Chapter 25: Skin

Question 1

What enzymatic changes occur with progressive maturation of nevus cells?

Answer 1

Loss of tyrosinase activity and acquisition of cholinesterase activity in neuroid nevus cells

Question 2

Why do the BRAF/NRAS mutations in nevi usually not evolve to melanoma?

Answer 2

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

Question 3

What genes have been identified in dysplastic nevus syndrome and what’s the inheritance pattern?

Answer 3

• autosomal dominant
• mutations in CDKN2A (9p21) and CDK4 (12q14)
• not all families with dysplastic nevi have these mutations

Question 4

What are common molecular abnormalities in melanoma?

Answer 4

• 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%

Question 5

What is CYLD?

Answer 5

• tumor suppressor that encodes a deubiquintinating enzyme that regulates NF-KB and the cell cycle
• mutated in Brooke Spiegler syndrome and familial trichoepithelioma syndrome

Question 6

What mutation is associated with pilomatricoma?

Answer 6

Activating mutations in CTNNB1 (beta catenin)

Question 7

What is the mechanism of UV damage in creating SCC?

Answer 7

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

Question 8

What is the hallmark of UV damage in some sporadic BCCs?

Answer 8

• specific C to T transition in PTCH
• also 60% have p53 mutations with specific UV signatures

Question 9

What stains dermal dendrocytes?

Answer 9

FXIIIA

Question 10

What is the molecular feature underlying DFSP

Answer 10

• 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

Question 11

Differentiate urticaria pigmentosa and systemic mastocytosis

Answer 11

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

Question 12

What are signs associated with mast cell disease?

Answer 12

Darier sign (wheal at site of rubbing)

Dermatographism (edema from stroking)

Question 13

What conditions are associated with erythema multiforme?

Answer 13

Infections (mycoplasma, histo, herpes, typhoid)

Drugs (sulfonamides, penicillin, barbituartes)

Malignancy (carcinoma, lymphoma)

Collagen vascular disease (lupus, DM, PAN)

Question 14

What is the pathogenesis of psoriasis?

Answer 14

• 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

Question 15

Distinguish histologically between EM and lichen planus?

Answer 15

Lichen planus has features of chronicity including epidermal hyperlasia, thickened granular layer and hyperkeratosis

Question 16

What is pemphigus erythematosus?

Answer 16

Less severe form of pemphigus foliaceus that may selectively involve the malar region in a lupus-like fashion

Question 17

Types of epidermolysis bullosa

Answer 17

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

Question 18

What is porphyria?

Answer 18

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

Question 19

What are the 4 key features of acne?

Answer 19

1. Follicular plugging by keratin
2. Hypertrophy of sebaceous glands
3. Overgrowth of P acnes (lipase synthesizing bacteria)
4. Inflammation of the follicle