History and exam

Key diagnostic factors

common

altered pigmented lesion (ABCDE signs)

A melanocytic lesion that is changing with regard to size, shape, or colour is of concern.[Figure caption and citation for the preceding image starts]: Superficial spreading melanomaFrom the personal collection of Dr Hobart Walling and Dr Brian Swick. [Citation ends].com.bmj.content.model.Caption@754949cc[Figure caption and citation for the preceding image starts]: Nodular melanomaFrom the personal collection of Dr Hobart Walling and Dr Brian Swick. [Citation ends].com.bmj.content.model.Caption@47019384 The American Cancer Society ABCD signs of melanoma mnemonic is useful for both physicians and patients in the early detection of melanoma.[52] The addition of evolving (letter E added to the ABCD mnemonic) has been proposed to increase the sensitivity and specificity of diagnosis using the ABCD rule.[50]

The mnemonic stands for: Asymmetry of the lesion, Border irregularity, Colour variability, Diameter >6 mm, Evolution.

melanocytic lesion that does not resemble surrounding melanocytic naevi ('ugly duckling')

Naevi in an individual share a common phenotypic profile. These common features inform the decision to biopsy a pigmented lesion. The presence of an 'ugly duckling' melanocytic lesion merits special attention, regardless of whether it is classed as atypical using the ABCDE rule.[50][53]

uncommon

spontaneous bleeding or ulceration of a pigmented lesion

A melanocytic lesion that spontaneously bleeds or ulcerates is concerning for melanoma.

constitutional symptoms

Weight loss, fatigue, night sweats, headache, or cough may be symptoms of a late presentation (with metastatic disease) or progression in a patient with a history of melanoma.

nail sign: persistent single-nail melanonychia striata

A persistent pigmented band in a single nail in an adult that is >5 mm in diameter and without a definite cause, such as medicine-induced pigmentation or trauma, is concerning for melanoma of the nail apparatus.[77][Figure caption and citation for the preceding image starts]: Subungual melanoma in situFrom the personal collection of Dr Hobart Walling and Dr Brian Swick. [Citation ends].com.bmj.content.model.Caption@b533cde

nail sign: Hutchinson's sign

In the setting of pigmented bands in the nail bed and matrix (melanonychia striata), this sign shows extension of pigment into the proximal or lateral nail fold.

atypical dermoscopy findings

Bluish-white veiled appearance within a melanocytic lesion corresponds to dermal fibrosis, with pigmented melanophages in the dermis on histological examination of the pigmented lesion. These features represent regression and are common features of melanoma.[Figure caption and citation for the preceding image starts]: Bluish-white veil of a melanomaFrom the personal collection of Dr Hobart Walling and Dr Brian Swick. [Citation ends].com.bmj.content.model.Caption@5f3cfd76

Dermoscopic findings may also include atypical globules and dots of different sizes and shapes, patches of atypical network, diffuse polymorphous vasculature, superficial spreading melanoma with pseudopods distributed asymmetrically around the lesion.

fixed lymphadenopathy

Fixed lymphadenopathy in a patient with a history of melanoma, especially in lymph node basins draining the site of melanoma excision, is concerning for metastasis.

in-transit metastases

Subcutaneous masses between the primary melanoma site and the draining lymph node basins should raise suspicion of in-transit metastases.

Risk factors

strong

sun exposure

Melanoma incidence increases with residence in, duration of residence in, and migration to, areas of high ambient solar radiation.[33] It is most common in people with Fitzpatrick type I (white) skin of European origin. Evidence suggests that the risk of melanoma increases with age due to the cumulative effects of sun exposure.[34]​ 

Melanoma is most common at body sites that have received intermittent sun exposure (in particular, a history of intermittent intense exposure as a child). Such sites include the back in men and the legs in women.[35] Melanoma is also common in people with predominantly indoor occupations whose sun exposure is limited to weekends and vacations. Increased frequency or severity of sunburn increases the risk of melanoma.[36]

family history of melanoma

Risk for individuals with a family history of melanoma has been estimated to be 1.74 (relative risk; 95% CI 1.41-2.14).[17] Among children of a parent with multiple myelomas, a standardised incidence ratio of 61.78 (95% CI 5.82 to 227.19) has been reported.[37]

Mutations in the CDKN2A gene on chromosome 9 have been found in families with the atypical or dysplastic naevus syndrome and in 20% of melanoma-prone families.[18][38]

personal history of melanoma

The relative risk of developing a subsequent melanoma after any first melanoma (measured as standardised incidence ratio) varies from 12.4 (invasive after invasive melanoma; 95% CI 11.6 to 13.2) to 26.4 (in situ after in situ melanoma; 95% CI 22.6 to 30.7) compared with the general population.[39] At 20-year follow-up, approximately 5% of patients with a first invasive melanoma had developed a second invasive melanoma.

personal history of skin cancer (including actinic damage)

Presence of actinic damage (premalignant and skin cancer lesions) increases the risk for melanoma (relative risk 4.28; 95% CI 2.80-6.55).[17]

history of atypical naevi

Patients with multiple naevi that are 6 mm or larger with irregular pigmentation, irregular ill-defined borders, and central papular component with peripheral macular pigmentation are at increased risk, especially if the naevi occur in families. The risk of melanoma in such families is approximately 10%, and 100% if a history of a previous melanoma is present.[40]

One meta-analysis of case-control studies found that the relative risk of melanoma is 1.45 in patients with one atypical mole compared with those with no atypical moles, and this increases to 6.36 in those with five atypical moles.[41]

Fitzpatrick skin type I or II (white skin)

Fitzpatrick type I or II (white) skin (burns easily) increases the risk of melanoma compared with Fitzpatrick type V or IV (brown/black) skin (relative risk 2.06; 95% CI 1.68-2.52).[17]

red or blond hair colour

People with red hair (relative risk 3.64; 95% CI 2.56-5.37) or blond hair (relative risk 1.96; CI 1.41-2.74) are at elevated risk of melanoma compared with people with brown/black hair.[17]

high freckle density

High density of freckles is associated with increased melanoma risk (relative risk 2.10; 95% CI 1.80-2.45).[17]

sun bed use

Compared with never using, the odds ratio for melanoma associated with ever using indoor tanning beds was 1.16 (95% CI 1.05-1.28). Increased exposure (>10 tanning sessions) is associated with greater risk (odds ratio 1.34, 95% CI 1.05-1.71).[15]

light eye colour

Blue eye colour modestly increases melanoma risk compared with dark eye colour (relative risk 1.47; 95% CI 1.28-1.69).[17]

Naevus-associated melanomas are associated with non-brown eye colour.[22]

increased numbers of benign-appearing melanocytic naevi

People with >50 naevi are at greater risk for developing melanoma.[42]

Compared with patients with de novo melanomas, those with naevus-associated tumours are more likely to self-report many moles on their skin as a teenager and have higher total naevus counts.[22]

large congenital naevi

People with large (>20 cm) congenital melanocytic naevi are at increased risk for malignant transformation compared with those who have smaller congenital naevi.[43]​ The estimated lifetime risk is between 5% and 20% for malignant transformation.[44]

immunosuppression

There is an increased risk for melanoma in the setting of immunosuppression, including iatrogenic immunosuppression secondary to immunosuppressive medicines and acquired immunosuppression secondary to HIV infection.[45][46]

xeroderma pigmentosum

Genetic syndrome with skin cancer predisposition.[47]

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