Dermatology - Skin Cancer, Acne, Hair and Nails Flashcards
Classification of neoplasia
Benign and malignant
Melanoma and non-melanoma
According to origin
Where do melanocytes arise from
Neuro-ectoderm
Mitotic rate of melanocytes
Low mitotic rate
Where can melanocytes in embryonal life be found
Diffusely in the dermis
Migration to final location is key
By the end of gestation, dermal melanocytes disappear except for
Head and neck
Dorsal aspects of distal extremities - typical sites for dermal melanocytosis and melanocytomas (blue naevi)
Pre sacral
What do ventral neural crest cells form (trunk NCCs)
Melanocytes
Neurons, glia of ganglia
Adrenal medulla
Schwann cells
What do cranial neural crest cells
Melanocytes Neurons, glia of ganglia Dermis of head Smooth muscles Chondrocyte osteocyte
Proportion of melanosomes in membrane bound packets in different races
11% for Africans
37% for Asians
85% for caucasians
Melanocyte/ keratocyte unit
Melanocytes present in epithelium 1: 20-40 keratocytes
Melanin stays above the nucleus of basal keratocytes, like an umbrella
How is melanin transferred
Transferred to epithelial cells via dendritic processes
What is melanin proaction driven by
UV exposure through POMC and alpha-MSH
Natural hx of nave
Simple lentigo –> junctional nevus –> compound naves –> intradermal naevus —> regressed naevus
Lentigo
Pigmented, flat or slightly raised lesion, not caused by sun exposure
Frequency of melanomas
3rd most frequent skin tumour
ABCD of histology of melanomas
Asymmetry
Border irregularity
Conspicuous junctional activity
Dermal mitoses
Major types of melanomas
Lentigo maligna (LMM)
Superficial spreading
Nodular
Acral-lentiginous
Acral
Affecting peripheral parts of body e.g. limbs, ears etc
What are melanoma lesions composed of
Melanocytes
Growth phases of melanomas
Radial (horizontal)
(Micro) invasive radial
Vertical
Sun damage/ area of LMM
Prominent
Sun damage/ area of superficial spreading melanoma
Intermittent sun exposure areas
Sun damage/ area of nodular melanoma
Anywhere, mainly intermittent
Sun damage/ area of acral lentiginous melanoma
Variable
Prognostic factors of melanoma
Breslow thickness Ulceration Mitotic rate Perineural/ Vascular invasion TILs
Dysplastic naevus
Abnormal but non-cancerous moles on the skin
How does UV rays act as a carcinogen
Inhibits DNA repair, apoptosis and cell signalling pathways that prevents skin cancers
Carcinogensis cycle in skin
UV
DNA lesion –> mutation —> gene —> cell phenotype —> clonal expansion —-> precancerous or carcinoma
How does UV trigger exposure differ between skin cancer
SCC –> flash fry (blistering burns)
BCC –> intermittent simmer (frequently tanning/ burns)
What proportion of BCCs are found on busy sites w. intermittent sun exposure
1/3 e.g. trunk and legs
Does the incidence of SCCs or BCCs increase more quickly w/ UV dose
SCC
Do SCCs or BCCs occur later in life
SCCs
How is vitamin D acquired
From UV skin exposure and diet
Calcitriol increases Ca levels
Risk factors for skin cancer
Skin types (Fitzpatrick I) Sunburns (esp childhood) Outdoor exposure - occupation (e..g builder) Living in sunny location Immunosuppressed Sunbeds & sunbathing Fhx PMH of skin cancers Genetic disorders e.g. albinism
Transplant pts and skin cancers
AK and SCC 10-20x increase in sun-exposed skin
Cancer develops due to imunosupression
SCCs are usually unaggressive
Relevant drugs given to transplant pts that have a relation w/ skin cancer
Cyclophosphamide, ciclosporin and azathioprine are mutagens when followed by UVA
Types of albinism
Occulocutaneous albinism
Occular albinism
Types of occulocutaneous albinism
Type 1: more severe - no melanin
Type 2: some melanin
Occular albinism
Normal, or slightly paler than normal for their ethnicity, skin and hair
