Malignancy of melanocytes; deadliest common skin cancer; early detection by ABCDE criteria saves lives.
Also known as: melanoma, malignant melanoma, superficial spreading melanoma, nodular melanoma, lentigo maligna, acral lentiginous melanoma
Overview
A malignancy arising from melanocytes (most commonly cutaneous, but also ocular, mucosal). Early-stage disease is curable by excision; metastatic disease has been transformed by immune checkpoint inhibitors and targeted therapy.
Epidemiology
Incidence rose for decades; ACS estimates ~112,000 new US invasive melanomas in 2026, plus roughly as many in situ. Average age at diagnosis ~67. ~8,500 US deaths annually. Lifetime risk ~1 in 33 for whites, 1 in 1000 for Black Americans (though acral and mucosal melanoma more common). One of the most common cancers in young adults, especially women; incidence in adolescents and young adults has declined since the mid-2000s while rising in older adults.
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Question 1DermatologyMedium
A 22-year-old man presents with a pigmented lesion on his back that he reports has enlarged over the past 3 months. On examination the lesion measures 8 mm, is asymmetric, and has irregular borders with several shades of brown and black. There is no ulceration or bleeding. Which of the following is the most appropriate next step in management?
AWide local excision with 1-cm margins
BExcisional biopsy with narrow margins
CShave biopsy of the visible lesion
DClinical observation for 12 months
EDermoscopic surveillance of the lesion
Reveal answer & full explanation
Correct answer: B — Excisional biopsy with narrow margins
AWide local excision with 1-cm margins
BExcisional biopsy with narrow margins✓
CShave biopsy of the visible lesion
DClinical observation for 12 months
EDermoscopic surveillance of the lesion
Why Excisional biopsy with narrow margins is correct
The lesion meets every ABCDE warning sign for melanoma: Asymmetry, Border irregularity, Color variegation, Diameter greater than 6 mm (8 mm), and Evolution over 3 months
A suspicious pigmented lesion requires tissue diagnosis, and excisional (full-thickness) biopsy with 1-2 mm margins captures the entire lesion
Removing the full depth allows accurate Breslow thickness measurement, which drives staging and surgical re-excision margins
Definitive wide local excision and consideration of sentinel node biopsy follow only after the diagnosis and depth are established
Why the others are wrong
Dermoscopic surveillance of the lesion — imaging alone cannot provide a histologic diagnosis once ABCDE criteria are met, so it inappropriately delays tissue sampling (premature closure)
Clinical observation for 12 months — watchful waiting risks progression of a lesion that is already evolving and high-risk (right-concern-wrong-action)
Shave biopsy of the visible lesion — may transect the base and underestimate Breslow depth, compromising staging of a suspected melanoma (right-procedure-wrong-technique)
Wide local excision with 1-cm margins — jumps to definitive surgery before a diagnosis exists; re-excision margins are chosen from the Breslow depth on the diagnostic biopsy, and wide excision first can disrupt the lymphatic drainage needed for accurate sentinel node mapping (right-treatment-wrong-time)
Question 2DermatologyMedium
A 45-year-old woman with fair skin presents with an asymmetric pigmented lesion on her back, 9 mm in diameter, with irregular borders and multiple colors (brown, black, and pink). It has been changing over 6 months. Dermoscopy shows an atypical pigment network. What is the next step?
