei, Gumma
b) Without necrosis
Tuberculoid leprosy,
Cut. Leishmaniasis(CL),
Late Syphilis,
Sporotrichosis;
FB granuloma,
Rosacea
2. Sarcoid
Infective:
Syphilis,
Fungal granulomas,
Non-infective:
Sarcoidosis,
Foreign body granuloma,
Few lymphomas

14. MACROPHAGE GRANULOMAS
1. Diffuse macrophage infiltrations
Cut Leishmaniasis, LL
2. Suppurative/ Mixed cell
Infective:Fungal, Atypical MB, CL,
Botryomycosis, Cat scratch dis., LGV,
Malakoplakia;
Non-infective: Follicular occlusion, Pyoderma Gangrenosum,
FB(suture), Halogenodermas
3. Xanthogranulomas
Infective: LL
Non-infective: Juvenile xanthogranuloma, Necrobiotic xanthogranuloma,
Reticulohistiocytic granuloma

15. PALISADING GRANULOMAS
(necrobiotic)
MISC.
1. Granuloma
annulare
2. Necrobiosis
lipoidica
3. Rheumatoid
nodule
4. Palisading
granulomatous
neutrophilic
dermatitis
5. Syphilis
6. FB
1. With Vasculitis:
Wegener’s granulomatosis
Allergic granuloma of Churg Strauss
Takayasu disease
2. Elastolytic
Granuloma
3. Granulomatous
Mycosis Fungoides

16. Epitheloid cell granuloma

17. Tuberculosis
Collection of epithelioid cells, surrounded by a mantle of lymphocytes

18. Sarcoid -naked granuloma
Nodular collections of epithelioid cells without a mantle of lymphocytes.

19. COMMON EPITHELOID GRANULOMAS

21. Cutaneous TB

22. Lupus vulgaris
● Epidermis: Atrophy or hypertrophy.
● Dermis(upper dermis): Tuberculoid
granulomas - epithelioid cells and
giant cells(LC,FB), lymphocytes
● Caseation necrosis-slight or
absent
● Granulomas cause destruction of
● Appendages,fibrosis, scarring.

23. Tuberculosis Verrucosa Cutis
(TBVC)
• Epidermis: hyperplasia with marked
hyperkeratosis, acanthosis, papillomatosis,
elongated rete ridges.
• Mixed lymphohistiocytic infiltrate with an
occasional sprinkling of neutrophils
• Abscess, tuberculoid granulomas are usually
present(40% cases)

24. Tuberculids
Papulonecrotic-
Wedge shaped necrosis in the epidermis and
upper dermis,
Vasculitic picture,
Granuloma formation-poor.
Lichen Scrofulosorum- small epithelioid
granulomas adjacent to hair follicles.
Erythema Induratum- Nodular vasculitis
Vasculitis, panniculitis and tuberculoid granuloma.

25. Lichen Scrofulosorum-
small epithelioid granulomas
adjacent to hair follicles.

26. Leprosy
● Spectrum of manifestations
● Hallmark- Involvement of appendages,
nerve, arrector pilorum
● Granulomas

28. TT
1.Normal Epidermis
2.Inflammatory infiltrate involving Grenz zone
3. Well formed tuberculoid granulomas, with
Langhan's giant cells
4. The granulomas are characteristically oval in
shape, located around appendages, and nerves
4. Thickened nerve twigs, infiltrated by
granuloma, lymphocytes

29. BT
1. Normal epidermis
2. Grenz zone +
3. Granulomas, with epithelioid cells,
foreign body giant cells. Number of
lymphocytes is less in number than
that in tuberculoid leprosy.
4. Thickened nerve twigs, infiltrated by
granuloma /lymphocytes

30. BB
Diffuse epitheloid cell granuloma
Lymphocytes are scanty
No Langhans giant cells
Difficult to diagnose histologically. Hence, not discussed.

31. BL
● Grenz zone +
● Activation of macrophages to form poorly
to moderately defined granulomas.
● Diffuse infiltrate.
● Foreign body giant cells.

32. LL
● 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
● Perineural fibroblast proliferation, forming
an “onion skin” in cross section, is typical
● No macrophage activation to form
epithelioid cell granulomas.

