AND OTHER SKIN CANCERS: A GUIDE FOR MEDICAL PRACTITIONERS Australia has among the highest rates of in the world. Two in three Australians will develop some form of skin cancer before the age of 70 years.

Skin cancer is divided into two main types Causes of melanoma and other Gender skin cancers Men are more likely to develop and die from • Unprotected exposure to UV radiation remains melanoma than women. Mortality from the single most important lifestyle risk factor melanoma rises for males from 40 years and for melanoma and other skin cancers. increases with age. Men over the age of 40, compared to women of similar age, are more Melanoma Non-melanocytic skin cancer • UVA and UVB radiation contribute to skin than one and a half times more likely to be Melanoma develops in the melanocyte (NMSC) damage, premature ageing and skin cancer. diagnosed with melanoma and more than twice (pigment-producing) cells located in the • Squamous cell carcinoma (SCC) • An intermittent exposure pattern carries the as likely to die from it. epidermis. Untreated, melanoma has a develops from keratinocytes in the highest risk for developing melanoma and The mortality rate for males aged 50–80 years is high risk for metastasis. epidermis and is associated with risk BCC. UV exposure in adulthood or childhood two to three times that of females. The most common clinical subtype is of metastasis. Overall, SCC is most contributes to BCC and melanoma risk. commonly found on the face, particularly superficial spreading melanoma (SSM), • Actinic keratoses and SCC are associated the lip region, ears, nose, cheek and Melanoma in Indigenous making up 55–60% of all melanoma. SSM with the total amount of sun exposure eyelid, and then on the neck, dorsum Australians and non- Caucasian is most commonly found on the head accumulated over a lifetime. and neck (per unit area). Other common of hands and forearms. In males, SCC is patients sites are the trunk in males and lower commonly found on the head and neck, • Other risk factors for NMSC can include exposure to some chemicals (e.g. arsenic); The incidence of melanoma in Indigenous extremities in females. and in females it is commonly found on Australians is low. For the period 2008–2012, the lower limbs, followed by the head and radiation therapy and psoralen (PUVA) However, SSM can develop on any part treatment for psoriasis; immunosuppressive twenty-two Indigenous Australians died from of the body, including parts not heavily neck. SCCs may arise from premalignant melanoma, representing 0.4% of all melanoma actinic keratoses. therapy; and some rare genetic conditions exposed to (UV) radiation. predisposing people to skin cancer (e.g. deaths. For the same period, there were 7,300 deaths from melanoma overall. The incidence • Basal cell carcinoma (BCC) also Xeroderma pigmentosum, albinism). In WA in 2017: of melanoma in non-Caucasians is also low. develops from keratinocytes in the • There were more than 1,400 new cases of However, non-Caucasians are more likely to epidermis and is the most frequently Risk factors for melanoma melanoma (11% of all cancer diagnoses) experience delayed diagnosis and have poorer diagnosed cancer in Australians. It can • Multiple naevi (moles) and over 130 deaths. clinical prognosis compared to Caucasians. be found most commonly on the head • Multiple dysplastic naevi • Men over the age of 40 were more and neck but also on the trunk and limbs. • Personal or family history of melanoma Non-Caucasians tend to develop than one and a half times more likely It can also be found in areas not exposed • Increasing age clinical melanoma subtypes that are rare in to be diagnosed with melanoma and to sunlight. • High levels of intermittent sun exposure Caucasian populations: more than twice as likely to die from it, (e.g. during outdoor recreation) • Acral lentiginous melanoma on the palms compared to women of similar age. In WA in 2014, there were 83,151 paid • Occupational sun exposure and soles. Medicare services for NMSC, and • The lifetime risk of developing melanoma • Personal history of NMSC • Subungual melanoma within the nail matrix. by age 85 years was one in 21 for men 82 deaths. • Fair skin that burns easily, freckles and does