Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Clinical Pathology in Action > Skin Pathology > Flashcards

Skin Pathology Flashcards

1
Q

What are the 3 layers of skin

A

Epidermis

Dermis

Hypodermis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the other structures found in the skin

A
  • Sweat glands - dermis layer
  • Sebaceous glands - dermis layer
  • Arrector pili muscle -hypodermis layer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the epidermis layer consist of

A

Keratinized, stratified, squamous epithelium

This layer is directly exposed to the outside world, and therefore is most vulnerable to its damaging effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is the skin renewed

A

There is the basal layer (Stratum basale) where there is constant proliferation of cells that move to the top where they replace cells that are continually shed

Melanocytes are found at the basal cell layer - the deepest part of the epidermis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the skin functions

A
  • Protection
  • Sensation
  • Thermoregulation
  • Metabolic functions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How does the skin protect

A

Against UV light, mechanical, thermal and chemical stresses, dehydration and invasion of microorganisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does the skin have sensation

A

The skin has receptors that sense touch, pressure, pain and temperature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does the skin thermoregulate

A

Various features of the skin are involved in regulating temperature of the body, such as sweat glands, hair and adipose tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the metabolic functions of the skin

A

Subcutaneous adipose tissue is involved in production of vitamin D, and triglycerides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do melanocytes in the Epidermis respond to UV light

A
  • Differentiated melanocytes produce melanin that transfers to the adjacent keratinocytes
  • Melanin absorbs light and dissipate over 99.9% of absorbed UV radiation, protecting skin from radiation damage and reducing the risk of cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does UVB do

A

Catalyses the activation of Vit D, essential for healthy bone mineralisation/development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does skin colour affect the risk of developing skin cancer

A

With a pale light skin colour there are greater risks of skin cancer and its highly sensitive to UV - always burns, never tans

With darker skin colours there is a much lower risk of developing skin cancer but in the case that it does develop, it can only be detected at a much later, more dangerous stage. Brown skin never burns and has minimal sensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the most common form of melanoma for people of colour

A

Acral lentiginous melanoma, which develops on hairless skin - more likely caused by genetic factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the worldwide distribution of melanomas

A

It is more common in western countries where people have white skin

There is malignancy of melanocytes, predominantly in skin, but also eyes, ears, GI tract, leptomeninges, and mucous membranes

Majority of skin cancers are caused by exposure to the sun

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the ABCD rule for pigmented lesions

A

This is done to check for main warning signs of melanoma

A - Asymmetry: two halves of a mole look different in shape/colour

B - Border: melanomas will often have a jagged, irregular, notched or blurred border

C - Colour: several different colors that is different to other moles

D - Dimensions: melanomas can spread outwards as a flat lesion, it can also grow upwards as a hard lump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How might nodular melanoma differ from other melanomas and what signs should it be looked out for

A
  • Nodular melanomas tend to grow rapidly and vertically into the deeper layers of the skin

The EFG rule should be applied

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the EFG rule

A

This is for nodular melanomas

E - Elevation

F - Firmness to touch

G - Growth: persistent growth for over one month

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is malignant melanoma

A

A serious type of skin cancer that develops when melanocytes, the cells that produce pigment in the skin, grow out of control

This is more common in paler skin types

Darker skin types tend to present with acral and subungual melanoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is Acral lentiginous melanoma

A

A type of melanoma that primarily develops on the palms, and under the nails (subungual melanoma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the embryological origin of melanocytes

A
  • Melanocytes come from a group of embryonic cells called the neural crest

During embryogenesis, these neural crest cells:

  • Migrate to various parts of the developing body
  • Some of them differentiate into melanocyte precursors
  • These precursors migrate into the skin and hair follicles, where they become mature melanocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the importance of neural crest-derived cells

A

This means that melanomas can occur not only on skin but other places where melanocytes exist like the eye, mucosa and meninges

They are biologically aggressive and capable of wide metastasis due to the inherent migratory ability of melanocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is are the 2 main phases of tumour progression in melanomas

A

1) Radial Growth Phase

2) Vertical Growth Phase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What happens in the Radial Growth Phase

A

It is the early stage

  • The tumour grows laterally within the epidermis and superficial dermis
  • Usually non-invasive and often curable if caught here
  • Example: Superficial spread melanoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the Vertical Growth Phase

