Skin Cancers: BCC, SCC & Melanoma
A high-yield Step 1/Step 2 CK dermatology lesson on the three major skin cancers, moving from UV-driven pathophysiology through classic morphology, biopsy choice, metastatic risk, and next-best-step management for BCC, SCC, and melanoma. Clinically reviewed: the draft was largely accurate; the only substantive fix corrects the melanoma growth line (radial/horizontal phase is low-risk but not synonymous with in situ), with minor precision edits (thymine-dimer wording, keratoacanthoma as well-differentiated SCC, HMB-45 specificity, BRAF prevalence). No fake mnemonics or invented facts were present. All three Wikimedia Commons images were verified to exist and match their captions.
Overview & Pathophysiology
Skin cancer is the most common malignancy in humans, driven overwhelmingly by UV radiation (UVB > UVA), which causes pyrimidine (thymine) dimer DNA damage and p53 mutation. Two lineages dominate the boards:
- Keratinocyte-derived (non-melanoma skin cancer, NMSC): basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Together the most common cancers overall — locally aggressive but rarely fatal.
- Melanocyte-derived: melanoma — far less common but responsible for the majority of skin-cancer deaths due to early metastatic potential.
Shared risk factors: fair skin (Fitzpatrick I–II), chronic sun exposure/tanning beds, older age, immunosuppression (especially solid-organ transplant, which sharply raises SCC risk), and inherited DNA-repair defects (xeroderma pigmentosum).
Exam tasks are consistent: recognize the classic lesion, choose the correct biopsy, know the metastatic risk, and pick first-line management for each tumor.
BCC — the most common human cancer
- Origin: basal keratinocytes; Hedgehog pathway activation from PTCH1 loss (or SMO gain).
- Syndrome: Gorlin (nevoid BCC) syndrome — germline PTCH1 → multiple BCCs, odontogenic keratocysts, palmar/plantar pits, medulloblastoma.
- Classic lesion: pearly/waxy papule with rolled (raised) borders, overlying telangiectasias, central ulceration = "rodent ulcer." May be pigmented.
- Distribution: sun-exposed face, especially the nose, and head/neck.
- Histology: nests of basaloid cells with peripheral palisading and stromal retraction (clefting) artifact.
- Behavior: locally invasive; metastasis is extremely rare.
- Management: surgical excision; Mohs micrographic surgery for face/high-risk sites. Superficial lesions → topical imiquimod or 5-FU. Advanced/metastatic → Hedgehog inhibitor vismodegib.
SCC — 2nd most common skin cancer
- Origin: malignant keratinocytes of the spinous layer.
- Risk (beyond UV): immunosuppression/organ transplant (SCC >> BCC in transplant patients), chronic wounds or burn scars (Marjolin ulcer), HPV, arsenic, and actinic keratosis — the key precursor.
- Precursor / in situ: actinic keratosis = rough, "sandpaper," scaly patch on sun-damaged skin; Bowen disease = SCC in situ (sharply demarcated erythematous scaly plaque).
- Classic lesion: firm, erythematous, scaly/hyperkeratotic or ulcerated nodule that bleeds; lower lip, ears, dorsal hands.
- Histology: keratin pearls, atypical keratinocytes with abundant eosinophilic cytoplasm and intercellular bridges.
- Keratoacanthoma: rapidly growing dome-shaped nodule with central keratin plug; well-differentiated SCC variant, still excised.
- Behavior: metastatic potential > BCC (higher for lip, ear, immunosuppressed).
- Management: excision / Mohs; treat AK with cryotherapy or topical 5-FU.
