Skin Cancer (only 2nd half) Flashcards
What are the 5 layers of skin?
Come Let’s get sun burnt!
What is melanoma
Malignant tumour arising from melanocytes
most common sc death (over 75%)
Where can melanoma arise besides regular skin
Can arise on mucosal surfaces (e.g. oral, conjunctival, vaginal) and within uveal tract of eye
genetic risk factors for skin cancer
Family history (CNKN2A mutations), MC1R variants
Lightly pigmented skin
Red hair
DNA repair defects (e.g. xeroderma pigmentosum)
environmental risk factors for melanoma
Intense intermittent sun exposure
Chronic sun exposure
Residence in equatorial latitudes
Sunbeds
Immunosuppression
phenotypic risk factors for melanoma
> 100 Melanocytic nevi
Atypical melanocytic nevi
What does BRAF substitution result in
BRAF mutations substitution leads to activation of mitogen-activated protein kinase (MAPK) pathway
melanoma
host response to melanoma
CD8+ T-cell recognise melanoma-specific antigens and if activated appropriately, are able to kill tumour cells.
CD4+ helper T-cells and antibodies also play a critical role
Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is natural inhibitor of T-cell activation by removing the costimulatory signal (B7 on APC to CD28 on T-Cell
immunotherapy for melanoma based on
CTLA-4 blockade – ipilimumab
- Also checkpoint inhibitors (PD-1, PDL1)
subtypes of melanoma
Superficial spreading
Nodular
Lentigo maligna
Acral lentiginous
Unclassifiable
features of superficial spreading melanoma
Most frequently seen on trunk of men and legs of women
regression (visible as grey, hypo-or depigmentation), due to reaction of host immune system with tumour
After a slow horizontal (radial) growth phase, limited to epidermis, a more rapid vertically oriented growth phase, which presents clinically with development of nodule
nodular melanoma epidemiology
2nd most common type of melanoma in fair skinned individuals
Most commonly trunk, head and neck
M>F
presentation of nodular melanoma
Usually present as blue to black, but sometimes pink to red, nodule – may be ulcerated, bleeding
Develops rapidly
Nodular melanoma is believed to arise as a de novo vertical growth phase without the pre-existing horizontal growth phase
Tend to present more advanced stage, with poorer prognosis.
lentigo maligna epidemiology
Occurs in chronically sun-damaged skin, most commonly on the face
>60 years old
rarer
presentation of lentigo maligna
Slow growing, asymmetric brown to black macule with colour variation and an irregular indented border
sun exposed areas e.g neck
In situ- termed ‘Lentigo Maligna’
Invasive (5%)- termed ‘Lentigo Maligna Melanoma’
acral lentiginous epidemiology
Typically occurs on palms and soles or in and around the nail apparatus
Incidence similar across all racial and ethnic groups
why BAME groups get acral lentiginous melanomas?
As more darkly pigmented Africans and Asians do not typically develop sun-related melanomas, ALM represents disproportionate percentage of melanomas diagnosed in Afro- Caribbean (up to 70%) or Asians (up to 45%)
public awareness of early detection of skin cancer
ABCDE
Asymmetry
Border irregularity
Colour variegation
Diameter greater than 5mm
Evolving
poor prognosis indicators (melanoma)
Increased Breslow thickness >1mm
Ulceration
Age
Male gender
Anatomical site – trunk, head, neck
Lymph node involvement
how to measure breslow thickness
From granular layer to bottom of tumor
what is dermoscopy
Investigation that can improve correct diagnosis of melanoma by nearly 50%
main features of general melanoma
Asymmetry
Presence of multiple colours
Reticular, globular, reticular-globular, homogenous
Starburst
removal of melanomas
primary excision - 2mm peripheral margin
wide excision - margin determined by breslow depth - 5mm in situ, 10mm for 1mm invasion
staging of melanomas
thickness
ulceration
TNM
unresectable melanoma management or metastatic
Immunotherapy
Mutated oncogene targeted therapy
mutated oncogene melanoma therapy
BRAF inhibitor and MEK inhibitor combined
keratinocyte dysplasia/carcinoma epidemiology
Predominantly pale skin types
Solar induced UV damage
types of skin carcinoma
Actinic keratoses
- Dysplastic keratinocytes
Bowen’s disease (Squamous cell carcinoma in situ)
Squamous cell carcinoma
- Potential for metastasis/death
Basal cell carcinoma (more common)
- rarely metastasises
- Locally invasive
BCC pathogenesis
stroma produced by dermal fibroblasts
crosstalk between tumour cells and mesenchymal stroma cells
proteolytic activity (invasion) via metalloproteinases and collagenases
UV radiation role in SCC
Develops through addition of genetic alterations – alterations in p53 are most common
risk factors of all keratinotye carcinomas (SCC,BCC etc)
- UV exposure
-PUVA - Genetic syndromes
-Xeroderma pigmentosum
-Oculocutaneous albinism
-Muir Torre syndrome
-Nevoid BCC syndrome - Nevus sebaceous
- Porokeratosis
- Organ transplantation (immunosuppressive drugs)
- Chronic non-healing wounds
- Ionising radiation
-Airline pilots - Occupational chemical exposures
-Tar, polycyclic aromatic hydrocarbons
what is actinic keratoses
Atypical keratinocytes confined to epidermis
Erythematous macule or scale or both-> thick papules or hyperkeratosis or both
Develop on sun-damaged skin - usually head, neck, upper trunk and extremities
what is bowens disease
Squamous cell carcinoma in situ
Erythematous scaly patch or slightly elevated plaque
may arise from existing actinic keratinosis
can resemble AK, psoriasis, chronic eczema
treatment of AK and bowens
5-fluorouracil cream
Cryotherapy
Imiquimod cream
Photodynamic therapy
Curettage and cautery
Excision
SCC presentation
Arises within background of sun-damaged skin
- Erythematous to skin coloured
- Papule
- Plaque-like
- Exophytic
- Hyperkeratotic
- ulcerated
red flags of SCC
rapid growth
immunosuppressed patient
inflammation
poorly differentiated
invasion beyond subcut fat
what is keratoacanthoma
sharply circumscribed, crateriform nodule with keratotic core
Most occur on head or neck / sun exposed areas
hard to distinguish from SCC
diagnosis of SCC
clinical sufficient
biposy maybe, ultrasound of lymph nodes if concerned
treatment SCC
Examination of rest of skin and regional lymph nodes
Excision
Radiotherapy
- Unresectable
- High risk features e.g. perineural invasion
Cemiplimab for metastatic SCC
types of basal cell carcinoma
Nodular
Superficial
Morpheic
Infiltrative
Basisquamous
Micronodular
most common type of BCC
Nodular
Accounts for approximately 50% of all Basal cell carcinomas
how does BCC often present
Typically presents as shiny, pearly papule or nodule
or superficial BCC - Well-circumscribed, erythematous, macule / patch or thin papule /plaque
diagnosis of BCC
clinical sufficient
biopsy maybe
BCC treatment
Standard surgical excision
Mohs micrographic surgery
Other options
when to use Mohs micrographic surgery
- recurrent BCC
- aggressive subtype - morpheic, infiltrative, micronodular
- critical sites
main features of merkel cell carcinoma
- Origin cell not a Merkel cell
- 80% associated with polyamovirus
- Solitary, rapidly growing nodule- pink-red to violaceous, firm, dome shaped,
- Ulceration can occur
merkel cell carcinoma treatment
Treated with surgery, radiation therapy
anti-PD1 (Pembrolizumab) / anti-PDL1 (Avelumab)
