Histologic features of melanoma associated with germline mutations of CDKN2A, CDK4, and POT1 in melanoma-prone families from the United States, Italy, and Spain.

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CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes.We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1.We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and non-carriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family.Histologic slides were evaluated for 290 melanomas (139 from 132 non-carriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in the majority of invasive melanomas from POT1 carriers (10 of 15 [67%], P


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