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BASICS

DESCRIPTION

Melanoma is a tumor arising from malignant transformation of melanocytes in the stratum basale of the epidermis.
- Most arise in the skin but can also present in ocular (uvea), GI, GU, lymph node, paranasal sinuses, nasal cavity, anorectal mucosa, leptomeninges.
- Extracutaneous sites have an adverse prognosis.
- Metastatic spread can occur to any body site.

Types of invasive cutaneous melanomas:

  • Superficial-spreading melanoma: ~70% cases; sun-exposed areas; most <1 mm thick; flat, slow-growing, irregular border; younger patients.
  • Nodular: 15-30% cases; older patients; ulcerate/hemorrhage; commonly thick and pigmented (>2 mm).
  • Lentigo maligna: melanoma in situ; slow growing; elderly; sun-exposed head/neck; invasive counterpart called lentigo maligna melanoma (LMM) (10-15% cases).
  • Acral lentiginous: <5%; most common melanoma in Black/Asian patients; palmar, plantar, subungual areas; may mimic warts, calluses.
  • Subtype: Subungual melanoma with Hutchinson nail sign (pigment extending to nail folds).
  • Amelanotic melanoma: <5%; mimics benign conditions; called “great pretender.”
  • Desmoplastic melanoma: ~1%; “neurotropic melanoma”; sarcoma-like; scar-like lesion; head/neck region.

Systems affected: Skin/exocrine

Geriatric Considerations

  • Lentigo maligna common on face in elderly; presents as circumscribed macular patch with mottled pigmentation.

Pediatric Considerations

  • Large congenital nevi (>5 cm) risk factor (>2% lifetime malignant conversion).
  • Blistering sunburns in childhood increase risk.

Pregnancy Considerations

  • No increased risk during pregnancy; wait 1-2 years post-treatment for pregnancy due to placental spread risk.

EPIDEMIOLOGY

  • 2023 estimated U.S. new cases: 97,610; deaths: 7,990.
  • Median diagnosis age: 66 years.
  • Sex: Male > Female (1.5x).
  • Melanoma >20 times more common in whites than African Americans.
  • Minority groups show increased metastasis, advanced stage at diagnosis, thicker lesions, earlier age, and poorer outcomes.
  • Fifth most common cancer in U.S.
  • Lifetime risk: men 1/28; women 1/34.
  • Accounts for 1.2% of all cancer deaths.

ETIOLOGY AND PATHOPHYSIOLOGY

  • DNA damage from UVA/UVB exposure.
  • Tumor progression: lateral growth (epidermis) → vertical growth.

Genetics

  • Dysplastic nevus syndrome: risk factor, close surveillance needed.
  • 8-12% of patients have family history.
  • BRAF (V600E) mutations in 50-60% cutaneous melanomas.
  • FAMMM syndrome: >50 atypical moles + family history.

RISK FACTORS

  • Genetic predisposition, personal/family melanoma history.
  • UV exposure, sunburns (>5 lifetime, blistering in childhood).
  • Dysplastic melanocytic nevi.
  • Fair complexion, freckles, blue eyes, blond/red hair.

  • 50 nevi is the highest predictor.

  • Tanning bed use before age 35 increases risk by 75%.
  • Large congenital nevi (>5 cm).
  • Chronic immunosuppression (CLL, NHL, AIDS, transplant).
  • High altitude living (>700 m).
  • Occupational ionizing radiation exposure.

GENERAL PREVENTION

  • Avoid sunburns, especially in childhood.
  • Use sunscreen SPF ≥30, reapply regularly and after swimming.
  • Avoid tanning beds (WHO class 1 carcinogen).
  • Biopsy suspicious lesions with narrow excision (1-3 mm margins).

COMMONLY ASSOCIATED CONDITIONS

  • Dysplastic nevus syndrome (>50 nevi).
  • Giant congenital nevus (6% lifetime melanoma risk).
  • Psoriasis post PUVA therapy.

DIAGNOSIS

HISTORY

  • Changes in pigmented lesion: hypo-/hyperpigmentation, bleeding, scaling, ulceration, size/texture changes.
  • Family history, sun exposure, tanning.

