skin cancer

Question 1

describe the skin microanatomy

Answer 1

have the epidermis

dermis

hypodermis - has subcutaneous fat

bm

muscle

Question 2

describe the structure of the epidermis `

Answer 2

have keratinocytes, melanocytes, DC - langerhans cells, merkle cells

keratinocytes start at the bm, mature and differentiate and move up through layers - get exposed to UV = mutatations

melanocytes are by the bm - can get exposed to UV = mutations

layers are:

• stratum corneum
• startum lucidum
• stratum granulosum
• stratum spinosum
• stratum basale

Question 3

what are the different types of skin cancer *

Answer 3

keratinocyte derived - basal cell carcinoma, squamous cell carcinoma (aka non melanoma skin cancer)

melanocyte derived - malignant melanoma

vascular derived - kaposi sarcoma (common in AIDS), angiosarcoma

lymphocyte derived - mycosis fungiodes

Question 4

general cause of skin cancer *

Answer 4

accumulation of mutations in key genes lead to uncontrolled cellular differentiation

Question 5

causes of skin cancer *

Answer 5

genetic syndromes - give predisposition to cancer

• Gorlin’s syndrome - tendancy for basal cell carcinoma - defect in ORC1 gene
• xeroderma pigmentosum - defect in DNA repair by UV - develop multiple skin cancers

viral infections

• HHV8 in kaposi sarcoma
• HPV in SCC - particularly in the immunosuppressed

uv light - main cause

• BCC, SCC, malignant melanoma

immunosuppression

• drugs
• old age = immunosuppression
• HIV
• leukaemia

Question 6

characteristics of malignant melanoma *

Answer 6

dark

irregular border

lumpy

Question 7

incidence of malignant melanoma *

Answer 7

increasing in whit people

pale skin - suseptible to UV damage

increasing because people are living longer, more sun and behaviour change

higher incidence where higher exposure eg cornwall and norfolk

Question 8

characteristics of basal cell carcinoma (BCC) *

Answer 8

pearly

grey/shiny

glistens

have telangiectasia - dilated small capillary blood vessels that look like they are branching

Question 9

incidence of BCC *

Answer 9

increasing

Question 10

describe how UV light contributes to skin cancer *

Answer 10

3 types UVA UVB UVC

UVC is blocked by the stratosphere

UVB and UVA hit the surface and contribute to mutations

UV damage to DNA leads to mutations in specific genes - cell division, DNA repair, cell cycle arrest - if these accumulate = cancer

Question 11

why is sunlight essential

Answer 11

for photosynthesis

infrarred spectrum provides warmth

effect ion human mood

stimulates the production of vitamin D in the skin

Question 12

describe how UVB causes skin cancer *

Answer 12

most important wavelength in carcinogenesis

directly induces mutations

induces photoproducts - these are cross links between bases - affects pyrimidines (C and T) - forming cyclobutane pyrimidine dimers eg T=T, T=C, C=C (ie thymine dimers etc)

this is usually repaired by nucelar exision repair

Question 13

describe role of UVA in skin cancer *

Answer 13

100x more penetrates to surface than UVB

major cause of skin aging - penetrates deeper and effects collagen in dermis

contributes to carcinogenesis - causes cyclobutane pyrimidine dimers but less effectively than UVB

also forms free radicals whcih damage DNA and cell mmebrane

Question 14

therapeutic use of UVA

Answer 14

in PUVA therapy for psoriasis

Question 15

how is UV damage usually repaired *

Answer 15

DNA nucleotide excision

Question 16

describe xeroderma pigmentosum *

Answer 16

genetic defect with nucleotide excision repair

means get skin cancer early with minimal exposure

ie <10yrs age, freckles and photosensitivity

sublings need to be tested

treated by removing the skin cancer and strict sun protection ie completely covered in sun including wearing a visor over face

Question 17

what are the mutations that can cause cancer *

Answer 17

stimulate uncontrolled cell proliferation - mutations in p53 gene

alter responses to growth stimulating/repressive factors

inhibit programmed cell death - apoptosis

Question 18

describe sunburn

Answer 18

the keratinocytes undergo apoptosis because of UV

this removes UV damaged cells that might otherwise form cancer cells

Question 19

summarise photocarcinogenesis *

Answer 19

UV causes DNA damage

DNA can be repaired = normal cells

or if damage too severe - apoptosis

or if mutation accumulate = cell will transform = skin cancer

Question 20

describe the immunomodulatory effects of UV *

Answer 20

UVA and B effect expression of genes in immunity - depletes the langerhans cells in the epidermis = immune suppression

there is reduced skin immunocompetence and immunosurveillance

further increases cancer causing potential of sun - normally langerhans cells (APC) cause cell death of cells exposed to UV

(basis for treatment of psoriasis - exposure to UV improves psoriasis)

Question 21

what determines the host response to UV *

Answer 21

genetic influences - especially phototype

Question 22

what are the fitzpatrick phototypes *

Answer 22

1 - always burns never tans

2 - usually burns, sometimes tans

3 - sometimes burns, usually tans

4 - never burns always tans

5 - moderate constitutive pigmentation - asian

6 - marked constituitive pigmentation - afro-carribean

Question 23

describe melanin *

Answer 23

melanin pigmentation is responsible for skin colour

produced by melanocytes within the basal layer of the epidermis

skin colour depends on the amount of melanin produced as baseline, not the number of melanocytes (number of cells is constant)

Question 24

describe melanocytes and production of melanin *

Answer 24

they are DC on the BM in epidermis that interdigitate and communicate with the keratinocytes - 1 melanocyte for 5 keratinocytes

they produce a baseline level of melanin

after UV exposure - keratinocytes send paracrine signal (MSH) that activates the melanocytes to make more melanin

melanin is taken up by keratinocytes and packaged around their nucleus to protect DNA

