7.5 - Skin cancer Flashcards
1
Q
What two investigation types are mainly used for neoplastic skin conditions?
A
- imaging (internal organ involvement, vascular supply)
- skin biopsy (microscopy)
2
Q
Define melanoma
A
Malignant tumour arising from melanocytes
3
Q
What cells do melanomas arise from?
A
Melanocytes
4
Q
How deadly is melanoma?
A
Causes 75% of skin cancer deaths (despite not being the most common type of skin cancer)
5
Q
Describe the incidence rates of melanoma worldwide.
A
Rising incidence rates observed worldwide (although mortality is stable)
6
Q
Where on the body can melanoma arise?
A
- mucosal surfaces (e.g. oral, conjunctival, vaginal) and within uveal tract of eye
- internal organs can be affected (even by primary melanoma not just metastatic) - probably due to impaired melanocyte migration during embryogenesis
7
Q
What are central depigmented parts of melanoma lesions due to?
A
Tumour regression
8
Q
What are the genetic risk factors for melanoma? (4)
A
- family history (CDKN2A mutations), MC1R variants
- DNA repair defects (e.g. xeroderma pigmentosum)
- lightly pigmented skin (fairer)
- red hair
9
Q
What are the environmental risk factors for melanoma? (3)
A
- sun exposure - intense intermittent, or chronic
- sunbeds
- immunosuppression
10
Q
What are the phenotypic risk factors for melanoma? (2)
A
- > 100 melanocytic nevi (moles)
- atypical melanocytic nevi (moles)
11
Q
How is the molecular pathogenesis of melanoma important clinically? (2)
A
- genetic mutations in this pathway can predispose to melanoma
- these processes can be targeted therapeutically e.g. BRAF, MEK
12
Q
Describe the epidemiology of melanoma.
A
- increasing worldwide
- develops predominantly in Caucasian populations
- incidence low amongst darkly pigmented populations
- 10-19/100k per year in Europe
- 60/100k per year in Australia/NZ
13
Q
What are the subtypes of melanoma? (5)
A
- superficial spreading
- nodular
- lentigo maligna
- acral lentiginous
- unclassifiable
14
Q
How common is superficial spreading melanoma?
A
60-70% of all melanomas
15
Q
Which group of people is superficial spreading melanoma most common in?
A
Fair-skinned
16
Q
Where is superficial spreading melanoma seen on the body most frequently?
A
- trunk of men
- legs of women
17
Q
How can superficial spreading melanoma arise?
A
Can arise de novo (no previous moles) or in pre-existing nevus (previous mole)
18
Q
How is regression seen in superficial spreading melanoma and why does it happen?
A
- in 2/3 of tumours, regression is visible as grey or hypopigmentation/depigmentation
- shows interaction of host immunity against tumour
19
Q
Describe the growth pattern of superficial spreading melanoma.
A
- horizontal (or radial) growth phase where you see 4 characteristic features:
- asymmetry (A)
- border irregularity (B)
- colour variation (C)
- diameter increase (D)
- vertical growth phase - leads to appearance of nodule or bump
20
Q
What is the ABCD rule that you see in superficial spreading melanoma (horizontal growth phase)?
A
- Asymmetry
- Border irregularity
- Colour variation
- increased Diameter
21
Q
How common is nodular melanoma?
A
15-30% of all melanomas
22
Q
Which groups of people is nodular melanoma common in? (2)
A
- 2nd most common type of melanoma in fair-skinned individuals
- more common in men than women
23
Q
Which body parts is nodular melanoma most common in?
A
Trunk, head and neck
24
Q
How does nodular melanoma present?
A
- usually as blue-black, but sometimes pink-red nodule (= a pigmented nodule)
- may be ulcerated, bleeding
- develops rapidly
(Trunk, head, neck)
25
What does amelanotic mean?
When a nodule has no pigment - always consider nodules even if not brown
26
Describe the growth of nodular melanoma.
- no horizontal/radial growth phase - features e.g. asymmetry, border irregularity, colour variation are not present/obvious
- only vertical growth phase - invades earlier and tends to present at more advanced stage with worse prognosis (vs superficial spreading)
27
In nodular melanoma, what does only having a vertical growth phase mean clinically?
It invades earlier and tends to present at more advanced stage with worse prognosis (compared to superficial spreading melanoma)
28
How common is lentigo maligna?
10% (minority) of cutaneous melanomas
29
Which groups of people is lentigo maligna most commonly in? (2)
- >60 years old
- occurs in chronically sun-damaged skin
30
Where is lentigo maligna most commonly seen on the body?
Most common on face
31
What does the term 'lentigo maligna' refer to?
