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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Melanoma is the deadliest common skin cancer because it metastasizes early through lymphatic and hematogenous spread
- Use ABCDE: Asymmetry, Border irregularity, Color variation, Diameter >6 mm, Evolving lesion; ugly duckling sign is highly testable
- Best initial diagnostic step for suspicious pigmented lesion: narrow-margin excisional biopsy down to subcutaneous fat
- Most important prognostic factor: Breslow thickness; ulceration and mitotic rate add risk
- Definitive treatment is wide local excision with margins based on Breslow depth; consider sentinel lymph node biopsy for tumors >=0.8 mm or ulcerated
Overview
Melanoma is a malignant tumor of melanocytes. It may arise de novo or from a pre-existing nevus and is clinically important because prognosis depends strongly on early recognition and depth at the time of excision. The major subtypes are superficial spreading melanoma (most common), nodular melanoma (rapid vertical growth and worse prognosis), lentigo maligna melanoma (chronically sun-damaged face of older adults), and acral lentiginous melanoma (palms, soles, nail apparatus; more common melanoma subtype in darker skin). Step 2 CK questions often test the diagnostic sequence: identify a changing pigmented lesion, perform excisional biopsy, then manage based on Breslow depth rather than shaving, freezing, or observing.
Epidemiology
Melanoma incidence has increased over recent decades in the United States. Risk factors include intermittent intense UV exposure and blistering sunburns, indoor tanning, fair skin, red or blond hair, light eye color, numerous or atypical nevi, family history, immunosuppression, xeroderma pigmentosum, and inherited CDKN2A variants. Although melanoma is less common than basal cell carcinoma or squamous cell carcinoma, it accounts for a disproportionate share of skin-cancer deaths. Acral lentiginous melanoma is not strongly linked to sun exposure and may be diagnosed late because lesions occur on soles, palms, or under nails.
Clinical Features
Symptoms
New or changing mole, especially one that is asymmetric or different from the patient's other nevi
ABCDE features: asymmetry, irregular border, multiple colors, diameter >6 mm, evolving size/shape/color
Bleeding, crusting, ulceration, itching, tenderness, or rapid growth
Dark longitudinal nail streak with pigment extending onto proximal nail fold (Hutchinson sign)
Nodular melanoma may be symmetric and uniformly dark but elevated, firm, and growing rapidly
Signs
Irregularly pigmented macule or papule with variegated tan, brown, black, blue, red, or white color
Ugly duckling lesion: one pigmented lesion looks different from the patient's background mole pattern
Palpable regional lymphadenopathy suggests nodal involvement
Acral lesion on sole, palm, or subungual area, especially if enlarging
Amelanotic melanoma may appear pink or red rather than brown/black
Investigations
First-line
Full-skin examinationAssess entire skin surface, mucosa when indicated, nail units, and regional lymph nodes. Compare with other nevi for ugly duckling pattern
Narrow-margin excisional biopsyPreferred diagnostic test: remove entire lesion with 1-3 mm margins and depth to subcutaneous fat. Provides Breslow thickness, ulceration, and mitotic information
HistopathologyReports subtype, Breslow thickness, ulceration, mitotic rate, margins, lymphovascular invasion, and regression when present
Second-line
Sentinel lymph node biopsy assessmentDiscuss for melanoma >=0.8 mm, ulcerated thin melanoma, or other high-risk features. It stages nodal basin and guides adjuvant therapy decisions
DermatoscopyUseful expert adjunct but does not replace biopsy when melanoma is suspected
Specialist
Cross-sectional staging imagingCT/PET-CT and brain MRI for clinically node-positive, stage III, stage IV, or symptomatic disease; not routine for very low-risk localized melanoma
Molecular testingBRAF mutation testing for advanced or metastatic melanoma to guide targeted therapy
1
Initial lesion management
- Do not reassure or observe a suspicious evolving pigmented lesion
- Perform narrow-margin excisional biopsy when feasible; avoid superficial shave if melanoma is suspected because it may underestimate Breslow depth
- If lesion is large or anatomically difficult (face, acral, nail), perform deep saucerization, punch/incisional biopsy of the most suspicious area, or refer urgently to dermatology/surgical oncology
2
Definitive local treatment
- Melanoma in situ: wide local excision, often 0.5-1 cm margins; staged excision or Mohs may be considered for lentigo maligna on cosmetically sensitive sites
- Invasive melanoma <=1 mm: wide excision usually 1 cm margin
- Breslow 1-2 mm: wide excision 1-2 cm margin
- Breslow >2 mm: wide excision 2 cm margin when anatomically feasible
- Sentinel lymph node biopsy generally discussed for >=0.8 mm or ulcerated tumors; positive node upstages disease
3
Regional or metastatic disease
- Node-positive disease: multidisciplinary management with surgical oncology, medical oncology, and dermatology
- Adjuvant immunotherapy: PD-1 inhibitors such as pembrolizumab or nivolumab for selected resected high-risk disease
- BRAF V600-mutant advanced melanoma: BRAF inhibitor plus MEK inhibitor is an option
- Unresectable/metastatic disease: immune checkpoint therapy, targeted therapy if BRAF-mutant, radiation for selected symptomatic metastases
4
Prevention and follow-up
- Sun protection: broad-spectrum sunscreen, protective clothing, shade, avoid indoor tanning
- Patient self-skin examination and clinician total body skin examination at risk-based intervals
- First-degree relatives may require skin surveillance, especially with familial atypical mole melanoma pattern
- Educate on new, changing, bleeding, or ugly duckling lesions
Complications
- Regional nodal metastasis: Sentinel node involvement changes staging and adjuvant treatment decisions
- Distant metastasis: Lung, liver, brain, bone, and skin/subcutaneous metastases are classic sites
- Local recurrence: Risk increases with inadequate excision margins or aggressive histology
- Second primary melanoma: Patients remain at increased risk and need ongoing surveillance
- Treatment toxicity: Checkpoint inhibitors can cause immune-mediated dermatitis, colitis, hepatitis, endocrinopathy, and pneumonitis
USMLE Step 2 CK Exam Tips
- 1Suspicious pigmented lesion = excisional biopsy. Do not choose cryotherapy, topical steroid, or watchful waiting
- 2Most important prognostic factor = Breslow thickness, not diameter or color
- 3ABCDE and ugly duckling sign are classic stems; evolving lesion is the most important ABCDE feature
- 4Nodular melanoma can violate ABCDE rules: elevated, firm, growing rapidly
- 5Acral lentiginous melanoma: enlarging pigmented lesion on sole/palm/nail; know Hutchinson sign
- 6Melanoma in situ is confined to epidermis; invasive melanoma needs Breslow-based excision margins
- 7Sentinel node biopsy is for staging clinically node-negative higher-risk melanoma, not for treating the primary lesion
- 8Avoid superficial shave biopsy when melanoma is strongly suspected because it may transect the lesion and underestimate depth
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