Common cutaneous precancerous lesions that are UV induced
Actinic (solar) keratoses (AKs)
Bowen’s disease (carcinoma in situ)
Lentigo maligna
PUVA keratoses
Common cutaneous precancerous lesions that are viral induced
Vulval intraepithelial neoplasms (VIN)
PIN (incl Bowenoid Papulosis)
AIN
Actinic keratoses
Solar keratoses
Proliferations of cytologically aberrant epidermal keratinocytes
AK’s and risk of skin cancer
Approx 1:100 to 1:1,000 risk of SCC per AK
Strong predictor of development of melanoma or non-melanoma skin cancers
Risk factors for AKs
Individual - older age, M, Fair skin, blonde hair Cumulative UV radiation exposure Immunosuppresion Prior hx of AKs of other skin cancers V rare genetic disorders
Genetic disorders that are risk factors for AKs
Xeroderma pigmentosum
Bloom syndrome
Rothmund-Thomson syndrome
Clinical findings of AKs
Sun exposure body sites
Pruritus, brining orb stinging pain, bleeding and crusting
2-6mm erythematous, flat, rough or scaly papule
Arsenical keratoses (ArKs)
Associated w. c/c arsenicism
From medicinal, occupational and environmental exposures
Common occupations for ArKs
Miners Smelters Agricultural Computer microchip Electroplating Glassmkainhg
What are ArK’s associated w/
Bowen’s disease
BCC
SCC
Internal malignancies
Potential to develop into invasive SCC
Latent period of ArKs
40yrs
Aetiology and pathogenesis of ArKs
Arsenic reacts w/ -SH (sulfhydrl groups) in tissue proteins
Chromosomal mutations and breaks occur in p53
Clinical findings of ArKs
2-10mm, punctuate, yellow, keratitis papules
Seen in palms and soles - thenar and lateral borders of the hands, side of fingers
Areas of constant pressure or repeated trauma
SCC in situ
Bowen’s disease
Potential to progress to invasive SCC
Can be seen in genital mms (papilloma virus)
Epidemiology of SCC in situs
Rare in individuals younger than 30 years except on genitals
Bowen’s aetiology and pathogenesis
UV exposure (sunlight and therapeutic)
Immunosuppression
Infection w/ HPV
C/c arsenicism
Clinical findings of Bowen’s disease
Discrete, slowly enlarging Pink to erythematous, thin plaque Well-dermacated, irregular borders Overlying scale or crust Sun-exposed areas
Lentigo maligna
Subtype of melanoma in situ
Seen in chronically sun-expsoed areas e.g. cheeks, nose, neck, scalp and ears
Common in 7th and 8th decades
Pathogenesis of lentigo maligna
Cumulative sun exposure
LM vs LMM
Lentigo maligna may progress to Lentigo Maligna Melanoma w/ time
LM clinical findings
Flat, slowly enlarging brown, freckle-like macule
Irregular shape and offering shades of brown and tan
Ill-defined borders
What are BCCs derived from
Non-kertainising cells originating in the basal layer of the epidermis
Epidemiology of BCCs aka rodent ulcer
Most common cancer in humans
Almost s common as all other others combined
Natural pathway of BCC
Untreates, will invade locally and compromised function and cosmoses
Metastasis in BCCs
Extremely rare
Risk factors for BCCs
UV exposure Light/ red hair Blue eyes Northern European ancestry Type 1 or 2 skin Freckles Fhx
Genetic causes of BCC
Gorlins syndrome (dental cysts and palm pits) - pITCH mutation Xeroderma pigmentosum
Clinical px of BCCs
Intermittent bleeding
May appear to heal
Pearly, translucent, ulceration, telangiectasis
Rolled edge
BCC subtypes
Nodular BCCs Pigmneted BCCs Superficial BCCs Morpheaform (sclerosing) BCCs Fibroepithelium of Pinkus
Features of nodular BCC - most common
Translucent papule or nodule seen in sun-exposed areas
Usually, telangiectasia and rolled border
Large lesions have central necrosis (rodent ulcer)
Features of pigmented BCC
Subtype of nodular BCC
increased melaninisation –> hyperpigmented, translucent papule/ nodule