ASentinel lymph node biopsy
BShave biopsy of the lesion
CExcisional biopsy with narrow margins
DPunch biopsy of the darkest area
EWide local excision with 1 cm margins
Reveal answer & full explanation
Correct answer: C — Excisional biopsy with narrow margins
ASentinel lymph node biopsy
BShave biopsy of the lesion
CExcisional biopsy with narrow margins✓
DPunch biopsy of the darkest area
EWide local excision with 1 cm margins
Why Excisional biopsy with narrow margins is correct
This lesion meets all ABCDE criteria: asymmetry, irregular borders, multiple colors (brown, black, pink), diameter above 6 mm (9 mm), and evolving over 6 months; an atypical pigment network on dermoscopy adds to the suspicion for melanoma
A narrow excisional biopsy with 1-3 mm clinical margins removes the entire lesion for histologic assessment and preserves the full Breslow depth needed for staging (AAD 2019, NCCN)
Breslow depth and ulceration on the biopsy then set the definitive wide-excision margins and determine whether sentinel lymph node biopsy is offered
Why the others are wrong
Wide local excision with 1 cm margins — definitive margins are chosen only after biopsy confirms melanoma and measures Breslow depth; excising widely before diagnosis can over- or under-treat the lesion and can disrupt the lymphatic drainage needed for accurate sentinel lymph node mapping
Shave biopsy of the lesion — a shave can transect the base of the lesion, so Breslow depth may be underestimated and staging compromised
Punch biopsy of the darkest area — samples only part of a 9 mm lesion and can miss the thickest or most atypical focus (sampling error); partial biopsy is reserved for very large lesions or sites such as the face or acral skin
Sentinel lymph node biopsy — nodal staging matters in melanoma, but sentinel lymph node biopsy is offered only after a biopsy has confirmed melanoma and reported Breslow depth and ulceration; performing it before the primary lesion is diagnosed skips the diagnostic step entirely
Additional high-yield points
Wide local excision margins after biopsy are based on Breslow depth: in situ = 0.5-1 cm; 1 mm or less = 1 cm; more than 1 mm to 2 mm = 1-2 cm; more than 2 mm = 2 cm
Sentinel lymph node biopsy is considered for melanomas thicker than 0.8 mm or with ulceration
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Relative strength: a personal history of melanoma and a high nevus count (>100) or multiple atypical nevi are the strongest predictors (roughly 6-10 times baseline risk); red hair (~3.5x), fair skin, blistering sunburns (~2x) and a single affected relative (~1.7x) are weaker. Intermittent intense UV with blistering sunburns is the strongest environmental factor.
Pathophysiology
UV-induced DNA damage drives MAPK pathway activation. Common driver mutations: BRAF V600E/K (~50%), NRAS (~20%), NF1 (~15%), KIT (acral/mucosal/CSD). PTEN, TP53, CDKN2A loss contribute. Tumor mutational burden among highest of all cancers, supporting immunotherapy response.
Most patient-detected — emphasize self-examination and 'ugly duckling' sign
Signs / physical exam
ABCDE criteria: Asymmetry, Border irregularity, Color variegation, Diameter >6 mm, Evolution (change over time)
'Ugly duckling sign': a pigmented lesion that looks different from a patient's other nevi
Subtypes:
• Superficial spreading melanoma (SSM, ~70%): variable color/shape, radial growth phase years, then vertical growth; trunk (men), legs (women)
• Nodular melanoma (~15%): dark blue-black or amelanotic pink nodule, rapidly growing, often ulcerated; vertical growth from outset
• Lentigo maligna / lentigo maligna melanoma (~10%): slow-growing irregular tan-brown patch on chronically sun-damaged skin of older adults; face/scalp
• Acral lentiginous melanoma (~5%, but predominant subtype in skin of color and Asians): palms, soles, subungual (look for Hutchinson sign — pigment extending onto nail fold from nail matrix)
Spitz nevus — Pink dome-shaped papule in children/young adults; can mimic melanoma — refer for expert review
Diagnostic workup
Diagnostic criteria
Histopathology + AJCC 8th edition staging: Breslow depth and ulceration (T), nodal status (N), distant metastases and LDH (M). Mitotic rate is still reported but is no longer used for T staging. Breslow depth is the single most important prognostic factor for clinically localized melanoma; Clark level is no longer part of staging.
Labs
EXCISIONAL biopsy with 1-3 mm margins down to subcutaneous fat is the diagnostic standard (preserves architectural assessment for Breslow depth)
Shave biopsy may transect deep margin and underestimate depth — avoid if melanoma strongly suspected
BRAF mutation testing for clinical stage IIC and higher (drives targeted therapy decisions); also NRAS, KIT, TERT in select cases
LDH baseline (stage IV prognostic)
CBC, CMP, LDH for advanced disease
Imaging
Stage IA-IIA: typically no imaging if asymptomatic
Stage IIB-IIC: imaging generally only to evaluate specific signs or symptoms (CT or PET/CT may be considered); routine chest X-ray is no longer recommended
Stage III-IV: baseline CT chest/abdomen/pelvis and/or PET/CT plus brain MRI (optional when stage IIIA disease is found only on sentinel node biopsy)
Sentinel lymph node biopsy considered for Breslow ≥0.8 mm or any thickness with ulceration or other high-risk features
Diagnostic algorithm
ABCDE Feature
Concerning Finding
A — Asymmetry
Lesion halves do not mirror each other
B — Border
Irregular, scalloped, or notched borders
C — Color
Variation (brown, black, red, white, blue) within lesion
D — Diameter
Larger than 6 mm (pencil eraser); smaller does not rule out
E — Evolution
Change in size, shape, color, symptoms over weeks-months
Ugly duckling
Lesion that looks unlike patient's other nevi
ABCDE criteria for melanoma screening.
