Pathology-Inflammatory Reaction Patterns(KVK) Flashcards
When working up vesiculobullous conditions, what 2 biopsies are taken, from where, and what media?
- Lesional in formalin for H+E
2. Perilesional, within 1 cm of lesion in michels for DIF
What are the H+e findings of pemphigus vulgaris, where is the split?
- Suprabasilar acantholysis with intraepidermal split
- Tombstoning of remaining basal keratinocytes
- Dermal papillae resemble “villae”
- Process extends into follicular structures
- Limmited spongiosis
- Mild mixed dermal inflammation with some eosinophilic component
What are the DIF findings in pemphigus vulgaris
Intercellular keratinocyte junctions, often lower epidermis
IgG and C3
What level is the split for pemphigus foliaceous?
Subcorneal/intragranular
What does pathology for paraneoplastic pemphgius show, comparatively to PV
Pemphigus features + interface dermatitis
DIF stains intercellular keratinocytes junctions + Basement membrane zone
Pathology for H+E for Hailey-Hailey vs. PV
Acantholysis extends to mid upper epidermis (vs. Suprabasilar)
No follicular involvement
Negative DIF
Fam hx
Pathology for Dariers and Grovers vs. PV
Acantholysis with prominent dyskeratosis
*Grovers-often other rxn patterns seen
What is pathological ddx for PV?
Pemphigus variants (foliacous, paraneoplastic) Hailey-Hailey Darier Grover HSV
What are the H+E findings for BP? What is the split level?
- Subepidermal blister
- Blister cavity tends to contain EOS
- Variable inflammation
- moderately dense lymphocytic and EOSINOPHILIC inflammatory infiltraet in superficial dermis +- deeper extension
- may be sparse inflammation also
- few lymphocytes and eos in edematous superficial dermis (urticaria like)
- some cases may be more neutrophilic predominent - Eosinophilic tagging at DEJ +- eosinophilic spongiosis
DIF findings of BP
Linear deposits of IgG and C3 and basement membrane zone
In BP, what side of blister fluoresces on salt split skin
Roof/epidermal side
What layer does salt split skin break at?
Lamina lucida of BMZ
What are the layers of BMZ
Basal keratinocyte
Hemi-desomosome
Lamina lucida (BPAG2, Integrin aplpha and beta)
Lamina densa (Laminin 5, Type IV collagen)
Sublamina Densa (Type VII collagen, elastin, Collagen I and III)
Name 2 fungal stains
PAS-D (diastase)-stains purple
GMS (dirtier)
Name 3 stains for mast cells
- Toludine blue
- Giemsa
- Leder
Name a stain for melanin
Fontana
Name 2 IHC tests for mast cells
CD117
Mast cell tryptase
What 2 stains would you order for suspected CTD
- Colloidal iron for mucin
2. PAS-D for BMZ
Name 1 stain for lieshmeniasis
Giemsea
2 stains for mycobacteria
- Zhiel Nielson for AFB-best for TB
2. Firth-best for atypicals or leprosy (modified ZN)
2 stains for mucin
Hales colloidal iron
Aclian blue
Stain for hemosiderin
PPB
3 stains for amyloid
Congo red
Crystal violet
Thioflavin T
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BP vs. Cicatricial pemphigoid: differences on H+E
- scarring later on
- mucous membranes, sometimes skin involvement
- adnexal extension
- neutrophils >eos
BP vs. Herpes gestationis
- history-pregnant female
- linear BMZ staining for C3 in all cases, fewer positive for IgG
- Occasional necrotic keratinocytes at DEJ
BP vs. EBA? How to tell on path
DIF —> salt split skin localizes to FLOOR, BP to roof
Bullous insect bite vs. BP
Inflammation more prominent with deeper extension and wedge shaped appearance
- spongiotic intraepidermal AND subepidermal vesicles from edema (tethering by fine goassame strands of collagen > true split
- negative DIF
DDX BP on H+E
Cicatricial Pemphigoid Insect bite Bullous drug DH EBA Urticaria Linear IgA
Main inflammatory infiltrates in: PV BP DH Linear IgA
PV-Eos + lymph
BP-Eos + lymph
Linear IgA-Neut
DH-neutrophils
H+E findings DH
Neutrophils localize at tips of dermal papillae
Subepidermal split —> often small, localized to tips dermal papillae
Early lesions—> neutrophilic tagging at DEJ w/ nuclear dust
Superficial +- deep perivascular and interstitial inflammation: Neut>lymph+eos
DIF for DH?
