Granulomatous

R
Reaction
i Pattern
P
Nathan C. Walk, M.D.
Granulomatous reaction pattern
„ “Granuloma”
„ Relatively discrete collection of histiocytes or epithelioid
histiocytes with a variable number of admixed multinucleate
ggiant cells and other inflammatoryy cells.

„ Divided by:
„ The arrangement of granulomas
„ The presence of accessory features
„ Central necrosis
„ Suppuration
„ Necrobiosis
„ Foreign materials
„ O
Organisms
i
Histological types of granulomas
„ Sarcoidal granulomas
„ Naked granuloma - Epithelioid histiocytes and giant cells with a paucity
of surrounding lymphocytes and plasma cells

„ Tuberculoid granulomas
„ Epithelioid histiocytes
histiocytes, giant cells of Langhans and foreign body type with
a more substantial rim of lymphocytes and plasma cells
„ Central “caseation” sometimes
„ Granulomas tend to become confluent

„ Necrobiotic granulomas
„ Poorlyy formed granulomas
g
„ A more diffuse array of histiocytes, lymphocytes and giant cells with
associated necrobiosis
„ Inflammatory cells are admixed with the necrobiosis or form a palisade
around it
Histological types of granulomas
„ Suppurative
pp ggranulomas
„ Epithelioid histiocytes and multinucleate giant cells with
central collections of neutrophils
„ Chronic
Ch i iinflammatory
fl t cells
ll att periphery
i h

„ Foreign body granulomas

„ Epithelioid histocytes, foreign body type giant cells and
foreign material (exogenous or endogenous in origin)

„ Miscellaneous granulomas
„ Variable appearance
Granuloma type and DDx….variable
„ Sarcoidal „ Suppurative
„ Sarcoidosis „ Fungal chromomycosis,
Fungal… chromomycosis phaeohypho-
phaeohypho-,
„ Rxn to foreign materials sporotrichosis, blasto, paracoccidio,
coccidio, mycetomas (nocardia,
„ Tuberculoid granulomas actinomycosis)
„ Tuberculosis „ Non--TB mycobacterial
Non
„ Tuberculids „ Cat--scratch
Cat
„ Leprosy „ Lymphogranuloma venereum
„ Late syphilis „ Pyogerma gangrenosum, variant
„ Leishmaniasis „ Ruptured cyst, haird follicle
„ Rosacea „ Foreign body
„ Crohn’ss
Crohn „ Endogenous material
„ Necrobiotic „ Exogenous material
„ Granuloma annulare „ Miscellaneous
„ Necrobiosis lipoidica „ Melkersson-Rosenthal syndrome
Melkersson-
„ Necrobiotic xanthogranuloma „ Elastolytic granulomas
„ Rheumatoid nodules „ Interstitial granulomatous dermatitis
„ Rheumatic fever nodules „ Interstitial granulomatous drug
„ Reactions to foreign material „ Granulomas in immunodeficiency
syndromes
„ Cincinnati Dermatopathology Diagnoses,
Granulomatous Pattern
„ Granuloma annulare
„ Interstitial granuloma annulare
„ Rheumatoid nodule
„ Sarcoidosis
„ Granulomatous rosacea
„ S t granuloma
Suture l
„ Keratin Granuloma
„ Necrobiosis lipoidica

„ Also mention of: Lupus vulgaris, scrofuloderma

„ Case 42
 Actinic granuloma
„ Histology
gy
„ Solar elastosis of peripheral unaffected skin
„ Foreign body giant cell reaction in association with, and
engulfing, fragmented elastotic material
„ Superficial dermis (where the solar elastosis is)
„ Chronic inflammation – mixed

„ C/w GA
„ Marked elastophagocytosis, on sun damaged skin
„ Mild scarring
i
„ No necrobiosis
„ No increased mucin
„ Case 43a and b
 Sarcoidosis
„ Cutaneous lesions occur in 20
20--35% of patients
with systemic sarcoid – types:
„ Nonspecific
p ((Most common,, Erythema
y nodosum))
„ Specific (Granulomatous)

„ Upp to 20
20--40% of p
patients with cutaneous
sarcoid do NOT have systemic disease.
„ Cutaneous lesions:
„ A/w poorer prognosis and increased incidence of
pulmonary fibrosis and uveitis
 Sarcoidosis
„ Histology:
„ Dermal infiltrate
(superficial only, or
throughout) of “naked”
granulomas
„ No particular localization
„ Asteroid bodies
„ Schaumann bodies
 Sarcoidosis
„ Mayy develop
p lesions:
„ Scars following trauma, tattoos, venipuncture, surgery.
„ A/w radiation, chronic infection

„ Caveat w/ “sarcoidal” granulomas (in my experience)

„ Usually NOT “naked”
„ M
More often
f a/w/ fforeign
i materials
i l than
h with
i h sarcoid
id

„ Sarcoidal granulomas a/w foreign material – doesn’t really tell you

anything
n thing about
bo t whether
hether or not the
they h
havee ssarcoid….
r oid
„ Only a reaction to foreign material in a patient without sarcoid – or -
„ Patient has sarcoid, reaction is at a site of scar where material was
impregnated
p g into the skin.
„ Case 45 (case 44 later)
 Necrobiosis lipoidica
„ Unknown etiology
„ 11% a/w Diabetes Mellitus at presentation
„ A ffurther
h 11% develop
d l DM