Pre-invasive, slow growing, asymmetric brown/black macule with colour variation and an irregular indented border
32
When do we call it lentigo maligna and when do we call it lentigo maligna melanoma?
- in situ - termed 'lentigo maligna'
- invasive - termed 'lentigo maligna melanoma'
- 5% of lentigo maligna progresses to invasive melanoma
33
How common is acral lentiginous melanoma?
Relatively uncommon - 5% of all melanomas
34
Which group is acral lentiginous melanoma diagnosed most frequently in?
7th decade of life (60s)
35
Where in the body does acral lentiginous melanoma occur?
Typically occurs on palms and soles OR in/around nail apparatus (melanonychia)
36
What is the incidence of acral lentiginous melanoma in different racial groups?
- similar across all racial and ethnic groups
- disproportionate % of melanomas diagnosed in Afro-Caribbean (up to 70%) or Asians (up to 45%) - as they do not typically develop sun-related melanomas
37
How are patients instructed to detect melanomas early?
Look for history of change in colour, shape or size of a pigmented skin lesion
38
What is the ABCDE public awareness campaign for melanomas?
- Asymmetry - one half does not match
- Border - uneven borders
- Colour - variety of colours
- Diameter - larger than a pencil eraser
- Evolution - change in size, shape, colour etc (most important)
39
What is Garbe's rule?
If a patient is worried about a single skin lesion, do not ignore their suspicion and have a low threshold for performing biopsy
40
How do we diagnose melanoma?
Skin biopsy
41
What are the differential diagnoses for melanoma? (3)
- basal cell carcinoma - can be pigmented
- seborrheic keratosis - harmless skin lesions that increase in number with age
- dermatofibroma - harmless benign skin tumour
42
What are poor prognostic features for melanoma? (6)
- increased Breslow thickness >1mm (measured histologically from stratum granulosum downwards to bottom of tumour)
- ulceration
- age
- male gender
- anatomical site - trunk, head, neck
- lymph node involvement
43
What are the survival rates for melanoma like?
- stage 1A melanoma have 10 year survival of >95%
- thick melanomas >4mm and ulceration (stage pT4b) have a 10 year survival of 50%
44
What technique do we use to investigate melanoma?
| (Alongside biopsy)
Dermoscopy - can improve correct diagnosis of melanoma by nearly 50%
45
What are the global features of melanoma seen on dermoscopy - not on slides, just be aware of? (11)
- asymmetry
- multiple colours
- reticular, globular, reticular-globular, homogenous
- starburst
- atypical network
- atypical dots or globules
- irregular blood vessels
- regression
- structures
- streaks
- blue-white veil (sign of vertical growth phase)
46
What else is important to consider other than dermoscopy when investigating melanoma?
Dermoscopic findings should not be considered in isolation - history and risk factor status are important
47
What do we do if in doubt about melanoma?
If in doubt, take it out - excise lesion for histological assessment if in any doubt (clinical features are not specific, low threshold for excision)
48
What are the stages of excision of a melanoma?
- primary excision down to subcutaneous fat (2mm peripheral margin)
- if melanoma confirmed, wide excision done
- margin determined by Breslow depth
- 5mm for in situ
- 10mm for
49
What does melanoma excision prevent?
Local recurrence or persistent disease
50
How do we stage melanoma?
- pathological staging occurs then clinical exam
- TNM staging happens in some instances
## Footnote
TNM staging T includes thickness + ulceration e.g.
pT1a <1mm no ulceration
pT4b >4mm with ulceration
51
What is a sentinel lymph node?
- initial node within a nodal basin that lymphatic drainage (of finite regions of skin) drains into (1st LN encountered)
- most likely nodes to contain metastatic disease
52
What types of TNM melanomas is sentinel lymphoma node biopsy available for?
Currently offered for pT1b and more advanced
53
What would extracapsular spread on lymph node biopsy of melanoma require?
Lymph node dissection
54
What two types of imaging are available for melanoma, and for what stages of melanoma are they available for?
- PET-CT
- MRI brain
- available for:
- stage IIc without SLNB (sentinel lymph node biopsy)
- stage III
- stage IV
55
What is a major prognostic indicator in melanoma?
LDH
56
What are two ways we can treat unresectable or metastatic melanomas?
- immunotherapy
- CTLA-4 inhibition - unresectable or metastatic BRAF -ve melanoma (e.g. Ipilimumab)
- PD-L1 (programmed cell death ligand) inhibitors (e.g. Nivolumab)
- mutated oncogene targeted therapy
- combination of a BRAF inhibitor (e.g. encorafenib, vemurafenib, dabrafenib) and MEK inhibitor (e.g. trametinib)
57
What groups of people do keratinocyte dysplasia/carcinoma mostly affect?
Predominantly pale skin types
58
What is the mechanism of keratinocyte dysplasia/carcinoma?