Question 25

what are the types of melanin and what determines them \*

Answer 25

eumelanin - brown/black - in later skin types phaeomelanin - yellowish/reddish brown - red hair and pale skin melanin is produced from tyrosine by a series of enzymes MCR1 gene has \>20 polymorphisms - the variation of melanin ratio produced depends on the polymorphism this explains the different hair and skin coulour types melanin detects skin sensitivity to UV damage

Question 26

describe malignant melanoma \*

Answer 26

tumour of the melanocytes - they become abnormal and have abnormal architecture caused by UV exposure and genetic factors there is a risk of metastasis leading to death

Question 27

describe lentigo maligna \*

Answer 27

it is melanoma in situ there is proliferation of malignant (atypical) melanocytes in the epidermis pagetoid spread - ie the melanocytes spread upwards, they should be at the bm no risk of metastisis because they havent breached the epidermis

Question 28

characteristics of lentigo maligna \*

Answer 28

irregular shape flaty light and dark brown colours \>2cm usually common in elderly at sites of skin exposure

Question 29

treatment of lentigo maligna

Answer 29

excision and skin graft

Question 30

descrive lentigo maligna melanoma \*

Answer 30

means there is invasion dark patch

Question 31

describe superficial spreading malignant melanoma \*

Answer 31

lateal proliferation of malignant melanocytes invade the bm risk of metastasis pagetoid spread - melanocytes in epidermis and dermis also spread out and downwards - when head out = radial growth phase, when down = vertical growth phase

Question 32

characteristics of superficial spreading MM \*

Answer 32

dark - blue colour irregular

Question 33

how do you diagnose a superficial spreading MM \*

Answer 33

ABCDE rule asymettry border irregular colour variation - dark brown/black diameter \>7mm and increasing erythma

Question 34

what is the significance of a superficial spreading MM being pale in middle \*

Answer 34

means middle has regressed - immune response against tumour bad prognosis because means thicker and more invasive and perhaps already metastised

Question 35

describe nodular malignant melanoma \*

Answer 35

vertical proliferation of melanocytes - grows up and down no previous horizontal growth risk of metastasis can arise from a mole/de novo

Question 36

characteristics of nodular MM \*

Answer 36

black and lumpy

Question 37

describe nodular melanoma arising within a superficial spreading melanoma \*

Answer 37

downward proliferation of malignant melanocytes previous horizontal growth nodule develops within an irregular plaque prognosis is worse can lose pigmentation can have erythma - superficial reddening, these are amelanotic areas of the melanoma

Question 38

describe acral lentiginous melanoma \*

Answer 38

on soles or palms lumps/flat pigmented plaques common in darker skin types

Question 39

describe amelanotic melanoma \*

Answer 39

not pigmented

Question 40

how do you determine the prognosis of melanoma

Answer 40

breslow thickness - depth of invasion of tumour cells in the skin measurement from granular layer (just under the stratum corneum) to bottom of tumour \<1mm = thin 4= thick 1-4 = intermediate

Question 41

what are the risk factors for the development of melanoma \*

Answer 41

FH of dysplastic nevi or melanoma UV irradiation sunburns during childhood intermittent burning exposure in unacclimitised fair skin - most important atypical/dysplastic nevus syndrome personal history of melanomas - if you have one you're likely to have another skin type 1/2 genetic markers - CDKN2A mutation cingenital nevi number of atypical nevi \>5 high socioaconomic status 1equatoral latitudes dna repair defects eg xeroderma pigmentosum immunosuppression

Question 42

describe kertaocanthoma \*

Answer 42

grow rapidly then involutes type of SCC from keratinocyte - if well differentiated it produces keratin

Question 43

describe SCC \*

Answer 43

malignant tumour of kertainocytes caused by UV, HPV, immunosuppression, may occur in scars/scarring process eg burns scar/disease with scar/long term ulcer risk of metastasis if poorly differentaited is 10% - this is less than for malignant melanomas well differentiated produces keratin - can see horns can occur on lower lip from sun adn smoking occur on ears of men and leg of women - exposed to sun

Question 44

describe BCC \*

Answer 44

malignant tumour from basal cell layer of epidermis caused by sun exposure, genetics slow growing - 3-4mm yr (can be faster) invades tissue but doesnt metastise common on face common around eye - has telangiectasia - lost eyelash so destructive process arborising telangiectasia - branching capillary bvs

Question 45

describe nodular BCC \*

Answer 45

glistening telangiectasia

Question 46

describe superficial BCC \*

Answer 46

have rolled edge glistening surface crusty

Question 47

describe mycosis fungoides \*

Answer 47

look like psoriasis/eczema pink scaly patch that progresses to plaque like lesion then tumour, then disseminates then die it is a T cell lymphoma of skin also called cutaneous T cell lymphoma

Question 48

describe kaposi's sarcoma \*

Answer 48

HIV and HHV8 associated - HHV8 in AIDs and not purplish nodules, plaques, flat legions arise from the endothelial cells in lymphatics orientation of plaque goes along the skin line on palate, sole of foot, skin treatment - excision, chemo/radio and treatment of HIV

Question 49

describe epidermodysplasia veruciformis \*

Answer 49

rare autosomal recessive condition predisposition ot HPV induced warts and SCCs

Question 50

role of immunomodulation in cancer

Answer 50

people with good immune systems resolve early cancers before they are detected in immunocomprised people there is an increased occurrence of keratinocyte-derived skin tumours on sun-exposed sites.

Question 51

role of p53 in skin cancer \*

Answer 51

normally mutations in DNA = activation of p53 = expression of Bax gene = apoptosis if you have p53 mutation - DNA with mutations might survive = more likely to get heratinocyte cancers