„ “Atypical necrobiosis lipoidica” of face and

p
scalp
„ Name chosen b/c of coexistence with NL
„ Micro different
„ Histology:
gy
„ More going on
„ Full thickness dermal involvement, sometimes with sub-
sub-Q fat (septa)
„ **Necrobiosis more extensive and less well defined than in GA
„ Layered appearance, open-
open-ended
„ Vascular changes (particularly deep) – endothelial swelling,
lymphocytic vasculitis
vasculitis, ?clot

„ Variable palisading of lymphocytes and histiocytes

„ Lipid in necrobiotic area, little/no mucin

„ Plasma cells
„ Case 46
 Necrotizing granulomatous
inflammation
„ Descriptive term pathologists use for a form of
palisading granulomatous inflammation
„ With liquefactive
q necrosis in the middle
„ Associated with Wegener’s granulomatosis,
connective tissue diseases,, fungal
g and
mycobacterial infections
„ Some overlap with “caseation”

„ Looks a lot like rheumatoid nodule,, deep

p GA
„ Case 47
 Tattoo granuloma
„ “Two
Two patterns of granulomatous dermatitis seen
in response to pigments used in tattooing:
„ Sarcoidal
„ Foreign body”
„ Case 48
Granuloma annulare
„ Dermatosis of unknown etiology
„ Possible triggering factors
„ insect bites
„ trauma
„ presence of viral warts
„ EM
„ exposure to Sunlight
„ Age of onset: children or young adults
„ F:M = 2:1
„ Duration of lesions: months to years
„ Clinical variants of GA
„ Localized form
„ Generalized form (15%)
„ Perforating GA
„ Subcutaneous or deep GA
„ GA has tendency to spontaneous regress
regress, 40% recur
 Different histological features of
granuloma annulare
„ Common features:
„ Necrobiosis
„ Increased dermal mucin
„ Colloidal iron or alcian blue at pH 22.55

„ Usual type
„ Necrobiosis + palisading histiocytes + mucin
„ NO plasma cells (supposedly) – c/w NLD
„ Superficial--mid dermis
Superficial
„ Deep GA
„ Deep dermis, subcutis and rarely deep soft tissue
„ L
Larger necrobiotic
bi i area than
h usuall type
 Different histological features of
granuloma annulare
„ Interstitial GA
„ No formed area of necrobiosis
„ Interstitial granulomatous drug reaction
„ Eosinophils
p
„ Interface changes, lichenoid reaction
„ Interstitial granulomatous dermatitis
„ Both eosinophils and neutrophils
„ O or more collagen
One ll fib
fibers with
ihb basophilic
hili hhue, palisaded
li d d bby hi
histiocytes
i
„ Disseminated form
„ Papillary dermis
„ I
Inconspicuous
i necrobiosis
bi i
„ Resemble Lichen nitidus, no claws
„ Perforating GA
„ C t l epidermal
Central id l perforation
f ti
„ Case 49
 Interstitial granuloma annulare
„ Histology:
„ “Busy dermis”
„ Dissecting histiocytes through collagen
„ No true areas of necrobiosis
„ Increased
d mucin,
i iincreased
d iinflammation
fl i – perivascular
i l and
d interstitial
i ii l

„ Differential diagnosis:
„ I
Interstitial
i i l granulomatous
l ddrug reaction
i
„ Eosinophils
„ Interface changes, lichenoid reaction
„ Interstitial granulomatous dermatitis = “Palisaded
Palisaded and neutrophilic
granulomatous dermatitis”
„ Both eosinophils and neutrophils
„ One or more collagen fibers with basophilic hue, palisaded by histiocytes
„ Case 44
 Deep granuloma annulare
„ ?Differentiate from Rheumatoid nodule…
nodule or
“necrotizing granulomatous inflammation”
„ Deep GA – **>mucin in middle
„ R. nodule – >fibrin in middle, clinical history

„ NGI – descriptive
descripti e term
„ Case 50
Foreign body granuloma
„ Case 51
„ Tuberculoid leprosy
„ Well--defined,
Well defined hypopigmented
hypopigmented, slightly
scaling, anesthetic macules and plaques
„ Histology: non-
non-caseating granulomas,
epithelioid cells
cells, Langhans giant cells and
lymphocytes
„ Bacilli are difficult to find (< 50% of
cases)
„ Lepromatous leprosy
„ Nodules and thick plaques
„ Hypopigmentation of the overlying skin
„ Symmetrical involvement
„ Histology:
gy sheets of heavilyy parasitized
p
macrophages (foamy appearance - lepra
cells or Virchow cells); globi = mass of
bacilli
„ Case 52 a and b
 Granulomatous panniculitis
„ + AFB
„ Atypical mycobacteria
„ Case 53
 Granulomatous rosacea
„ Mixed lymphohistiocytic infiltrate, related to:
„ Vessels
„ Pilosebaceous units
„ Eventually, may form “tuberculid” granulomas
„ Telangiectasias
„ May have caseation in ~11%

„ Ddx:
„ Lupus vulgaris – tuberculid granulomas w/ tendency to confluence
(>inflammation); few organisms; may caseate…tough to see on AFB; + PCR;
most common form
„ Scrofuloderma – caseation…direct extension from deep p infx,, + organisms
g
„ Lichen scrofulosorum – looks just like G. rosacea on histo; + PCR
„ Lupus miliaris disseminatus faciei – looks like G rosacea + caseation; ?related to
rosacea
Extras…