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Phoon YW, Butt S, Affleck A. Early detection of cutaneous melanoma improves prognosis. Practitioner September 2021;265(1851):21-25

Early detection of cutaneous melanoma improves prognosis

24 Sep 2021

AUTHORS

Dr Yee W Phoon MBBS MMed (Int Med) MRCP (UK) FAMS (Derm), Mohs Fellow

Dr Sanaa Butt BMBS MRCP, Specialist Registrar

Dr Andrew Affleck BSc (Hons) MB ChB MRCP, Consultant Dermatologist and Mohs Surgeon, Ninewells Hospital, Dundee, UK

Competing interests: None

Article

The risk of developing melanoma increases with age. Each year 28% of all new melanoma cases in the UK are diagnosed in people aged 75 and over and 47% of melanoma deaths occur in this age group. Exposure to intermittent intense sunlight and sunburn (especially in childhood) are the most common modifiable risk factors for melanoma. Individuals with lighter skin tones are at greatest risk (Fitzpatrick skin types I-II). A history of melanoma increases the risk of a further melanoma eight-fold. Approximately 5-10% of melanoma cases are estimated to be familial. The 7-point checklist is recommended by NICE to help determine when a referral is indicated. Major features score 2 points and include change in size, irregular colour, irregular shape with minor features scoring 1 point such as: inflammation, oozing or crusting, diameter > 7 mm, sensory change or itch. A score of 3 or more warrants urgent referral. Checklists should not be used in isolation as some melanomas will be missed. Amelanotic melanomas, estimated at 10% of all melanomas, remain a challenge as they are pink in colour and often have a global symmetric appearance which can result in delayed or missed diagnosis. The EFG tool, which assesses for elevation, firmness and continuous growth for more than a month, is recommended with these types of suspicious lesions. All lesions seen by a GP in which melanoma is suspected should be referred to secondary care via an urgent 2-week wait suspected cancer pathway referral.


Melanoma is the fifth most common cancer in the UK.1 The incidence of melanoma in the UK has increased by around 135% since the early 1990s, with more than 16,000 people diagnosed each year.1 In the USA, the incidence has increased six-fold over the past 40 years.2

Early detection of melanoma, especially if limited to in situ disease, improves prognosis.1 Invasive melanoma has metastatic potential. Diagnosis may be challenging for GPs who on average would be expected to see a single case of melanoma every two years.

Risk factors

The risk of developing melanoma increases with age. Each year more than a quarter (28%) of all new melanoma cases in the UK are diagnosed in people aged 75 and over and almost half (47%) of melanoma deaths occur in this age group.1

Exposure to intermittent intense sunlight and sunburn (especially in childhood) are the most common modifiable risk factors for melanoma.

Social trends have led to increased use of sun tanning beds which largely emit UVA radiation. Iatrogenic exposure may occur through the use of PUVA and necessitates caution with repeated use.3

Individuals with lighter skin tones are at greatest risk (Fitzpatrick skin types I-II) because of their increased susceptibility to sunburn. Blue eyes, numerous freckles and fair or red hair are also common in this phenotype (see box 1).

A history of melanoma confers an eight-fold increased risk of a further melanoma.4 Approximately 5-10% of melanoma cases are estimated to be familial (i.e. where two first-degree blood relatives or any three blood relatives on one side of the family have had a melanoma).5 Risk factors for melanoma are listed in table 1.

Approximately one third of melanomas are thought to arise from existing naevi with the remaining occurring de novo.6 Patients with high counts of naevi (> 50) and clinically atypical moles (defined as benign melanocytic naevi with clinical features overlapping with melanoma such as size > 5 mm, asymmetrical, irregular and multicoloured) are also at increased risk. Large congenital naevi, measuring > 20 cm have the propensity to evolve into melanoma.

Genetic conditions such as familial atypical multiple mole melanoma  (FAMMM) syndrome, an autosomal dominant syndrome characterised by multiple melanocytic naevi, a positive family history of melanoma and the CDKN2A gene mutation also raise an individual’s risk profile. Patients with xeroderma pigmentosa have a higher incidence of melanoma due to ineffective DNA repair mechanisms following photodamage.

