| Background
Melanocytic nevi typically harbour single mutations in components of MAPK pathway and are known to promote cellular proliferation. Studies show that 80% of common acquired nevi typically have a single BRAFV600E mutation (Pollock et al, 2002; Shain et al, 2016), congenital and a fraction of acquired nevi harbour NRAS mutation, Spitz nevi an HRAS mutation or a kinase fusion of ALK, BRAF, ROS1, NTRK1, NTRK3, MET or RET, while blue nevi have a GNAQ or GNA11 mutation (WHO, 2018). Also, 60-80% of dysplastic nevi are shown to harbour mutations in BRAF (Pollock et al, 2002; Uribe et al, 2006; Wu et al, 2007). BRAFV600E mutation is among others reported in 50-66% of melanomas (Davies et al, 2002; Palmieri et al, 2018). The melanocytic lesions in body areas of intermittent sun exposure show more frequently BRAF mutations than those in areas of chronic sun damage (CSD) and, even if it is not a common UV signature, it is proposed to be UV-induced (Shain et al, 2016).
Immunohistochemistry using a highly sensitive and specific monoclonal antibody to BRAFV600E mutation has been developed (Anwar et al, 2016) and in St John’s Dermatopathology department (Orchard et al, 2019), this immunomarker has been used in assessing the presence of this mutation in melanoma as it correlates very well with molecular analysis and as an adjunct in the diagnosis of difficult lesions with spitzoid features; at these occasions the finding of a positive BRAF immunostaining would raise the suspicion of melanoma.
BRAF mutation has been linked to specific dermoscopic patterns in common nevi and melanomas. Specifically, this mutation is shown to be more likely associated with the globular and peripheral rim of globules patterns in acquired nevi, whereas NRAS mutation to be more prevalent in the reticular pattern (Zalaudek et al, 2011; Tan et al, 2018). In melanomas, BRAF mutation has been associated with the dermoscopic features of blue-white veil (Armengot-Carbó et al, 2018) and blue-grey peppering; the latter been also associated with NRAS mutation (Pozzobon et al, 2014).
Objective
1)To determine if BRAF immunostaining could help in the diagnosis of melanoma in difficult melanocytic lesions with Spitzoid features.
2)To establish the correlation between the dermoscopic features of these difficult melanocytic lesions and BRAF immunostaining.
Methods
A retrospective, observational study to be performed by retrieving the cases of all the melanocytic lesions that were BRAF immunostained and had dermoscopic images. The outcome of BRAF immunostaining, patient age, sex, anatomic location and diagnosis are going to be reported having anonymized the data. The dermoscopic images will be analysed by 2 independent blind observers using the same dermoscopic assessment guide.
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