Pathology Flashcards
Pathology of dermatological diseases
What are the functions of the skin?
Barrier Thermoregulation Fluid and electrolyte balance Endocrine function Melanin pigment Immune function Sensory function
Describe the papillary dermis
Thin, lies just beneath the epidermis
Describe the reticular dermis
Thicker bundles of type 1 collagen and contains appendage structures
Define hyperkeratosis
Increased thickness of the keratin layer
Define parakeratosis
Persistence of nuclei in the keratin layer
Define acanthosis
Increased thickness of the epithelium
Define spongiosis
Oedema in the epidermis
What are the 4 main reaction patterns for inflammatory skin disease
Spongiotic-intraepidermal oedema
Psoriaform elongation of the rete ridges
Lichenoid basal layer damage
Vesiculobullous blistering
Describe the Koebner phenomenon
New psoriasis lesions arising at sites of trauma
What are lichenoid disorders characterised by?
Damage to the basal epidermis
Histology of lichen planus
Irregular sawtooth acanthosis
Band like upper dermal infiltrate of lymphocytes
Basal damage with formation of cytoid bodyes
What is irregular sawtooth acanthosis?
Jagged appearance of the rete ridges of the epidermis
What is the presentation of immunobullous disorders?
Vesicles and bullae occur as secondary phenomena in many skin diseases
What happens to form bullae in pemphigus?
Loss of integrity of epidermal cell adhesions
Describe the mechanism of pemphigus vulgaris
IgG auto-antibodies made against desmoglein 3
Desmoglein 3 maintains desmosomal attachments
Immune complexes form on the cell surface
Complement activations and protein release
Disruption of desmosomes
Acantholysis
What happens to form bullae in bullous pemphigoid
Sub-epidermal blister without evidence of acantholysis
What is dermatitis herpetiforms strongly associated with
Coeliac disease
What are the hallmarks of dermatitis herpetiforms?
Papillary dermal micro-abcesses
What is the mechanism of dermatitis herpetiforms?
Direct immunoflouresence shows deposits of IgA in the dermal papilla
Targets the gliadin component of gluten but cross react with connective tissue matrix proteins
Immune complexes form in dermal papilla and activate complement
What is acne a disorder of?
The sebaceous glands
What is the mechanism of acne?
Keratin plugging of pilosebaceous units
What is the prevalence of rosacea in caucasian adults?
~10%
How does rosacea present?
Recurrent facial flushing
Leading to eventual thickening of the skin
What is often noted in rosacea?
Follicular demodex mites
What is an oncogene?
An overactive form of a gene that positively regulates cell division
What is a tumour suppressor
A gene that down regulates cell division
What are the two forms of melanin and which is more efficient?
Eumelanin and pheomelanin
Eumelanin is more efficient
What are the 5 types of DNA damage?
Altered or missing base Incorrect base Insertion/deletion Strand break Crosslinking
What are the two major types of UVB-induced DNA lesions?
Cyclobutane pyrimidine dimers
Pyrimidine-pyrimidone (6-4) photo-products
What repairs UVB induced lesions
DNA polymerase
How does UVA cause damage to DNA
Via the oxidation of DNA bases
Outline excision repair of DNA
Repair of oxidised bases
- Recognition of chemically altered base causing slight helix distortion
- Cleavage of altered base from the deoxy-ribose by DNA glycosylase
- Base-free deoxyribose cleaved away endonuclease
- Single nucleotide gap filled by DNA polymerase beta
- DNA ligase seals the end
How do UV rays induce immunosuppression?
Depletion of langerhans cells
UV induced regulatory T cells with immune supressive activity
Secretion of anti-inflammatory cytokines by macrophages and keratinocyes
What mutations are important in BCC?
Mutations in PTCH1
Key component of hedgehog signalling pathway
What does hedgehog signalling do?
Activates transcription factors Gli 1/2, leading to induction of cell proliferation genes and angiogenesis factors
What drug can be used in the case of mutation in PTCH1?
Vismodeglib
What genes have been linked to familial melanoma?
CDKN2A
CDK4
What does CDKN2A do?
Prevents cells from replicating when they contain damaged DNA by activating G1/S
What does CDK4 do?
Permits cell cycle progression by phosphorylation of retinoblastoma protein
What are the important mutations in melanoma?
Ras/Raf/MAPK signalling pathways
~50% of melanomas have activating BRAF mutations
Which drugs target the mutated form of BRAF?
Vemurafenib and dabrafenib
Apart from verumafenib and dabrafenib what type of drugs are starting to be used in melanoma?
Target MEK
Trametinib
What gene determines how pigmented we are?
MCR1 gene
1 defective = freckles
2 defective = freckles + red hair
What are actinic lentigines?
Age or liver spots, related to UV exposure
What are junctional naevi?
Melanocyte nests develop along the dermal epidermal junction
What are compound naevi?
Juntional clusters and dermis involvement
Junctional naevi, compoun naevi, and _______ naevi
Intradermal naevi
What are the two clinical settings of dysplastic naevi?
Sporadic
Familial (lifetime MM risk 100%)
What are the rarer naevi?
Halo naevi
Blue naevi
Spitz naevi
Is malignant melanoma entirely dependant on UV exposure?
No, it is mostly dependant on UV exposure but it is multi factorial and genetics also plays a role
What are the 4 main types of melanoma?
Superficial spreading
Acral/mucosal letigo
Letigo maligna
Nodular
What is melanoma prognosis largely related to?
Breslow thickness
Define breslow thickness
The distance between the upper layer of the epidermis and the deepest layer of the cancer
In ulcerated cancers measurement is from the base of the ulcer
What is seborrhoeic keratosis?
Benign profliferation of the epidermal keratinocytes
What are the 3 main types of basal cell carcinoma?
Nodular
Superficial
Infiltrative
How are BCCs described?
Slow growing
Locally destructive
Poorly defined margins
What is Bowen’s disease?
A precursor of SCC
Scaly patch, irregular border, no dermal invasion
What is actinic keratosis?
A precursor of SCC
Sun exposed skin
several atypical bowenoid lesions
Where do SCCs occasionally arise?
Chronic leg ulcers
Sites of burn
Adverse prognostic features of SCC
> 4mm
Vessel invation
Perineural spread
