c Flashcards
what is melanoma? how dangerous is it?
- Malignant tumour of melanocytes
- Most dangerous/fatal
what is the incidence of melanoma + demographic?
Rising incidence: high in white, low in darker people
which areas can melanoma affect
skin, Mucosal surfaces (oral, conjunctival, vaginal) + uveal tract of eye
what are genetic risk factors for melanoma
family history (CDKN2A mutations can cause MAPK pathway activation), MC1R variants, light skin, red hair, DNA repair defects (xeroderma pigmentosum)
what are environmental risk factors for melanoma
intense sun exposure, chronic sun exposure, equatorial latitudes, sunbeds, immunosuppression
what are phenotypic risk factors for melanoma
> 100 melanocytic nevi, atypical melanocytic nevi
what does the MAPK pathway regulate
cellular proliferation, growth and migration
what do CDKN2A mutations do
- can cause MAPK pathway activation.
- CDKN2A encodes tumour suppressor P16 that binds to CDK4/6 preventing formation of cyclin-D1-CDK4/6 complex which phosphorylates Rb inactiving it & leading to E2F release (promotes cell cycle progression)
- mutation promotes cell cycle progression
what is the usual immune response to melanoma? what molecule interferes with this process & how?
- CD8+ T cells recognise melanoma antigens + if activated properly kill them. CD4+ helper T cells & antibodies involved.
- CTLA-4 inhibits T-cell activation by removing co-stimulatory signal.
what immunotherapy drugs are made for melanoma
CTLA-4 blockade (ipilimumab) + checkpoint inhibitors (PDL1/PD1)
where are KIT mutations found?
acral, mucosal melanomas + sun exposed skin (copy number amplifications or activating mutations of KIT)
what genes could be activated in melanoma
-Activation mutations of NRAS gene & BRAF gene (high in those with intermittent UBV exp. But low in those with cumulative UBV)
what are the subtypes of melanoma
Superficial spreading, nodular, lentigo maligna, acral lentiginous, unclassifiable
what are the characteristics of superficial spreading subtype of melanoma?
- majority.
- Common in white.
- Trunk on men, legs of women.
- De novo or pre-existing nevus.
- Most show regression (grey. Hypo-or depigmentation) shows interaction of host immune system with tumour.
- First grow horizontally, then vertically (forms bump)
what are signs of melanoma regression?
grey. Hypo-or depigmentation shows interaction of host immune system with tumour
what are characteristics of nodular melanoma
=2nd common in white.
- Trunk, head & neck.
- M>F.
- blue-black, sometimes pink-red nodule (can be ulcerated, bleeding).
- Rapid.
- No horizontal growth, only vertical.
what are characteristics of lentigno maligna melanoma
-minority.
>60yrs – chronically sun-damaged.
-Face.
-Slow growing, asymmetric brown-black macule, colour variation & irregular border.
-Lentigo maligna (in situ) can lead to invasive lentigo maligna melanoma (5%) (sun damage)
characteristics of acral lentignous melanoma
- uncommon.
- 7th decade.
- Palms & soles in/around nail apparatus.
- Not racist (black peeps don’t get others, get this, seen more commonly in them)
what is amelanotic melanoma
lacks pigment
how can you detect melanoma early
change in color, shape, size of pigmented skin lesion
characteristics for public to detect melanoma
ABCDE:
-asymmetry, border irregularity, colour variation, diameter>5mm (>pencil eraser), evolving
what is garbe’s rule
don’t ignore worries of patient, low threshold for biopsy
what are differentials for melanoma
Basal cell carcinoma, seborrheic keratosis (harmless age>), dermatofibroma (benign tumour)
what are poor prognostic features of melanoma
increased Breslow thickness >1mm (depth melanoma – from granular layer to bottom of tumour), ulceration, age, male, anatomical site (trunk, head, neck), LN
-Survival decreases as stage increases
what investigation for melanoma (to see features)?
Dermoscopy: improves diagnosis melanoma. findings shouldnt be considered in isolation. Hisotry/risk important. Excise lesion histology if needed (if in doubt, take it out)
global features of melanoma
asymmetry, multiple colours, reticular, globular, reticular-globular, homogenous, starbust
what are other potential features of melanoma
-Atypical network, streaks, atypical dots, globules, irregular blood vessels, regression structures, blue-white veil
managmenet for melanoma?
- Primary excision down to subcutaneous fat (2mm peripheral margin)
- Wide excision (margin by Breslow depth, 5mm for in situ, 10mm for = 1mm) to prevent local recurrence/persistent disease
in melanoma what investigation to see potential lymph node spread?
Sentinel lymphoma node biopsy: primary spread node = sentinel node. Represent most likely nodes to contain metastasis. Offered for pT1b+. extracapsular spread on LMB needs LN dissection
what imaging for melanoma
stage III, IV & stage IIC without SLNB,. PET-CT, MRI brain.
what is a major prognostic factor for metastatic melanoma
LDH
what do you do if unresectable or metastatic melanoma
- immunotherapy: CTLA-4 inhibition (unresectable/metastatic BRAF negative – ipilimumab). PDL1 inhibitors (nivolumab).
- mutated oncogene targeted therapy: combo of BRAF inhibitor & MEK inhibitor
what used for staging melanoma
-Pathological, TNM (imaging + biopsy are used
demographics for keratinocyte dysplasia
Pale. UVB damage. M>W. 68 median age diagnosis.
what are types of keratinocyte dysplasia
- Acitinic keratoses (dysplastic keratinocytes)
- Bowen’s disease (squamous cell carcinoma in situ)
- Sqaumous cell carcinoma (potential metatastasis/death)
- Basal cell carcinoma (never metastases, locally invasive)
what are risk factors for keratinocyte carcinomas
UV (PUVA), fair, genetic syndromes (xeroderma pigmentosum, oculocutaneous albinism, muir torre syndrome, nevoid BCC syndrome), nevus sebaceous, porokeratosis, organ transplantation (immune drugs), chronic non-healing wounds, ionising radiation (airline pilots), chemical exposure (tar, hydrocarbons)
most common keratinocyte carcinoma
basal cell carcinoma
