MELANOMA AND OTHER SKIN : A guide for medical practitioners

Australia has one of the highest rates of skin in Causes of melanoma and Gender the world. About 2 in 3 people in Australia will develop some other skin cancers In Victoria, males are 1.3 times more likely to form of before the age of 70 years. • Unprotected exposure to UV radiation remains be diagnosed with melanoma and almost the single most important lifestyle risk factor for 2.5 times more likely to die from it than females melanoma and other skin cancers. (after allowing for differences in age). Skin cancer is divided into two main types: • UVA and UVB radiation contribute to skin Mortality from melanoma rises steeply for males damage, premature ageing of the skin and from 60 years and increases with age. Melanoma Non-melanocytic skin skin cancer. Melanoma develops in the melanocytic cancer (NMSC) • Melanoma and BCC are associated with both Melanoma in non-Caucasians (pigment-producing) cells located in the • Squamous cell (SCC) amount and pattern of sun exposure, with an The incidence of melanoma in non-Caucasians epidermis. Untreated, melanoma has develops from the keratinocytes in the intermittent pattern carrying the highest risk. is low. However, non-Caucasians are more likely a high risk for . The most epidermis and is associated with risk • Premalignant and SCC to experience delayed diagnosis and have poorer common clinical subtype is superficial of metastasis. SCC is most commonly are associated with the total amount of sun clinical prognosis compared to Caucasians. spreading melanoma (SSM) and is most found on the face, particularly the lip exposure accumulated over a lifetime. commonly found on the trunk in males region, ears, nose, cheek and eyelid, and lower limbs in females. Melanomas • Other risk factors for NMSC can include PreventionDesign elements can develop on any part of the body, and then on the neck, dorsa of hands exposure to some chemicals (e.g. arsenic), and forearms in both sexes. In males, CancerThe following are design Councilelements that can be Victoria recommends five steps including parts not heavily exposed to radiation therapy, UVA and psoralen (PUVA) incorporated into SunSmart resources. For examples of their use in current publications, ultraviolet (UV) radiation. SCC is commonly found on the treatment for psoriasis, immunosuppressive tosee the protectSample resources section against (pg 25). sun damage during daily sun Design elements head and neck, and in females, it is therapy and some rare genetic conditions protection times: The following are design elements that can be In Victoria: commonly found on the upper limbs, predisposing to skin cancer. incorporated into SunSmart resources. For examples of their use in current publications, followed by the head and neck. It is see the Sample resources section (pg 25). Slip on sun-protective clothing – • Melanoma is the fourth most common that30+ covers as much skin as possible. cancer diagnosed. believed that many SCCs arise from Design elements premalignant actinic keratoses. Risk factors for melanomaThe following are design elements that can be incorporated into SunSmart resources. Slop on SPF30 (or higher) • Every year, more than 2000 new cases For examples of their use in current publications, • Personal history of melanoma see the Sample resources section (pg 25). 30+ are diagnosed and there are almost • Basal cell carcinoma (BCC) also Design elements sunscreen – make sure it is broad- develops from keratinocytes in the • Multiple dysplastic naevi (>5) The following are design elements that can be spectrum and water-resistant. 300 deaths from the disease. incorporated into SunSmart resources. 30+ For examples of their use in current publications, epidermis and is the most frequently • Multiple naevi (>100 or >11 onsee arm) the Sample resources section (pg 25). Design elements • The risk of developing melanoma diagnosed cancer in Australians. BCC 30+ Slap on a hat – that protects the face, • Family history of melanoma/PersonalThe following are design elements that can be increases with age. However, is most commonly found on the face: incorporated into SunSmart resources. head, neck and ears. history of NMSC For examples of their use in current publications, 30+ melanoma is the second most the eyelid, lip and nasolabial fold, see the Sample resources section (pg 25). SunSmart Victoria style guide 14 30+ Seek shade. common cancer in males and females followed by ears, nose and cheek in • Having fair or red hair and blue or green eyes aged 25–59 and the third most both sexes. In males, BCC is common • Fair skin that burns easily, freckles and does Slide on sunglasses – thatSunSmart meet Victoria style guide 14 common cancer in females aged 30+ on the neck, back and shoulders, and not tan 30+ 15–24 years. Australian Standards. in females, on the neck, shoulders and • High levels of intermittent sun exposure (e.g. outer arms. Check the daily sun protection times on the free • In Australia, the lifetime risk of during outdoor recreation or sunny holidays)30+ SunSmart Victoria style guide 14 developing melanoma by age 75 years • Immune suppression and/or transplant recipients SunSmart app. is about 1 in 23 for males and 1 in 33

• Increasing age 30+ for females. SunSmart Victoria style guide 14

Clinical Practice Guidelines for the Management of Melanoma in Australia and New Zealand. www.nhmrc.gov.au SunSmart Victoria style guide 14 Clinical Practice Guide: Basal cell carcinoma, squamous cell carcinoma (and related lesions) – a guide to clinical management in Australia. www.cancer.org.au Melanoma diagnosis