Solar-induced UV damage
59
What are the stages of development of keratinocyte dysplasia?
- actinic keratoses - dysplastic + atypical keratinocytes
- Bowen's disease - squamous cell carcinoma in situ (full thickness)
- squamous cell carcinoma - potential for metastasis/death (full thickness and invasion)
60
What type of keratinocyte carcinoma does not metastasise?
Basal cell carcinoma - virtually never metastasises, locally invasive
61
What are the two types of keratinocyte carcinomas?
- squamous cell carcinoma
- basal cell carcinoma
62
What is the epidemiology of keratinocyte carcinoma (BCC vs SCC)?
- basal cell carcinoma most common skin cancer
- BCC:SCC = 4:1
- both commoner in paler skin types
- both more common in men than women (2/3 : 1)
- median age at diagnosis of BCC is 68
63
What are the risk factors for keratinocyte carcinomas? (9)
- UV exposure e.g. PUVA
- fair skin
- genetic syndromes (xeroderma pigmentosum, oculocutaneous albinism, Muir Torre syndrome, naevoid basal cell carcinoma syndrome)
- nevus sebaceous
- porokeratosis
- organ transplantation (immunosuppressive drugs)
- chronic non-healing wounds
- ionising radiation e.g. airline pilots
- occupational toxic exposures e.g. tar, polycyclic aromatic hydrocarbons
64
What is a significant risk factor for basal cell carcinoma?
UV radiation
65
What happens between tumour cells and mesenchymal cells of stroma in basal cell carcinoma?
- cross talk occurs, including with platelet-derived growth factor (PDGF)
- receptors for PDGF are upregulated in stroma but PDGF is upregulated in tumour cells
66
What kind of activity do basal cell carcinomas have and how does that help them?
- proteolytic activity e.g. metalloproteinases and collagenases
- degrade pre-existing dermal tissue and facilitate spread of tumour cells
67
Loss of function of what genes can contribute to **basal cell carcinoma** progression and can be targeted for treatment? (2)
- loss of function in **chromosome 8q (PTCH gene)**
- **p53** mutations also important - majority are missense mutations that carry UV signature
68
What is a significant risk factor for squamous cell carcinoma?
UV radiation
69
What causes **squamous cell carcinoma** to develop?
- develops through a series of genetic alterations
- alterations in **p53** are most common
- **CDKN2A** alterations also common
- **NOTCH1 or NOTCH2** (Wnt/b-catenin) signalling pathway also plays a role
70
What are actinic keratoses?
Atypical dysplastic keratinocytes confined to the epidermis (not full thickness)
71
Where do actinic keratoses develop?
- develop on sun-damaged skin
- usually head, neck, upper trunk and extremities
72
How do actinic keratoses present? (3)
- macules or papules
- red or pink
- usually some scale - may be thick scale
73
When would a biopsy be needed for actinic keratoses?
The distinction of actinic keratoses from SCC is sometimes difficult so a biopsy is required
74
What is there a risk of with actinic keratoses?
Progression to squamous cell carcinoma (0.025-16% per year for any single lesion)
75
What is Bowen's disease?
Squamous cell carcinoma in situ (full thickness)
76
How does Bowen's disease present?
Erythematous scaly patch, or slightly elevated plaque
77
How may Bowen's disease arise?
May arise de novo or from pre existing actinic keratoses
78
What may Bowen's disease resemble? (3)
- actinic keratoses
- psoriasis
- chronic eczema
79
What is the treatment for actinic keratoses and Bowen's disease? (6)
- 5-fluorouracil cream (topical chemo)
- cryotherapy (freeze with liquid nitrogen)
- imiquimod cream (stimulate immune system to kill)
- photodynamic therapy (apply porphyrin and shine light to generate free radicals and cause apoptosis)
- curettage and cautery (scrape under local anaesthetic)
- excision
80
What is squamous cell carcinoma?
- invasive atypical keratinocytes
- potential for metastasis/death
81
What skin do squamous cell carcinomas arise in?
Arises within background of sun-damaged skin
82
How can squamous cell carcinomas present? (6)
- erythematous or skin-coloured
- papule
- plaque-like
- exophytic
- hyperkeratotic
- ulceration
83
What high risk clinical features of squamous cell carcinoma are there? (6)
- localisation and size:
- trunk and limbs >2cm
- head/neck >1cm
- periorificial zones
- ill-defined margins
- rapidly growing
- immunosuppressed patients
- previous radiotherapy or site of chronic inflammation
- histology (do not need to know)
84
What histological features are high-risk for squamous cell carcinoma? (5 - do not need to know for exam)
- poorly differentiated
- acantholytic, adenosquamous, demosplastic subtypes
- tumour thickness - Clark level >6mm, Clark IV, V
- invasion beyond subcutaneous fat
- perineural, lymphatic or vascular invasion
85
How do we investigate squamous cell carcinoma?
