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)
4.
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
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
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
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
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+/-
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
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