and one in 30 for women. not tan • Fair or red hair and blue or green eyes • Immune suppression and/or being a transplant recipient. Melanoma diagnosis The ABCD(E) acronym can help distinguish Superficial spreading an SSM from a normal mole: Any lesion that displays the EFG features over melanoma (SSM) Asymmetry: the lesion is irregular in a period of more than one month should be Melanoma can develop in pre-existing moles or A shape or pattern. more commonly, de novo. investigated. • SSM is the most common form of Border: the border or outline of a If melanoma is suspected, diagnosis should not be B melanoma is usually irregular. melanoma. delayed and urgent referral or immediate excision • SSM can appear as a new spot or as a Colour: there is variation in colour change in the size, colour or shape of an with a 2mm margin is recommended. C within the lesion. existing mole. • A patient diagnosed with SSM is at Diameter: the lesion is usually greater increased risk of developing a new primary than 6 mm across. melanoma. D However, suspect lesions of smaller Lentigo Maligna (LM) Diagnosis tools diameter should also be investigated. A slow growing form of melanoma in situ that Dermoscopy uses a hand-held magnifying Nodular melanoma (NM) can be difficult to recognise. LM can resemble device to allow the visualisation of diagnostic Evolving: the lesion changes over This is a dangerous form of melanoma that a freckle. It develops in sun-damaged older features of skin lesions that are not seen with E time (size, shape, surface, colour, skin, especially on the head and neck. Margin the naked eye. It increases diagnostic accuracy can metastasise early. It differs from SSM in symptoms e.g. itch). appearance. determination can be challenging and local and reduces unnecessary excision of benign recurrence is more common than in other types • NM has no radial growth within the epidermis lesions. Training in dermoscopy is recommended of melanoma. Incidence is increasing. but penetrates vertically into the dermis for clinicians routinely involved in skin cancer early. The ABCDE acronym cannot be used to aid treatment. diagnosis of NM but the following features Biopsy and excision • Sequential digital dermoscopy imaging • NM can develop de novo in normal- for melanoma or suspicious appearing skin or within another type of EFG – can assist with the diagnosis (SDDI) involves the assessment of successive naevi dermoscopic images to allow the detection of melanoma. Elevated: the lesion can appear as • Excision of the entire lesion with a suspicious dermoscopic change in • NM is more likely to be symmetrical and a small, round and raised lump on 2mm margin is recommended. that lack dermoscopic evidence of melanoma uniform in colour (red, pink, brown or black), E the skin. Colour may be uniform at a particular time. is more frequently lighter coloured than SSM, throughout the lesion and may be • Partial biopsies (punch biopsy or shave and feels firm to the touch. black, brown, pink or red. excision) are less accurate than excisional • Total body photography allows the detection of suspicious changes and is useful in high- • Over time, NM may develop a crusty surface biopsy and should be avoided. If complete Firm: the lesion feels firm to the risk patients or patients with dysplastic that bleeds easily. excision is impractical, a large incisional F touch biopsy incorporating as much of the atypical naevus syndrome. • NM develops most commonly on sun- part of the lesion as possible is the best • In vivo confocal microscopy allows damaged skin and in older people, Grows: a nodule that has been alternative. non-invasive “optical biopsy” with the particularly men. growing progressively for more than a G • The excision or biopsy should not interfere visualisation of the morphology and • Approximately 10–15% of total melanomas month should be assessed as a matter organisation of the cells in deeper layers of of urgency. with subsequent treatment. For this diagnosed are NM. reason, wide excisions, flap reconstructions the skin. It is useful for difficult diagnoses and curettage of suspicious lesions are and margins (i.e. amelanotic melanoma, LM) contraindicated. and is used in specialised centres.