May be eroded
Features of superficial BCCs
Commonly on trunk
Erythematous patch
May resume eczema
When to suspect superficial BCC
Isolated patch of ‘eczema’ that doesn’t respond to treatment
Features of morpheaform (scleroisng) BCC
Aggressive variant
Ivory-white appearance
May resemble a scar or morphea
When to suspect morpheaform BCC
Unexplained scars
Features of fibroepithelioma od pinkus
Pink plywood lesion, commonly on lower back
May be difficult to distinguish from a skin tag
V rare
What is a SCC
Malignant neoplasm derived fron suprabasal epidermal keratinocytes
Usually evolves from AKs or Bowen’s disease
Clinical px variable
Predisposing factors for SCC
Precursor lesions, UV, immunosupression Burns or long term heat exposure - Marjolin's syndrome C/c scarring Smoking Some c/c infl dermatoses Papillomavirus infection Geno dermatoses
Geno dermatoses
Albinism
Xeroderma pigmentosum
Prokeratosis
Epidermolysis bulls
Clinical findings of SCC
Flesh-colour or erythematous
Hyperkertatotic, bleeding, oozing, crusting
Papule, nodule or plaque
What may SCC look like
May be pigmented or ulcerate (wet beefy appearnce)
May be cutaneous iron
May be verruccous (wart-like)
Rarely, like an abscess, particularly if in perifungal location
Commonest locations of cutaneous melanoma
Men - back
Women - legs, then trunk
Risk factors for cutaneous melanoma
UV radiation exposure Phenotypic characteristics Hx of prior melanoma Fhx of melanomas Mutation in p16, BRAF or MCR1R Xeroderma pigmentosum
Phenotypic characteristics as risk factors
Fair skin, tendency to sunburn or freckles
Blue/ green eyes
Red/ blonde hair
Numerous typical Nervi and/ or more than one typical naevus
Large congenital naevus
Subtypes of melanoma
Superficial spreading malignant melanoma (SSMM)
Nodular melanoma
LMM
Acral lentiginous melanoma
Features of SSMM
Most common sub-type
Most frequently the lower legs of women and upper back of men
Wide range of aprerance
Associated w/ pre-existing naevi
Epidemiology of SSMM
Most commonly 4th to 5 th decade on intermittently sun-exposed areas
Most common subtype of melanoma
Most common site of nodular melanoma
Trunk
Typically, uniformly dark blue-black or bluish-red raised lesion
Common areas for LMM
Face
Many have sub-clinical lateral growth so higher recurrence rates
Epidemiology of Acral Lentiginous Melanoma
2% of melanoma in Caucasian
Most common form in darker pigmented
Common in elderly
Most common site of acral lentiginous melanoma
Sole, then palm, then subungual
Does hx of trauma exclude dx of acral lentiginous melanoma
No
Hutchinson’s sign
Pigment on nail fold
Seen in acral lentiginous melanoma
Features of sebborrheic keratosis
Well-demarcated, ‘stuck-on’ appearance*
Usually, rough surface
Breslow thickness
Predicts melanoma survival
Top of granular layer of the epidermis yo the greatest depth of the tumour in mm
Should a bx be done for melanomas
No
Diagnostic methods of skin cancer
Hx
Physical examination
Dermascopy
Histopathology
Dermoscopy
Simple non-invasive technique to dx skin cancer
Looks at pigment network
Improves sensitivity and specificity for clinical dx
Histopathology for making a dx of skin cancer
Gold standard for diagnosing pigmented skin lesion
Based on architectural and cytologic features
Immunohistochemistry may be useful in melanoma dx
Sentinel lymph node bx
Staging and prognostic tool for skin cancers
Detects micrometastases in regional LNs
Blue dye + technetium-99 labelled radio colloid solution are injected intradermally at the primary site
When should cutaneous lymphoma be considered
In eczema which hasn't respond to topical steroids Usually, scaly red rash Less itchy than eczema Not as thick as psoriasis Slowly progressive over decades
Features of dermis
