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Case report 1
A 30-year-old woman with multiple moles was referred to dermatology with a changing mole on her back. She had multiple moles but was concerned that a longstanding mole on the right upper back had grown in size, become darker in colour and developed black and red areas at the edges over the preceding four months. The patient had a history of blistering sunburn in childhood, sunbed use in adulthood and fair skin. There was no family history of melanoma and she had never been immunosuppressed.
On full skin examination there were >100 naevi of varying size, shape and colour consistent with atypical naevus syndrome (Figure 1). The lesion on the right upper back measured 1cm in diameter, was asymmetrical with irregular borders, and was multi-coloured with brown, red and black areas (Figure 2). An excision biopsy was performed on the same day and the lesion was excised with a 2mm clinical margin and a cuff of subcutaneous fat.
Histopathological evaluation showed a malignant melanoma, superficial spreading type with a Breslow depth of 1.25mm and a mitotic count of 2/mm2. There was no ulceration of overlying epidermis. Following discussion at the regional skin cancer multidisciplinary team meeting, the patient was referred to plastic surgery for a wide local excision with 2cm margins and a sentinel node biopsy. There was no residual melanoma present in the wide local excision specimen and two sentinel nodes were identified but did not contain evidence of metastases on histopathological or immunohistochemistry evaluation.
The patient was given verbal and written education on melanoma, changes to look for in moles (ABCDE criteria, Table 2), technique for regular self skin examination, photoprotection and vitamin D supplementation. Full skin examination and assessment for lymphadenopathy and organomegaly is performed at three-monthly intervals until three years have passed from the date of diagnosis.
Case report 2
A 74-year-old man presented to his GP with a lesion on the lower back. Initially the lesion was thought to be a seborrheic keratosis and had been treated with cryotherapy. On review there was concern about pigmentation at the base of the lesion and the patient was referred to the regional pigmented lesion clinic.
There was no history of occupational sun exposure, no family history of melanoma, no sunbed use and the patient went on two sun holidays a year. Clinically the lesion measured 5mm and had pale and dark areas (Figure 3). There was a blue veil seen on dermoscopy. The lesion was excised with a 2mm clinical margin and histopathology showed a melanoma, Breslow depth 0.8mm with no adverse prognostic features (ie, ulceration or mitoses).
The patient had a subsequent wide local excision with a 1cm margin four weeks later and there was no residual melanoma seen. His serum vitamin D level was reduced at 34nmol/L (normal range >50nmol/L). The patient was reviewed in dermatology outpatients every three months for twelve months following diagnosis. During this time he was educated on self skin checks, changes to look for in moles and the importance of photoprotection. Full skin examination and clinical evaluation of regional lymph node basins were performed at every visit.
The incidence of malignant melanoma is increasing worldwide, particularly in countries with skin type and climate similar to Ireland. Every year there are over 700 new cases of melanoma diagnosed and there are 100 melanoma related deaths. Figures from the National Cancer Registry Ireland (NCRI) show that melanoma is the fifth most common cancer diagnosed, accounting for 4.4 per cent of all malignant neoplasms and 1.7 per cent of all cancer deaths. During 1995-2007 the number of new cases diagnosed increased at approximately 5 per cent per annum overall.
GPs are the first point of medical contact for the majority of patients with suspicious skin lesions. The National Cancer Control Programme (NCCP) produced pigmented lesion referral guidelines in 2010. A national referral form has been launched recently to facilitate rapid access to consultant dermatologists and plastic surgeons for patients with lesions clinically suspicious for melanoma based on known patient risk factors (Table 1) and suspicious features of individual lesions (Table 2).
The processes underlying the development of melanoma are complex and vary between individuals. The risk factors for melanoma are outlined in Table 1.
The most significant risk factors are number of naevi (RR 9.8 if >100 naevi) and presence of atypical naevi (RR 6.3 if ≥6). Risk of melanoma rises with increasing number of as well as atypical naevi, from a small risk in those with few common naevi, to a higher risk in those with larger numbers of common naevi, to a very high risk in those with multiple, clinically atypical naevi. Atypical naevi are present in 2-5 per cent of Caucasians. The International Agency for Research on Cancer (IARC) uses the following criteria to identify atypical naevi: A macular component in at least one area in addition to three of the following features: border not well defined, size ≥5mm, colour variegated, contour uneven, presence of erythema.
In a systematic review of patients with giant congenital melanocytic naevi, ie >20cm adult size, the incidence of melanoma is estimated to be 2.3 per 1,000 patient-years.
Other risk factors
Other risk factors associated with the development of melanoma include sunburn (RR 2-3.7), red hair (RR 2.38) and family history of melanoma (RR 2.06). The use of sunbeds is associated with a significant increased risk of melanoma (RR 1.20), and this risk increases with young age at initial exposure and number of sunbed sessions. The risk seems to be greatest in patients with a history of intermittent intense sun exposure and blistering sunburn in childhood.
Lifestyle factors are known to have a relationship with the development of melanoma and it is known that incidence is increased in higher socioeconomic groups. However, patients from deprived backgrounds tend to have a greater risk of dying from melanoma because they present with later stage disease (data from NCRI). Patients with long-term immunosuppression, due to treatment with anti-rejection drugs following organ transplantation or with HIV infection, are also at increased risk of melanoma.