Smartphone applications for pigmented lesions Melanoma apps are smartphone applications that assess risk of pigmented lesions using a smartphone camera and underlying algorithm. None of the melanoma apps tested have shown high enough agreement with a specialist clinical opinion to be considered adequate for assessing high-risk pigmented lesions. Treatment for melanoma Other treatment options Appropriate primary treatment will depend on the Breslow thickness of the tumour. Surgery • Sentinel lymph node biopsy (SLNB) should T cells, (namely the cytotoxic T lymphocyte Tis - Melanoma Melanoma cells are found only in the non-vascular epidermis be discussed with all patients with lesions associated protein 4 (CTLA-4) receptor and and have not penetrated into the dermis. over T1b (>0.8mm). These patients should be the programmed death 1 (PD-1) receptor). in situ. discussed at a multidisciplinary melanoma The combination of immunological therapies meeting such as the Western Australian seems more efficient but more toxic (possible The melanoma is less than 1 mm thick. T1 Kirkbride Melanoma Advisory Service side-effects include fatigue, arthralgia, joint (WAKMAS) before definitive treatment is pain and major autoimmune disease). The melanoma is between 1 mm and 2 mm thick. T2 undertaken. –– Current immunotherapy drugs in use include • Resection of isolated metastases can be Nivolumab, Ipilimumab and Pembrolizumab. T3 The melanoma is between 2 mm and 4 mm thick. performed in both therapeutic and palliative The first two may be used in combination settings. therapy to increase efficacy whilst T4 The melanoma is more than 4 mm thick. Radiation Pembrolizumab is used as monotherapy. • Radiotherapy may be considered as adjuvant Trials for combination therapy and monotherapy treatment where the lesion has a high of these drugs and new drugs for different • The T1-T4 (Primary Tumour Thickness) classification is further divided into groups depending on risk of local recurrence (e.g. Desmoplastic stages of melanoma are ongoing and are presence of ulceration (a or b). melanoma) constantly being introduced. For information –– Treatment is based on tumour thickness and involves the removal of the melanoma with a • Radiotherapy may be used for palliative on trials that may be available for your patients margin of excision based on the Tis-T4 classification. management of cerebral and bone with advanced stage 2 disease (melanoma metastases and for other metastatic lesions greater than 2.0mm thick with ulceration or over where systemic treatment has failed. 4.0mm thick), please contact WAKMAS. Tis 5 mm clearance Oncology treatments Follow-up for melanoma • Systemic treatment is now available for Due to the risk of tumour recurrence and new T1 - T3 1 cm clearance patients with metastatic (including positive primary melanomas, all patients require regular SLNB) or inoperable melanoma. Survival follow-up, as follows: in patients with metastatic disease has • 6-monthly intervals for 5 years then yearly for Consider a 2 cm clearance T4 improved significantly since the introduction patients with insitu disease of the following agents. • 3- 4-monthly intervals for 3 years, then 6 Note: –– Targeted therapy monthly until 5 years, and yearly follow-up Inhibits the mitogen activated protein kinase thereafter for patients with invasive lesions. The optimal excision margin for melanoma 2–4 mm thick is debated. There is currently no evidence to pathway (BRAF and MEK inhibitor) in V600 support a clinical excision margin over 1cm for these lesions. • 3 monthly intervals for patients with BRAF mutant melanoma. These therapies metastatic disease Discussion about sentinel lymph node biopsy (SLNB) is now considered the standard of care for all are now used mostly in combination in order • Patients who have had a positive SLNB who lesions >T1b (over 0.8mm Breslow thickness). SLNB may not be offered to patients who have had to achieve greater efficacy and reduced side have not tolerated adjuvant treatment or who their lesion excised with a wide margin. Definitive excision of these lesions should not be performed effects (in particular the development of do not have adjuvant treatment should have before the patient has discussed SLNB with a surgeon who performs this procedure. squamous cell carcinomas and minor skin 3-4 monthly ultrasound scans of the affected disruptions). The current BRAF inhibitors used Flap reconstruction interferes with lymphatic drainage and should not be undertaken if SLNB has not lymph node basin for a minimum of for targeted therapies include Dabrafenib been discussed with suitable patients (>T1b). three years. and Vemurafenib. These are combined with In Australia, up to 75% of patients detect their If a partial biopsy has been performed and the Breslow thickness is under 0.8mm, excision of the MEK inhibitors (Trametinib and Cobimetinib own recurring melanomas. Patients should be remaining lesion with a 2mm margin should be performed before definitive treatment of the lesion, in respectively) to reduce toxicities and improve educated on recognising changes in their skin, case a Breslow thickness over 0.8mm is confirmed. In this case, SLNB would then need to be discussed. efficacy. have a professional full skin examination as –– Immunological therapy deemed appropriate, and have further testing Modulates host/tumour immune responses as required. via inhibitors of immune checkpoints on Non-melanoma skin cancer (NMSC) diagnosis Treatment for NMSC Screening for Treatment options for NMSC include: Squamous cell carcinoma (SCC) Basal cell carcinoma (BCC) • surgical excision of the tumour and melanoma and NMSC • SCC can spread to other parts of the body if • BCC is the most common and least dangerous surrounding tissue There is no evidence demonstrating that population-based screening for melanoma not treated. Lesions on the face and scalp, form of skin cancer. • radiotherapy histologically aggressive and/or larger and NMSC is effective in reducing morbidity or • BCC appears as a well-defined lump or scaly • curettage and electrodesiccation for larger tumours, and tumours arising in immune- mortality. area that is red or pearly in appearance. lesions on the trunk. suppressed individuals have a higher risk of Skin surveillance is recommended for patients • BCC may bleed or become ulcerated early on, metastasis. For biopsy-proven superficial lesions: identified as high risk for melanoma and NMSC, then heal and break down again. • cryotherapy • SCC appears as a thickened, red, scaly nodule including patients with a previous diagnosis • BCC usually grows relatively slowly. that may bleed and ulcerate over time. • application of topical agents of melanoma. • High-risk BCC subtypes (eg micronodular, (imiquimod cream, 5-fluorouracil cream, • SCC grows over a period of weeks infiltrating or morphoeic) and BCCs inimmune photodynamic therapy). to months and may be painful. suppressed individuals tend to have higher Skin self-examination In general, the choice of treatment will rates of recurrence after treatment. depend on: (SSE) for melanoma • Tumour size, thickness and anatomic site and NMSC • Patient preference, age and Approximately 50% of melanomas are medical comorbidities. detected by the patient. There is no specific SSE A course on skin biopsy procedures is available technique or recommended frequency of self- for GPs, for more information please contact examination that has been shown to reduce The Royal Australian College of General morbidity. However, regular skin examination Practitioners (RACGP). may increase the probability of detecting skin cancer at an early and treatable stage. Follow-up for NMSC Patients at high risk for melanoma Frequency of follow-up of patients treated for should 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 recognise suspicious lesions. They should have a depend on histological clearance and risk level full body examination with a clinician every 6 to of the tumour. Patients with multiple previous 12 months. skin cancers should be followed up more Patients treated for NMSC should be taught to regularly (three to six monthly) and educated self-screen and recognise changes to their skin. on recognising changes in their skin (including They should have a full body examination with a Squamous cells Epidermis examination of draining lymph nodes for clinician every 6-12 months or more frequently Basement patients with SCC). for patients at higher risk. Basal cells membrane (Germinal layer) For the general population, the Australasian

