Next generation sequencing of the nidus of early (adenosquamous proliferation rich) radial sclerosing lesions of the breast reveals evidence for a neoplastic precursor lesion

We sought to determine if adenosquamous proliferation of early cellular radial sclerosing lesions of the breast harbours hot spot mutations and to help clarify its relationship to low-grade adenosquamous carcinoma as a potential form of early neoplasia. Four low-grade adenosquamous carcinomas, early radial sclerosing lesions from 13 individuals, and 4 benign proliferative breast lesions were microdissected and assessed with a 50-gene Hot-spot cancer panel. Early radial sclerosing lesions were selectively microdissected concentrating on their adenosquamous proliferation (nidus). Hot spot mutations in PIK3CA were detected in ten (77% of) radial sclerosing lesions, in one low-grade adenosquamous carcinoma, and in usual ductal hyperplasia and apocrine adenosis. Over three quarters of individuals with cellular (adenosquamous proliferation rich) early radial sclerosing lesions tested harboured somatic mutations in PIK3CA suggesting that adenosquamous proliferation is a clonal lesion. Its relationship to low-grade adenosquamous carcinoma remains unclear in view of the small sample size and unmatched radial sclerosing lesions and low-grade adenosquamous carcinomas.