Dermatology · PANCE / PANRE

Melanoma

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

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 rising for decades — ~100,000 new US invasive cases annually + ~100,000 in situ. Median age at diagnosis ~65. ~7,000 US deaths annually. Lifetime risk ~1 in 30 for whites, 1 in 1000 for Black Americans (though acral and mucosal melanoma more common). Fastest growing cancer in adolescents and young adults.

Try two board-style Melanoma questions

Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.

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?
  • ADermoscopic surveillance of the lesion
  • BExcisional biopsy with narrow margins
  • CClinical observation for 12 months
  • DShave biopsy of the visible lesion
Reveal answer & full explanation
Correct answer: B — Excisional biopsy with narrow margins
  • ADermoscopic surveillance of the lesion
  • BExcisional biopsy with narrow margins✓
  • CClinical observation for 12 months
  • DShave biopsy of the visible 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)
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?
  • ATopical hydroquinone application
  • BExcisional biopsy with narrow margins
  • CShave biopsy of the lesion
  • DPunch biopsy of the darkest area
Reveal answer & full explanation
Correct answer: B — Excisional biopsy with narrow margins
  • ATopical hydroquinone application
  • BExcisional biopsy with narrow margins✓
  • CShave biopsy of the lesion
  • DPunch biopsy of the darkest area

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
  • Excisional biopsy with 1-2 mm clinical margins is required to preserve the full Breslow depth needed for staging and prognosis
  • Excisional biopsy provides complete histologic assessment of the entire lesion

Why the others are wrong

  • C) Shave biopsy — destroys the depth measurement, making accurate Breslow staging impossible
  • D) Punch biopsy of the darkest area — introduces sampling error by only sampling one area of the lesion
  • A) Topical hydroquinone application — topical treatments do not address malignancy risk
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Risk factors

  • UV exposure, especially intermittent intense (blistering sunburns); tanning bed use (risk increases 75% if first use before age 35)
  • Fair skin (Fitzpatrick I-II), light/red hair, blue/green eyes, freckles
  • Personal history of melanoma (~5% develop second primary)
  • Family history of melanoma in ≥2 first-degree relatives (CDKN2A, CDK4, BAP1 germline mutations)
  • Multiple (>50) common nevi or any atypical/dysplastic nevi
  • Giant congenital nevus (>20 cm) — ~5% lifetime melanoma risk
  • Immunosuppression
  • Xeroderma pigmentosum, FAMMM syndrome

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.

Clinical presentation

Symptoms

  • New or changing pigmented lesion (ABCDE criteria)
  • Pruritus, bleeding, tenderness, ulceration (later signs)
  • 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)
  • • Mucosal, ocular, desmoplastic, amelanotic variants

Classic findings

ABCDE positive pigmented lesion + ugly duckling; for acral/subungual — Hutchinson sign (periungual pigment extension).

Differential diagnosis

  • Atypical (dysplastic) nevus — Asymmetric, irregular border, varied color, but stable; biopsy if changing
  • Seborrheic keratosis — Waxy 'stuck-on' appearance, sharply demarcated; dermoscopy shows milia-like cysts, comedo-like openings
  • Pigmented BCC — Pearly rolled border, telangiectasias, blue-gray pigment globules
  • Solar lentigo — Uniformly tan-brown macule on sun-damaged skin; stable
  • Blue nevus — Uniform blue-black papule; stable
  • Subungual hematoma (vs acral melanoma) — Trauma history, grows out with nail, no Hutchinson sign
  • Pyogenic granuloma (amelanotic melanoma DDx) — Rapidly growing red friable papule; biopsy
  • 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 based on Breslow depth, ulceration, mitotic rate (T), nodal status (N), distant metastases and LDH (M).

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
  • Histopathology: report Breslow depth (mm), ulceration, mitotic rate, regression, lymphovascular invasion, microsatellites, margin status
  • 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-IIIA: consider chest X-ray, CT chest/abdomen/pelvis; brain MRI for stage IIIC+
  • PET/CT for stage IIIB and higher; brain MRI for stage III/IV
  • Sentinel lymph node biopsy considered for Breslow ≥0.8 mm or any thickness with ulceration or other high-risk features

Diagnostic algorithm

ABCDE FeatureConcerning Finding
A — AsymmetryLesion halves do not mirror each other
B — BorderIrregular, scalloped, or notched borders
C — ColorVariation (brown, black, red, white, blue) within lesion
D — DiameterLarger than 6 mm (pencil eraser); smaller does not rule out
E — EvolutionChange in size, shape, color, symptoms over weeks-months
Ugly ducklingLesion 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
  • Mohs micrographic surgery for lentigo maligna and selected facial/acral melanomas (specialized centers)
  • Adjuvant therapy for resected stage III and high-risk stage IIB/IIC:
  • • Anti-PD-1 (pembrolizumab or nivolumab) × 1 year (most patients)
  • • Targeted therapy for BRAF V600E/K mutant: dabrafenib + trametinib × 1 year
  • 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
  • • Anti-PD-1 + anti-LAG-3 (nivolumab + relatlimab) — newer combination
  • Targeted therapy for BRAF V600 mutant: dabrafenib + trametinib, encorafenib + binimetinib, vemurafenib + cobimetinib
  • 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

Complications

  • Regional and distant metastasis — lymph nodes (most common), lung, liver, brain, bone, intestine
  • Locoregional recurrence (satellite/in-transit metastases)
  • Immune-related adverse events from immunotherapy: thyroiditis, hypophysitis, colitis, hepatitis, pneumonitis, dermatitis, type 1 diabetes — can be life-threatening; permanent endocrine dysfunction common
  • Targeted therapy adverse effects: pyrexia, photosensitivity, secondary cutaneous SCC (with single-agent BRAFi — combination therapy reduces risk)
  • 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 — biopsy required.
  • 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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Commonly confused with

vs Basal Cell Carcinoma

Related Dermatology diagnoses

Acne VulgarisRosaceaAtopic Dermatitis (Eczema)Allergic and Irritant Contact DermatitisSeborrheic DermatitisPsoriasisLichen PlanusPityriasis RoseaTinea Infections (corporis, capitis, pedis, cruris, versicolor)Cutaneous CandidiasisScabiesPediculosisImpetigoHerpes Zoster (Shingles)

Differentials & related conditions

Pyogenic Granuloma

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