Skin Pathology Flashcards
What are prickle cells?
Prominent desmosomes
What is the granular layer rich in?
Keratohyalin granules
What is present in the corneal layer?
Differentiated keratinised cells
Where is the papillary dermis found?
Lies just beneath epidermis, thin
What is present in the reticular dermis?
Thick bundles of type 1 collagen, also appendage structures: sweat glands, pilosebaceous units
What is the epidermal basement membrane made of?
Laminin and collagen IV
What are the 4 main reaction patterns in classification of inflammatory skin diseases?
Spongiotic, Psoriasiform, Lichenoid, Vesiculobullous
What does Psoriasiform mean?
Elongation of the rete ridges e.g. psoriasis
What does Lichenoid mean?
Basal layer damage e.g. lichen planus and lupus
What does Vesiculobullous mean?
Blistering e.g. pemphigoid, pemphigus and dermatitis herpetiformis
What is the Koebner phenomenon?
New psoriasis lesions arising at the sites of trauma
What possible pathogenesis occurs to form psoriasis?
Epidermal hyperplasia resulting in increased epidermal turnover. Complement mediated attack on keratin layer- complement attracts neutrophils to layer
What are the causes of acne?
Increased androgens at puberty, increased androgen sensitivity of sebaceous glands, increased keratin plugging of pilosebaceous units, infection with anaerobic bacterium corynebacterium acnes
What is the term for thickening of the skin in rosacea?
Rhinophyma
What are some factors involved in rosacea pathology?
Vascular ectasia Patchy inflammation with plasma cells Pustules Perifollicular granulomas Follicular Demodex mites often noted Allergic reaction to mites? Or reaction to bacteria on mite
What is the primary features of immunobullous diseases?
Blisters
What occurs in the epidermis in pemphigus?
Loss of integrity of epidermal cell adhesion
What is Pemphigus vulgaris?
AI condition, IgG auto-antibodies made against desmoglein 3.
What is the pathophysiology of pemphigus vulgaris?
Desmoglein 3 maintains desmosomal attachments, immune complexes form on cell surface. Complement activation and protease release. Disruption of desmosomes. End result is Acantholysis
What kind of blister is found in Bullous pemphigoid?
Subepidermal
What is the pathophysiology of Bullous pemphigoid?
Circulating antibodies (IgG) react with a major and/or minor antigen of the hemidesmosomes anchoring basal cells to basement membrane. The result is local complement activation and tissue damage
What haplotype is dermatitis herpetiformis associated with?
HLA-DQ2
What disease is strongly associated with Dermatitis herpetiformis?
Coeliac disease
What is the hallmark of Dermatitis herpetiformis?
Papillary dermal microabscesses
What is the pathophysiology surrounding IgA in dermatitis herpetiformis?
DIF shows deposits of IgA in dermal papillae
IgA antibodies target gliadin component of gluten but cross react with connective tissue matrix proteins
Immune complexes form in dermal papillae and activate complement and generate neutrophil chemotaxins.
Where are melanocytes derived from?
Neural crest
Early in embryogenesis melanoblasts migrate from the neural crest to where to form melanocytes?
Skin, uveal tract, leptomeninges
What gene encodes MC1R protein?
Melanocortin 1 receptor gene
What does MC1R protein and gene determine?
Balance of pigment in skin and hair
What melanin colours hair apart from red, and which one colours red?
Eumelanin all apart from red, phaeomelanin causes red
What does MC1R to do phaeomelanin?
Turns it into eumelanin
What does 1 defective copy of MC1R cause?
Freckles
What do 2 defective copies of MC1R cause?
Freckles and red hair
What is the medical term for freckles?
Ephilides (single ephelis)
What do ephilidies reflect?
Clumpy distribution of melanocytes
What are age/liver spots called?
Actinic or solar lentigines
Where can actinic lentigines be found on the surface and histologically?
Face, forearms and dorsal hands. Found in epidermis elongated rete ridges.
What do actinic lentigines represent?
Increased melanin and basal melanocytes
How are congenital melanocytic naevi sized?
Small 2cm but
What causes the formation of simple naevi?
During infancy the melanocytes : keratinocyte ratio breaks down at several cutaneous sites
Describe acquired naevi development
Junctional naevus- melanocytes proliferate > clusters of cells at DEJ. Compound naevus- junctional clusters + groups of cells in dermis. Intradermal naevus- all junctional activity has ceased; entirely dermal
What are common features of dysplastic naevi?
