Pathology of Skin Cancer Flashcards
During embryonic development, melanoblasts migrate from the neural crest to where?
skin
uveal tract (gives pigment in eye)
leptomeninges (in the brain)
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)
What gene determines balance of pigment in skin and hair?
Melanocortin 1 receptor gene
MC1R
Turns phaeomelanin into eumelanin
What compound is responsible for giving people red hair?
Phaeomelanin causes red hair
What compound causes any hair colour other than red?
Eumelanin
How many faulty copies of the MC1R gene do you need to have freckles?
1
If you have red hair and freckles, how many mutated copies of the MC1R gene do you have?
2
What are freckles (ephilides) ?
Patchy increase in melanin pigmentation
Occurs after UV exposure
Reflects clumpy distribution of melanocytes
What are solar letigines?
age’ or ‘liver’ spots
Related to UV exposure
Where are solar letigines usually found?
Face, forearms and dorsal hands
How do patients get melanocytic naevi?
congenital or acquired
How are congenital naevi classified?
Small <2cm diameter
Medium >2cm but <20cm diameter
Giant-garment type lesions
What is the risk associated with large congenital melanocytic naevi ?
10-15% risk of melanoma
May need staged surgical excision
How are melanocytic naevi usually acquired?
During infancy the melanocytes : keratinocyte ratio breaks down at a number of cutaneous sites
=> formation of SIMPLE NAEVI
What is thought to contribute to acquired naevi?
Immunosuppresion
- immunosuppressed leukaemic children have more naevi
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
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
Give 3 examples of less common types of naevi
dysplastic, Spitz, blue
Describe the general appearance of a dysplastic naevi?
> 6mm diameter
Variegated pigment
Border asymmetry
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%
What diagnosis is often confused with severe dysplastic naevi?
Severe dysplasia may be difficult to distinguish form melanoma in-situ
What is indicated by a “Halo” naevi?
peripheral halo of depigmentation
- show inflammatory regression
- overrun by lymphocytes
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
