Skin Cancer Flashcards
What is a melanoma?
Malignant tumour arising from melanocytes
Leads to >75% of skin cancer deaths
Can arise on mucosal surfaces (e.g. oral, conjunctival, vaginal) and within uveal tract of eye
What are some risk factors for melanoma? (genetic,environmental,phenotypic)
Genetic factors
Family history (CDKN2A mutations), MC1R variants
DNA repair defects (e.g. xeroderma pigmentosum)
Lightly pigmented skin
Red hair
Environmental factors
Sun exposure – intense intermittent or chronic
Sunbeds
Immunosuppression
Phenotypic
>100 Melanocytic nevi
Atypical melanocytic nevi
What role does the MAPK (RAS-RAF-MEK-ERK) pathway play in the pathogenesis of skin cancer?
It regulates cellular proliferation, growth and migration
What are the subtypes of melanoma?
Superficial spreading
Nodular
Lentigo maligna
Acral lentiginous
Unclassifiable
How common is superficial spreading as a subtype of melanoma?
60-70% of all melanomas
Where is superficial spreading most typically found?
Trunk of men and legs of women
In superficial spreading how does growth occur?
Horizontal growth then vertical growth through the skin layers
What is the second most common type of melanoma?
Nodular
15-30% of all melanomas
Where does nodular melanoma typicaly present?
trunk, head and neck
What type of growth is shown in nodular melanoma?
Only vertical growth
What population is lentigo maligna most prevelent in?
> 60 years old
- Occurs in chronically sun-damaged skin
- Most common on face
What is lentigo maligna?
Slow growing, asymmetric brown / black macule with colour variation and an irregular indented border.
In situ – termed ‘Lentigo Maligna’
Invasive termed ‘Lentigo Maligna Melanoma’
5% of lentigo maligna progresses to invasive melanoma
Where is acral lentiginous typical presentation?
Typically palms and soles or in/around nail apparatus
What is the ABCDE for detection of melanoma?
Asymmetry
Border irregularity
Colour variation
Diameter greater than 5mm
Evolving
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 a biopsy
What are some poor prognostic features?
Increased Breslow thickness >1mm
Ulceration
Age
Male gender
Anatomical site – trunk, head, neck
Lymph node involvement
What is investigation for melanoma and what is to be noted about it?
Dermoscopy –can improve correct diagnosis of melanoma by nearly 50%
NB
Dermoscopic findings should not be considered n isolation
History and risk factor status are important
Excise lesion for histological assessment if in any doubt
What is the typical management for melanoma?
Primary excision down to subcutaneous fat
- 2mm peripheral margin
Wide excision
- Margin determined by Breslow depth
- 5mm for in situ
- 10mm for </=1mm
Prevents local recurrence or persistent disease
What is sentinel lymphoma node biopsy?
Lymphatic drainage of finite regions of skin drain specifically to an initial node within a given nodal basin - the ‘sentinel node’
Most likely nodes to contain metastatic disease
Currently offered for pT1b+
Extracapsular spread on lymph node biopsy – needs lymph node dissection
What imaging is done for melanoma?
Stage III, IV
And Stage IIc without SLNB
PET-CT
MRI Brain
What is a mojor prognostic indicator in melanoma?
LDH
What are two methods used in unresectable or metastatic melanoma?
Immunotherapy and mutated oncogene targeted therapy
What does immunotherapy involve?
CTLA-4 inhibition – unresectable or metastatic BRAF negative melanoma (Ipilimumab)
PD-L1 (Programmed cell death ligand) inhibitors (Nivolumab)
What does mutated oncogene targeted therapy involve?
- Combination of aBRAFinhibitor (e.g. encorafenib, vemurafenib, dabrafenib) andMEK inhibitor (e.g. trametinib)
What are some examples of keratinocyte dysplasia?
Actinic keratoses
- Dysplastic keratinocytes
Bowen’s disease (Squamous cell carcinoma in situ)
Squamous cell carcinoma
- Potential for metastasis/ death
Basal cell carcinoma
- (Virtually) never metastasises
- Locally invasive
What is the pathogenesis for basal cell carcinoma?
Cross talk between tumour cells and mesenchymal cells of stroma
- Receptors for PDGF are upregulated in Stroma but PDGF is upregulated in tumour cells
BCC has proteolytic activity e.g. metalloproteinases and collagenases
– degrade pre-existing dermal tissue and facilitate spread of tumour cells
Loss of function in chromosome 8q (PTCH gene)
- p53 mutations are also important – majority are missense mutations that carry a UV signature
What is the pathogenesis for squamous cell carcioma?
