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c Flashcards

1
Q

what is melanoma? how dangerous is it?

A
  • Malignant tumour of melanocytes

- Most dangerous/fatal

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2
Q

what is the incidence of melanoma + demographic?

A

Rising incidence: high in white, low in darker people

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3
Q

which areas can melanoma affect

A

skin, Mucosal surfaces (oral, conjunctival, vaginal) + uveal tract of eye

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4
Q

what are genetic risk factors for melanoma

A

family history (CDKN2A mutations can cause MAPK pathway activation), MC1R variants, light skin, red hair, DNA repair defects (xeroderma pigmentosum)

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5
Q

what are environmental risk factors for melanoma

A

intense sun exposure, chronic sun exposure, equatorial latitudes, sunbeds, immunosuppression

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6
Q

what are phenotypic risk factors for melanoma

A

> 100 melanocytic nevi, atypical melanocytic nevi

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7
Q

what does the MAPK pathway regulate

A

cellular proliferation, growth and migration

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8
Q

what do CDKN2A mutations do

A
  • 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
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9
Q

what is the usual immune response to melanoma? what molecule interferes with this process & how?

A
  • 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.
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10
Q

what immunotherapy drugs are made for melanoma

A

CTLA-4 blockade (ipilimumab) + checkpoint inhibitors (PDL1/PD1)

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11
Q

where are KIT mutations found?

A

acral, mucosal melanomas + sun exposed skin (copy number amplifications or activating mutations of KIT)

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12
Q

what genes could be activated in melanoma

A

-Activation mutations of NRAS gene & BRAF gene (high in those with intermittent UBV exp. But low in those with cumulative UBV)

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13
Q

what are the subtypes of melanoma

A

Superficial spreading, nodular, lentigo maligna, acral lentiginous, unclassifiable

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14
Q

what are the characteristics of superficial spreading subtype of melanoma?

A
  • 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)
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15
Q

what are signs of melanoma regression?

A

grey. Hypo-or depigmentation shows interaction of host immune system with tumour

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16
Q

what are characteristics of nodular melanoma

A

=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.
17
Q

what are characteristics of lentigno maligna melanoma

A

-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)

18
Q

characteristics of acral lentignous melanoma

A
  • uncommon.
  • 7th decade.
  • Palms & soles in/around nail apparatus.
  • Not racist (black peeps don’t get others, get this, seen more commonly in them)
19
Q

what is amelanotic melanoma

A

lacks pigment

20
Q

how can you detect melanoma early

A

change in color, shape, size of pigmented skin lesion

21
Q

characteristics for public to detect melanoma

A

ABCDE:

-asymmetry, border irregularity, colour variation, diameter>5mm (>pencil eraser), evolving

22
Q

what is garbe’s rule

A

don’t ignore worries of patient, low threshold for biopsy

23
Q

what are differentials for melanoma

A

Basal cell carcinoma, seborrheic keratosis (harmless age>), dermatofibroma (benign tumour)

24
Q

what are poor prognostic features of melanoma

A

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

25
Q

what investigation for melanoma (to see features)?

A

Dermoscopy: improves diagnosis melanoma. findings shouldnt be considered in isolation. Hisotry/risk important. Excise lesion histology if needed (if in doubt, take it out)

26
Q

global features of melanoma

A

asymmetry, multiple colours, reticular, globular, reticular-globular, homogenous, starbust

27
Q

what are other potential features of melanoma

A

-Atypical network, streaks, atypical dots, globules, irregular blood vessels, regression structures, blue-white veil

28
Q

managmenet for melanoma?

A
  • 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
29
Q

in melanoma what investigation to see potential lymph node spread?

A

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

30
Q

what imaging for melanoma

A

stage III, IV & stage IIC without SLNB,. PET-CT, MRI brain.

31
Q

what is a major prognostic factor for metastatic melanoma

A

LDH

32
Q

what do you do if unresectable or metastatic melanoma

A
  1. immunotherapy: CTLA-4 inhibition (unresectable/metastatic BRAF negative – ipilimumab). PDL1 inhibitors (nivolumab).
  2. mutated oncogene targeted therapy: combo of BRAF inhibitor & MEK inhibitor
33
Q

what used for staging melanoma

A

-Pathological, TNM (imaging + biopsy are used

34
Q

demographics for keratinocyte dysplasia

A

Pale. UVB damage. M>W. 68 median age diagnosis.

35
Q

what are types of keratinocyte dysplasia

A
  1. Acitinic keratoses (dysplastic keratinocytes)
  2. Bowen’s disease (squamous cell carcinoma in situ)
  3. Sqaumous cell carcinoma (potential metatastasis/death)
  4. Basal cell carcinoma (never metastases, locally invasive)
36
Q

what are risk factors for keratinocyte carcinomas

A

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)

37
Q

most common keratinocyte carcinoma

A

basal cell carcinoma

BRS (81 decks)

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