Treatment
First-line
Wide local excision based on Breslow depth (AAD/NCCN):
• In situ — 5-10 mm margins
• ≤1.0 mm — 1 cm margins
• 1.01-2.0 mm — 1-2 cm margins
• >2.0 mm — 2 cm margins
Sentinel lymph node biopsy for stages T1b (≥0.8 mm or ulcerated) through T4; if the sentinel node is positive, completion lymph node dissection is no longer routine (MSLT-II, DeCOG-SLT: no melanoma-specific survival benefit), so use nodal ultrasound surveillance plus adjuvant systemic therapy
Mohs micrographic surgery for lentigo maligna and selected facial/acral melanomas (specialized centers)
Adjuvant therapy after resection (stage IIB/IIC and stage III):
• Anti-PD-1 (pembrolizumab or nivolumab) × 1 year for most patients, and the only approved adjuvant therapy for stage IIB/IIC (KEYNOTE-716, CheckMate 76K); adjuvant interferon and ipilimumab are no longer preferred
• Targeted therapy for resected stage III BRAF V600E/K-mutant melanoma only: dabrafenib + trametinib × 1 year (COMBI-AD)
Surveillance after curative resection: skin exam every 3-12 months depending on stage; total body photography for high-risk patients
Stage IV (metastatic) melanoma
First-line immunotherapy:
• Anti-PD-1 monotherapy (nivolumab or pembrolizumab) — favorable side-effect profile
• Combination anti-PD-1 + anti-CTLA-4 (nivolumab + ipilimumab) — higher response but more toxicity
Targeted therapy for BRAF V600 mutant: dabrafenib + trametinib, encorafenib + binimetinib, vemurafenib + cobimetinib (generally used as an alternative to immunotherapy rather than combined with it; starting with immunotherapy is generally preferred, DREAMseq)
Tumor-infiltrating lymphocyte therapy (lifileucel) — newer option for refractory disease
Stereotactic radiosurgery for brain metastases
Talimogene laherparepvec (T-VEC) — oncolytic HSV-1 for unresectable cutaneous/nodal disease
Lentigo maligna (in situ on face/scalp)
Mohs or staged excision (preferred at specialized centers)
Topical imiquimod 5% cream — alternative for non-surgical candidates
Radiation as alternative
Second-line / adjunct
Annual to biannual total body skin examination + self-skin exams monthly
Genetic counseling for familial cases (CDKN2A) and offer cascade testing
Sun protection: SPF 30+ daily, sun-protective clothing, hat, shade, avoid tanning beds
USPSTF 2023: insufficient evidence for routine population screening, but high-risk patients benefit from dermatology surveillance
Immune-related adverse events from immunotherapy: thyroiditis, hypophysitis, colitis, hepatitis, pneumonitis, dermatitis, type 1 diabetes — can be life-threatening; permanent endocrine dysfunction common
Psychological distress, depression, fear of recurrence
Lymphedema after lymph node dissection
PANCE pearls
ABCDE + ugly duckling: any one feature alone is non-specific, but combinations and change over time are highly suspicious.
Excisional biopsy (1-3 mm margins, down to fat) is the diagnostic standard — shave biopsy may transect and obscure depth.
Hutchinson sign (periungual pigment extension onto nail fold) is highly suspicious for subungual melanoma. Red flags in longitudinal melanonychia: a single digit (thumb, great toe), band ≥3 mm, widening or darkening, irregular color or lines, adult onset. Biopsy the nail MATRIX, where the pigment is made, not the nail bed.
Acral melanoma is the most common subtype in skin of color — check palms, soles, and nails routinely.
Anti-PD-1 immunotherapy has transformed metastatic melanoma — survival has shifted from <1 year to >50% 5-year survival in many series.
References
NCCN 2024 — NCCN Clinical Practice Guidelines in Oncology — Cutaneous Melanoma (Version 2.2024)
AAD 2019 — Guidelines of Care for the Management of Primary Cutaneous Melanoma (Swetter et al., J Am Acad Dermatol 2019)
AJCC 8th Edition — American Joint Committee on Cancer Staging Manual — Cutaneous Melanoma (Gershenwald et al., CA Cancer J Clin 2017)
USPSTF 2023 — USPSTF Recommendation: Screening for Skin Cancer (JAMA 2023)
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