Develops through addition of genetic alterations – alterations in p53 are most common
- CDKN2A also
NOTCH1 or NOTCH2 (Wnt / β-catenin signalling) also plays role
Which is more common between basal cell carcinoma na d squamous cell carcinoma?
BCC:SCC 4:1
Both commoner in pale skin types
Both more common in men vs women (2-3:1)
Median age at diagnosis of BCC is 68
What are some risk factors for keratinocyte carcinomas?
UV exposure
- PUVA
Fair skin
Genetic syndromes
- Xeroderma pigmentosum
- Oculocutaneous albinism
- Muir Torre syndrome
- Nevoid basal cell carcinoma syndrome*
Nevus sebaceous
Porokeratosis
Organ transplantation (immunosuppressive drugs)
Chronic non-healing wounds
Ionising radiation
- Airline pilots
Occupational chemical exposures
- Tar, polycyclic aromatic hydrocarbons
What are some characteristics of actinic keratoses?
Atypical keratinocytes confined to epidermis
Develop on sun-damaged skin - usually head, neck, upper trunk and extremities
Macules or papules
Red or pink
Usually some scale – may be thick scale
Distinction from squamous cell carcinoma sometimes difficult – requiring biopsy
What is bowen’s disease?
Squamous cell carcinoma in situ
Erythematous scaly patch or slightly elevated plaque
May arise de novo or from pre-existing AK
May resemble actinic keratoses, psoriasis, chronic eczema
what is the treatment for bowen’s disease and actinic keratoses?
5-fluorouracil cream
Cryotherapy
Imiquimod cream
Photodynamic therapy
Curettage and cautery
Excision
What might squamous cell carcinoma look like?
Erythematous to skin coloured
- Papule
- Plaque-like
- Exophytic
- Hyperkeratotic
- Ulceration
What are some clinical features of squamous cell carcinoma?
Localisation and size:
- Trunk and limbs > 2cm
- Head / neck > 1cm
- Periorificial zones
Margins: Ill-defined
Rapidly growing
Immunosuppressed patients
Previous radiotherapy or site of chronic inflammation
What are keratoacanthoma (how they present, how they resolve, where they present, what are they similar to)?
Rapidly enlarging papule that evolves into a sharply circumscribed, crateriform nodule with keratotic core
Resolves slowly over months
Most occur on head or neck / sun exposed areas
Difficult to distinguish clinically and histologically from squamous cell carcinoma
What are some diffrential diagnoses for squamous cell carcinoma?
Basal cell carcinoma
Viral wart
Merkel cell carcinoma
What is the treatment for squamous cell carcinoma?
Examination of rest of skin and regional lymph nodes
Excision
Radiotherapy
- Unresectable
- High risk features e.g. perineural invasion
Cemiplimab for metastatic SCC
Secondary prevention
- Skin monitoring advice
- Sun protection advice
What are the main subtypes for basal cell carcinoma?
Nodular
Superficial
Morpheic
Infiltrative
Basisquamous
Micronodular
Describe nodular basal cell carcinoma
Most common subtype
Accounts for approximately 50% of all Basal cell carcinomas
Typically presents as shiny, pearly papule or nodule
Describe superficial basal cell carcinoma?
Well-circumscribed, erythematous, macule / patch or thin papule /plaque
Describe morphoeic basal cell carcinoma?
Less common
Slightly elevated or depressed area of induration
Usually light-pink to white in colour
More aggressive behaviour
- Extensive local destruction
Describe basisquamous basal cell carcinoma
Histological features of both basal cell carcinoma and squamous cell carcinoma
Describe micronodular basal cell carcinoma?
Resembles nodular basal cell carcinoma clinically
More destructive behaviour – high rates of recurrence and subclinical spread
What are soem diffrential diagnosis for basal cell carcinoma?
Squamous cell carcinoma
Adnexal (sebaceous) carcinoma
Merkel cell carcinoma
What are the main teeatment options for basal cell carcinoma?
Standard surgical excision
Mohs micrographic surgery
- Recurrent basal cell carcinoma
- Aggressive subtype (morpheic / infiltrative / micronodular)
- Critical site
What are some other options for treating basla cell carcinoma?
Topical therapy e.g. 5-Fluorouracil, Imiquimod
Photodynamic therapy
Curettage
Radiotherapy
Vismodegib - selectively inhibits abnormal signalling in Hedgehog (Hh) pathway
What are origin cell for merkel cell carcinoma?
Origin cell not a Merkel cell – are highly anaplastic cells which share features with neuroectodermally derived cells (including Merkel cells)
How does merkel cell carcinoma present?
Predilection for the head and neck region of older adults
Solitary, rapidly growing nodule- pink-red to violaceous, firm, dome shaped,
- Ulceration can occur