Superficial spreading Nodular melanoma (NM) melanoma (SSM) This is an aggressive form of melanoma that grows quickly. Melanoma can develop in pre-existing moles in NM differs from SSM in appearance and is easily misdiagnosed. the skin, or more commonly in the melanocytes NM has little radial growth within the epidermis but penetrates found in the epidermis (i.e. de novo). vertically into the dermis early. It is more likely to be symmetrical • SSM is the most common form of and uniform in colour (red, pink, brown or black), is more melanoma. frequently less pigmented than SSM, and feels firm to touch. Over time, it may develop a crusty surface that bleeds easily. • SSM can appear as a new spot, or an existing spot, freckle or mole that changes • NM can become life threatening in 6–8 weeks. size, colour or shape. • Approximately 15% of total melanomas diagnosed are NM. • A patient diagnosed with melanoma is at • NM does not necessarily arise from a pre-existing mole and is increased risk of new primary melanomas commonly found on the head and neck. (relative risks ranging above 10). • NM develops most commonly in older people, particularly men.

The ABCDE acronym can The ABCDE acronym cannot be used help distinguish a superficial to aid diagnosis of nodular melanoma; spreading melanoma from a however, the following features can be of help: normal mole: Elevated: the lesion can appear as a small, round A Asymmetry: the lesion is irregular in E and raised lump on the skin. Colour may be shape or pattern. uniform throughout the lesion and may be black, B Border: the border or outline of a brown, pink or red. melanoma is usually irregular. Firm: the lesion feels firm to touch. F C Colour: there is variation in colour Growing: a nodule that has been growing within the lesion. G progressively for more than a month should be assessed as a matter of urgency. D Diameter: the lesion is usually greater than 6 mm across. However, suspect lesions of smaller diameter should also be investigated. If nodular melanoma is suspected, diagnosis should not E Evolving: the lesion changes over be delayed, and urgent referral to a dermatologist or time (size, shape, surface, colour, immediate excision is recommended. symptoms e.g. itch). Biopsy and excision for melanoma or suspicious naevi • Complete excision biopsy with a 2 mm margin is recommended. • Partial biopsies (e.g. punch biopsies and shave excisions) can be less accurate than excisional biopsy and should be performed by trained practitioners. • If a thick melanoma is suspected, refer patient to a dermatologist or a surgeon with an interest in melanoma as a matter of urgency. Treatment for melanoma

Selecting appropriate primary treatment will Radiation and not continued indefinitely because risk of depend on the Breslow thickness (vertical Other treatment options Radiation treatment can be used to treat recurrence diminishes with time. Follow-up depth) of the tumour. Breslow thickness is lentigo maligna when surgical approaches for future primary melanomas is done at 6 to measured using the following system: Surgery are considered less suitable. Post- 12 month intervals and should be continued biopsy (SLNB) should long term. • (pTis) Melanoma in situ. The abnormal cells be discussed with patients with pT2 and operative radiotherapy can be performed are found only in the non-vascular epidermis thicker lesions, and performed by trained for melanomas likely to recur locally or In Australia, up to 75% of patients detect their and have not penetrated into deeper tissue practitioners. Surgical resection of isolated regionally. Radiotherapy can be used for own recurring melanomas. Patients should that contains blood vessels. metastases can be performed in both palliative management of cerebral and bone be educated on recognising changes in their • (pT1) Melanoma cells reach the upper part definitive and palliative treatment settings. metastases, and for other metastases where skin, have a professional full skin examination of the dermis. The melanoma is less than temporary local control is needed. as deemed appropriate, and have further 1 mm thick. Immunotherapy testing as required. • (pT2) Melanoma cells reach the upper part • For unresectable stage III or stage IV Follow-up for melanoma of the dermis. The melanoma is between metastatic melanoma Due to the risk of tumour recurrence and Survival 1 mm and 2 mm thick. • PD-1 inhibitors (Nivolumab, new primary melanomas, all patients require In Australia, for the period 2006–2010, Pembrolizumab): given as IV infusion every routine follow-up, the frequency of which the 5 year survival for melanoma was 94% • (pT3) Melanoma cells reach deeper into the 3 weeks dermis. The melanoma is between 2 mm will depend on the risk of both metastatic for females compared with 89% for males.* • CTLA-4 inhibitor (Ipilimumab): given as IV recurrence and further new melanomas. and 4 mm thick. Clinical Practice Guidelines for the infusion every 3 weeks for 4 doses Follow-up for metastatic disease is done • (pT4) Melanoma is more than 4 mm thick or Management of Melanoma in Australia more frequently in the early part of follow-up it has invaded through the dermis and into Targeted therapy and New Zealand. www.nhmrc.gov.au the underlying fat. • BRAF inhibitors (Dabrafenib and Treatment is based on the T1–T4 Vemurafenib): for treatment of BRAF V600 classification. The surgical removal of the +ve unresectable stage III or stage IV tumour with recommended margins of metastatic melanoma, oral tablets excision for each of the T-classification • ~50% of all melanomas have mutation in groups are: BRAF gene • (pTis) Melanoma in situ: 5–10 mm clearance • Used in combination with MEK inhibitor (Trametinib) • (pT1) Melanoma <1.0 mm: 1 cm clearance • (pT2) Melanoma 1.0–2.0 mm: Chemotherapy 1–2 cm clearance • May be offered for treatment of metastatic • (pT3) Melanoma 2.0–4.0 mm: disease. 1–2 cm clearance • Interferon may be offered following surgical removal of melanoma that has not • (pT4) Melanoma >4.0 mm: 2 cm clearance. progressed past lymph nodes. Note: evidence for optimal excision clearance for melanoma 2–4 mm thick is unclear. The Clinical Practice Guidelines recommend it Vaccines remain experimental, may be desirable to take a wider margin (2 cm) but may be offered within the for these tumours, depending on tumour site context of clinical trials. and surgeon/patient preference.