A
  • Tumour cells begin to invade deeper into the dermis and possibly subcutaneous tissue
  • Associated with increased risk of metastasis
  • At this stage, cells often show features of malignancy, including increased mitotic rate and cellular atypia
25
What are the key molecular alterations in melanoma
- BRAF mutations (V600E): driving uncontrolled growth - NRAS, KIT and TERT mutations - p16 (CDKN2A) inactivation affects cell cycle regulation
26
What is the sequence of histological changes that are associated with the initiation and progression of the melanoma tumour
This would be the Clark Model 1) Nevus: increased of nested melanocytes 2) Dysplastic nevus: random and discontinuous atypia 3) Radial growth phase: Cells proliferate intraepidermally 4) Vertical growth phase: cells penetrate through the basal membrane 5) Metastatic melanoma
27
What happens biologically and molecularly in the Dysplastic Nevus phase
Biologically: Premalignant lesions may regress and there is random atypia Molecularly: - CDKN2A loss - PTEN loss
28
What happens biologically and molecularly in the Radial Growth phase
Biologically: Decreased differentiation, unlimited hyperplasia, clonal proliferation Molecularly: - Increased CD1
29
What happens biologically and molecularly in the Vertical Growth phase
Biologically: Crosses basement membrane. Forms tumour Molecularly: E-cadherin loss, N-cadherin expression, MMP-2 expression, Survivin
30
What happens biologically and molecularly in the metastatic melanoma phase
Biologically: dissociates from primary tumour and grows at distant site Molecularly: the same thing happens as the vertical growth phase
31
What are the histological features of melanoma in-situ
- Obscured dermoepidermal junction - Pagetoid spread individually and in clusters throughout epidermis - Prominent melanin production - Large cells with abundant finely granular eosinophilic cytoplasm - Nuclear pseudoinclusions, folds or grooves - Marked atypia with pleomorphic nuclei with large eosinophilic nucleoli
32
What are the 4 major subtypes of invasive melanoma
- Acral lentiginous - Lentigo maligna - Nodular - Superficial spreading
33
What are helpful features of melanoma that differentiate from benign lesions
- Asymmetry - Atypia - Lack of maturation of dermal tumour cells - Lateral extension of individual melanocytes - Melanocytes with clear cytoplasm and finely dispersed chromatin - Mitotic figures in melanocytes - Pleomorphism of tumour cells - Presence of chromosomal gains or losses
34
What features do the pathologists assess to predict the prognosis of a patient with melanoma
- Thickness (Breslow Thickness): measures how deep the tumour invades the skin - Ulceration: the epidermis over the melanoma is broken - it is a strong negative prognostic factor as more ulceration means a worse outcome - Microsatellite lesions (indicating lymphatic spread): tiny groups of melanoma cells separate from the main tumour located in the dermis or subcutis
35
How does the melanoma thickness and spread into the skin affect prognosis
The deeper the melanoma spreads, the richer it gets in lymphatics and vasculature The deeper the invasion, the lower the 10 year survival rates
36
What features do pathologists asses to predict the prognosis of a patient with melanoma
Lymph node metastasis (strongest predictor of survival) - however when examining the initial biopsy, it is unknown whether the melanoma has spread into the lymph nodes Tumour regression is a poor prognostic indicator Wide local excision - margins for local recurrence
37
Why is regression a poor prognostic indicator
When the tumour has been destroyed by the immune system, the pathologist doesn't see tumour cells in that area but rather fibrosis, small blood vessels and chronic inflammation. The true size of the tumour still matters because depth of tumour correlates with how likely it was to have spread. Histological changes in regression can also happen in benign skin inflammation, making it hard to confidently diagnose
38
How does a wide local excision help with diagnostics
- Done to ensure there are no residual tumour cells at the edges. - Pathologists assess how close the tumour came to the edge of the removed tissue - close or involved margins = higher risk of recurrence
39
What is the RAS-RAF-MEK-ERK pathway Growth factor signalling
1) Cell surface receptor tyrosine kinase, which upon ligand binding, becomes autophosphorylated 2) RTK associates with RAS through various adaptor proteins 3) Activated RAS triggers a phosphorylation cascade that involves RAF, MEK and ERK 4) Activated ERK translocates to the nucleus where it activates transcription factors important for cell proliferation
40
What proteins in this pathway are proto-oncogenes and how can they cause cancer
