Skin Cancer (Clinical)
Pearly, scaly, or changing: the three skin cancers and how to stage them
Risk factors and actinic keratosis
UV is the main driver. Cumulative UV exposure is the dominant cause of skin cancer; UVB damages DNA directly by forming pyrimidine dimers. Risk is amplified by fair skin (Fitzpatrick types I–II), immunosuppression, ionizing radiation, arsenic, and chronic wounds or scars. Nonmelanoma (keratinocyte) skin cancers are the most common malignancies overall.
Immunosuppression favors SCC. Organ transplant recipients skew toward squamous cell carcinoma, reversing the usual BCC-predominant ratio, and their tumors behave more aggressively.
Marjolin ulcer: squamous cell carcinoma arising in a chronic non-healing ulcer or old burn scar. A long-standing wound that changes, grows, or stops healing needs a biopsy.
Actinic keratosis (AK). The precursor of squamous cell carcinoma: a rough, scaly, sandpaper-like erythematous papule on sun-damaged skin (face, scalp, dorsal hands), often easier to feel than to see. Only a small percentage progress, but AKs mark field damage. Treat isolated lesions with cryotherapy and field disease with topical 5-fluorouracil, imiquimod, or photodynamic therapy.
Seborrheic keratoses are benign, waxy, "stuck-on" papules with no malignant potential. A sudden eruption of many (Leser-Trélat sign) suggests an internal malignancy, classically gastric adenocarcinoma.
Keratinocyte cancers: BCC, SCC, and keratoacanthoma
| Feature | Basal cell carcinoma | Squamous cell carcinoma | Keratoacanthoma |
|---|---|---|---|
| Frequency | Most common human cancer | Second most common skin cancer | Considered an SCC variant |
| Look | Pearly or waxy papule, rolled borders, telangiectasias, central ulceration (rodent ulcer) | Firm, hyperkeratotic or ulcerated non-healing nodule | Dome-shaped nodule with a central keratin-filled crater |
| Classic site | Sun-exposed face (upper lip) | Sun-exposed skin, ear, lower lip | Sun-exposed skin |
| Risk clues | UV; hedgehog pathway (PTCH1) | AK precursor, immunosuppression, Marjolin ulcer | Grows over weeks |
| Behavior | Locally invasive; rarely metastasizes | Metastasizes more than BCC, especially from ear or lip and in the immunosuppressed | May regress spontaneously |
| Histology | Basaloid nests with peripheral palisading | Keratin pearls, atypical keratinocytes | Well-differentiated squamous proliferation |
SCC in situ (Bowen disease) is a well-demarcated, scaly, erythematous plaque; it is treated like a superficial SCC.
Basal cell nevus (Gorlin) syndrome is a germline PTCH1 defect: many BCCs at a young age, jaw keratocysts, and palmar pits.
Treatment. Excision treats most BCCs and SCCs. Mohs micrographic surgery examines margins intraoperatively and gives the highest cure rate with maximal tissue sparing, so it is preferred for the face and other cosmetically sensitive sites, recurrent tumors, and high-risk lesions. Superficial lesions may respond to topical 5-fluorouracil or imiquimod, and advanced BCC responds to hedgehog inhibitors (vismodegib).
Melanoma: recognition and biopsy
ABCDE plus the ugly duckling. Screen pigmented lesions for Asymmetry, Border irregularity, Color variegation, Diameter over 6 mm, and Evolution (change in size, shape, color, or symptoms). A mole that looks different from the patient's other moles (ugly-duckling sign) is suspicious even when it does not meet ABCDE criteria. Risk factors: UV exposure, fair skin, many atypical nevi, family history, and CDKN2A mutations.
- Suspicious lesionABCDE or ugly-duckling sign.
- Excisional biopsyFull-thickness with narrow margins; never a shave, which cuts through the tumor and destroys the depth measurement.
- Breslow depthMeasured on the biopsy; the key prognostic factor.
- Sentinel node if indicatedConsider at 0.8 to 1 mm (or under 0.8 mm with ulceration); recommended for tumors over 1 mm.
| Subtype | Typical patient and site | Behavior |
|---|---|---|
| Superficial spreading | Most common overall; sun-exposed trunk and limbs | Prolonged radial (horizontal) growth before invasion |
| Nodular | Rapidly enlarging dark nodule | Most aggressive; early vertical growth |
| Lentigo maligna | Elderly; chronically sun-damaged face | Slow; best prognosis |
| Acral lentiginous | Palms, soles, nail beds; most common subtype in darker-skinned patients | Not UV-related; often found late |
A pigmented band under a nail with pigment spreading onto the proximal nail fold (Hutchinson sign) suggests subungual acral lentiginous melanoma and needs a biopsy.
Melanoma: prognosis, staging, and treatment
Breslow depth rules prognosis. Tumor thickness in millimeters is the single most important prognostic factor in localized melanoma; deeper tumors do worse, and ulceration and mitotic rate add risk. The older anatomic Clark level is now little used, and lesion diameter and color carry little prognostic weight.
Sentinel lymph node biopsy stages the regional nodal basin. A positive node worsens the stage and prognosis and guides further treatment, but the biopsy is a staging step, not a therapeutic one.
Definitive surgery. After the diagnostic biopsy, wide local excision removes the primary with margins scaled to Breslow depth.
| Breslow depth | Clinical margin |
|---|---|
| In situ | 0.5–1 cm |
| ≤1 mm | 1 cm |
| 1–2 mm | 1–2 cm |
| >2 mm | 2 cm |
AJCC staging uses T (Breslow thickness plus ulceration), N (nodes), and M (distant metastasis, with serum LDH). Melanoma often metastasizes to the brain.
Advanced or metastatic disease is treated with checkpoint inhibitors (the PD-1 inhibitors nivolumab and pembrolizumab, and the CTLA-4 inhibitor ipilimumab). Tumors with a BRAF V600E mutation can also be treated with combined BRAF/MEK inhibition (dabrafenib plus trametinib).
Dysplastic nevi and prevention
Dysplastic (atypical) nevi are irregular, larger (over 5–6 mm), variegated moles. They mark increased melanoma risk, particularly in familial atypical multiple mole melanoma (FAMMM) syndrome (CDKN2A), but most individual nevi never progress. Manage with surveillance, total-body photography, and excision of changing lesions, not prophylactic removal of every mole.
Sun protection.
- Broad-spectrum sunscreen (blocking UVA and UVB) with SPF 30 or higher, reapplied regularly and after swimming or sweating
- Sun-protective clothing, hats, and shade
- Avoiding peak sun, 10 am to 4 pm
- No tanning beds, which are a class I carcinogen
High-risk patients (many atypical nevi, prior skin cancer, family history, transplant recipients) need regular skin examinations, because early detection drives melanoma survival.