PHYSICAL EXAM

  • ABCDE:
  • Asymmetry
  • Border irregularity
  • Color variegation (red, white, black, blue)
  • Diameter >6 mm
  • Evolution over time
  • Location: Caucasians (back, lower leg), African Americans (hands, feet, nails).
  • Mucosal surfaces may be involved.
  • High-risk individuals require ocular exam for iris and retina melanoma.

DIFFERENTIAL DIAGNOSIS

  • Cutaneous squamous cell carcinoma
  • Basal cell carcinoma
  • Dysplastic and blue nevi
  • Vascular skin tumor
  • Pigmented actinic keratosis
  • Traumatic hematoma
  • Pigmented basal cell carcinoma, seborrheic keratoses
  • Common or atypical melanocytic nevi
  • Lentigo
  • Pyogenic granuloma

DIAGNOSTIC TESTS & INTERPRETATION

  • LDH, chest/abdomen/pelvic CT ± PET/CT for baseline and metastatic monitoring.
  • Brain MRI if CNS symptoms.
  • Dermoscopy: limited evidence but used for lesion magnification.
  • Full-thickness excisional biopsy: gold standard; elliptical excision, punch, or scoop shave (avoid superficial shave).
  • Sentinel lymph node biopsy: staging and prognosis; indicated for T1b, T2-T4; not for melanoma in situ or T1a.
  • Staging per AJCC TNM: thickness, ulceration, lymph nodes, distant mets, serum LDH.

TREATMENT

GENERAL MEASURES

  • Full surgical excision standard of care.
  • Curative in most stage I-II melanomas.

MEDICATION

  • Clinical trial recommended.
  • FDA first-line for unresectable/metastatic melanoma:
  • Anti-PD-1 monotherapy: pembrolizumab, nivolumab
  • Anti-PD-1/anti-CTLA-4 combo: nivolumab + ipilimumab (61% response rate)
  • BRAF/MEK inhibitors (if BRAF V600 mutation): dabrafenib/trametinib, vemurafenib/cobimetinib + atezolizumab, encorafenib/binimetinib
  • Adjuvant therapy for high-risk post-surgery (stages IIIA-IV).
  • Other regimens: dacarbazine, temozolomide, paclitaxel, BCNU, cisplatin, carboplatin, vinblastine.
  • Imatinib for c-KIT mutation tumors.
  • Interferon-α: adjuvant, improves relapse rate but no survival benefit, significant toxicity.

ISSUES FOR REFERRAL

  • Oncology and surgery as per nodal/metastatic disease extent.

ADDITIONAL THERAPIES

  • Local therapy for stage III in-transit disease: intralesional injections (T-VEC, IL-2, BCG, IFN), topical imiquimod, laser, radiation.

SURGERY/OTHER PROCEDURES

  • Excision margins:
  • In situ: 0.5-1.0 cm
  • ≤1 mm (T1): 1 cm
  • 1.01–2.00 mm (T2): 1-2 cm
  • 2.01–4.00 mm (T3): 2 cm
  • ≥4 mm (T4): 2 cm
  • Sentinel lymph node biopsy for T1b and above.
  • Mohs surgery increasing in melanoma in situ but not standard for invasive melanoma.
  • Radiotherapy for lentigo maligna and palliation.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • Total body photography, dermoscopy for patients with >5 atypical nevi.
  • NCCN: screen every 3-12 months depending on recurrence risk; annual exams after 5 years if stable.
  • Imaging (CXR, CT, MRI, PET) every 3-12 months for 3-5 years based on clinical judgment.
  • Labs and imaging low yield post stage I-II treatment.

PATIENT EDUCATION

  • Teach regular full-body skin exam using ABCDE criteria, especially in high-risk or previous melanoma patients.

PROGNOSIS

  • Breslow thickness is strongest prognostic factor.
  • Median age at death: 70 years.
  • Highest survival: women <45 years at diagnosis.
  • Metastatic melanoma: 6-9 months median survival; 15-20% 5-year survival.
  • Stages I & II treated have 20-year survival: 90% & 80%.

Clinical Pearls

  • Teach regular skin exams with ABCDE rule.
  • Location differs by race (white: back, legs; black: hands, feet, nails).