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  • Major consequence of environmental conditions in this country.
  • First slide = nodular melanoma on scalp


In Australia:

  • Carcinomas of the skin are the most common malignancies (and increasing)
  • Approximately 370,000 (2%) people require treatment of at least one skin cancer/year
  • More than 1000 people die of skin cancer/year; 80% of these deaths due to melanoma
  • Queensland has the world's highest incidence of melanoma

Anatomy of normal skin

  • Statified squamous epithelium, keratinising
  • Adnexie e.g. sweat glands, sebaceous gland, hair follicles, ducts, nerve endings
  • Dermis: reticular (loosely packed) and papillary (eosinophilic, densely packed)
  • Subcutaneous fat
  • Epidermis
    • Basal layer: stratum basale has stem cells (replicative ability)
    • Stratum spinosum: prickle cell layer w/ desmosomes
    • Stratum granulosum: keratinising layers
    • Stratum corneum: flattened out, fully keratinised
  • Whole process from bottom to top takes 28 days
  • Specialised cells: melanocytes (transfers melanin to keratinocytes to protect them from UV) and Langerhans cells (APCs of the skin; immune function), Merkel cells (part of sensory system)

Functions of normal skin

  • Appearance
  • Physical barrier to microbial invasion and fluid loss (burn --> bacterial infection, poor fluid balance)
  • Protection from ultraviolet radiation
  • Temperature regulation
  • Sensory function
  • Immune function (Langerhans cells)


  • UV radiation (Sunlight) - particularly UVB (wavelength 280-315 nm; UVC is absorbed by ozone, although it has shorter wavelength and higher energy). UVA is not innocent. (Depends on latitude (closer to equator), altitude (higher), occupation, lifestyle). Risk of SCC, BCC related to cumulative lifetime UV exposure (so usually in most sun-exposed part of the body and later in life). Relationship of UV exposure to risk of melanoma is more complex (NB sunburn in childhood <15 years). Brief intense exposure may also affect SCC and BCC. Peak in UV exposure is between 10 and 2 (winter). (11 and 3 in daylight savings). Sunsmart behaviour of children is related to that of parents. SPF = the ratio of time it would take you to burn with it on compared to without it on.
  • Immunosuppression e.g. Organ transplantation, HIV/AIDS esp non-melanoma carcinogens
  • Hereditary factors e.g. Xeroderma pigmentosum (Autosomal recessive disorder: abnormality of DNA repair genes - nucleotide excision pathway for DNA repair), Dysplastic naevus syndrome (familial melanoma syndrome - inherit an abnormal copy of a gene and it greatly increases melanoma risk). Basal cell naevus syndrome = predisposes to BCC (genes involved in a number of phases of development e.g. Sonic the Hedgehog genes).
  • Others include industrial carcinogens e.g. hydrocarbons, chronic ulcers and sinuses, ionising radiation, chewing tobacco and betel nuts
  • Constitutional: fair skin, blue eyes, blonde or red hair, freckles, burn rather than tan following sun exposure (e.g. anglo-celtic background) AND the above hereditary factors



These lesions are markers of sufficient UV damage to increase risk of skin cancer:

Actinic (Solar) Keratosis and Bowen's Disease (SCC in situ)

  • Occur on sun-exposed skin in 40-50% of Australians over age 40! Face, ears, neck, dorsum of hands. Tan, red or skin coloured, rough, scaling lesion. Atypical changes in basal cells of epidermis as well as hyperkeratosis (scaling); elastosis (breaking of dermal collagen fibres) in sun-damaged dermis. Low incidence of malignant change per year (SCC). High incidence of skin cancers in nearby areas. There is evidence that sunsmart behaviour can cause regression of these.
  • Low incidence of malignant change (usually SCC), but high incidence of skin cancers in nearby areas
  • Dysplastic changes in the cells of the epidermis (prominent nucleoli and large nuclei). Single cell keratinisation = dyskeratosis. Thickening of stratum corneum (hyperkeratosis)