Supportive connective tissue matrix
Loss of collagen and elastic
Highly vascularised
What is the s/c layer of skin made up of
Loose connective tissue & adipose tissue
What is a wound
Loss of integrity of skin tissue
What its considered a c/c wound
Disruption in normal healing process (systemic/ local factors)
Slowed/ incomplete healing (usually at infl of proliferative phases)
Stages of wound healing
Haemostasis
Infl phase
Proliferative phase
Maturation & remodelling phase
These phases may overlap
How long does the infl phase of wound healing last
0-3 days
Clinical signs seen in infl stage of wound healing
Rubor
Calor
Tumour
Dolor
Haemostasis in wound healing
Aggregation and degranulation of platelets
Blood clotting and formation of a fibrin plug (eschar) initially fills wound
Role of immune cells in infl opals of wound healing
Polymorphonuclear leukocytes, monocytes, macrophages and lymphocytes invade fibrin plug space and secrete growth factors and cytokines to help modulate response
Role of fibroblasts in infl phase of wound healing
Help blood vessels from deep fascia and surrounding dermis lay down temp matrix of granulation tissue —> serve as guide for migrating and proliferating cells
How long does the proliferative phase in wound healing last
3-21 days
Clinical signs of proliferative phase of wound healing stage
No infl signs
Reduced swelling
Reduced wound size (contraction)
Itch
Features of proliferative phase of wound healing
Net collagen synthesis
Increased wound tensile strength
Scar formation
Net collagen synthesis in proliferative phase of wound healing
Mediated by growth factors, ECM molecule and their receptors
Extensive cell-cell interactions to control cellular behaviour
Increased wound tensile strength in proliferative phase of wound healing
Epidermal cells proliferative and move to wound edge to granulation tissue - closes wound
Wound contcraction via forces within myofibroblast
Scar formation in proliferative phase of wound healing
Apoptosis of immune cells, fibroblasts, endothelial cells
Remaining fibroblasts continue to lay down collagen (I and III)
How long does the maturation & remodelling phase last in wound healing
21 days to 2 years
Why is the duration of maturation & remodelling phase variable in wound healing
Depends on: Age Wound type Body location Duration of infl phase
What occurs in the maturation and remodelling phase
Reorganisation of collagen - Type 3 replaced by Tye 1
Temsile strength improves
What can affect speed of wound healing?
Size of wound Blood supply to area Presence of origin bodies or micro-organisms Age and health of pt Nutritional status Drugs
Types of wound healing
Primary intention
Secondary intention
Tertiary intention
Primary intention e.g. surgical incision
Immediate closure of wound edges when no loss of tissue has occurred
Features of primary intention wound healing
Rapid epithelial cover,
Fast healing
Better cosmetic
Secondary intention of wound healing
Examples incl excessive trauma, difficult wound closure, tissue loss
Spontaneous healing of wound direct closure (intentionally left open)
Tertiary intention of wound healing
Examples incl traumatic injury, dirty surgery, delayed primary intervention or surgical wounds
Initially left open after removal of non-viable tissue
Wound edges brought together after few dats when wound is clean
Examples of -pre-cancerous lesions
AK
Dysplastic naevus/ atypical naevus
Bowens disease
Lentigo maligns
Examples of benign skin lesions
Keratoacanthoma Seborrheic wart Cutaneous horn Viral wart Epidermoid cyst
Cryotherapy
Sin lesions frozen w/ cryogen - usually liquid N
How does cryotherapy cause cells etch
Ice crystal formation
Osmotic differences –> cell disruption
Iscahemic damage