Epidemiology

Etiology

Melanocyte is in the stratum basale of the skin, i.e. the dermoepidermal junction

UV radiation exposure
Light skin types
Genetic mutations, including:
- BRAF gene mutations
  - Seen in 50% of melanomas
  - V600E mutation (most common): an activating mutation in the BRAF gene that substitutes glutamic acid for valine at amino acid position 600
- CDKN2A gene mutations

A = Asymmetry
B = Border (irregular border with indistinct margins)
C = Color (variegated pigmentation within the same lesion)
- Red areas are due to vessel ectasia (dilation) and local inflammation.
- Brown or black, flared areas along the border are due to advancing, neoplastic melanocytes.
- White and gray areas appear when cytotoxic T lymphocytes recognize tumor antigens (eg, melan-A) and induce apoptosis, leading to malignant melanocyte regression (cleared patches).
D = Diameter > 6 mm
E = Evolving (a lesion that changes in size, shape, or color over time)

Core Concept: Melanoma in situ on chronically sun-damaged skin.
- Characterized by a prolonged radial (horizontal) growth phase, where atypical melanocytes are confined to the epidermis and contiguous adnexal structures.
- Can progress to invasive lentigo maligna melanoma when neoplastic cells breach the basement membrane and enter the dermis (vertical growth phase).
Patient Profile: Elderly pt with a Hx of extensive sun exposure.
Classic Location: Face, neck, scalp, dorsal forearms.
Clinical Presentation: A large, flat (macule/patch), slow-growing lesion with irregular borders and variegated color (tan, brown, black).
High-Yield Sign of Progression: The development of a nodule or papule within the flat lesion signifies transformation into invasive lentigo maligna melanoma.
Diagnosis & Tx:
- Dx: Biopsy (excisional preferred).
- Tx: Surgical excision.
Prognosis: Excellent if treated as in situ disease. Prognosis worsens with invasion, determined by Breslow depth.

Histopathology revealed poorly differentiated cells with abundant mitotic activity and necrosis.
- Breslow depth: Distance from stratum granulosum to deepest tumor cells
Immunostaining was positive for S-100 (a protein expressed in cells derived from the neural crest such as melanocytes) and HMB-45 (a marker for immature melanosomes found in melanocytic tumors) indicating melanoma.
- S-100 is also expressed in Schwannoma