Snapshot A 46-year old woman presents to her primary care physician for a dark spot on the back of her right hand. She states that the spot first appeared about 2 years ago and has slowly been growing. It does not burn, itch, or sting. She has a history of regular suntanning and minimal sunscreen use. On exam, there is a 2-cm, asymmetric, thin, brownish-blue plaque with somewhat ill-defined borders and an irregular pattern of coloration. Introduction Overview malignant tumor of melanocytes most commonly affects the skin other sites of involvement brain uvea intestines mucosa melanocytes are of neural crest cell origin 4 types of cutaneous invasive melanoma superficial spreading (most common) usually seen in sunexposed areas nodular (second most common) usually seen in men and often associated with ulceration acral most commonly seen in Asians, Hispanics, and patients from African descent lentigo maligna (invasive melanoma) typically seen in elderly patients Epidemiology incidence most commonly seen between the ages of 40-60 risk factors dysplastic nevi multiple nevi ultraviolet radiation exposure fair-skin color immunsuppresion Pathophysiology Clark model of pathogenesis melanocytes proliferate to form a benign nevus genetic mutations (e.g., BRAF) lead to the nevus to become dysplastic (pre-malignant) radial growth → vertical growth can eventually metastasize BRAF mutation seen in ~50% of patients with metastatic cutaneous melanoma secondary to a valine-to-glutamic acid substitution at codone 600 (V600E) Prognosis prognostic favorable favorable localized disease with the tumor being ≤ 1 mm deep negative metastatic disease Presentation Physical exam pigmented skin lesion ABCDEs Asymmetric Border irregularity Color variation Diameter ≥ 6 mm Evolution over time Studies Serum labs S-100 tumor marker Invasive studies excisional biopsy indication preferred biopsy method to confirm the diagnosis findings atypical melanocytes and architectural disorder atypical larger than normal melanocytes large hyperchromatic nuclei irregular nuclear shape abnormal chromatin pattern architectural disorder asymmetry nests of melanocytes of varying sizes and shapes Differential Actinic keratosis differentiating factors secondary to proliferation of atypical epiderminal keratinocytes lesions are small, rough papules that are erythematous or brownish Basal cell carcinoma differentiating factors lesions are waxy, pink, and pearly can have central crusting or ulceration histology demonstrates palisading nuclei Treatment Medical vemurafenib indication BRAF kinase inhibitor that can be considered in patients with metastatic or unresectable melanoma with BRAF V600E mutations typically given with cobimetinib can lead to T cell mediated destruction of malignant melanocyte Surgical wide local excision indication mainstay of treatment for primary cutaneous melanoma Complications Metastatic melanoma lung brain liver bone intestines