Melanoma

Melanoma - Basics & Bad Seeds

• Malignant tumor of melanocytes; commonest skin cancer causing death.
• Etiology: UV radiation (UVB > UVA) is the primary modifiable risk factor, causing DNA damage.
• Risk Factors:
  • Sun exposure (intense, intermittent > chronic).
  • Fair skin, >50 common nevi, atypical nevi.
  • Family history (e.g., FAMMM syndrome, CDKN2A gene).
  • Immunosuppression.
• Indian Context: Acral lentiginous melanoma (palms, soles, subungual) is more prevalent.

⭐ Intermittent, intense sun exposure is a higher risk factor for melanoma development than chronic, cumulative exposure.

Melanoma - Rogue Cells & Faces

• Pathogenesis: Key mutations: BRAF, NRAS, c-KIT. Growth phases: Radial (intraepidermal) then Vertical (invasive, ↑metastatic potential).
• Precursor Lesions: Giant congenital nevi (>20cm), dysplastic nevi.
• Major Clinicopathological Types: 📌 Superficial Nodules Linger Around Amelanotic spots.
  • Superficial Spreading (SSM): Most common overall.
  • Nodular (NM): Worst prognosis, rapid vertical growth.
  • Lentigo Maligna Melanoma (LMM): Elderly, sun-exposed areas.
  • Acral Lentiginous Melanoma (ALM): Palms, soles, subungual; common in darker skin.
  • Amelanotic Melanoma: Difficult diagnosis, lacks pigment.

⭐ Nodular melanoma has no significant radial growth phase, presenting early with vertical growth.

Melanoma - Spotting the Enemy

• Clinical Clues: New/changing mole; symptoms like itching, bleeding.
• ABCDE Rule (📌):
  • Asymmetry
  • Border irregularity
  • Color variegation (multiple shades)
  • Diameter >6mm
  • Evolving/Elevation (change in size, shape, color, elevation)
• Glasgow 7-Point Checklist:
  • Major (3): Change in size, shape, color.
  • Minor (4): Diameter >6mm, inflammation, oozing/bleeding, altered sensation.
• Diagnosis:
  • Dermoscopy for initial evaluation.
  • Excisional biopsy (gold standard) with 1-3mm margins for suspicious lesions. Avoid shave/punch biopsy.

⭐ Excisional biopsy is the diagnostic procedure of choice for a suspected melanoma.

Melanoma - Sizing Up Trouble

• Microstaging: Key for prognosis.
  • Breslow Thickness: Depth in mm; most crucial prognostic factor.
  • Clark Level: Anatomical invasion level; less used now.
• TNM Staging (AJCC 8th Ed.): Guides treatment.
  • T: Tumor thickness (Breslow), ulceration.
  • N: Nodal involvement (number, burden).
  • M: Distant metastasis.
• Key Prognostic Factors:
  • Breslow depth, ulceration, mitotic rate.
  • Lymph node status, distant metastasis, LDH levels.
• Sentinel Lymph Node Biopsy (SLNB):
  • Indications: Breslow >1mm, OR Breslow >0.8mm if ulceration/high mitotic rate present.

⭐ Breslow thickness is the single most important prognostic factor in localized melanoma.

Melanoma - Battle Plan Alpha

Multidisciplinary team essential.

• Surgical Management: Wide Local Excision (WLE) primary. Margins by Breslow depth:
  • In situ: 0.5-1cm
  • <1mm: 1cm
  • 1-2mm: 1-2cm

  • 2mm: 2cm

• Adjuvant Therapy (High-risk: Stage IIB/C, III):
  • Immunotherapy (Nivolumab, Pembrolizumab)
  • Targeted (BRAF V600): Dabrafenib/Trametinib
• Metastatic (Stage IV): Systemic therapy (Immunotherapy, Targeted). Chemo limited.
• Radiotherapy: Palliative; adjuvant in select cases.

⭐ For BRAF V600-mutated metastatic melanoma, combination BRAF/MEK inhibitors show improved outcomes over BRAF inhibitor monotherapy.

High-Yield Points - ⚡ Biggest Takeaways

• Breslow thickness: Single most important prognostic factor.
• ABCDE criteria: For clinical diagnosis (Asymmetry, Border, Color, Diameter >6mm, Evolving).
• Superficial Spreading Melanoma: Most common subtype.
• Acral Lentiginous Melanoma: Common in dark skin (palms, soles, nail beds).
• Nodular Melanoma: Worst prognosis due to rapid vertical growth.
• BRAF V600E mutation: Key therapeutic target.
• Sentinel Lymph Node Biopsy (SLNB): For tumors >1mm or ulcerated_