Skin Cancer Flashcards
What are Melanomas?
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
Rising incidence rates observed worldwide
What are the risk factors for Melanoma?
Genetic factors
Family history (CNKN2A mutations), MC1R variants
Lightly pigmented skin
Red hair
DNA repair defects (e.g. xeroderma pigmentosum)
Environmental factors Intense intermittent sun exposure Chronic sun exposure Residence in equatorial latitudes Sunbeds Immunosuppression
Phenotypic
>100 Melanocytic nevi
Atypical melanocytic nevi
What is the Pathogenesis of Melanoma?
Mitogen-activated protein kinase (MAPK) [RAS-RAF-MEK-ERK] pathway regulates cellular proliferation, growth and migration
KIT mutations - 30-40% of acral and mucosal melanomas – also melanomas from chronically sun-exposed skin harbour activating mutations or copy number amplifications of KIT gene.
What are the Activate mutations in Melanoma?
NRAS gene (15-20% of melanomas) BRAF gene (50-60%) – high in melanomas of skin with intermittent UV exposure, yet low in melanomas of skin with high cumulative UV exposure
What happens in CDKN2A mutations?
Inherited CDKN2A mutations also cause MAPK pathway activation
P16 - tumour suppressor encoded by CDKN2A
- Binds to CDK4/6, p16 prevents formation of cyclin D1-CDK4/6 complex
- Cyclin D1-CDK4/6 complex phosphorylates Rb, inactivating it, leading to E2F release (once released, E2F promotes cell cycle progression)
What is the hosts 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 based on CTLA-4 blockade – ipilimumab
- Also checkpoint inhibitors (PD-1, PDL1)
What is the epidemiology of Melanoma?
Increasing worldwide
Develops predominantly in Caucasian populations
Incidence low amongst darkly pigmented populations
10-19/100,000 per year in Europe
60/100,000 per year in Australia / NZ
What are the subtypes of Melanoma?
Superficial spreading Nodular Lentigo maligna Acral lentiginous Unclassifiable
What happens in superficial spreading melanoma?
60-70% of all melanomas
- Most common type in fair-skinned individuals
Most frequently seen on trunk of men and legs of women
Can arise de novo or in pre-existing nevus
In up to 2/3 of tumours, regression (visible as grey, hypo-or depigmentation), reflecting the interaction of host immune system with tumour.
How do superficial spreading melanomas grow?
Horizontal and then vertical
What happens in Nodular melanoma?
2nd most common type of melanoma in fair skinned individuals
15-30% of all melanomas
Most commonly trunk, head and neck
M>F
Usually present as blue to black, but sometimes pink to red, nodule – may be ulcerated, bleeding
Develops rapidly
How do nodular melanomas grow?
only vertically
What happens in Lentigno maligna melanoma?
Minority of cutaneous melanomas (around 10%) and is
>60 years old
- Occurs in chronically sun-damaged skin, most commonly on the face
Slow growing, asymmetric brown to black macule with colour variation and an irregular indented border.
Invasive Lentigo Maligna Melanoma arises in a precursor lesion termed lentigo maligna (in situ melanoma) in sun damaged skin).
It has been estimated that 5% of lentigo maligna lesions progress to invasive melanoma
What happens in Acral Lentiginous Melanoma?
Relatively uncommon: ~5% of all melanomas
Diagnosed most frequently in 7th decade of life
Typically occurs on palms and soles or in and around the nail apparatus
Incidence similar across all racial and ethnic groups
- 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%)
What is the public awareness campaign for Melanoma suspicion?
Asymmetry Border irregularity Colour variegation Diameter greater than 5mm E evolving
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 gives a poor prognosis following Melanoma Diagnosis?
Poor Prognostic features Increased Breslow thickness >1mm Ulceration Age Male gender Anatomical site – trunk, nhead, neck Lymph node involvement
Stage 1A melanoma have 10 year survival of >95% whereas thick melanomas >4mm and ulceration pT4b have a 10 year survival rate of 50%
What is Breslow thickness?
Measurement from granular layer to the bottom of the tumour.
What do you look for in a Dermoscopy of Melanoma?
Dermoscopy –can improve correct diagnosis of melanoma by nearly 50%
Global features: Asymmetry Presence of multiple colours Reticular, globular, reticular-globular, homogenous Starburst
Atypical network, streaks, atypical dots or globules, irregular blood vessels, regression structures, blue-white veil
What is important with Melanoma investigations?
Dermoscopic findings should not be considered n isolation
History and risk factor status are important
Excise lesion for histological assessment if in any doubt
“If in doubt, take it out”
What is the management for Melanomas?
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
How do you stage melanomas?
Pathological
TNM
What is Sentinal lymphoma node biopsy?
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’
Represent most likely nodes to contain metastatic disease
Currently offered for pT1b+
Extracapsular spread on lymph node biopsy – needs lymph node dissection
What is the imaging for melanoma?
Stage III, IV
And Stage IIc without SLNB
PET-CT
MRI Brain
LDH is MAJOR prognostic factor in metastatic melanoma