Nerve 2-4 mm College of Dermatologists recommends SSE Dermis 4 times a year or as often as recommended by Sweat gland their medical practitioner. Hair follicle

Fat layer Blood vessels Image references Key references

Superficial spreading melanoma (SSM) >> Cancer Council Australia Melanoma Guidelines Working Party. Clinical practice guidelines for the Diagnosis and Management of Melanoma (Features of melanoma, Biopsy, Sentinel Node Biopsy, Excision Margins). Sydney: Cancer Council Australia. October 2016.

>> Australian Cancer Network Melanoma Guidelines Revision Working Party. Clinical Practice Guidelines for the Management of Melanoma in Australia and New Zealand . Cancer Council Australia and Australian Cancer Network, Sydney and New Zealand Guidelines Group, Wellington; 2008.

>> Cancer Council Australia and Australian Cancer Network. Clinical Practice Guidelines for Keratinocyte Cancer. 2019. (under review)

Nodular melanoma (NM) >> Cancer Institute NSW. Melanoma. September 2016.

>> Western Australian Cancer Registry. Cancer incidence and mortality in , 2017. Statistical Series Number 105. Perth: DoHWA; 2019. (unpublished)

>> Australian Institute of Health and Welfare. Skin Cancer in Australia 2016. Cat.no. CAN96. Canberra: AIHW; 2016.

Squamous cell carcinoma (SCC) Specialised melanoma and non-melanoma advisory services >> The Australasian College of Dermatologists website provides a “Find a Dermatologist” search function to assist in finding Dermatologists by location. dermcoll.edu.au

>> Western Australian Kirkbride Melanoma Advisory Service (WAKMAS) Comprehensive advice from a multidisciplinary panel of specialists regarding the management of complex, advanced and metastatic malignant melanoma. Harry Perkins Institute of Medical Research Basal cell carcinoma (BCC) 6 Verdun St, QEII Medical Centre, Nedlands T. 08 6151 0860 F. 08 6151 1032 [email protected] wakmas.org.au

>> The Australian Society of Plastic Surgeons website provides a “Find a Surgeon” search function to assist in finding plastic surgeons by location. p: 02 9437 9200 | f: 02 9437 9210 [email protected] plasticsurgery.org.au CAN10455 11/19

Images are supplied courtesy of the Sydney Melanoma Diagnostic Centre. Cancer information

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