When evaluating a mole for melanoma the ABCDE criteria, as outlined in Table 1, are significant.
The ABCD mnemonic (asymmetry, border, colour variegation, diameter >6mm) was published in 1985 in an effort to educate doctors and the public on changes that might indicate melanoma in early clinical stages. It has been a very successful tool and the depth of melanoma diagnosed in the US is now much thinner than prior to its introduction. Not all melanomas will be picked up by ABCD and therefore history of evolution can be an important clue. The letter E, for evolution, was added in 2004 when it was recognised that changes in appearance or symptomatology of moles may indicate melanoma. Evolution can be an important signal especially for nodular, desmoplastic and amelanotic melanomas, which may not be picked up using just the ABCD mnemonic and which often present as thick, dangerous lesions. In order for patients to be aware of changes in pre-existing naevi it is important to encourage regular self-skin checks. The ‘ugly duckling’ sign, ie a naevus out of keeping with an individual’s mole pattern, is another useful tool in assessing naevi.
Screening is controversial and up until recently there was no evidence to support population screening for melanoma. However, evidence is mounting for the implementation of a melanoma cancer screening programme.
In Germany a skin cancer screening programme was introduced in one state with a resultant 48 per cent reduction in melanoma deaths. The initial whole-body examination was performed by the GP in 72 per cent of cases and all suspicious skin lesions were referred to a consultant dermatologist for further evaluation. The melanoma mortality rate remained stable in the rest of Germany and in neighbouring countries, in comparison.
Screening campaigns have been in place in Australia for many years and a trend towards thinner melanomas and improved survival has been observed. A population-based study in Australia showed that patients who had a whole body skin examination in the three years preceding diagnosis of melanoma were 38 per cent more likely to be diagnosed with a thin melanoma, ie ≤0.75mm.
As more evidence becomes available current attitudes to screening may need to change.
NCCP guidelines suggest that patient with suspicious pigmented lesions should be referred to dermatology or plastic surgery with the lesion intact. Pigmented lesion clinics have been set up in many centres to facilitate rapid access for these patients. Best practice is that skin lesions suspected of being melanoma should be excised completely with a 2-3mm clinical margin, and a cuff of fat. This allows for accurate measurement of the Breslow depth and planning of definitive treatment. All specimens should be sent for histological analysis. All invasive melanomas should be discussed at the regional melanoma multidisciplinary team meeting.
Further treatment is decided based on the histopathological features of the tumour after discussion at the regional skin cancer multidisciplinary team meeting. For all patients with in situ or invasive disease a wide local excision (WLE) of the scar is performed, the extent of which depends on the Breslow depth of the tumour (Table 3). For patients with thin melanoma, ie <1mm, this may be curative and is the only treatment required. Sentinel lymph node biopsy is usually offered to patients with melanoma of ≥1mm depth. This procedure involves injection of a radiolabelled dye to the scar from the primary excision and subsequent identification of the first node that area drains to in the regional lymph node basin.
Following WLE all cases are further discussed at the regional skin cancer multidisciplinary team meeting and follow up is recommended based on this. Sentinel node biopsy offers prognostic information but its role in improving outcomes is controversial. There is no role for staging investigations in early disease but they may be performed on the advice of the multidisciplinary team meeting for more advanced disease.
The treatment of metastatic melanoma has undergone a revolution in the last five years with the development of treatments that may improve survival from metastatic disease. The development of immunotherapies such as ipilimumab, anti-CTLA4, and newer anti-programmed death 1 agents has changed the outlook for patients with metastatic melanoma and offers hope of prolonged overall survival. Up to 50 per cent of cutaneous melanomas carry a mutation in the BRAF gene. Vemurafenib, a monoclonal antibody targeted against the BRAF V600E mutation, has been shown to improve overall and progression-free survival in patients with the mutation.
While our understanding of, and the treatment options for, metastatic melanoma are evolving and newer treatments offer hope of prolonged overall survival for patients, early detection still gives patients the best chance of survival.
There are three main reasons for follow up after treatment of primary cutaneous melanoma:
- To detect recurrence when further treatment can improve the prognosis.
- To detect further primary melanomas.
- To provide support, information and education.
Ideally patients should be seen at dedicated melanoma follow up clinics. For patients with a single melanoma in situ that has been treated, no regular follow up is necessary once they have been informed of the diagnosis, full skin examination for other pigmented lesions has been performed and they have been educated on self skin examination, the ABCDE criteria and photoprotection. Patients with stage Ia melanoma, ie, Breslow depth <1mm, are usually followed for 12 months, educated as above and then discharged to perform regular self-examination. All patients with invasive melanoma >1mm are followed up at regular intervals for five years after diagnosis as most relapses occur within this time frame. It is important to note, however, that late recurrences do occur and patients need to remain vigilant with self skin checks throughout life.
Patients should be taught to self-examine to detect locoregional recurrence and new primary melanoma. All patients are educated verbally and with the use of information leaflets on the importance of regular self skin checks for getting to know what their moles look like, changes to watch for in pigmented lesions and the importance of photoprotection. Overall the most important treatment is early diagnosis as excision can be curative.
References available on request