Clinical Presentation & Diagnosis

1. The ABCDE Rule

The ABCDE mnemonic, introduced by Friedman et al. (CA 1985) as ABCD and extended to ABCDE (Abbasi et al., JAMA 2004), remains the lay and primary- care backbone for early melanoma recognition:

Sensitivity of ABCDE in trained primary-care: ~80–90%; specificity ~70–80%. Children, nodular melanoma, and amelanotic melanoma routinely fail the ABCDE test, motivating supplementary signs.

2. The Ugly-Duckling Sign

An adult’s nevi tend to share a personal “signature” — most benign moles look broadly similar to each other on a given individual. The ugly-duckling sign (Grob & Bonerandi, Arch Dermatol 1998) flags a lesion that looks different from the individual’s other moles, even if it does not fail ABCDE in isolation.

The ugly-duckling sign is especially powerful in patients with many nevi: rather than examining each lesion in isolation, the clinician scans the whole field for an outlier. Combined sensitivity of ABCDE + ugly-duckling for melanoma in expert hands ~95% in screened populations.

Other supplementary mnemonics: EFG (Elevated, Firm, Growing — for nodular melanoma); the Glasgow 7-point checklist (3 major + 4 minor features).

3. Superficial Spreading Melanoma (SSM)

The commonest subtype in fair-skinned populations (\( \sim 60\%\) of cutaneous melanomas):

• Sites: trunk in men, lower limbs in women.
• Age: peak 40s–50s.
• Phase: long radial-growth phase (in-situ or microinvasive) measured in years before transition to vertical growth.
• Histology: pagetoid (single-cell upward) spread of atypical melanocytes through the epidermis.
• Genetics: classic BRAF V600E (~80%); intermittent intense UV exposure pattern.
• Clinical: asymmetric, variegated, slowly enlarging plaque; classically passes ABCDE.

SSM is the prototype that ABCDE was designed to recognise — flat or slightly raised, multicoloured, evolving over months. Catching it during the radial phase gives a 99% 10-year survival; missing it into vertical growth phase changes the trajectory entirely.

4. Nodular Melanoma (NM)

The second-commonest subtype (\( \sim 15\)–25%), with disproportionate mortality — nodular melanoma is responsible for nearly half of all melanoma deaths despite being a minority of cases.

• Phase: very short or absent radial phase — goes directly to vertical growth.
• Clinical: rapidly growing, often symmetric, often uniformly black or even amelanotic (skin-coloured); may bleed or ulcerate within weeks.
• EFG: Elevated, Firm, Growing — the supplementary mnemonic developed to catch what ABCDE misses.
• Sites: trunk and head/neck of men.
• Genetics: NRAS more common than in SSM; high mitotic rate.

Because nodular melanoma can pass ABCDE (a small symmetric uniformly-pigmented papule), public-health messaging has increasingly emphasised the “new growing lump” heuristic: any new firm papule that grows, especially in fair-skinned adults, deserves urgent specialist review.

5. Lentigo Maligna & Lentigo Maligna Melanoma

\( \sim 10\)–15% of cutaneous melanoma. The chronic-sun-damage subtype of older adults:

• Sites: face (especially cheek and temple) and other heavily sun-damaged head/neck skin.
• Age: typically >60.
• Lentigo maligna (LM) = melanoma in situ on chronically sun-damaged skin; lentigo maligna melanoma (LMM) = invasive.
• Phase: very long radial phase, sometimes a decade or more; vertical-phase transition triggers diagnosis.
• Clinical: slowly enlarging tan-brown irregular macule; difficult to distinguish from solar lentigo and pigmented actinic keratosis without dermoscopy and biopsy.
• Genetics: NF1 and NRAS more common; BRAF V600 less common; high TMB.

Surgical management is challenging because of subclinical extension at the dermal- epidermal junction; staged excision (“slow Mohs”), Mohs micrographic surgery, or radiation are options on the face for cosmetic preservation. Imiquimod has an off-label role for non-surgical patients with LM in situ.

6. Acral Lentiginous Melanoma (ALM)

The dominant subtype in non-fair-skinned populations — in East Asia and Sub- Saharan Africa it accounts for >50% of melanoma. In fair-skinned populations it represents only ~5% but is often diagnosed late.

• Sites: palms, soles (esp. heel and great-toe ball), nail apparatus.
• Subungual ALM: Hutchinson’s sign — pigmentation of the proximal nail fold extending from a longitudinal melanonychia — is highly suggestive of subungual melanoma.
• Phase: prolonged radial phase, often misdiagnosed as a bruise, tinea, or wart, leading to delayed diagnosis.
• Genetics: KIT (~15%), BRAF (~15%), structural rearrangements common; SBS7/UV signature largely absent — a non-UV biology.
• CARP rule: Coloured nail-streak that is Asymmetric, Rapidly changing, in a Patient >30 with no prior trauma history.

Bob Marley died of ALM under the great-toe nail (then misdiagnosed as a soccer injury) at age 36 — a high-profile reminder that melanoma is not exclusively a disease of UV-exposed skin in white populations.

7. Differential Diagnosis of Pigmented Lesions

The clinical task is rarely “is this melanoma vs nothing”: it is “is this melanoma vs. several common, very-prevalent, generally benign mimics”.

When in doubt: excisional biopsy with narrow (1–3 mm) margins is the gold standard, providing the entire lesion to the pathologist for full thickness assessment. Shave biopsy is acceptable only if deeper than the suspected pathology; punch biopsy of part of a lesion can under-represent the worst area and mis-stage.

8. Dermoscopy — the 7-Point Checklist

Dermoscopy (epiluminescence microscopy) uses a hand-held magnifier with polarised light to visualise pigment and vessel patterns invisible to the naked eye. In trained hands it boosts sensitivity ~10–25% and specificity ~10% over naked-eye inspection (Vestergaard et al., BJD 2008).

The Argenziano 7-point checklist (Argenziano et al., Arch Dermatol 1998) is one of several validated algorithms:

Total score ≥3 prompts excisional biopsy. Sensitivity ~95%, specificity ~75%.

Other algorithms include pattern analysis (Argenziano), the 3-point checklist (asymmetry, atypical network, blue-white structures — for non-experts), the Menzies method, and the CASH algorithm.

9. Reflectance Confocal Microscopy & AI

Reflectance confocal microscopy (RCM) uses 830 nm near-infrared light to image the epidermis and superficial dermis at near-histological (~1 μm) resolution in vivo:

• Resolves single melanocytes, distinguishing pagetoid spread (melanoma) from regular nests (nevus).
• Sensitivity ~93%, specificity ~78% for melanoma diagnosis when combined with dermoscopy.
• Particularly useful for facial lesions (LM vs. solar lentigo vs. pigmented AK) where surgical biopsy is cosmetically costly.
• Reduces benign-to-malignant biopsy ratio from ~15:1 (clinical alone) toward ~5:1 (combined).

Optical coherence tomography (OCT) and line-field OCT (LC-OCT) extend imaging deeper at coarser resolution and are increasingly used to assess Breslow thickness preoperatively.

Convolutional-neural-network skin-lesion classifiers have approached or exceeded dermatologist-level performance in single-image diagnostic tasks (Esteva et al., Nature 2017; Tschandl et al., Nat Med 2020). In real-world deployment, however, the tools perform best as decision-support for primary care — not replacement of dermatologic exam — because of selection bias in training data and limited generalisation across phototype.