Histopathology COPY Flashcards
What are the patterns of the stratum corneum that can be seen on histopathology?
Basket weave (lacy) **normal
Lamellar/laminated (condensed, but separates)
Compact (dense, does not separate)
Parakeratotic (retained nuclei) versus normal orthokeratotic
What is parakeratosis indicate on histopathology?
Incomplete keratinocyte maturation or a defect in filaggrin conversion
Young Cocker spaniel
Epidermal hyperplasia (mild to papillated
Alternating vertical tiers of ortho- and parakeratosis)
Follicular plugging and follicular ostia w/ parakeratotic caps/epaulettes
Suggestive of primary seborrhea (ddx: allergy, Vit A-responsive)
10 yr MC Cocker spaniel with alopecic plaques and follicular casts
Severe follicular keratosis
Distended ostia with plug protrusion (follicular fronds)
Suggestive of vitamin A-responsive dermatosis
What do you expect to see on histopathology of non-epidermolytic ichthyosis?
Lamellar / laminated to compact orthohyperkeratosis (mild to severe)
- “filo dough effect”
- Goldens: abnormal keratin rather than ↑
- Focal parakeratosis can happen
Perinuclear clear spaces in granular layer
What do you expect to see on histopathology of epidermolytic ichthyosis?
Lamellar / laminated to compact orthohyperkeratosis (mild to severe)
Lysis of upper epidermal layers
Hypergranulosis with abnormal keratohyalin granules
Diffuse keratinocyte ballooning
What form of ichthyosis is this?
Non-epidermolytic
What form of ichthyosis is this?
Epidermolytic
What stains can be used to highlight the BMZ?
PAS - purplish
Which autoimmune subepidermal blistering diseases show dermal positioning of collagen IV/PAS staining of the blister using anti-collagen IV IHC or IF or PAS staining (patient’s biopsy sections)?
BP, PG, JEBA
Which autoimmune subepidermal blistering diseases show mixed positioning of collagen IV/PAS staining of the blister using anti-collagen IV IHC or IF or PAS staining (patient’s biopsy sections)?
JEBA
Which autoimmune subepidermal blistering diseases show epidermal positioning of collagen IV/PAS staining of the blister using anti-collagen IV IHC or IF or PAS staining (patient’s biopsy sections)?
EBA, bullous SLE
What are the advantages and disadvantages of indirect immunofluorescence?
Advantages
- Secondary signals may be amplified
- A few labeled secondaries can detect many primaries
- Greater flexibility
- Easy to change colors
Disadvantages
- Two-step staining process
- potential cross reactivity
- finding labeled primary antibody which is more difficult to get especially for multiple labeling experiments
Salt split skin, staining on roof
BP, PG
Salt split skin, staining on floor
EBA, JEBA, mixed, bullous SLE
Which AISBD is this most consistent with?
Mucous membrane pemphigoid
What can be used to differentiate MMP from EBA?
A positive PAS staining and/or anti-collagen IV IHC should label the dermal side (floor) of the blister in biopsies of MMP, not EBA
Which AISBD is this most consistent with?
Bullous pemphigoid, dog
What are the histopathologic findings associated with bullous pemphigoid?
Level of split: lamina lucida
Histopathology: subepidermal vesiculation +/- eos, neuts, fibrin
- Eos in the superficial dermis
- IgG, IgM, or IgA and/or complement deposited at the BMZ
Which AISBD is this most consistent with?
Bullous pemphigoid, horse
Which AISBD is this most consistent with?
EBA
What are the histopathologic findings associated with epidermolysis bullosa aquisita (EBA)?
Level of split: sublamina densa
Histopathology:
- subepidermal vesiculation with no to variable amounts of neutrophilic inflammation +/- fibrin or minor hemorrhage
- vacuolation and rowing of neutrophils and/or histiocytes occurs just below the BMZ
- Superficial dermal perivascular to interstitial dermatitis
This is a biopsy sample from a young Yucatan mini-pig. Which AISBD is this most consistent with?
