Melanoma

Epidemiology and Etiology

It is estimated that nearly 100,350 new cases of cutaneous melanoma were diagnosed in 2020 in the US.¹ The main risk factors include exposure to ultraviolet (UV) radiation (particularly UVB), light skin, tendency to freckle, presence of dysplastic nevi, personal history, and family history.

Pathology

Melanoma is usually recognized using the ABCDE criteria which includes asymmetry, border irregularity, color variegation, diameter gt;6 mm, and e volving characteristics such as change in size, shape, or color. In patients with multiple pigmented lesions, the detection of melanoma may be improved with intra­patient comparison and search for the “ugly duckling sign,” which is represented by a nevus with different color or size compared to other lesions.

Diagnostic Testing

The workup often involves adequate sampling of the lesion, IHC for markers of melanocytic origin (S100, MART1, HMB45), and molecular profiling for detection of mutations in the BRAF gene and overall tumor mutational burden. Primary lesions gt;0.75 mm in Breslow thickness, with ulceration, #8805;1 mitoses/mm², or lymphovascular invasion require a sentinel lymph node biopsy. In the presence of positive lymph nodes, whether if clinically palpable or after SLNB, patients should undergo imaging studies including CT scans or PET CT and brain MRI.

Staging

Stages I and II are based on tumor thickness (T1 up to 1 mm, T2 gt;1-2 mm, T3 gt;2-4 mm, T4 gt;4 mm) and absence (T1a, T2a, T3a, or T4a) or presence (T1b, T2b, T3b, or T4b) of ulceration. Whereas regional lymph node involvement and distant metastases characterizing stage III and IV respectively.

TREATMENT

• Patients with resected stage I or II melanoma do not require adjuvant therapy. Patients with stage III disease may be treated with adjuvant nivolumab or pembrolizumab, or dabrafenib plus trametinib if BRAF V600E mutated.²⁹

• Patients with metastatic melanoma may be treated with pembrolizumab, nivolumab, or one of the combinations of BRAF and MEK inhibitors including vemurafenib plus cobimetinib, dabrafenib plus trametinib, and encorafenib plus binimetinib if BRAF V600E mutated. Treatment options after the first- line therapy include combination ICI and ipilimumab, interleukin-2, and talimogene laherparepvec (T- VEC), which is a genetically modified HSV-1 virus with decreased virulence and selective intratumoral replication injected into the tumor which may induce an immune response to the malignancy.²⁹