BCC vs SCC vs Melanoma
| Feature | BCC | SCC | Melanoma |
|---|---|---|---|
| Cell of origin | Basal keratinocyte | Spinous keratinocyte | Melanocyte |
| Frequency | Most common | 2nd most common | Less common, most lethal |
| Classic lesion | Pearly papule, rolled borders, telangiectasias, "rodent ulcer" | Scaly/ulcerated firm nodule that bleeds | Asymmetric pigmented lesion (ABCDE) |
| Precursor | — | Actinic keratosis / Bowen | Dysplastic nevus |
| Key site | Face (nose), upper lip | Lower lip, ears, dorsal hands | Back (men), legs (women); any |
| Histology | Basaloid nests, peripheral palisading, clefting | Keratin pearls, intercellular bridges | S-100/HMB-45/Melan-A + (IHC) |
| Metastasis | Very rare | Low–moderate | High (vertical growth) |
| Preferred biopsy | Shave/punch | Shave/punch | Excisional, full-thickness |
| First-line Rx | Excision / Mohs | Excision / Mohs | Wide local excision ± SLNB |
Melanoma — melanocyte-derived; drives most skin-cancer deaths
- Risk: intermittent intense/blistering sunburns, fair skin, dysplastic nevi, high nevus count, family history, CDKN2A mutation, immunosuppression, xeroderma pigmentosum. BRAF V600E mutation is common (~half of cutaneous melanomas) and targetable.
- Subtypes:
- Superficial spreading — most common; prolonged radial growth.
- Nodular — most aggressive; early vertical growth, no radial phase.
- Lentigo maligna — elderly, chronically sun-damaged face.
- Acral lentiginous — palms/soles/nail beds; most common subtype in darker-skinned patients; not UV-related.
- Growth: radial/horizontal growth phase (low metastatic risk; in situ or minimally invasive) → vertical growth phase = metastatic potential.
- Prognosis: Breslow depth (tumor thickness) is the single most important prognostic factor; ulceration and mitotic rate also matter (Clark level is older/less used).
- IHC markers: S-100 (most sensitive), HMB-45 (more specific), Melan-A/MART-1, SOX10.
- Management: wide local excision (margin set by Breslow depth) + sentinel lymph node biopsy for intermediate thickness; advanced → checkpoint inhibitors (anti-PD-1, anti-CTLA-4) and BRAF/MEK inhibitors if BRAF+.
ABCDE — the classic melanoma warning signs:
- Asymmetry
- Border irregularity (notched, ragged)
- Color variegation (multiple colors in one lesion)
- Diameter >6 mm
- Evolving (changing size, shape, or color; new symptoms)
Add the "ugly duckling sign" — the nevus that looks unlike all the patient's other moles. Any suspicious feature warrants excisional biopsy.
Stem: A 52-year-old fair-skinned man has a 1-cm pigmented lesion on his back that his wife says has grown and darkened over 4 months. Exam: an asymmetric brown-black lesion with irregular, notched borders and variegated color.
- Diagnosis: Melanoma (clinically) — ABCDE positive.
- Next best step: Excisional biopsy with narrow (1–3 mm) margins, full-thickness to fat — this permits accurate Breslow depth.
- Avoid: a shave biopsy of a suspected melanoma (may transect the base → depth cannot be measured), and do not perform primary wide excision before a tissue diagnosis.
- After diagnosis: definitive wide local excision (margin per Breslow depth) ± sentinel lymph node biopsy for tumors ≥0.8 mm or with high-risk features; staging imaging/systemic therapy for advanced disease.
Stem: A 70-year-old golfer has a slowly enlarging "pimple that won't heal" on the side of his nose for a year. Exam: a pearly, dome-shaped papule with rolled borders, fine telangiectasias, and a central crusted ulcer.
- Diagnosis: Basal cell carcinoma ("rodent ulcer").
- Next best step: Shave or punch biopsy to confirm — expect basaloid nests with peripheral palisading.
- Treatment: Mohs micrographic surgery is preferred for this high-risk facial site (maximal cure with tissue sparing).
- Contrast — SCC clue: a renal transplant patient with a rapidly growing, tender, hyperkeratotic/ulcerated nodule on the lip or dorsal hand → think SCC (immunosuppression dramatically raises SCC risk, with higher metastatic potential than BCC).
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