BP
Why might the the sensitivity of PAS staining to determine if the roof or floor is stained be limited?
BMZ degradation during the blistering process
What is the histopathology associated with Junctional EBA?
Level of split: lamina lucida
Histopathology: subepidermal vesiculation +/-neutrophilic inflammation +/- eos
- potential superficial dermal perivascular to interstitial inflammation
What are the histopathologic signs associated with mixed AISBD?
Level of split: lamina lucida
Histopathology: microscopic subepidermal vesiculation with mixed neutrophilic eosinophilic inflammation
Is PAS, anti-collagen IV, or salt-split indirect IF staining is specific enough to confirm the diagnosis of mixed AISBD?
No
advanced immunotesting is needed to identify the mixed target autoantigens
not readily available in veterinary medicine
What are the histopathologic findings of Linear IgA Disease (LAD)?
Level of split: lamina lucida
Histopathology: microscopic subepidermal vesiculation +/- minimal neutrophilic inflammation
20 day old Eurasier dog. What genetic mutation is this associated with?
PLEC (autosomal recessive)
Epidermolysis bullosa simplex
What is the key histopathologic feature of pemphigus foliaceous?
acantholytic cells present in intraepithelial pustules and/or serocellular crusting
Pustular dermatophytosis
What are the histopathologic findings consistent with PV?
Intraepidermal clefts with suprabasilar acantholysis
Bulla base: row of plump/rounded basal keratinocytes (“tombstone”)
- Epidermis and/or follicles
+/ Acantholytic cells in clefts
Uninflammed if pustule is intact / neuts if detached
Ulcer + exudate are common
Dermis with lymphocytes/plasma cells, neuts (more lichenoid if junction)
IgG > C3 transepidermal and superficial follicular deposits
PV (note “tombstones”)
PV (note “tombstones”)
What is an important feature about the histopathology of pemphigus vegetans?
PV-type suprabasal acantholysis might not be present in all biopsies or it could have disappeared in some chronic lesions of PVeg, and thus multiple skin biopsies and a compatible clinical diagnosis might be required
What form of pemphigus is this consistent with?
PVeg
What are the histologic features of paraneoplastic pemphigus?
looks like PV (“tombstones”) + pustules + acantholysis + apoptotic keratinocytes (PV + EM +/- PF)
Clefts might be in variable layers (ex, lower spinosum) due to many targets
Variable neutrophil amounts
What form of pemphigus is this most consistent with?
paraneoplastic pemphigus
note apoptotic keratinocytes and tombstoning
PV + EM +/- PF
Canine Darier’s disease
This is a biopsy from a 4 month old dog. What genetic mutation is this associated with?
ATP2A2, Canine Darier’s disease, setters
What stain highlights collagen on histopathology?
Masson Trichrome
What special stains do you use for elastin?
Verhoff-van Gieson
acid orcein-Giemsa
Weigert
What color does mucin stain on H&E?
Blue
What stain is best to highlight mucin?
Alcian blue*
You can also use colloidal iron or mucicarmine
What does solar elastosis look like on histopathology?
Sad blue spaghetti
Can stain with van Geison or PAS
Solar elastosis
What is the best stain for proteoglycans on histopathology?
PAS
What special stains are best for looking for melanocytes on histopathology??
DOPA oxidase reaction
Fontana-Masson stain
Schmorl’s method
Which IHCs are best for looking at melanocytes on histopathology?
vimentin
S-100 protein
MelanA
*Early vitiligo
Lymphocytes infiltrate the basal layer of the epidermis (arrow heads) in
very low numbers at the junction of depigmented and non-depigmented epidermis
Pigmentary incontinence (arrow) accompanied by a very mild, mononuclear, perivascular, inflammatory cell infiltrate.
What are the histopathologic findings associated with canine uveodermatologic syndrome?