33. Indeterminate Leprosy
Mild lymphocytic and macrophage accumulation
around NVB, superficial and deep dermal vessels,
sweat glands, and arrector pili muscle.
Focal lymphocytic invasion into the lower epidermis
and into dermal nerves may be observed
No formed epithelioid cell granulomas
Schwann cell hyperplasia+/-

34. 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

35. 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

36. 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.

37. Mixed Cell Granulomas

38. LEISHMANIASIS
● Dense mixed dermal inflammatory
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
● LD bodies seen inside macrophages.

39. Foreign body granuloma
● Histiocytes, FB giant cells, lymphocytes
surrounding foreign body
● Foreign material within macrophages
and giant cells
● Silica- sarcoidal granuloma, birefringent.
● Zirconium- sarcoid granuloma,not
birefringent.
● Tattoo- FB or Tuberculoid granuloma
● Others- Silk,nylon sutures,wood, talc,
surgical glove starch powder and sea
urchin spines.

40. JUVENILE XANTHOGRANULOMA
● Foam cells with mixed cell infiltrate of
plasma cells, lymphocytes,
polymorphs, eosinophils.
● Touton Giant Cells - wreath of nucleus.

41. Palisading/Necrobiotic granuloma

42. GRANULOMAANNULARE
● Epidermis- Normal/ Parakeratosis
● Dermis- Ring shaped areas of
necrobiosis (pale), surrounded by
palisading histiocytes
● Eosinophils in large numbers
● Increased mucin - hallmark
● Changes limited to upper and mid
dermis

43. 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.

44. Necrobiosis lipoidica
● Epidermis- normal, atrophic.
● Dermis- Horizontal shelf like areas of
necrobiosis, vertically alternating with
cellular areas.
● Infiltrate-Histiocytes, plasma cells,
lymphocytes, FB giant cells(Granuloma
disciformis of Meissner)
● Infiltrate extending to subcutis -
panniculitis.
● Vasculitis+/-
● Sclerosis+

45. COMMON PALISADING GRANULOMAS

47. APPROACH TO GRANULOMAS

48. MACROPHAGE
GRANULOMA
EPITHELIOID PALISADING

49. EPITHELOID GRANULOMA
TUBERCULOID
(with lymphocyte cuff)
SARCOIDAL
(No lymphocyte cuff)
NON INFECTIVE
SARCOIDOSIS
FOREIGN BODY- ZIRCONIUM, SILICON
INFECTIVE
SYPHILIS
FUNGAL GRANULOMAS
TUBERCULOID
GRANULOMA without
necrosis
TUBERCULOID
GRANULOMA with
necrosis
INFECTIVE
Tuberculoid Leprosy
Cut. TB
NON INFECTIVE
Lupus miliaris
Disseminatus et faciei
INFECTIVE
Cut. TB
NON INFECTIVE
Foreign body granuloma
Zirconium, silicon,
aluminium

50. MACROPHAGE
GRANULOMA
MIXED
GRANULOMA
DIFFUSE
MACROPHAGE
INFILTRATION
LD BODIES
CUT.
LEISHMANISIS
M. LEPRAE
LL
INFECTIVE
FUNGAL
ATYPICAL
MYCOBACTERIAL
CUT.
LEISHMANISIS
NON-INFECTIVE
FOREIGN BODY
GRANULOMA
PYODERMA
GANGRENOSUM
XANTHOGRANULOMA
TOUTON
GIANT CELL
RETICULO
HISTOGRANUL
OMA

51. PALISADING
GRANULOMA
WITH NUCLEAR DUST AND
NEUTROPHILS
PALISADING
GRANULOMATOUS
NEUTROPHILIC
DERMATITIS
SUBCUTANEOUS
NECROBIOSIS
RHEUMATOID NODULE
PLATE- LIKE NECROBIOSIS
NECROBIOSIS LIPOIDICA
RING SHAPED NECROBIOSIS
GRANULOMA ANNULARE

52. CONCLUSION
Granulomas of the skin may sometimes resolve on their or may lead to
complications such as:
* Persistence or worsening of symptoms
* Interference with normal function
* Damage to surrounding tissue leading to scarring.
* Complications from underlying condition: an untreated infection could spread to
other areas of the body

53. References
Lever’s Histopathology of Skin
IADVL Textbook of Dermatology
Bolognia Textbook of Dermatology
Fundamentals of Pathology of Skin

54. Thank you