Pathology - Skin and Eye Flashcards
What is the end game for a naevus?
Neurotization:
The naevus cells enter the dermis and mature, becoming smaller and non-pigmented, resembling neural tissue.
What are the different types of melanocytic nevi?
Junctional nevi - the earliest lesions found at the dermo-epidermal junction.
Compound nevi - develop as nest reaching into the dermis
Dermal nevi - the epidermal component is lost.
What are the most consistent clinical signs of cutaneous melanoma?
Recent change in size, shape, or colour.
Name the seven prognostic factors in melanoma:
With each factor, state the more favourable determinant
Breslow thickness (less than 1.7mm) Number of mitoses (few) Evidence of regression (absent) Presence of tumour infiltrating lymphocytes (many) Gender (female) Location (extremity) Sentinal node micrometastases (absent)
What proportion of melanomas arise in the familial setting?
10-15%
Which gene is most frequently associated with familial melanoma?
p16INK4A.
Codes for a kinase inhibitor, when mutated its absence allows for unchecked cell growth.
Apart from p16INK4A, which two other genes are involved in the pathogenesis of melanoma?
CDK4: A melanoma susceptibility gene
BRAF: A component of the RAS/RAF/MAP pathway. Involved in 60-70% of melanomas, late in the piece.
What is actinic keratosis?
What causes it? How can it be treated?
A premalignant dysplastic lesion associated with chronic sun exposure, especially in light skinned individuals.
UV, radiotherapy, hydrocarbons, and arsenic.
Treated with excision or Imiquimod.
What 2 factors increase the incidence of BCC?
Immunosuppression
Defects in DNA repair (xeroderma pigmentosum)
What is PTCH? Which skin cancer does it relate to?
“Patched” is a gene coding for a receptor for Sonic Hedgehog protein. When unbound to SHH, PTCH inhibits another membrane protein SMO from activating a transcription pathway.
In patients with Gorlin syndrome, or Nevoid BCC syndrome, one PTCH allele is inactivated and the second hit occurs in life. In sporadic cases, both alleles are spontaneously inactivated.
What is the Koebner phenomenon?
The genesis of new lesions at sights of trauma.
Occurs in psoriasis and lichen planus.
Describe the features of dysplastic naevi:
Larger than most acquired naevi (>5mm). May occur as hundreds of lesions on the body. Manifest as either flat macular lesions/plaques with a pebbly surface, or target like lesions with a darker raised centre and irregular flat periphery.
May occur on non-sun exposed skin.
What is the cell of origin of retinoblastoma?
Although the name suggests origin from a primitive retinal stem cell, it is now clear that retinoblastomas originate from neuronal cells.
What determines prognosis of retinoblastomas?
All bad:
Extra ocular extension
Invasion along the optic nerve
Choroid all invasion (maybe)
What is the RB gene?
Explain its role in retinoblastoma.
The RB gene codes for a product which controls the cell cycle: in its hypophosphorylated state, RB binds tightly with tfE2F and prevents progression of the cell cycle.
In familial retinoblastoma (40% of cases) children inherit one defective germ line copy of RB and acquire the second hit.
In sporadic cases, a single retinoblast loses both alleles to mutation.