- RTKs: EGFR mutations cause constant amplification - RAS: NRAS in melanoma leads to constant GTP-bound active state - RAF: BRAF V600E mutation - MEK and ERK are rarely mutated themselves but are always activated downstream When any of these components are mutated, the pathway is turned on continuously, even without any external signal, driving uncontrolled cell proliferation, resistance to cell death, and ultimately tumor formation.
41
What is the most common mutation in melanomas
Mutation of BRAF or NRAS in 50% of melanomas
42
How does BRAF mutation lead to benign melanoma
BRAF is also mutated in a large number of benign moles, suggesting an early involvement in the oncogenic process, but that is also insufficient for malignant transformation BRAF mutations may cause melanocytes to initially divide more than normal but after a while the cell may enter senescence - BRAF may be involved in both promoting cell growth and senescence
43
What is the p16 INK4A -CDK4/6-RB pathway in charge of
This is a key regulatory pathway that controls whether cell progresses from the G1 phase to the S phase in the cell cycle. The transition is critical because S phase is when DNA replication occurs (gets ready to divide)
44
What is p16 INK4A
It is a tumour suppressor protein It inhibits the activity of CDK4 and CDK6
45
What is CDK4 and CDK6
These are enzymes that, when active, phosphorylate (inactivate) another tumour suppressor protein called Rb
46
What is the Rb protein
In its hypophosphorylated (active) form, Rb blocks cell cycle progression by binding to and sequestering transcription factors (like E2F), preventing them from activating genes needed for DNA replication
47
How does the p16 INK4A pathway work normally
1) p16 INK4A inhibits CDK4/6 2) CDK4/6 cannot phosphorylate Rb and therefore Rb stays active 3) Rb binds to E2F and keeps it inactive 4) Cell cycle is paused in G1 phase, preventing uncontrolled division
48
What happens when p16 INK4A is inactivated
CDK4/6 activity becomes unregulated - CDK4/6 hyperphosphorylates Rb, inactivating Rb - Rb lets go of E2F - E2F then activates the genes for S-phase entry leading to uncontrolled cell proliferation
49
What is the PI3K-AKT pathway
One of the most important cell signalling pathways involved in cell growth, proliferation, metabolism, and survival. When overactivated it can lead to cancer
50
What is the pathway of PI3K-AKT
1) RTK autophosphorylation which then activates PI3K 2) PI3K acts on PIP2 which is a lipid in the cell membrane which converts it into PIP3 3) PIP3 recruits AKT (a kinase) to the cell membrane and once it is at the cell membrane, AKT is phosphorylated. 4) AKT phosphorylation leads to proteins that promote cell survival, stimulate cell growth, enhance metabolism and support angiogenesis 5) PTEN is a tumour suppressor that turns off this pathway by dephosphorylates PIP3 back to PIP2. If PTEN is lost or mutated, this brake is gone, and the pathway stays switched on, promoting cancer
51
In melanoma, how is the PI3K-AKT pathway mutated
- PTEN is inactivated leading to constant pathway activation - NRAS activation - stimulated PI3K directly - PI3K gene amplification or mutation increasing the pathway signalling
52
What is the first stage of tumour progression in melanomas
BRAF, NRAS, KIT mutation Molecular pathway that is affected: Activation of the RAS-RAF-MEk-ERK This leads to uncontrolled cell proliferation and apoptosis evasion
53
What is the second stage of tumour progression in melanomas
p16 (INK4A), CDK4 mutation Molecular pathway that is affected: inactivation of p16-CDK4-Rb This causes evasion of cellular senescence
54
What is the third stage of tumour progression in melanomas
TP53 and ARF Molecular pathway that is affected: Inactivation of TP53 and ARF This leads to inactivation of DNA damage and response and evasion of cellular senescence
55
What is the fourth stage of tumour progression in melanomas
PTEN, PIK3CA (NRAS, KIT) Activation of the PI3K-AKT pathway Promotes cell survival, invasion of local tissue and metastasis to distant sites
56
What are the 3 drug targets for metastatic melanoma
- Drugs that target cells with the BRAF mutation - Drugs that target cells with changes in the C-KIT gene - Drugs that target other gene or protein changes
57
How do drugs that target cells with BRAF mutations work
These drugs have been shown to shrink many of these tumours, especially when BRAF and MEK inhibitors are combined. These drugs selectively bind to the BRAF protein and inhibit its kinase activity, stopping it from activating MEK and then ERK This halts abnormal signalling and reduces tumour survival, cell proliferation and tumour size
58
How do drugs that target cells with C-KIT mutations work
This is more likely to target acral lentiginous melanomas - tumours shrink rapidly and progression slows Drug examples: Imatinib, Dasatinib and Nilotinib C-KIT is an RTK that triggers pathways like RAS-RAF-MEK-ERK (growth), PI3K-AKT (survival), JAK-STAT (proliferation) These drugs bind to the ATP-binding pocket of C-KIT receptors which prevent its activation

Clinical Pathology in Action (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions