Pathology of Pigmented Lesions Flashcards
where do melanoblasts migrate to from the neural crest to become melanocytes?
skin
uveal tract
leptomeninges
how is the melanocyte:basal cell ratio affected by race?
its the same
just produce more melanin in darker skin
what do melanocytes look like?
have a slight halo around them
don’t have pigment around them
the ones with pigment are squamous
what does the MC1R gene do?
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)
what are freckles?
ephilides
patchy increase in melanin production due to mutated MC1R gene
what are actinic lentigines?
“liver spots” or “age spots” related to sun exposure
causing increase in basal melanocytes and therefore melanin
what are melanocytic naevi?
Moles
can be congenital or acquired
rare to be born with them but can develop in 1st and 2nd decade
what are the 3 types of melanocytic naeivi?
dysplastic
spitz
blue
what are the 3 types of congenital melanocytic naevi?
small (<2cm)
medium (>2cm <20cm)
giant garment type lesions
do congenital melanocytic naevi carry a melanoma risk?
if large
what are usual type acquired naevi?
melanocyte:keratinocyte ratio breaks down at some cutaneous sites
causes formation of simple naevi
- very common
- very low malignant potential
are naevi immune related?
possibly
immunosuppressed have more
what are the 3 stages of naevi development?
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
what do naevi look like on histology?
melanocytes form a nest
can be near the junction if younger or dropped into dermis if older
what are dysplastic naevi?
> 6mm
asymmetric border
variegated pigment
what are the 2 clinical settings of dysplastic naevi?
sporadic - a couple of atypical naevi - low malignant risk - not inherited familial - inherited (autosomal) - hundreds of atypical naevi - almost 100% melanoma lifetime risk
name 2 rarer types of naevi?
halo - peripheral halo of depigmentation (benign)
blue - only dermal (never been junctional) with pigment rich dendritic cells, can mimic melanoma
which naevi is common in young children?
spitz naevi
describe spitz naevi
large spindle and/or epitheloid cells
can closely mimic melanoma but are usually benign
difficult diagnosis as there is a malignant variant
what do spitz naevi look like on histology?
clefting around the nests of melanocytes
how do most melanoma arise?
most are de novo
but some can arise in dysplastic naevi
multifactorial - sun, genetics (skin type, dysplastic naevi)
who/where is melanoma more common in?
females
incidence peaks in middle aged
in sun exposed sites
what are some characteristics of a melanoma?
change in shape irregular colour bleeding ulceration new pigmented lesion in adulthood development of small nodules around the mole or ABCDE
what are the 4 main types of melanoma?
superficial spreading - trunk and limbs
acral/mucosal lentiginous - acral and mucosal
lentigo maligna - sun exposed face, neck, scalp
nodular - trunk
what are regressed areas and what do they suggest?
depigmented areas of a lesion
indicate a melanoma whch has began to invade? as immune response is attacking parts
what is subungual acral melanoma?
black fingernail
melanoma at fingernail
how do SSM, A/MLM and LMM all begin?
flat macules which radiate outwards (RGP)
melanoma cells then invade downwards into dermis forming a mass (VGP)
which phase of melanomas can metastasise?
melanomas in VGP
what is pagetoid/in situ invasion?
hasn’t crossed basement membrane so is basically harmless
shot gun groups of melanoma cells
how do nodular melanomas develop?
don’t have a RGP/flat phase so just suddenly appear as a lump/nodule
very aggressive/invasive
what is Breslow thickness?
depth from granular layer
what are the categories of Breslow thickness and survival rate?
pTis = in situ = 100% survival pT1 = <1mm = 90% pT2 = 1-2mm = 80% pT3 = 2-4 = 55% pT4 = >4mm = 20%
what other factor of melanoma determines prognosis?
ulceration
indicated by suffix b
through what 3 methods can melanoma spread?
local dermal lymphatics (satellite deposits in skin)
regional lymph node metastases
blood spread (soft tissue, GI etc)
what is sentinel node?
the lymph node draining the melanoma
often removed
how is melanoma treated?
primary excision to remove lesion
some have a sentinel node biopsy and if +ve have a regional lyphadenectomy
chemo/immunotherapy, genetic therapy
how can melanomas be treated genetically?
some have c-kit or b-raf mutations which can be targetted
how are B-RAF inhibitors used?
often in conjunction with MEK inhibitor
what is seen in actinic lentigines on histology?
elongated rete ridges
what are the features of dysplasia?
architectural and cellular atypia
fibrosis and inflammation
epidermis unaffected
what is BRAF?
cytosolic proto-oncogene which when mutated drives cell proliferation by up-regulating MEK and ERK
