Snapshot A 43-year-old man presents to his primary care physican for a pigmented lesion on his right forearm. He has had multiple sunburns in the past and works as a farmer, spending most of the day outside. Physical examination is notable for a 7-mm hyperpigmented lesion that is asymmetric with irregular borders and color variation. He undergoes an excisional biopsy, which demonstrates larger than normal melanocytes of various sizes with large hyperchromatic nuclei in the lower epidermis and dermis. Introduction Overview malignant tumor of melanocytes most commonly affects the skin other sites of involvement brain uvea intestines mucosa 4 types of cutaneous invasive melanoma superficial spreading (most common) usually seen in sunexposed areas nodular 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) invasive melaoma Epidemiology Incidence most commonly seen between the ages of 40-60 Risk factors dysplastic nevi multiple nevi ultraviolet radiation exposure fair-skin color immunsuppresion ETIOLOGY Pathophysiology Clark model of pathogenesis melanocytes proliferate to form a benign nevus genetic mutations (e.g., BRAF) lead to the nevus becoming dysplastic (pre-malignant) radial growth → vertical growth can eventually metastasize 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 Surgical local wide excision indication mainstay of treatment for primary cutaneous melanoma Complications Metastatic melanoma lung brain liver bone intestines Prognosis Prognostic favorable favorable localized disease with the tumor being ≤ 1 mm deep negative metastatic disease