Histopathology - Skin Flashcards
Haematoxylin + Eosin stain
- Haematoxylin Blue/purple stain – stains RNA + DNA (nucleus)
- Eosin stain cytoplasma, collagen
- Nuclei > cytoplasm – tissue looks more blue/purple
- Cytoplasma/collagen > nuclei – tissue looks more pink
Layers of the epidermis
“come, lets get some beers”
o Stratum basale – blue (little cytoplasm, more nuclei), where the keratinocytes are born (there are stem cells within the basal epidermis which divide to produce the rest of the epidermis) (most deep) - melanocytes usually seen here
o Stratum spinosum – thickest layer, desmosomes/spines connect keratinocytes to each other, this gives strength to the epidermis
o Stratum granulosum – purple granules in cytoplasm
o After this, the cells die and lose their nuclei – left with keratin shells
o Stratum lucidum
o stratum corneum (most superficial)
Eczema under the microscope
Defect in epidermis
Spongiosis/ intercellular oedema (white spaces bn cells)
Exocytosis of lymphocytes into the epidermis
Blisters/Vesicles containing oedema, lymphocytes, Langerhans cells
What is acanthosis?
Increase in stratum spinosum
Acute and chronic histology of atopic and contact dermatitis
Acute
- Spongiosis
- Inflammatory infiltrate in the dermis
- Dilated dermal capillaries
Chronic
- Acanthosis
- Crusting, scaling
What are Wickham striae?
• White striations over the surface of the lichenification
Lichen planus pathophysiology
• Autoimmune disease
o T-cell mediated, T lymphocytes start attacking the base of the epidermis
• Liquefaction degeneration of the basal layer of the epidermis
o T-lymphocytes have destroyed bottom keratinocytes
o Creates band-like inflammation
• Band of lymphocytes at the dermal-epidermal interface
o Cannot see where dermis finished, and epidermis starts
Give examples of spongiotic reaction
Eczema
Discoid eczema
Contact dermatitis
Give examples of lichenoid inflammation
Lichen planus
Erythema multiforme
Steven Johnson syndrome
Toxic epidermal necrolysis
Lichenoid inflammation pathophysiology
Lymphocytes attacking the base of the epidermis
Band of lymphocytes, dead keratinocytes, basal vacuolation
Liquefaction degenerating of the basal layer of the epidermis
Band of inflammatory cells beneath epidermis
Melanin beneath the epidermis
Irregularly thickened epidermis
TEN vs SJS
- TEN widespread process, sloughing off of the skin
- SJS mucus membranes are also affected
Skin detachment
<10% body surface area in SJS
>30% in TEN
Erythema multiforme causes causes
Infections – HSV, mycoplasma
Drugs – SNAPP – Sulphonamides, NSAIDs, Allopurinol, Penicillin, Phenytoin
What is
- Auspitz’s sign
- Koebner phenomenon
Signs of psoriatic arthritis
- Auspitz’s sign – rubbing them causes pin point bleeding
- Koebner phenomenon – lesions form at sites of trauma
Hallmarks of psoriasis under microscope
Acanthosis = increase in stratum spinosum
Parakeratosis = nuclei in s. corneum
o Histo – parakeratosis, acanthosis, loss of granular layer, clubbing of rete ridges giving “test tubes in a rack” appearance, Munro’s microabscesses
Psoriasis pathophysiology
Defect in epidermis
o Normal keratinocyte turnover time = 56 days
o Psoriasis keratinocyte turnover time = 7 days – increased proliferation rate
o Rapid turnover thicker epidermis = acanthosis
o Hypogranulosis No time for a granular layer to form stratum granulosum disappears
o Parakeratosis = Keratinocytes carry their nuclei into the stratum corneum (no time for nuclei to be lost)
o Inflammatory cells/lymphocytes attract neutrophils – Neutrophils in stratum corneum
o Munro’s microabscesses form (recruitment of neutrophils)
o Dilated vessels form
o Pathophysiology – Type IV T cell hypersensitivity reaction
• accumulation of thick scale over sites of frequent trauma or irritation
Give examples of vesiculobullous reaction pattern
• Antibodies attacking the epidermis
Dermatitis herpetiformis
Bullous Pemphigoid
Pemphigus vulgaris
Pemphigus foliaceus
Pemphigoid vs pemphigus
• Different forms based on which part of the epidermis these antibodies attack
o Pemphigoid – antibodies attack the BM (SUBepidermal blisters)
o Pemphigus – antibodies against the desmosomes (INTRAepidermal blisters)
Pemphigus foliaceous – superficial form
Pemphigus vulgaris – deep form
Pathophysiology + histology of dermatitis herpetiformis
coeliac disease, itchy vesicles on elbows + buttocks
IgA ab bind to BM - subepidermal blisters
Histo
Microabscesses coalesce together forming subepidermal blisters
IgA +neutrophil deposits at tips of dermal pappilae
Bullous pemphigoid what is affected?
