1b Skin Cancer Flashcards
What are the 5 layers of skin?
Come Let’s get sun burnt!
What are 5 points of self detection for skin lesions that may turn cancerous?
ABCDE
What is a malignant 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
Outline the epidemiology of malignant melanomas.
- Rising incidence rates observed 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 (Sunny locations)
What are the risk factors of malignant melanomas (Genetic 3 / Environmental 3 / Phenotypic 2)?
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:
* Patient who has more than 100 melanocytic nevi on the whole body
* Patient who has atypical melanocytic nevi
What are the main different subtypes of malignant melanoma (5)?
- Superficial spreading (Horizontal growth then Vertical growth)
- Nodular (Only vertical growth)
- Lentigo maligna
- Acral lentiginous
- Unclassifiable
A patient present with the following symptoms:
What is the most likely diagnosis?
- Superficially spreading malignant melanoma
Epidemiology:
* 60-70% of all melanomas
* Most common type in fair-skinned individuals
* Most frequently seen on trunk of men and legs of women
Pathogenesis:
* Can arise de novo or in pre-existing nevus
* In up to 2/3 of tumours, regression (visible as grey, hypo-or depigmentation), due to host immune system reacting to tumour
Pathophysiology:
* After a slow horizontal (radial) growth phase, limited to epidermis, a more rapid vertically oriented growth phase: development of nodule
Differential diagnosis:
* Dermatofibroma
A patient present with the following symptoms:
What is the most likely diagnosis?
- Nodular malignant melanoma
Epidemiology:
* 2nd most common type of melanoma in fair skinned individuals
* 15-30% of all melanomas
* Most commonly trunk, head and neck, M>F
Pathogenesis:
* Usually dark nodule -but can be pink or red, may be ulcerated, bleeding
* Develops rapidly
Pathophysiology:
* De novo vertical growth phase without the horizontal growth phase. Present more advanced stage, with poorer prognosis.
Differential diagnosis:
* Basal cell carcinoma
A patient present with the following symptoms:
What is the most likely diagnosis?
- Lentigo maligna (malignant melanoma)
Epidemiology:
* 5% progress to invasive melanoma
* > 60 yo chronically sun damaged skin
Pathophysiology:
* Slow growing macule
* It is an in-situ melanoma
Differential diagnosis:
* Seborrhoeic keratosis
A patient present with the following symptoms:
What is the most likely diagnosis?
- Acral lentiginous (malignant melanoma)
Epidemiology:
* Uncommon: ~5% of all melanomas
* Most frequently 70yo
* Incidence similar across all age groups
What investigations are suggested in suspected malignant melanomas (2)?
- Examination with a dermatoscope
- Excision biopsy for histological assessment
- Measure Breslow thickness: prognosis worse if >1mm
What is the management of malignant melanomas (Surgery 2 / Imaging 1 / Immunotherapy 2)?
Surgery:
* Wide local excision
* Margin depends on Breslow thickness
* Sentinel lymph node biopsy - lymph node dissection
Imaging:
* TNM staging
Immunotherapy:
* CTLA-4 inhibition (Ipilimumab)
* PD-L1 (Programmed cell death ligand) inhibitors
* (Nivolumab)
What are the 3 stages of keratinocyte dysplasia?
Actinic keratoses
* Dysplastic keratinocytes
Bowen’s disease
* Squamous cell carcinoma in situ
Squamous cell carcinoma
* Invasive cancer
* Potential for metastasis/ death
Predominantly pale skin types
Solar induced UV damage
A patient present with the following symptoms:
What is the most likely diagnosis?
Actinic keratoses
* Dysplastic keratinocytes
A patient present with the following symptoms:
What is the most likely diagnosis?
Bowen’s disease
* Squamous cell carcinoma in situ
What is the management of actinic keratosis and bowen’s disease (6)?
- 5-fluorouracil cream
- Cryotherapy
- Imiquimod cream
- Photodynamic therapy
- Curettage and cautery
- Excision
A patient present with the following symptoms:
What is the most likely diagnosis?
- Squamous Cell Carcinoma (SCC)
Pathophysiology:
* Can have different appearances
* Erythematous to skin coloured
* Papule
* Plaque-like
* Exophytic
* Hyperkeratotic
* Ulceration
* Arises within background of sun-damaged skin
* Rapidly growing
Differential diagnosis:
* Basal cell carcinoma
* Viral wart
* Merkel cell carcinoma
What investigations are recommended for suspected squamous cell carcinoma (SCC) (2)?
Often clinical diagnosis sufficient
- Diagnostic biopsy may be taken if diagnostic uncertainty
- Ultrasound of regional lymph nodes ± FNA if concerns regarding regional lymph node metastasis
What is the management of squamous cell carcinoma (SCC) (5)?
- 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
A patient present with the following symptoms:
What is the most likely diagnosis?
-
Keratoacanthoma
- Pseudo-malignancy VS Variant of SCC (still unclear)
- Rapidly enlarging papule that evolves into a sharply circumscribed, crateriform nodule with keratotic core
- Resolves slowly over months to leave atrophic scar
- Most occur on head or neck / sun exposed areas
- Difficult to distinguish clinically and histologically from squamous cell carcinoma, so often excision
A patient present with the following symptoms:
What is the most likely diagnosis?
- Basal Cell Carcinoma (BCC)
Main subtypes: Nodular- Superficial
* Nodular:
* Most common subtype
* Approximately 50% of all BCCs
* Typically: shiny, pearly papule or nodule
* Superficial:
* Well-circumscribed, erythematous, macule/plaque
Differential diagnosis:
* Squamous cell carcinoma
* Adnexal (Sebaceous) carcinoma
* Merkel cell carcinoma
What investigations are recommended for suspected basal cell carcinoma (BCC) (1)?
Often clinical diagnosis sufficient
- Diagnostic biopsy may be taken if diagnostic uncertainty
What is the management of basal cell carcinoma (BCC) (1)?
- Standard surgical excision
A patient present with the following symptoms:
What is the most likely diagnosis?
- Merkel Cell Carcinoma
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)