Perivascular to lichenoid inflammation (but not interface)
* Macrophages (dust melanin / “peppered”)»_space; neuts, lymphs, plasma cells
* Inflammation can be periadnexal and nodular
Partial to complete loss of basal cell melanin / melanocytes
* Depigmentation
Exocytosis of lymphocytes and/or neutrophils
*but basal keratinocyte damage (interface dermatitis) is limited or absent
canine uveodermatologic syndrome
lymphocyte satellitosis around melanocytes
“peppered”/dust-like melanosomes
What are the histopathologic findings associated with non-ectodermal hair follicle dysplasias in dogs?
Normal epidermis and dermis
Infundibular dilatation and keratin plugging (hyperkeratosis)
Hair follicle w/ irregular outer contours +/- vacuolar change
Scattered clumps of melanin
Small anagen or telogen (but decreased number in anagen)
Variably distorted/atrophic (absent, fragmented, or thin) hair shafts
What is the histopathology of recurrent flank alopecia?
Mildly acanthotic epidermis
Often hypermelanotic epidermis (including SC and sebaceous glands)
Infundibula are dilated, elongated, and plugged with orthokeratosis
Lower compound HF are short, atrophic, distorted
- “witches’ feet”
Recurrent flank alopecia
This dog was born looking like this. What genetic mutation do you suspect?
A form of ectodermal dysplasia (probably FOX13)
White arrows: dysplastic epidermal portion of follicle
Black arrows: mesenchymal cells aggregates
A Spanish water dog presents with regionalized hair loss on the dorsum, the rump, and parts of the lateral thorax. What is occuring?
Follicular dysplasia in Spanish and Portuguese water dogs
note
- B: shaft and IRS formation is impaired in the suprabulbar region
- C: fragmented hair shaft
- D: Vacuolar changes in the IRS and the matrix cells
Color dilution alopecia
What are the histopathologic findings of alopecia X?
reduced number of anagen follicles
relatively high number of telogen/kenogen/atrophic follicles
looks similar to endocrinopathies (esp hyperestrogenism)
Bald thigh syndrome
note that hair shafts are fractured and trichilemmal keratin is assembled underneath the hair shaft
What are the histopathologic features typical of hyperestrogenism?
decreased anagen follicles
mainly telogen and kenogen follicles
*like alopecia X
*may also have follicular atrophy
What are the histopathologic features typical of hyperadrenocorticism?
abundant kenogen follicles
severe follicular, dermal, and epidermal atrophy
- atrophy of sebaceous glands to
comedones
+/- calcinosis cutis
What are the histopathologic features typical of hypothyroidism?
primary hairs in anagen or telogen, normal size
secondary hairs in kenogen or atrophic
epidermal hyperplasia (if concurrent infections are present)
rare dermal mucinosis
What are flame follicles?
exaggerated regressing follicles with large spikes of fused keratin protruding thru ORS to vitreous layer –> result in abnormal catagen phase with overabundant tricholemmal keratin
Alopecia areata
(good differential would be cutaneous epitheliotropic lymphoma since it can preferentially affect hair follicles)
What are the typical histopathologic findings associated with alopecia areata?
Lymphocytic bulbitis which may progress to isthmus
- “swarm of bees”
What are the histopathologic signs associated with sebaceous adenitis?
mild to moderate acanthosis
moderate to severe hyperkeratosis with follicular plugging
granulomatous to pyogranulomatous reactions at level of sebaceous gland
- histiocytes, neutrophils, lymphocytes and plasma cells
in chronic stages there will be a loss of sebaceous glands
perifollicular fibrosis can be present
What is histopathology finding associated with ischemic dermatopathy?
Histopathology:
- primary and secondary HFs are severely atrophic and may be absent
–> aka “fading” follicles
- Perifollicular collagen is prominent and homogenized
- +/- lymphoplasmacytic cell poor interface dermatitis
- inflammation of the vessel walls is seen rarely in dogs
–> may have loss of vascular distinction or endothelial cells
What IHC stain is useful for diagnosis of vascular neoplasms and for identification of vascular invasion by neoplasms?
