Pathology of Skin Cancer Flashcards by Zoe Doak

During embryonic development, melanoblasts migrate from the neural crest to where?

skin
uveal tract (gives pigment in eye)
leptomeninges (in the brain)

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Where do melanocytes usually sit and where do they transfer their pigment to?

Sit on basement membrane

Transfer pigment to keratinocytes (can often be seen histologically)

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What gene determines balance of pigment in skin and hair?

Melanocortin 1 receptor gene
MC1R
Turns phaeomelanin into eumelanin

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What compound is responsible for giving people red hair?

Phaeomelanin causes red hair

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What compound causes any hair colour other than red?

Eumelanin

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How many faulty copies of the MC1R gene do you need to have freckles?

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If you have red hair and freckles, how many mutated copies of the MC1R gene do you have?

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What are freckles (ephilides) ?

Patchy increase in melanin pigmentation
Occurs after UV exposure
Reflects clumpy distribution of melanocytes

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What are solar letigines?

age’ or ‘liver’ spots

Related to UV exposure

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Where are solar letigines usually found?

Face, forearms and dorsal hands

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How do patients get melanocytic naevi?

congenital or acquired

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How are congenital naevi classified?

Small <2cm diameter
Medium >2cm but <20cm diameter
Giant-garment type lesions

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What is the risk associated with large congenital melanocytic naevi ?

10-15% risk of melanoma

May need staged surgical excision

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How are melanocytic naevi usually acquired?

During infancy the melanocytes : keratinocyte ratio breaks down at a number of cutaneous sites
=> formation of SIMPLE NAEVI

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What is thought to contribute to acquired naevi?

Immunosuppresion

- immunosuppressed leukaemic children have more naevi

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How many simple melanocytic naevi does an average person usually posses? And are they dangerous?

average person has 20 - 30 naevi

common naevi have low malignant potential

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Describe the path of acquired naevi development from childhood to adulthood

CHILDHOOD =Junctional naevus
=> clusters of cells at DEJ

ADOLESCENCE = Compound naevus
=> junctional clusters + groups of cells in dermis

ADULTHOOD = Intradermal naevus
=> all junctional activity has ceased; entirely dermal

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Give 3 examples of less common types of naevi

dysplastic, Spitz, blue

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Describe the general appearance of a dysplastic naevi?

> 6mm diameter
Variegated pigment
Border asymmetry

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Dysplastic naevi can either be sporadic or familial. Describe the difference between the two

SPORADIC
not inherited
1+ atypical naevi
risk of MM slightly raised

FAMILIAL
strong FH of melanoma
autosomal inheritance
high penetrance eg CDKN2A
lots of atypical naevi
lifetime risk melanoma up to 100%

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What diagnosis is often confused with severe dysplastic naevi?

Severe dysplasia may be difficult to distinguish form melanoma in-situ

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What is indicated by a “Halo” naevi?

peripheral halo of depigmentation

show inflammatory regression
overrun by lymphocytes

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Where are Blue naevi found and what do they contain?

entirely dermal

consist of pigment rich dendritic spindle cells

At what age is a Spitz naevus common?

Usually occur <20 years

What do Spitz lesions contain?

Consist of large spindle and/or epithelioid cells **May closely mimic melanoma BUT Most are entirely benign

Why do many Spitz naevi display a pink discolouration?

Prominent surface vasculature

What sites does melanoma commonly affect?

sun-exposed sites scalp, face, neck, arm, trunk, leg

What sites are rarely affected by melanoma?

eye, meninges, oesophagus, biliary tract, anus

What factors can make you more likely to suspect melanoma?

``` Change in shape Irregular pigmentation Bleeding Development of satellite nodules Ulceration New pigmented lesion develops in adulthood ```

What are the four main types of melanoma?

Superficial spreading Acral/mucosal lentiginous Lentigo maligna Nodular

Where are superficial spreading melanomas most commonly seen?

trunk and limbs

Where are lentigo maligna melanomas often seen?

sun-damaged face/neck/scalp

Where are nodular melanomas often seen?

varied sites but often trunk

What factors determine melanoma prognosis?

Breslow Thickness and Ulceration

What is Breslow Thickness?

Measurement from the granular layer to the deepest tumour cell

What is the difference in survival rate between a melanoma of Breslow thickness <1mm and a tumour >4mm?

pT1-tumour < 1mm-90% survival pT4-tumour > 4mm thick-20% survival

How is melanoma usually treated?

Primary excision to give clear margins Some also receive a sentinel node biopsy If SN positive - regional lymphadenectomy advanced disease = difficult Chemo, immunotherapy, genetic therapies

What mutation is common in acral melanomas and what treatment can be used for this?

c-kit mutations | treated with imatinib

What is seborrhoeic keratosis and where does it usually occur?

Benign proliferation of epidermal keratinocytes Common on face and trunk in ageing skin

Describe the morphology of lesions in seborrhoeic keratosis

Stuck on appearance-greasy hyperkeratotic surface

What is Leser-Trelat's sign?

Eruptive appearance of many lesions indicating internal malignancy

What age groups usually get Basal Cell Carcinoma?

middle aged and elderly people in the UK *on Sun-exposed sites* **younger people more likely to develop BCC in Australia**

What are the three categories of Basal Cell Carcinoma?

Nodular Superficial Infiltrative (morphoeic)

Do basal cell carcinomas usually grow quickly or slowly?

Slowly

DO basal cell carcinomas metastasize?

Almost never metastasises | May kill by invading eye/brain

What factors make resection of basal cell carcinomas difficult?

Margins are poorly defined | May spread along nerves

Give examples of precursors for squamous cell carcinoma

Bowen’s disease - on legs Actinic keratosis - on head/neck Viral lesions - on anogenital skin

What do precursors of squamous cell carcinoma show?

squamous DYSPLASIA

Describe the morphology of a Bowen's disease lesion

Scaly patch/plaque Irregular border No dermal invasion **Squamous cell carcinoma in –situ*

Where does actinic keratosis usually present?

Sun-exposed skin esp. scalp, face, hands

How is Actinic Keratosis usually defined and what is it a precursor of?

Variable epidermal dysplasia Precursor for INVASIVE SCC

What variation of HPV is involved in dysplasia?

HPV Type 16 **HPV in almost 100% penile dysplasia

In what percentage of invasive penile SCC is HPV involved?

50%

Give some examples of common, less common and rare cases in which SCC would arise

COMMON: - sun exposed sites in the elderly LESS COMMON - chronic leg ulcers - burns RARE - xeroderma pigmentosum - epidermolysis bullosa

Give examples of tissues and other types of cell (NOT melanocyte/basal cell/ squamous cell) from which dermatological tumours can arise

``` Langerhans cells Merkel cells subcutaneous fat smooth muscle of arrector pili lymphoid tissue ```