Frequent PIK3CA activating mutations in nipple adenomas

Aims: Nipple adenoma (NA) is a rare benign epithelial tumour occurring in the nipple. Histologically, it exhibits variable and often mixed adenosislike and usual ductal hyperplasia-like growth patterns. Morphologically, it is similar to other benign proliferative breast lesions occurring in the breast parenchyma, which have been shown to harbour activating mutations in PIK3CA, AKT1 or, less frequently, in RAS in more than 50% of cases. In this study, we aimed to analyse the mutation status of PIK3CA, AKT1, RAS and BRAF in NAs and correlated the mutation status with the histological features. Methods and results: Mutation analysis of PIK3CA, AKT1, RAS and BRAF was performed in 24 NAs by Sanger sequencing. Our results showed that activating PIK3CA mutations were identified in eight of the 15 NAs (53%) with a predominantly adenosis-like pattern and four of the nine NAs (44%) with a predominantly usual ductal hyperplasia-like pattern. One tumour with a PIK3CA H1047R mutation also had a KRAS Q61H mutation. Two tumours with an adenosis- like pattern had BRAF V600E mutations. Overall, half of the NAs (12 of 24, 50%) in our series had PIK3CA mutations and 58% (14 of 24) had PIK3CA, RAS or BRAF mutations. Conclusions: Our data indicate that, similar to other benign proliferative lesions occurring in the breast parenchyma, activating PIK3CA mutations are very common in NAs, and KRAS mutation may occur concurrently with PIK3CA mutation. In addition, as BRAF mutation has not been identified in benign proliferative lesions in previous studies, BRAF-mutated NAs appear to have distinct pathogenesis.