GRanular IgA and C3 at tips of dermal papillae +- BMZ
Pathology for Linear IgA BD
Large subepidermal blisters with DIFFUSE SUPERFICIAL DERMAL NEUTROPHILS
DIF shows linear staining for IgA at BMZ
What is included in DDx for perivascular dermatitis pattern?
Urticaria Dermal hypersensitivity rxns to BUGS, DRUGS (bug bite, drug rxn) Gyrate erythemas Urticarial vasculitis Normal skin UP/TMEP LyP, other cutaneous lymphoproliferative disorders PMLE, Sweets
What are the major inflammatory reaction patterns
- Epidermal
- spongiotic
- psoriasiform
- interface
- vesiculobullous - Dermal
- perivascular
- Nodular and diffuse infiltrates (granulomatous)
- vasculitis/vasculopathy
- skin appendegeal (alopecia, folliculitis,)
- panniculitis
What 5 things to consider when looking at perivascular dermatitis
Distribution (lichenoid, perivascular, periadnexal, interstial-ie in between collagen away from vessels)
Depth: superficial, deep, both
Density: sparse (e.g urticaria) vs. Dense (arthropod bite)
Compositions/type of infilrate: lymph, eos, neut, plasma cells, histiocytes, granulomatous, mast cells
Degree of perivascular “cuffing”—> tight suggesting more gyrate erythema vs. Urticaria tends to be looser
*Other changes like epidermal change, stromal alteration, vascular injury
Name 5 pathological features of urticaria
- Reticular dermal edema (increased space between collagen bundles, more clear)
- Dilated BV
- Sparse to MILD mixed superficial +- deep perivascular inflammation with lymphocytes, eos, neuts, and mast cells
- Interstitial granulocyte
- Margination of neutrophils against vessel wall lumnes
*May be increased neutrohpilic component = neutrophilic urticaria (tend to be phyiscal or longer lasting lesions)
DDX for urticaria on pathology-name 6
- Dermal hypersensitivity rxn (drugs, bugs)
- usually some epidermal change, more inflammation, less dermal edema - Gyrate erythema
- More intense inflammation and tight cuffing - Urticarial vasculitis
- More like neutrophilic urticaria, vasculitis - Normal skin
- UP or TMEP
- INCREASED MAST CELLS
- *mast cell stains
Name 7 findings on H+e of arthropod assault
- Dense wedge shaped perivascular inflammation, almost nodular with sup and deep inflammation
- Small activate lymphocytes + interstial EOS, minimal other cell types
- Can see flame figures, lymphoid nodules, vascular reaction
- Small focus epiderma/dermal necrosis
- Limited focus sponiosis and spongiotic vesicle
- Can have MASSSIVE superficial papullar dermal edema= both sup and intraepidermal vesicles, tether with collagen
- Arthropod remnants
- Scratching findings
*May need more levels
Name 2 diseases (other than arthropod bite) withmassive papillary dermal edema
Sweets
PMLE
*usually no eos
DDx for granulomatous dermatitis-What are the 7 main categories
- Sarcoidal
- Tuberculoid
- Suppurative
- Foreign body
- Palisading
- Elastolytic
- Interstitial granulomaous inflammation
DDx for sarcoidal pattern granulomas
Sarcoid
Infection
Other
DDX for tuberculoid granuloma pattern
Rosacea
Cuaneous chrons
Infection—> TB, leprosy, late syphillis, leish
DDX for suppurative granulomatous
Infection-deep fungal, atypical mycobacteria, other bacteria
Ruptured cyst/follicle
DDx for foreign body granuloma
Ruptured cyst/follicle
Tattoo
Cosmetics
Other stuff-sutures
DDX-name 3 things for ddx of palisading granulom
GA
Necrobiosis lipoidica
Rheumatoid nodule
*Palisading granulomatous dermatitis ?
