Melanoma: Pathogenesis and clinical findings
Tanning beds No sunscreen Sun exposure
Ultraviolet (UV) light exposure • Short wavelength UV worse due to higher photon energy; UVB (280-315nm) is worse than UVA (315-400nm). • Short duration intense exposure (i.e. sunburns) worse than long duration low intensity exposure.
Genetics • Fair skin and/or many nevi • Other disease (e.g. Xeroderma pigmentosum) • Most melanomas involve somatic mutations to BRAF (proto-oncogene), but germline mutations can occur such as CDKN2A (this has high penetrance but low incidence).
Keratinocyte damage Energy applied to Extensive damage, non-and release of inflammatory cytokines melanocytes recognition, or immunosuppression 71r Neutrophilic Formation of DNA Failure of DNA repair inflammatory response ♦ pyrimidine dimers mechanisms
Epidermis Melanocytes Mitotic activity
dr • Dermal invasion
Abnormal melanocyte DNA
Authors: Ryan T. Lewinson Reviewers: Harjot Atwal Gurleen Chahal Usama Malik *Habib A Kurwa * MD at time of publication
Notes: • Usually, melanoma will undergo radial growth first, followed by vertical growth (exception is nodular melanoma). • Breslow thickness most important prognostic factor. • Mechanical loading may also be implicated in pathogenesis (plantar melanomas develop on regions of foot with highest pressures). • Solar radiation is 95% UVA, 5% UVB.
• Dysregulated cell transition from G1 phase (cell growth) to S phase (DNA replication)
Accelerated and uncontrolled melanocyte replication
• fro) • Cell atypia AL Melanocyte nest Metastasis (e.g. brain, liver, lungs, bone) Resistance to radiation therapy Asymmetry: One half of lesion does not look like the other Borders: Irregular, poorly defined, or scalloped appearance Color: Varied throughout lesion; e.g. can be black, blue, or red Diameter: Usually greater than 5 mm Evolving: Changing in shape, size, or color