Factor VIII-related antigen
What IHC stain would you use to identify veil cells?
Factor XIIIa (indicates that it is part of the dermal dendrocyte system)
What are the histopathologic findings of rabies vaccine-associated vasculitis?
- Lymphocytic vasculitis and cuffs in subcutis
Cell-poor interface dermatitis, vacuolation in basal cell layer, pigmentary incontinence, and mural folliculitis - Amorphous blue-to-gray granules (vaccine material)
Macrophages or free in matrix
Atrophy and hyalinization of the dermis with mucin (pallor & smudgy)
Marked atrophy and pale staining of hair follicle
From a hyperpigmented patch on the right hip of a Yorkshire terrier
Post-rabies vaccination vasculitis/panniculitis
What is typical of histopathology of acute and sub-acute vasculitis?
There are well circumscribed dermal and epidermal areas of coagulation necrosis, micro-hemorrhages, marked protein-rich edema and deposition of fibrin
The vessel walls are thickened and edematous with hyalinization and fibrinoid necrosis; the endothelial cells are swollen and necrotic (cell-poor vasculitis or vasculopathy)
Degenerative changes may be associated with intramural inflammation. The presence of degenerative neutrophils, referred to as leukocytoclasia, is pathognomonic for vasculitis
Presence of inflammatory cells within arterial and venous walls indicates vasculitis, as leukocyte migration does not occur through arteries and veins
The nature of the inflammatory infiltrate may change over time.
There may be deposition of PAS-positive material within the vessel walls
What is seen on histopathology of lymphocytic vasculitis?
tight cuffs of small CD8+ lymphocytes surrounding primarily small arterioles
When is lymphocytic vasculitis typically seen on histopathology?
chronic resolving stages of immune-complex vasculitis (vaccine-induced panniculitis, vasculopathy of German Shepherds, drug reactions)
What is typical of histopathology of chronic vasculitis?
Predominant changes are atrophy of the hair follicles and adnexal glands
The subepidermal collagen is homogenized and pale
Newly formed, arborizing thin collagen btw preexisting dermal collagen
Mucin deposition may be present
The number of small dermal vessels may be decreased
The vascular walls appear thickened and hyalinized and a decrease of factor VIII+ endothelial cells is apparent
The overlying epidermis may be atrophic
Features of cell-poor interface dermatitis are common
Larger areas of scaring may be present
5-year old male Labrador Retriever that presented with bilateral ulceration and necrosis of its ear tips
Thrombovascular necrosis of pinnae (pinnal margin vasculopathy aka ischemic necrosis of pinnae)
Arteriopathy, nose
(a) discrete linear epidermal ulceration (arrow) and underlying dermal arteriopathy (arrowhead); (b) marked acanthosis with underlying dermal arteriopathy (arrowheads). (c–e) High-power fields showing a dermal arteriole: (c) with a markedly expanded tunica intima/media and no adjacent vessel-oriented inflammation; (d) with strong Alcian blue uptake within the tunica intima/media, consistent with mucin deposition; (e) with strong tunica intima/media basophilic staining using Masson’s trichrome, consistent with collagen deposition.
pastern leukocytoclastic vasculitis
What are the histopathologic findings for leukocytoclastic vasculitis?
intramural inflammatory cells (blood vessels)
leukocytoclasia with nuclear dust
microhaemorrhages
thickening of the vessel wall
What histochemical stains are good for staining mast cell granules?
toluidine blue or Romanowsky combination dyes
*due to proteoglycans such as heparin
Alcian blue and safranin
Sudan Black B
Luna stain
Ziehl-Neelsen
Which IHC stains are good for mast cells?
c-kit
CD31
tryptase and chymase