Immunosuppressed patients such as those with an organ transplant or who have HIV or lymphoma, are also more likely to develop a melanoma which is often accompanied by a worse prognosis.7,8

Assessment

A comprehensive history should include the timeline of change, whether the lesion is new or occurred in an existing naevus, changes in size, shape and colour. Symptoms such as pain, itch and bleeding should be noted. The risk factors outlined in table 1 should be evaluated.

During examination, the lesion should be palpated and inspected closely in good light and its appearance and size documented.

A full body skin assessment is very useful and allows comparison of the index lesion with other skin lesions.

A melanoma tends to be an outlier in its appearance that does not fit the individual’s usual pattern of signature naevi; the ugly duckling sign.9

Various assessment tools may be employed during the skin assessment e.g. the ABCDE criteria (Asymmetry, irregular Borders, Colour variation, Diameter > 6 mm, Evolution) which are quick and easy to use.10

The 7-point checklist is recommended by NICE to help determine when a referral is indicated. Major features score 2 points and include change in size, irregular colour, irregular shape with minor features scoring 1 point such as; inflammation, oozing or crusting, diameter > 7 mm, sensory change or itch.11 A score of 3 or more warrants an urgent referral. However, these checklists should not be used in isolation as some melanomas will be missed.

Amelanotic melanomas, estimated at 10% of all melanomas, remain a challenge as they are pink in colour and often have a global symmetric appearance which can result in delayed or missed diagnosis. The EFG tool, which assesses for elevation, firmness and continuous growth for more than a month, is recommended with these types of suspicious lesions.12

A high index of suspicion for melanoma is needed especially when: risk factors are present, there is a history of change and patient anxiety and the index lesion is clinically non-specific, and should prompt further evaluation.

For lesions on acral skin, nails and mucosa assessment by a dermatologist is indicated and is outside the scope of this article.

All lesions seen by a GP in which melanoma is suspected should be referred to secondary care via an urgent 2-week wait suspected cancer pathway referral.

The COVID-19 pandemic has resulted in reduced melanoma referrals during lockdown.13 Many consultations carried out, both in general practice and secondary care, were virtual which carries an associated risk because of the variable quality of the clinical images submitted. In person assessment and examination is the gold standard especially in suspected melanoma.

Dermoscopy

Visual inspection alone will miss 1 in 10 melanomas. Dermoscopy is widely used to improve clinical diagnostic accuracy by detecting features not visible to the naked eye. For those GPs who are skilled in the use of dermoscopy attaching a dermoscopic image to the referral is very useful in triage.14

Dermoscopic features suggestive of melanoma include an asymmetrical atypical pigment network, irregular streaks and regression structures.

The presence of a blue-white veil, milky pink areas and atypical vessels may be more commonly seen in nodular melanomas.

 

Clinical presentation

Melanomas are categorised into four histopathological subtypes. Although each subtype has distinct features, their heterogeneous clinical morphological presentations can lead to challenges in diagnosis.

Melanomas may mimic benign lesions (e.g. melanocytic naevi, seborrhoeic keratosis, dermatofibroma, pyogenic granuloma), inflammatory conditions or non-melanoma skin cancers (see table 2 and figure 2).

 

Subtypes

1 Superficial spreading melanoma (SSM) is the most common subtype accounting for approximately 70% of melanomas and is characterised by a slow radial growth phase.15 It has a predilection for the trunk in men and lower limbs in women. It tends to appear as a variably pigmented macule or patch with irregular borders, (see figure 1).

2 Nodular melanoma, the second most common subtype, commonly presents with a dome-shaped nodule, often with reduced or absent pigmentation and may masquerade as the more common non-melanoma skin cancers such as basal cell carcinoma and squamous cell carcinoma. It has a predilection for the head and neck.12

3 Lentigo maligna is typically an asymmetrical pigmented macule or patch on the head and neck area in elderly patients. These lesions are often slow growing, present for many years before sometimes developing nodular areas suggesting invasive transformation to lentigo maligna melanoma.

4 Acral lentiginous melanoma which affects acral sites especially the soles of the feet and the nail unit is the rarest subtype and is outside the scope of this article. Assessment of lesions at these sites should always be undertaken in secondary care.

