Chapter 25: Skin Flashcards
What enzymatic changes occur with progressive maturation of nevus cells?
Loss of tyrosinase activity and acquisition of cholinesterase activity in neuroid nevus cells
Why do the BRAF/NRAS mutations in nevi usually not evolve to melanoma?
Their activation causes a limited period of proliferation that is followed by permanent growth arrest mediated by the accumulation of p16/INK4a.
This process of senescence is disrupted in melanomas
What genes have been identified in dysplastic nevus syndrome and what’s the inheritance pattern?
- autosomal dominant
- mutations in CDKN2A (9p21) and CDK4 (12q14)
- not all families with dysplastic nevi have these mutations
What are common molecular abnormalities in melanoma?
- CDKN2A mutations (especially p16, p14)
- RAS pathways (BRAF in 60-70%, NRAS in 10-15%)
- c-KIT mutations (receptor upstream of both RAS/RAF and PI-3K/AKT pathways)
- silencing of PTEN (a tumor suppressor that acts downstream of PI-3K/AKT) epigenetically in 20%
What is CYLD?
- tumor suppressor that encodes a deubiquintinating enzyme that regulates NF-KB and the cell cycle
- mutated in Brooke Spiegler syndrome and familial trichoepithelioma syndrome
What mutation is associated with pilomatricoma?
Activating mutations in CTNNB1 (beta catenin)
What is the mechanism of UV damage in creating SCC?
p53 normally repairs DNA damage caused by UV light
When p53 function is lost, repair is prone to errors, leading to mutations
The p53 mutations that result initially are in pyrimidine dimers, which may also be caused by UV damage
Mutations in the nucleotide excision repair pathway underly xeroderma pigmentosum which also leads to cancer risk
What is the hallmark of UV damage in some sporadic BCCs?
- specific C to T transition in PTCH
- also 60% have p53 mutations with specific UV signatures
What stains dermal dendrocytes?
FXIIIA
What is the molecular feature underlying DFSP
- t(17;22) COL1A1 and PDGFRB
- results in overexpression of PDGFRB which drives tumor cell growth
- can be targetted by imatinib which inhibits PDGFBR activation
Differentiate urticaria pigmentosa and systemic mastocytosis
UP: usually in kids, localized cutaneous form; small oval papules and small plaques
Systemic: adults, similar skin lesions but also bone marrow, spleen, liver and nodal involvement with poor prognosis
What are signs associated with mast cell disease?
Darier sign (wheal at site of rubbing)
Dermatographism (edema from stroking)
What conditions are associated with erythema multiforme?
Infections (mycoplasma, histo, herpes, typhoid)
Drugs (sulfonamides, penicillin, barbituartes)
Malignancy (carcinoma, lymphoma)
Collagen vascular disease (lupus, DM, PAN)
What is the pathogenesis of psoriasis?
- strong association with HLAC
- Th1 and Th17 mediated cytokine soup and growth factor production resulting in keratinocyte proliferation
- TNF may be a major mediator and is the target of treatment
Distinguish histologically between EM and lichen planus?
Lichen planus has features of chronicity including epidermal hyperlasia, thickened granular layer and hyperkeratosis
What is pemphigus erythematosus?
Less severe form of pemphigus foliaceus that may selectively involve the malar region in a lupus-like fashion
Types of epidermolysis bullosa
Simplex: mutations in keratin 14 or 5
Junctional type: blisters at the lamina lucida
Dystrophic type: blisters beneath lamina dense due to mutations in COL7A1
What is porphyria?
Disease with disturbance in porphyrin metabolism; porphyrins are present in hemoglobin, myoglobin, cytochromes.
Serum proteins including immunoglobulins typically form glassy deposits in the walls of superficial dermal microvessels
5 types
What are the 4 key features of acne?
- Follicular plugging by keratin
- Hypertrophy of sebaceous glands
- Overgrowth of P acnes (lipase synthesizing bacteria)
- Inflammation of the follicle
