Melanomas are known as the great mimicker and must be considered in the differential diagnosis of any fine-needle aspirations (FNA). Despite recent advancements in understanding of the mutational landscape of melanomas, there still exists a divide between the genetic and morphologic correlates. A consecutive cohort of 39 FNA of clinically verified metastatic melanomas with concurrent BRAF V600 assessment were selected [positive (n = 18) and wild-type (n = 21)]. The melanoma cytology specimens were evaluated blinded to the BRAF mutation status in a dichotomized fashion for the presence of 8 selected morphologic classifiers. When comparing the BRAF-mutated vs. BRAF-wild type cohorts, the percentage of cases were, respectively: macronucleoli (56 and 52%), intranuclear inclusions (50 and 33%), pigment (44 and 24%), binucleation/multinucleation (78 and 57%), nuclear pleomorphism (72 and 67%), cytoplasmic vacuolization (22 and 29%), spindle cell morphology (61 and 29%), and necrosis (11 and 10%). The average age of the BRAF-mutated cohort was 52.2 years, compared to the BRAF wild-type cohort at 65.2 years. The prevalence of sex ratio and the location of the primary melanoma were matched between cohorts. Spindle cell morphology was more correlated with BRAF V600-mutated melanomas. Clinicians utilized the BRAF status to alter clinical decisions with use of BRAF inhibitors.

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