Dermo epidermal junction
IgG antibodies + C3 bind to hemidesmosomes of BM –> elastase released by oesinophils destroys anchoring proteins –> fluid fills space between epitheliumand BM –> subepidermal bullae
Bullae
- SUBepidermal
- Deep
- Tense
- Do not rupture as easily as in pemphigus
Histo
- Linear deposition of IgG along BM (IgG antihemidesmosome)
- Subepidermal bulla with oesinophils
What is pemphigus foliaceous
- Epidermis
- Superficial form
- Top layer is very thin – never blisters
• Pathophysiology
o IgG-mediated
o Outer layer of striatum corneum shears off
• Diagnose with immunofluorescence
Pemphigus vulgaris pathophysiology + histology
Epidermis
IgG antibodies against desmoglein 1 + 3
- INTRAepidermal bullae
- Acantholysis (keratinocytes in stratum spinosum fall apart bc f antibodies)
- Flaccid blisters, rupture easily - red raw surface
- Nikolsky’s sign +ve
Histology
- INTRAepidermal bulla
- Acantholysis
- Intracellular IgG deposition in a netlike/chickenwire pattern around the keratinocytes
What is pyoderma gangrenosum?
- Vasculitis
- Non-healing ulcer
- Often first manifestation of a systemic disease – colitis, hepatitis, leukaemia
Seborrhoeic keratosis buzzwords
Cauliflower appearance
stuck on appearance
benign
Histology horn pseudocyst acanthosis ordered and benign growth of epidermis http://mohs-md.com/wp-content/uploads/2018/05/seborrheic-keratosis.jpg
Histology of actinic keratosis
Pre-malignant cells are proliferating at the base of the epidermis
BM is not lost
SPAIN Solar elastosis Parakeratosis Atypia/Dysplasia Inflammation Not full thickness
general structure of skin
Epidermis
Basement membrane
Dermis
What is a keratoacanthoma
- Rapidly growing dome shaped nodule
- May develop a necrotic, crusted centre
- Grows over 2-3 weeks + clears spontaneously
- Similar histology to SCC – hard to differentiate
What is Bowen’s disease
• intra-epidermal Squamous cell carcinoma in situ (i.e. pre-cancerous)
o Full thickness dysplasia (whole thickness of the epidermis)
o BM is still intact i.e. not invading the dermis
- Hasn’t yet become invasive
- Flat, red, scaly patches on sun exposed areas
- Not always in the context of sun exposure
SCC buzzwords
squamous cell carcinoma
When Bowen’s disease invades the BM –> atypia/ dysplasia throughout the epidermis, nuclear crowding and spreading through BM into dermis
Similar to Bowen’s disease but may ulcerate
Pink under the microscope
Peri-neural invasion
Can metastasise through blood vessels
Keratin pearls
Keratinocytes in dermis
Basal cell carcinoma buzzwords
Commonest form of skin cancer
PTCH mutation
Arises from stratum Basale - mass of basal cells (cancer from keratinocytes at the bottom of the epidermis)
nuclei > cytoplasm = blue tumour
Palisading
Does not invade the BM –> does not metastasise
Where do melanocytes normally exist?
Basal layer of epidermis
Dermis as single cells
- Junctional naevus
- Compound naevus
- Intradermal naevus
• Junctional naevus
o Melanocytes nest in the epidermis
o Flat and coloured
• Compound naevus
o Melanocytes nest in the epidermis and dermis
o Raised area
o Surrounded by flat pigmented area
• Intradermal naevus
o Melanocytes nest in the dermis
o Raised area
o Skin-coloured or pigmented
Mutations associated with malignant melanoma
BRAF V600E mutation
How do melanocytes grow in malignant melanoma?
Initially grow horizontally (radial growth phase)
then vertically (vertical growth phase)
vertical growth phase produces “buckshot appearance” - pagetoid spread (upward spreading of abnormal melanocytes in the epidermis (these cells are normally found along the base of the epidermis))
what is pagetoid spread
pagetoid spread (upward spreading of abnormal melanocytes in the epidermis (these cells are normally found along the base of the epidermis))
seen in malignant melanoma
Most important prognostic factor for malignant melanoma
Breslow thickness
<0.8mm good prognosis
>4mm >50% mortality
measured for granular layer of epidermis to last abnormal melanocyte
Behaviour of melanocytes in the dermis in malignant melanoma
large melanocytes with mitotic activity in the dermis
Normal physiology
- Bigger melanocytes between the dermal/epidermal junction and then they get smaller as they go down into the dermis
- You shouldn’t be seeing mitotic activity in the dermis
The junctional melanocytes are no longer maturing + dropping out of the dermis
They are moving up through the dermis instead = pagetoid spread
This is not normal
o Melanocyte immunomarkers that can be stained using immunohistochemistry
Melanin A
S100
HMB45
What is Pityriasis Rosea
o Salmon pink rash appears first (= herald patch)
o Followed by oval macules in Christmas tree distribution
o Appears after viral illness
o Remits spontaneously