DDX-name 3 things on ddx for interstial granulomatous inflammation
Interstitial GA
Interstitial granulomatous drug rxn
Interstitial granulomatous dermatitis/rheumatoid papules
What is a granuloma
Focus of histiocytes
*GRanulmatous infiltrates is generally where histiocytes are predominant cell =abundant pale cytoplasm
What is the branch point after granulomas in terms of classification
Naked/sarcoidal granuloma=few or no lymphocytes surrounding the macrophages
Tuberculoid granuloma= many lymphocytes surrounding
Palisading= infiltrate forms around central area of degenerating connective tissue or necrosis
Foreign body =surrounds foreign body
Suppurative =many surrounding neutrophils
Elastolytic= granuloma in setting sun damaged skin
Interstitial=
How do we classify/appraoch nodular/diffuse infiltrates? What is defining feature?
Little to no epidermal involvement
Diffuse or localized aggreagations (nodular) of cell infiltrates
7 categories based on cell infiltrating:
- Eosinophil
- Mast cell
- Neutrohpilic
- Suppurative (robust neutrophilic)
- Lymphoplasmacytic
- Diffuse histiocytoses
- Granulomatous—> sarcoidal, tuberculoid, foreign body, palisading, interstitial, elastolytic, suppurative
What are the 2 histopathological types of GA? What do they each show on path?
- Interstitial
- busy dermis with increased interstitial histiocytes and stellate fibroblasts
- rare giant cells
- perivascular lymphocytes
- Increased dermal mucin - Palisading pattern
- Central zone of degenerate altered collagena nd mucin in ddermis=blue grauloma
- surrounding central zone are palisading giant cells and histiocytes
What is on DDX for GA (path wise i.e. for increased interstitial histiocytes)
- Other palisading granulomatous dermatoses:
- Necrbiosis lipoidica diabeticorum
- Rheumatoid nodule
- palisaded neutrophilic and granulamtous dermitis or rheumatoid papules
- infectious palisaded granuloma - Interstitial granulomatous drug reaction
- Actinic granuloma (DISTINCT from GA on sun damaged skin)
- Granulomatous MF (clinically MF, MF in epidermis, but intestitium shows GA or sarcoid like granulomas)
Name 4 palisaded granulomatous dermatoses
Necrobiosis lipoidica diabeticorum
Palisaded neutrophilic and granulamtous dermaittis
Rheumatoid nodule
Infectious palisaded granuloma
Pathology for NLD?
Dermis adjacent to the palisaded granuloma is altered (vs. Normal in GA)
Increased collagen degeneration and fibrosis
No central mucin=red granuloma
Palisaded granulomata arranged as horizontally oriented tiers (gA-round to oval shaped)
Prominent plasma cells
“Dirtier” component, may be vasculitic
Path for Rheumatoid nodule
Palisading granuloma surrounds zone of eosininophi;lic fibrinoid necrosis
May see residual vlood vessel/vasculitic process in centre with occasional neutrophil
No central mucin
What is the pathological finding in palisaded neutrophilic granulomatous dermatitis
GA with central vasculitis and lots of neutrophils
Path for infectious palisaded granuloma
Central necrosis with abundant neutrophils
What is pathological findings of erythrotelangiectatic rosacea?