  • 20% of skin cancer
  • 90% arise in sun-exposed areas
  • More common > 50 years of age (related to cumulative lifetime exposure); males > females
  • Red, scaling nodule; may ulcerate and bleed; may be tender
  • Atypical proliferating cells resemble keratinocytes; may produce keratin
  • Slow to metastasise (<2%); higher risk from lip or ear (10-15%) Differential diagnosis includes Keratoacanthoma
    • Lip/ear = more lymphatic drainage (carcinomas spread to lymph nodes first).
  • SCCs centrally ulcerate. Have a turned-out or everted edge.
  • Microscopically: nests of cells that invade from epidermis into underlying dermis. In the centre we see the production of keratin whirls/pearls (keratinisation). Abnormal staining of dermis (normally stains pink with eosin. Here it's staining basophilic -- due to damage to fibroblasts -- solar elastosis -- due to UV injury).
    • Note ulceration on surface and abnormal staining in dermis due to solar elastosis
  • Pleomorphism, high N:C ratio, frequent mitotic figures, intercellular bridges between adjacent tumour cells (joined by desmosomes) -- a feature of SCC (replicate shape and relationship with adjacent cells of the stratum spinosum). Surrounding stroma is a loose fibrovascular network; has inflammatory cells (due to ulcer), bacteria in ulcer
  • Don't tend to metastasise far, just nearby structures (can kill through local invasion e.g. into artery)


  • 90% of UVB is absorbed by the epidermis including nuclei of keratinocytes, resulting in DNA damage (pyrimidine dimers)
  • Failure of DNA repair (via nucleotid excision) leads to transcriptional errors, resulting in mutations in oncogenes and tumour suppressor genes (p53).
  • In the epidermis, UVB impairs T cell activation by Langerhans cells while T cell suppressor pathways remain intact
  • Local immunosuppresion may allow the proliferation and progrerssion of a mutant clone of keratinocytes
  • HPV may play a rele in the development of SCC in immunosuppressed individuals e.g. cancer treatment of HIV/AIDS
  • Keratoacanthoma
    • Rapidly developing neoplasm that may resemble SCC clinically and histologically
  • Dome-shaped nodule with central keratin plug
  • Typically occur on face, ears, dorsum of hands
  • Unusual natural history: spontaneous regression typically occurs (due to cell mediated immune response).
  • We recommend removal of keratoacanthoma because we can't be certain it's not an SCC.


  • 75% of skin cancer (least lethal)
  • 80-85% arise in sun-exposed areas on head and neck
  • More common > 40 years of age
  • Painless, "pearly" edged nodule with dilated vessels (telangectasiae) on surface
  • May ulcerate ("rodent ulcers")
  • Cells resemble basal layer of epidermis; proliferate in nests
  • Virtually never metastasise, locally invasive and may ulcerate or invade into local structures (rodent ulcers)
  • Rolled, pearly edge with dilated blood vessels running across surface
  • Even though it doesn't metastasise it can still invade and needs to be treated
  • Histo
    • Nodules of basal epithelial cells invading into the dermis, like knuckles of a fist, causing a raised lesion
    • Palisading lining of surface cells wrapping tumour cells. Don't exhibit desmosomes. Less likely to have keratinising nests
    • Stroma is often rich in lymphocytes (may be involved in preventing metastasis??) - more likely to do with cell-cell communications within the tumour cells
    • Solar elastosis - basophilia of dermis nearby the tumour; fibroblast damage = collagen synthesis is abnormal. Causes fragmentation of dermal collagen leading to abnormal basophilic staining.
  • Differentil diagnosis of pigmented skin lesions


  • Seborrhoeic Keratosis
    • Typically occur on the trunk of middle aged or older indivudals
  • Round flat brown to black, velvety lesions
  • Appear to be stuck on to the skin surface
  • Sheets of basaloid cells containing melanin pigment, together with keratin filled cysts
  • Benign
  • Melanocytic Naevi (Moles)
    • Congenital or acquired neoplasm of melanocytes (average 10-30 per person)
    • Most are acquired in the first one to two years of life
    • May continue to emerge through to teenage years
    • Mutations in BRAF and NRAS oncogenes are common, almost identical to those in melanomas. Don't go on to melanomas usually because the mutations in BRAF and NRAS cause proliferation of these cells and then they fall out of the cell cycle - oncogene induced senescence (by activation of p16inc4a tumour suppressor gene which, if mutated, then can cause melanoma)
    • Typical progression:
      • 1) JUNCTIONAL NAEVUS (flat, brown spot)
      • 2) COMPOUND NAEVUS (elevated with junctional and dermal nests; smooth, elevated lesion with junctional and intradermal nests)
      • 3) INTRADERMAL NAEVUS (elevated, skin tag); junctional component undergoes apoptosis - more neural phenotype.
      • Melanocytes proliferate at the dermo-epidermal junction and more mature ones deeper into the mass.

