HISTO: Skin Pathology Flashcards
What are the layers of the skin? How thick is it?
Epidermis, dermis and subcutaneous fat = ~6 mm thickness
Under this there is a supportive matrix of collagen and elastic fibres. With age both layers become thinner.
Where are sebaceous glands not found?
palmar-plantar skin
Label this diagram.
Label this diagram.
List the types of inflammatory reaction patterns.
Epidermis:
- Spongiotic
- Lichenoid
- Psoriasiform
- Vesiculobullous
Dermis
- Vasculitis
- Granulomatous
Subcutis
- Pannicullitis (e.g. erythema nodosum)
Give examples of spongiotic reactions in the skin.
Eczema -
What are the features of spongiotic reaction on histology?
Spongiosis = intraepidermal oedema
Superficial perivascular lymphocytic infiltrate
Spongiosis with exocytosis of lymphocytes into the epidermis; vesicles containing antigen presenting Langerhan cells and T cells
Give an example of lichenoid inflammation.
- Lichen planus
- Erythema multiforme - targetoid lesions
- Toxic epidermal necrolysis
- Stevens-Johnson syndrome
In the last few, lymphocytes attack the base of the epidermis causing basal vacuolation.
What are the charactristics of lichen planus?
Shiny, purple, flat topped scaly papules and plaques
Wickham striae
Autoimmune disease where T cells attack the epidermis
What are the histological features of lichen planus?
- Irregularly thickened epidermis
- Degenerative skin cells
- Liquefaction degeneration of the basal layer of the epidermis
- End of inflammatory cells just beneath the epidermis
- Melanin (pigment) beneath the epidermis
- There is damage to the epidermis and vacuolar degeneration of keratinocytes and cell death (i.e. loss of nucleus causing the pink cells shown below)
Which cells mediate lichen planus?
T lymphocytes form a band at the junction between the epidermis and dermis and create band-like inflammation so that it is difficult to distinguish the junction between dermis and epidermis
What is the name given to white lines in the mouth seen in lichen planus?
Wickham striae
Give an example of a psoriasiform reaction.
Psoriasis
What are the characteristics of psoriasis and its histology findings?
Abnormally rapid turnover of the epidermis results in accumulation of thick scale over sites of frequent trauma and irritation like extensor surfaces. Silver plaques form.
- Acanthosis
- Hypogranulosis (less granular layer)
- Parakeratosis (cells in the stratum corneum retain their nuceli as there is no time to lose them)
- Neutrophils in the stratum corneum forming Munro’s microabscesses
What is the normal time for keratinocyte turnover and what is the turnover in psoriasis?
Normal - 28-56 days
Psoriasis - 7 days (much shorter than normal)
What is an example of vesiculobullous reaction pattern?
Autoimmune vesiculobullous disorders i.e. antibodies attacking the epidermis
- Pemphigoid
- Pemphigus
What part of the skin layers is affected in bullous pemphigoid vs pemphigus vulgaris?
Bullous pemphogoid = dermo-epidermal junctions
Pemphigus vulgaris = epiderma-epidermal junctions
Describe the pathophysiology of bullous pemphigoid.
- Epidermal basement membrane is destroyed by autoantibodies (IgG and C3)
- Eosinophils recruited to release elastase which damages anchoring proteins
- Direct immunofluorescence will show linear IgG (anti-hemidesmosome)
- Fluid fills the gap between the BM and epithelium
What is the difference between bliseters in pemphigoid and pemphigus?
Pemphigoid - tense
Pemphigus - flaccid
Who is most affected by bullous pemphigoid? Where do lesions form? What is the mortality rate?
- Elderly, autoimmune, high mortality rate (10-20%)
- Flexor surfaces, tense bullae
What are the two types of pemphigus?
- Pemphigus foliaceous - superficial form
- Pemphigus vulgaris - deep form
What is the pathophysiology of pemphigus vulgaris?