Sun damaged skin
Increased telengiectatic vessels
Mild derma edema
Mild perivascular, perifollicular and periinfundibular infiltrate, superficial to mid dermis
Lymph + histio + plasma cells seen
DEmodex mites in follicles
Epidermis normal or non specific acanthosis/scale
Low level follicular inflammation or spongiosis
What are the path findings of acne rosacea with papulopustules predominantly
Compared to erythrotelengiectatic form:
- more inflammation
- lymphochistiocytic folliculitis
- may see neutrophils
- may see increased perifollicular histiocyes, poorly formed perifullicular granulomata—> well formed perifullicular tuberculoid granulomata =folliculocentric poorly formed granulomata
- granulomata often poorly formed, non necrotizing, may be suppurative
Name the single feature needed for vasculitis dx
Fibrinoid necrosis
What is the progression of cellular infiltrate in vasculitis over tiem
Neutrophilic—> Mixed neuts and lymphocytes —> less inflammation, more lymphocytic and histiocytic
Name 8 findings in LCV on H/E
Fibrinoid necrosis * Nuclear dust Extrav RBC Perivascular fibrin deposition Endothelial cell swelling and vessel wall edema Occlusion by fibrin thrombi Neutrophilic perivascular infiltrate DIF may show granular staining in vesseles for IG and/or C3
*Epidermis usually normal, may blister from epidemia, if pustules in epidermis think infection, if vacuolar interface change think CTD, drug reaction
What 2 biopsies do you want for vasculitis/
- Lesional palpable purpuric lesion, <48 hrs for H/E
- DIF also lesional, early erythematous or purpuric lesion
* 3-4 mm punch
What are the immune complex mediated LCV?
IgA vasculitis Urticarial vasculitis AI CTD Cryoglbulinemia Serum sickness *Skin only —> IgG/IgM
Name 4 things on DDx for LCV on path?
- Vasculitis secondary to another cause (ulcer base, excoriation, necrotic tissue)
- Small + large vessel vasculitis
- PPD
- should be PURE lymphocytic
- superficial perivascular and lichenoids
- ++ extrav RBC with no vsaculitis
- hemosiderin pigment +- melanin pigmenet - Neutrophilic dermatoses
- more neutrophils vs. Vascular damage
Name 3 categories of folliculitis
Infectious-bacterial. Fungal, viral
Eosinophilic
Acneiform (follicular epithelium attenuated, follicle dilated with keratin plugging it
What do you see on path in folliculitis?
“Uneven” vasculitis with splaying of neutrophils and nuclear dust in dermis
Infiltrate of neutrophils, later lymph +macrophages
On path, how to distinguish scarring vs. Non scarring alopecia
Non scarring=normal quantity of follicles present
Scarring= follicles destroyed and replaced with collagen
What is dyskeratosis
Abnormal keratinization typically indicating cell death
Denseley eosinophilic cytoplasm with pyknotic hyperchromatic nucleas
DDx acantholytic dyskeratosis
Darier
Warty dyskeratoma
Acanthoma (groin?)
AK, SCC
DDX acantholysis w/out dyskeratosis
Pemphigus and variants including paraneoplastic
Grovers (PV like, PF like, spongiotic, HH like, Darier like, over acrosynrgia)
Hailey-Hailey
Gali-Gali
What is the cornoid lamella
Seen in parakeratosis
Clinically correlated to thin thread like border around lesions
Thin, obliquley at 45 degree orientation, column of parakeratosis with diminshed granular layer
Name a stain for calcium
Von Kossa
Name the stain for Fibrin
MSB
Name the stain for elastin? Collagen?
Elastin=elastin
collagen=Trichrome
Stain for hemosiderin?
PPB
What is polarized light on microscopy useful for?
Foreign bodies (granuloma, panniculitis, tatoos)
Crystals (gout)
Dense scarred collagen
Bone
Hair shaft abnormalities
When is it good to use a GMS stain for fungi?
Lots of PMNs, on PAS-diastase can look very dark purple
Color of fungi on PAS-D? GMS?
PAS- purple
GMS-black on green background
What do dermatophytes look like on path?
Hyphae with septae, branching
Mold
Candida on path?
Spores (yeasts) with psuedohyphae (sausage links)
Malassezia on path
Small yeasts and hyphae= spaghetti and meatballs
Syphillis stain?
Warthin starry
*TPAL IHC is better
3 indications for DIF
AI vesiculobullous
Vasculitis
CTD (e.g. lupus)
What are 8 things on DDX for invisible dermatoses?
- Urticaria
- Hyperpigmentation d/o -melasma, ephelid, lentigo, cALM
- Hypopigmentation-vitiligo, peibaldism, nevus depigemntosus
- Urticaria pigementosa/TMEP
- MAcular amyloidosis
- Tinea
- Porokeratosis
- Ithcytosis
- Argyria
- Dermal mucinosis
- Anetoderma
- Atrophoderma
Others