Certain types of naevi are premalignant:

Dysplastic Naevi (Clinically Atypical Moles)

  • Occur in 2-10% of people
  • Usually >6 mm diameter; often multiple; show variation in pigmentation: pebbly surface or irregular border, red border
  • Compound naevi with cytological and architectural atypia
  • If no family history of melanoma, approximately 6% lifetime risk of malignancy
  • If positive family history of melanoma, may be associated with dysplastic naevus syndrome (autosomal dominant; abnormalities of TS genes e.g. CDKN2a and P16/INC4a gene) - 50% lifetime risk of melanoma
  • Cytological features of malignancy: High N:C ratio etc, linear fibrosis in papillary dermis near dermo-epidermal junction. Dusty pigment within them - so they are melanocytes. Eosinophilic fibrosis (Linear fibrosis) underneath dermo-epidermal junction. This is a compound naevus: proliferation of melanocytes at dermo-epidermal junction and nests within the dermis. Only mildly elevated over surrounding skin.
  • Problem: risk factor for melanoma
  • Clinical features suspicious for malignant transformation of a mole include:
    • Enlargement
    • Itch or pain (invasion into dermis, nociceptive fibres)
    • Change in colour
    • Change in contour (formation of nodule)
    • Change in border (irregularity, notching)
    • Ulceration and bleeding
      • New pigmented lesion in adulthood (MOST IMPORTANT). Very few melanomas arise in pre-existing naevi.
  • ABCDE acronym: asymmetry, irregular border, variation in colour, diameter (>6mm), elevation above surrounding skin.


  • <5% of all skin cancers; often lethal tumours
  • Approximately 30% arise in pre-existing naevi (high suspicion for any new pigmented lesion in adulthood)
  • Others may resemble common naevi in early stage
  • Occur from adolescence onward - peak at 45 years of age
  • Common sites: back (males); leg (females); can arise in eye, nose, oesophagus
  • Proliferation of nests of large, pleomorphic cells, with fine "dusty" pigment
  • Four common types:
    • 1) SUPERFICIAL SPREADING MELANOMA (irregular border, red halo around it, nodular elevation)
    • 2) NODULAR MELANOMA (most aggressive)
    • 3) LENTIGO MALIGNA MELANOMA (face of elderly; least aggressive)
    • 4) ACRAL LENTIGINOUS MELANOMA (palms, soles, nail beds; only one that Black people can get)
  • Histo
    • Proliferation of melanocytes; a lot of brown pigment is not within the melanocytes (they become incontinent with pigment, lost to macrophages). High N:C ratio, prominent nucleoli, mitotic figures, cells with the most pigment are the macrophages that take it up.
  • Two growth phases (can both occur in one lesion):
    • 1) RADIAL - tendency to grow horizontally within the epidermis and superficial dermis - melanoma cells remain localised. Clinically it appears flat. Correlates with inability to metastasise (growing in dermis and dermo-epidermal junction).
    • 2) VERTICAL - downward growth into deeper dermal levels associated with the development of a nodule correlates with the emergence of cells with metastatic potential. "Nodule" clinically means a subgroup of the cells in the tumour have undergone a mutation allowing them to invade beyond local tissue. Cells invade in nests into underlying dermis (most of these cells have very little pigment in them).
  • Overall 10 year survival approximately 80%
  • Prognostic factors:
    • Depth of invasion

Clark's levels

  1. malignant cells confined to epidermis
  2. malignant cells invade into papillary dermis
  3. malignant cells fill the papillary dermis
  4. malignant cells invade into the reticular dermis
  5. malignant cells invade into subcutaneous fat

A better indicator for nodular lesions is tumour thickness (Breslow) - measured from top of stratum granulosum to the deepest malignant cell

  • <0.75 mm thick - virtually never metastasise, 95% survival
  • ≥1.0 mm thick - if sentinel lymph node biopsy is positive, regional lymph node dissection recommended despite morbidity
  • >4.0 mm thick - 25% survival
  • Lymph node metastases (NB role of sentinel lymph node biopsy)
  • Also site, sex (males get them on back - worse, harder to notice, women get them on legs), type (nodular worse, lentigo maligna better), mitoses, host lymphocyte response (better lymphocyte response = better prognosis)
  • Metastases. Can metastasise widely before clinical detection.
    • Satellite spread to surrounding skin
    • Lymphatic spread to regional lymph nodes
    • Haematogenous spread to lung, liver, brain (predilection to this), bone and unusual sites e.g. intestines or wall of heart.
    • Behaviour unpredictable - may present with metastases many years after primary lesion excised.
      • Once someone has had a melanoma removed they need to be followed up for life
  • Regression (where dark parts have turned light again) is a poor prognostic indicator
  • Lentigo melanoma tends to remain in a radial growth phase for a long period of time

  • Predisposing condition: dysplastic naevus syndrome (mutation in tumor suppressor gene that codes for cyclin dependent kinase)