Pathology of Pigmented Lesions

Question 1

where do melanoblasts migrate to from the neural crest to become melanocytes?

Answer 1

skin
uveal tract
leptomeninges

Question 2

how is the melanocyte:basal cell ratio affected by race?

Answer 2

its the same

just produce more melanin in darker skin

Question 3

what do melanocytes look like?

Answer 3

have a slight halo around them
don’t have pigment around them
the ones with pigment are squamous

Question 4

what does the MC1R gene do?

Answer 4

encodes MC1R protein that sits on cell surface
determines the balance of pigment in skin/hair
2 mutated gene = red hair and freckles
1 mutated gene = one or the other
turns phaelomelanin into eumelanin (brown)

Question 5

what are freckles?

Answer 5

ephilides

patchy increase in melanin production due to mutated MC1R gene

Question 6

what are actinic lentigines?

Answer 6

“liver spots” or “age spots” related to sun exposure

causing increase in basal melanocytes and therefore melanin

Question 7

what are melanocytic naevi?

Answer 7

Moles
can be congenital or acquired
rare to be born with them but can develop in 1st and 2nd decade

Question 8

what are the 3 types of melanocytic naeivi?

Answer 8

dysplastic
spitz
blue

Question 9

what are the 3 types of congenital melanocytic naevi?

Answer 9

small (<2cm)
medium (>2cm <20cm)
giant garment type lesions

Question 10

do congenital melanocytic naevi carry a melanoma risk?

Answer 10

if large

Question 11

what are usual type acquired naevi?

Answer 11

melanocyte:keratinocyte ratio breaks down at some cutaneous sites
causes formation of simple naevi
- very common
- very low malignant potential

Question 12

are naevi immune related?

Answer 12

possibly

immunosuppressed have more

Question 13

what are the 3 stages of naevi development?

Answer 13

junctional naevus - melanocytes proliferate causing nests of cells at junction
compound naevus - nests of cells at junction and some in dermis
intradermal naevus - all nests of melanocytes in dermis

Question 14

what do naevi look like on histology?

Answer 14

melanocytes form a nest

can be near the junction if younger or dropped into dermis if older

Question 15

what are dysplastic naevi?

Answer 15

> 6mm
asymmetric border
variegated pigment

Question 16

what are the 2 clinical settings of dysplastic naevi?

Answer 16

sporadic
- a couple of atypical naevi
- low malignant risk
- not inherited
familial
- inherited (autosomal)
- hundreds of atypical naevi
- almost 100% melanoma lifetime risk

Question 17

name 2 rarer types of naevi?

Answer 17

halo - peripheral halo of depigmentation (benign)

blue - only dermal (never been junctional) with pigment rich dendritic cells, can mimic melanoma

Question 18

which naevi is common in young children?

Answer 18

spitz naevi

Question 19

describe spitz naevi

Answer 19

large spindle and/or epitheloid cells
can closely mimic melanoma but are usually benign
difficult diagnosis as there is a malignant variant

Question 20

what do spitz naevi look like on histology?

Answer 20

clefting around the nests of melanocytes

Question 21

how do most melanoma arise?

Answer 21

most are de novo
but some can arise in dysplastic naevi
multifactorial - sun, genetics (skin type, dysplastic naevi)

Question 22

who/where is melanoma more common in?

Answer 22

females
incidence peaks in middle aged
in sun exposed sites

Question 23

what are some characteristics of a melanoma?

Answer 23

change in shape
irregular colour
bleeding
ulceration
new pigmented lesion in adulthood
development of small nodules around the mole
or ABCDE

Question 24

what are the 4 main types of melanoma?

Answer 24

superficial spreading - trunk and limbs
acral/mucosal lentiginous - acral and mucosal
lentigo maligna - sun exposed face, neck, scalp
nodular - trunk

Question 25

what are regressed areas and what do they suggest?

Answer 25

depigmented areas of a lesion | indicate a melanoma whch has began to invade? as immune response is attacking parts

Question 26

what is subungual acral melanoma?

Answer 26

black fingernail | melanoma at fingernail

Question 27

how do SSM, A/MLM and LMM all begin?

Answer 27

flat macules which radiate outwards (RGP) | melanoma cells then invade downwards into dermis forming a mass (VGP)

Question 28

which phase of melanomas can metastasise?

Answer 28

melanomas in VGP

Question 29

what is pagetoid/in situ invasion?

Answer 29

hasn't crossed basement membrane so is basically harmless | shot gun groups of melanoma cells

Question 30

how do nodular melanomas develop?

Answer 30

don't have a RGP/flat phase so just suddenly appear as a lump/nodule very aggressive/invasive

Question 31

what is Breslow thickness?

Answer 31

depth from granular layer

Question 32

what are the categories of Breslow thickness and survival rate?

Answer 32

``` pTis = in situ = 100% survival pT1 = <1mm = 90% pT2 = 1-2mm = 80% pT3 = 2-4 = 55% pT4 = >4mm = 20% ```

Question 33

what other factor of melanoma determines prognosis?

Answer 33

ulceration | indicated by suffix b

Question 34

through what 3 methods can melanoma spread?

Answer 34

local dermal lymphatics (satellite deposits in skin) regional lymph node metastases blood spread (soft tissue, GI etc)

Question 35

what is sentinel node?

Answer 35

the lymph node draining the melanoma | often removed

Question 36

how is melanoma treated?

Answer 36

primary excision to remove lesion some have a sentinel node biopsy and if +ve have a regional lyphadenectomy chemo/immunotherapy, genetic therapy

Question 37

how can melanomas be treated genetically?

Answer 37

some have c-kit or b-raf mutations which can be targetted

Question 38

how are B-RAF inhibitors used?

Answer 38

often in conjunction with MEK inhibitor

Question 39

what is seen in actinic lentigines on histology?

Answer 39

elongated rete ridges

Question 40

what are the features of dysplasia?

Answer 40

architectural and cellular atypia fibrosis and inflammation epidermis unaffected

Question 41

what is BRAF?

Answer 41

cytosolic proto-oncogene which when mutated drives cell proliferation by up-regulating MEK and ERK