Generally >6mm diameter, variegated pigment, border asymmetry
Describe sporadic dysplastic naevi
Not inherited, one to several atypical naevi, risk of MM slightly raised
Describe familial dysplastic naevi
Strong FHx of melanoma, autosomal inheritance, high penetrance e.g.CDKN2A, atypical naevi++, lifetime risk of melanoma up to 100%
What atypia occurs in dysplastic naevi?
Architectural and cellular
What is the host reaction in dysplastic naevi?
Fibrosis and inflammation.
What occurs to the epidermis in dysplastic naevi?
Epidermis is not effaced (unlike melanoma)
What are halo naevi?
Rare naevi that have a peripheral halo of depigmentation. Show inflammatory regression and are overrun by lymphocytes
What are blue naevi?
Rare naevi, entirely dermal and consist of pigment rich dendritic spindle cells. Cellular variant may have mitoses and mimic melanoma
What are Spitz naevi?
Rare naevi, used to be known as benign juvenile melanoma. Usually occur
Where are malignant melanoma commonly found?
Any site in skin, for females leg is most common, trunk for men. Females 2:1 Males. Rare in childhood, incidence peaks middle age. Sun exposed sites most common
What is the aetiology of malignant melanoma?
Sun exposure (esp childhood). UV exposure important in skin/eye melanomas. Multifactorial, genetic risk)- skin colour and/or dysplastic naevi.
Where does malignant melanoma rarely occur?
Eye, meninges, oesophagus, biliary tract, anus
What factors would you look out for to make you suspect melanoma?
New pigmented lesion develops in adulthood, change in shape, irregular pigmentation, bleeding, development of satellite nodules, ulceration
What are the 4 main types of melanoma?
Superficial spreading-commonest-trunk and limbs
Acral/mucosal lentiginous-acral and mucosal
Lentigo maligna-sun-damaged face/neck/scalp
Nodular-varied sites but often trunk
What does acral mean?
On palms, soles or under nails
Describe the growth of SSM, A/MLM, LMM
Grow as macules when either entirely in-situ or with dermal microinvasion - this is RGP
Eventually the melanoma cells invade the dermis forming an expansile mass with mitoses - this is VGP
Only VGP melanomas can metastasise
Describe growth of nodular melanoma
No clinical/microscopic evidence of RGP. Simply nodule of VGP tumour, possibly more aggressive
What melanoma lesions have RGP +/- VGP?
SSM, A/MLM, LMM
What melanoma lesions have VGP only?
Nodular melanoma
What does Breslow mean?
Deepest tumour from granular layer in mm
Describe the classification of melanoma prognosis
pTis-melanoma is in-situ-100% survival
pT1-tumour 4mm thick-20% survival. Suffix b (pT4b) indicates tumour with ulceration
What is a strong prognostic indicator in melanoma?
Ulceration
What are other strong prognostic indicators other than ulceration in melanomas?
High mitotic rate, lymphovascular invasion, satellites, sentinel lymph node involvement
What is the order of spread of malignant melanoma?
- Local dermal lymphatics > satellite deposits of MM
- Regional lymph node metastases-common pattern. Nodes will be excised (radical lymphadenectomy).
- Blood spread > skin/soft tissue, heart, lungs, GI tract, liver, brain
Describe melanoma treatment
Primary excision to give clear margins
Some also receive a sentinel node biopsy
If SN positive - regional lymphadenectomy
Treatment of advanced disease difficult
Chemo, immunotherapy, genetic therapies
Describe melanoma excision treatment
Narrow complete excision needed. If in-situ then clear by circa 5mm, if invasive but 1mm thick: 2cm clearance. SNB if >1mm thick or thinner with mitoses
What genetic angles have been discovered in melanoma?
Some acral melanomas have c-kit mutations and may be treated with imatinib
Melanomas on intermittently sun-exposed skin may have a BRAF mutation
Can test for mutations on paraffin fixed tissue
What is wild type BRAF?
Weak cytosolic proto-oncogene
What happens if BRAF is mutated, and what drugs have been developed to interfere with this pathway?
Drives cell proliferation by up regulating MEK/ERK. Dabrafenib and vemurafenib used to block action of BRAF
Name some epidermal tumours
Benign-seborrhoeic keratosis
Precancerous dysplasias-Bowen’s disease, actinic keratosis and viral lesions
Invasive malignancies-basal and squamous cell carcinoma
Descrive seborrhoeic keratosis’
Benign proliferation of epidermal keratinocytes. Common face/trunk. Stuck on appearance- greasy hyperkeratotic surface.
Describe the pathophysiology of BCC
Basal cells sprout from epidermis
Groups of cells invade dermis
Peripheral palisading
Mitoses and apoptoses very numerous
Slow growing, locally destructive
Almost never metastasises
May kill by invading eye brain