* Australian Institute of Health and Welfare 2012. Cancer survival and prevalence in Australia: period estimates from 1982 to 2010. Cancer Series no. 69. Cat. no. CAN 65. Canberra: AIHW. Non-melanoma skin cancer (NMSC)

Diagnosis Treatment Screening for melanoma Squamous cell carcinoma (SCC) Basal cell carcinoma (BCC) Treatment options for non-melanoma and NMSC • SCC can spread to other parts of the body • BCC is the most common and least skin cancer include: There is no evidence demonstrating that if not treated. Lesions on the ears and lips dangerous form of skin cancer. • Surgical excision of the tumour and population-based screening for melanoma have a higher risk of metastasis. • It appears as a well-defined lump or scaly surrounding tissue and NMSC is effective in reducing morbidity or mortality, and it is not recommended. • It appears as a thickened, red, scaly nodule area that is red or pearly in colour. • Curettage and cautery that may bleed and ulcerate over time. • It may bleed or become ulcerated early on, • Application of topical agents (imiquimod Skin surveillance is recommended for patients • It grows over a period of some months. then heal and break down again. cream, fluorouracil cream, photodynamic identified to be at high risk of melanoma and Rapid growth is associated with increased NMSC, including patients with a previous • It usually grows relatively slowly. therapy) risk of mortality. diagnosis of melanoma. • Cryotherapy • Radiotherapy Skin self-examination The choice of treatment will depend on: Approximately 50% of melanomas are • Histological features detected by the patient. There is no specific • Tumour size technique or recommended frequency of self-examination that has shown to reduce • Thickness and grade morbidity; however, regular skin examination • Anatomical site may increase the probability of detecting skin Victorian Melanoma Units • Patient factors cancer at an early and treatable stage. Patients at high risk for melanoma Melanoma Units provide specialised diagnostic services and treatment services. Melanoma management Follow-up and treatment is guided by a multidisciplinary panel including services, medical specialists, should: Frequency of follow-up of patients treated for treatment options and clinical trials. Patients may be referred to these units by their GP or specialist. • Be taught to self-screen (including NMSC for evidence of recurrence, metastasis examination of draining lymph nodes) and and/or any new primary skin cancers will Victorian Melanoma Alfred Hospital, Commercial Road, Melbourne Ph: 9076 0365 recognise suspicious lesions depend on histological clearance and risk Service VIC 3004 Fax: 9076 5799 level of tumour. Patients should be educated • Have a full body examination with a clinician every 6 to 12 months. Melanoma and Peter MacCallum Cancer Centre, 305 Grattan on recognising changes in their skin (including Ph: 8559 5000 Skin Service Street, Melbourne VIC 3000 examination of draining lymph nodes for Patients treated for NMSC should: patients with SCC), have a professional full • Be taught to self-screen and recognise skin examination as deemed appropriate, and Royal Melbourne changes to their skin Hospital Melanoma 300 Grattan Street, Parkville VIC 3052 Ph: 9342 8187 have further testing as required. • Have a full body examination with a clinician Service Clinical Practice Guide: Basal cell every 12 months. Medical Unit carcinoma, squamous cell carcinoma Austin Hospital Ph: 9496 5763 For the general population, the Level 6, Harold Stokes Building (and related lesions) – a guide to Melanoma Clinic Fax: 9457 6698 Australasian College of Dermatologists 145-163 Studley Road, Heidelberg VIC 3084 clinical management in Australia. recommends that people examine their skin www.cancer.org.au 4 times a year or as often as recommended St Vincent’s Ph: 9231 2898 41 Victoria Parade, Fitzroy VIC 3065 by their medical practitioner. Dermatology Clinic Fax: 9231 3489

Skin and Cancer Level 1, 80 Drummond Street, Ph: 9623 9400 Foundation Carlton VIC 3053 Adapted and revised with kind permission from Cancer Council New South Wales, 2016. Images are supplied courtesy of the Sydney Melanoma Diagnostic Centre and the Victorian Melanoma Service