- often clinical diagnosis is sufficient
- diagnostic biopsy may be taken if diagnostic uncertainty
- ultrasound of regional lymph nodes +/- fine needle aspiration, if concerns of regional lymph node metastasis
86
What differentials are there for squamous cell carcinoma? (3 + 1)
- basal cell carcinoma
- viral wart
- Merkel cell carcinoma
- (keratoacanthoma)
87
How do we treat squamous cell carcinoma? (5)
- examination of rest of skin and regional lymph nodes
- excision
- radiotherapy if unresectable / high-risk features e.g. perineural invasion
- Cemiplimab (PD1 inhibitor) for metastatic SCC
- secondary prevention e.g. skin monitoring advice and sun protection advice (high risk of developing another SCC)
88
What is a keratoacanthoma?
Rapidly enlarging papule that evolves into a sharply circumscribed, crateriform nodule with keratotic core
89
How do we treat keratoacanthoma?
Resolves slowly over months
90
Why is keratoacanthoma difficult to diagnose/classify?
- difficult to distinguish clinically and histologically from SCC
- can only tell it was keratoacanthoma if/when it resolves
91
Where do keratoacanthomas occur on the body?
Most occur on head or neck / sun-exposed areas
92
What are the 6 main subtypes of basal cell carcinoma?
- nodular
- superficial
- morpheic
- infiltrative
- basisquamous
- micronodular
93
How does nodular basal cell carcinoma present?
- typically presents as shiny, pearly papule or nodule
- on dermoscopy you can see arborising (branching) blood vessels
94
How common is nodular basal cell carcinoma?
- most common subtype of BCC
- accounts for approximately 50% of BCC
95
How does superficial basal cell carcinoma present?
- well-circumscribed, erythematous macule/patch or thin papule/plaque
- can resemble actinic keratosis, Bowen's disease, eczema
96
How does morphoeic basal cell carcinoma present?
- slightly elevated or depressed area of induration
- usually light pink to white in colour
- aggressive behaviour - extensive local tissue destruction
97
How common is morphoeic basal cell carcinoma?
Less common than other subtypes
98
What features does basisquamous basal cell carcinoma have?
Histological features of both basal cell carcinoma and squamous cell carcinoma, can metastasise
99
What are the features of micronodular basal cell carcinoma?
- resembles nodular basal cell carcinoma clinically
- more destructive behaviour - high rates of recurrence and subclinical spread
100
How do we investigate basal cell carcinoma?
- often clinical diagnosis sufficient
- diagnostic biopsy may be taken
101
What differentials are there for basal cell carcinoma? (3)
- squamous cell carcinoma
- adnexal (sebaceous) carcinoma
- Merkel cell carcinoma
102
What treatments are there for basal cell carcinoma? (7)
- standard surgical excision
- Moh's micrographic surgery
- topical therapy e.g. 5-fluorouracil, Imiquimod
- photodynamic therapy (superficial BCC)
- curettage (superficial BCC)
- radiotherapy (>70yo)
- Vismodegib - selectively inhibits abnormal signalling in Hedgehog pathway
103
When is Moh's micrographic surgery used? (3)
- recurrent basal cell carcinoma
- aggressive subtype (morpheic/infiltrative/micronodular)
- critical site
104
What is bread loafing?
- when you send a histological specimen for analysis, it is sectioned using bread loafing technique
- some areas of skin may be missed = falsely reassuring report, false-negative tumour margins
105
How does Moh's micrographic surgery avoid the problems of bread loafing?
- you remove the tumour
- you then take thin onion skin layers from the margin and examine them repeatedly until you see healthy tissue
- helps us have healthy margins without removing excess skin
- but this process takes hours and requires highly skilled surgeon
106
What is Merkel cell carcinoma?
Malignant proliferation of highly anaplastic (lack identifiable features) cells which share features with neuroectodermally derived cells (including Merkel cells)
107
Why is the name Merkel cell carcinoma misleading?
They are not actually derived from Merkel cells
108
What are risk factors for Merkel cell carcinoma? (2)
- 80% associated with polyomavirus
- UV exposure is also an aetiological factor
109
Where in the body does Merkel cell carcinoma tend to develop?
Predilection for head and neck region of older adults
110
How does Merkel cell carcinoma present? (3)
- solitary, rapidly growing nodule
- pink-red to violaceous, firm, dome-shaped
- ulceration can occur
111
How does Merkel cell carcinoma behave?
- aggressive, malignant behaviour (most aggressive type of skin cancer)
- >40% develop advanced disease (metastatic)
