Diagnosis

Malignant melanoma

Etiology

Cause [pmp]

• UVB and UVA radiation exposure

• Spontaneous mutation

Pathophysiology [pmp]

1. Ionizing radiation from cumulative solar damage

   • Atmospheric absorption

   • Cloud cover

   • Ozone layer depletion

2. DNA injury

3. Mutation in the tumor suppressor genes (BRAF)

4. Malignant transformation (nevus --> melanoma)

5 different histologic malignant melanomas

• Superficial spreading: 70% of melanomas, any body surface

• Nodular: 10-15% of melanomas, any body surface

• Lentigo maligna: 10-15% of melanomas, sun-exposed areas

• Acral lentiginous: palms, soles, and subungual areas

• Mucosal lentiginous: 3% of the melanomas, mucosal epithelium that lines the respiratory, gastrointestinal, genitourinary tracts, conjunctiva, oral cavity and esophagus

Risk factors [pmp]

• Family history

• Lifetime sun exposure

• Personal characteristics

  • Blue eyes

  • Fair or red hair

  • Pale complexion

  • History of sunburns

  • Freckled skin

  • More than 50 nevi

• Sporadic dysplastic nevi

• Congenital nevus

• Immunosuppression

Complications [pmp]

• Metastasis

• Lymphedema after sentinel surgery

Epidemiology

Incidence per 100.000 [mas][3eq][rsu][rtz][7nb]

Approach

• Dematoscopy:

  • Asymmetry

  • Border/Bleeding: irregular, ragged, notched, or blurred edges

  • Color: very dark or variable

  • Diameter > 6 mm

  • Evolving: changes in size, shape, or color

• Blood test: Complete blood count, ALP, ASAT, ALAT, albumin, lactate dehydrogenase

• Biopsy

• Sentinel node biopsy

• Blood test: ALP, transaminases, albumin and LD

• Chest x-ray

• MR caput

• CT thorax/abdomen

• PET-CT

Clark staging

• I - All tumor cells above basement membrane (in situ)

• II - Tumor extends into papillary dermis

• III - Tumor extends to interface between papillary and reticular dermis

• IV - Tumor extends between bundles of collagen of reticular dermis

• V - Tumor invasion of subcutaneous tissue

Breslow classification (thickness)

• < 0.75 mm

• 0.76-1.5 mm

• 1.51-4 mm

• > 4 mm

Treatment

1. Prophylaxis: Sun-protective behaviors can reduce harmful exposure to UV [ts8]

   • Sunscreen

   • Sun-protective clothing

2. Early-stage melanoma: Stage I-II [pmp]

   • Excision:

     • Melanoma in situ (Tis): 0.5 to 1 cm margin

     • T1 (≤1 mm): 1 cm margin

     • T2 (≥1 to 2 mm): 1 to 2 cm margin

     • T3 or T4 (>2 mm): 2 cm margin

   • Sentinel lymph node biopsy: if increased risk of regional node metastasis

     • Depth of melanoma (Breslow's depth) T1b or higher staging

   • Preoperative (neoadjuvant) therapy may be appropriate in select cases

3. Advanced, metastatic, unresectable, or recurrent melanoma: Adjuvant therapy

   • Immunotherapy: Nivolumab, pembrolizumab, ipilimumab, and relatlimab

   • Signal-transduction inhibitor: BRAF and MEK inhibitors

   • Intralesional therapy (talimogene laherparepvec)

   • Chemotherapy

   • Palliative local therapy

   • Stereotactic radiosurgery

   • External-beam radiation

Differential diagnoses

Actinic keratosis, Atypical fibroxanthoma, Basal cell carcinoma, Cutaneous T-cell lymphoma, Hemangioma, Histiocytoid hemangioma, Lentigo, Mycosis fungoides, Nevus, Sebaceous carcinoma, Squamous cell carcinoma