- IgG attacks between the keratin layers (epiderma-epidermal junctions) and the cell connections between keratinocytes fall apart by acantholysis
- Top epidermis sloughs off
- Immunofluorescence shows intercellular deposits of IgG in a chicken wire pattern (IgG is surrounding individual keratinocytes)
What are the clinical features of pemphigus?
- Flaccid blisters which rupture easily
- Also affects mucous membranes
What are the features of pemphigus foliaceus?
- Top layer is affected
- IgG mediated - outer layer of stratum corneum shears off
- Never blisters as the top layer of skin is very thin
What are the histopathological features of seborrhoeic keratosis?
- Acanthosis
- Horn pseudocysts
- Well defined borders
- Stuck on appearance
What are the clinical features of basal cell carcinomas? Which mutation is the underlying cause in some BCC?
- Most common form of skin cancer
- Rolled, pearly-edge, central ulcer, telangiectasia
- Occurs on sun exposed areas
- Benign but can disfigure - “rodent ulcer” as it burrows away
PTCH mutation
What are the histological features of basal cell carcinoma?
- Basaloid - cancer arises from the keratinocytes at the bottom of epidermis
- Peripheral palisading
- Clefting
- Mitotic activity
- “Blue” tumour as more nucelus than cytoplasm seen unlike SCC
Describe the hitological and clinical features of actinic keratosis.
- Pre-cancerous areas of thick, scaly skin due to keratinocyte damage by UV exposure.
- Affect the basal epidermis
- Dysplasia
- Abnormal stratum corneum - parakeratosis (mode of keratinization characterized by the retention of nuclei in the stratum corneum)
What is another name for SCC in situ? What are the histological features?
Bowen’s disease = SCC in situ i.e. pre-cancerous
- Full thickness atypia
- BM intact
- Increased mitotic activity
- Keratinocytes become pleiomorphic and larger with mitosis
- Dysplasia can be low, moderate or high grade
What does “poorly differentiated” SCC mean?
You cannot identify the origin cell lineage
What are the histological features of SCC?
- “pink” tumour unlike BCC which is more blue due to more nuceli
- Irregular aggregates of pink cells
- Infiltrating the dermis
- Keratin pearls often characteristic of SCC
- May show local invasion
- Can metastasise
Name 3 types of benign naevi.
- Junctional nevus
- Compound nevus
- Intradermal nevus
What is the general histological feature of benign naevi?
- Found in organised nests
- Mature with depth and cells get smaller the deeper they are
- No mitotic activity in dermis
- Junctional naevus - nests in the epidermis
- Comound naevus - nests in epidermis and dermis
- Intradermal naevus - nests in dermis
What are the A-G features of malignant melanoma?
Where are melanocytes usually found in the skin? What happens with age?
Usually in the basal layer of the epidermis but can also exist in the dermis
With age more melanocytes enter the dermis and so you may get more junctional naevi
What are the histological features of malignant melanoma?
- Cellular atypia
- Asymmetry
- Pagetoid spread is marker of melanoma (individual cell proliferation in the upper levels of the epidermis)
Which markers can be found in melanoma by immunohistochemistry?
- Melan A
- S100
- HMB45
What is the strongest prognostic factor in melanoma? What is the second most useful prognostic factor?
- Breslow thickness
- Ulceration
Then others include:
- Lymphovascular invasion
- Perineural invasion
- Clark level
- Microsatellites
- TILs
- Regression
- Mitotic index
Which mutation is found in 50% of melanomas?
About 50 % of melanomas harbors activating BRAF mutations (over 90 % V600E) - not necessarily a change in prognosis
Define Breslow thickness. When is prognosis best?
Breslow thickness is measured from the top of the granular layer of the epidermis (or from the base of the ulcer) to the deepest invasive cell across the broad base of the tumour (dermal/subcutaneous).
Described by Breslow
Prognosis best with thickness <0.8mm.
Define pagetoid spread.
- The junctional melanocytes are not normally maturing and dropping out of the dermis – they are moving up through the dermis instead = “Pagetoid spread” this is NOT normal