Diagnosis

Diagnosis should always be confirmed by biopsy, ideally with an initial complete excision. Staging is performed in line with the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines using the TNM classification system. The Breslow thickness is the measurement of the tumour depth and is the most important prognostic factor.

Other poor prognostic features include tumour ulceration, lymphovascular invasion, tumour subtype and mitotic activity which measures tumour growth. As a general rule, any patient with nodal metastasis has stage III disease and any patient with organ metastasis has stage IV disease.

All patients with melanoma should be discussed at a multidisciplinary team (MDT) meeting to determine the most appropriate treatment plan. This typically consists of dermatologists, plastic and maxillofacial surgeons, oncologists, radiologists and dermatopathologists.

Complications

Melanoma may metastasise to local lymph nodes or distant organs. If lymphadenopathy is detected clinically, fine needle aspirate or nodal excision is indicated for histological assessment. Imaging with CT, PET-CT or MRI is indicated in those with positive nodal disease to assess for further metastatic disease.

The estimated five-year survival rate for patients whose melanoma is detected early is around 99%, but in those with nodal involvement or distant metastasis, this falls to 66% and 27% respectively.16

Treatment

Surgery

National guidelines recommend that primary excision of the lesion should be undertaken in secondary care with a peripheral margin of 2 mm.17,18 In certain anatomical areas such as the nose, ear and acral sites, in the case of large lesions or where diagnostic uncertainty exists, a diagnostic biopsy can be performed from representative parts of the lesion to help plan further management. Following diagnosis, a wide local excision is performed. The width and depth of the re-excision is dependent on the Breslow thickness and anatomical features.

 

Sentinel lymph node biopsy

Sentinel lymph node biopsy (SLNB) is the most sensitive method of detecting microscopic metastatic nodal disease and so providing further prognostic information. It is indicated in patients with melanoma > 1 mm Breslow thickness or 0.8-1 mm with ulceration.19

SLNB involves preoperative lymphoscintigraphy in which a blue dye and radioactive tracer is injected around the scar at the site of the initial melanoma excision. The sentinel node is identified as the first node to take up the dye and tracer and is removed and examined for micrometastasis. SLNB is best performed at the time of wide local excision under a general anaesthetic.

 

Lymph node clearance

Total lymph node clearance is no longer routinely recommended after a positive SLNB, as there is no evidence of benefit.20 However, it may be indicated in some individual cases after MDT discussion.

 

Systemic therapy

Systemic therapy may be indicated in those with nodal disease or metastatic organ disease. Eligible patients should be referred on to the oncology team for consideration. In the past decade, the discovery of new systemic treatments has revolutionised the therapeutic landscape of metastatic melanoma including genetically targeted agents e.g. BRAF inhibitors and immunotherapy e.g. pembrolizumab.

Systemic treatments may be used as adjuvant therapy to reduce rate of recurrence or as primary therapy for unresectable metastatic disease. Conventional chemotherapy cytotoxic agents are now rarely used.

Monitoring and follow-up

Skin surveillance follow-up varies depending on the clinical staging of the melanoma (see table 3). The optimal duration of follow-up remains controversial. Skin surveillance consists of a full skin assessment, examination of the scar and lymph node examination.

Patients should be educated on self-examination of their skin and lymph nodes, so that they can carry this out between appointments and following discharge.

Conclusion

Melanomas are a heterogeneous group of skin cancers and may be challenging to diagnose.

Classical variably pigmented lesions are obvious but there is a significant group of melanomas which mimic benign lesions and are harder to diagnose. GPs need to have a high index of suspicion to minimise the chance of missing such presentations.

Prompt referral is warranted when faced with a lesion suggestive of melanoma, atypical and clinically non-specific lesions that are evolving or whenever there is any diagnostic uncertainty. Early recognition of cutaneous melanoma leads to improved prognosis.

REFERENCES

1 Cancer Research UK. Melanoma skin cancer statistics. www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/melanoma-skin-cancer#heading-Zero. [Last accessed 28 Aug 2021]

2 Welch HG, Mazer BL, Adewole SA. The rapid rise in cutaneous melanoma diagnoses. N Engl J Med 2021;384(1):72-79

3 Stern RS. The risk of melanoma in association with long-term exposure to PUVA. J Am Acad Dermatol 2001;44(5):755-61

4 Beroukhim K, Pourang A, Eisen DB. Risk of second primary cutaneous and noncutaneous melanoma after cutaneous melanoma diagnosis: a population-based study. J Am Acad Dermatol 2020;82(3):683-89

5 Gandini S, Sera F, Cattaruzza MS et al. Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur J Cancer 2005;41(14):2040-59

6 Harley S, Walsh N. A new look at nevus-associated melanomas. Am J Dermatopathol 1996;18(2):137-41

7 Kubica AW, Brewer JD. Melanoma in immunosuppressed patients. Mayo Clin Proc 2012;87(10):991-1003

8 Brewer JD, Christenson LJ, Weaver AL et al. Malignant melanoma in solid transplant recipients: collection of database cases and comparison with surveillance, epidemiology, and end results data for outcome analysis. Arch Dermatol 2011;147(7):790-96

9 Grob JJ, Bonerandi JJ. The “ugly duckling” sign: identification of the common characteristics of nevi in an individual as a basis for melanoma screening. Arch Dermatol 1998;134(1):103-a-104

10 Abbasi NR, Shaw HM, Rigel DS et al. Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria. JAMA 2004;292(22):2771-76

11 Walter FM, Prevost AT, Vasconcelos J et al. Using the 7-point checklist as a diagnostic aid for pigmented skin lesions in general practice: a diagnostic validation study. Br J Gen Pract 2013;63(610)

12 Chamberlain AJ, Fritschi L, Kelly JW. Nodular melanoma: patients’ perceptions of presenting features and implications for earlier detection. J Am Acad Dermatol 2003;48(5):694-701

13 Venables ZC, Ahmed S, Bleiker TO et al. The impact of the COVID-19 pandemic on skin cancer incidence and treatment in England, 2020. Br J Dermatol 2021;185(2):460-62

14 Dinnes J, Deeks JJ, Chuchu N et al. Dermoscopy, with and without visual inspection, for diagnosing melanoma in adults. Cochrane Database Syst Rev 2018;2018(12)

15 Elder DE, Bastian BC, Cree IA et al. The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: detailed analysis of 9 distinct subtypes defined by their evolutionary pathway. Arch Pathol Lab Med 2020;144(4):500-22

16 Cancer Research UK www.cancerresearchuk.org/about-cancer/melanoma/survival

17 Scottish Intercollegiate Guidelines Network. SIGN 146. Cutaneous melanoma. SIGN. Edinburgh. 2017 www.sign.ac.uk/our-guidelines/cutaneous-melanoma/ [Last accessed 30 Aug 2021]

18 National Institute for Health and Care Excellence. NG14. Melanoma: assessment and management. NICE. London. 2015 www.nice.org.uk/guidance/ng14 [Last accessed 30 Aug 2021]

19 Wong SL, Faries MB, Kennedy EB et al. Sentinel lymph node biopsy and management of regional lymph nodes in melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. J Clin Oncol 2018;36(4):399-413

20 Broman KK, Hughes T, Dossett L et al. Active surveillance of patients who have sentinel node positive melanoma: an international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2). Cancer 2021;127(13):2251-61

PRESET SEARCHES

US National Cancer Institute 

PDQ® (Physician Data Query) is NCI's cancer database of  peer-reviewed, regularly updated evidence-based, referenced summaries

Melanoma

PubMed

Melanoma

NICE

Melanoma evidence search

UK's PCDS - clinical guidance
This section is an educational tool, written in chapters very much like an up-to-date dermatology textbook. Each chapter introduces the relevant skin condition, highlights key diagnostic features and provides advice on management.

Melanoma: an overview 

Melanoma: acral-lentiginous melanoma (including subungual melanoma)

Melanoma: lentigo maligna melanoma (including lentigo maligna)

Melanoma: nodular melanoma

Melanoma: superficial spreading melanoma (including melanoma in situ)