Primary mucinous cystadenocarcinoma of the breast commonly harbours TP53 mutations and PI3K/AKT pathway alterations.

Primary mucinous cystadenocarcinoma (MCA) of the breast is an invasive breast carcinoma characterized by cystic structures lined by tall columnar cells with abundant intracytoplasmic mucin, resembling pancreatobiliary or ovarian mucinous cystadenocarcinoma. Fewer than 50 cases have been reported worldwide so far. In this series, we describe the clinical, morphologic, immunohistochemical, and molecular features of 5 cases of breast MCA. The median age of the patients was 54 years (range: 53 to 64 years) and invasive size was 2 mm to 30 mm (our study reported the smallest invasive size to date in case 5). DCIS was present in 4 of 5 cases. Despite the prevailing view that breast MCA may be indolent, our cases exhibit robust growth, characterized by a relatively high Ki67 index, brisk mitosis, and 1 case of micrometastasis of axillary lymph node micrometastasis. Moreover, we conducted large panel sequencing on 4 cases, and emphasize their molecular essence; that is, breast MCA exhibits a high frequency of TP53 mutations and PI3K/AKT pathway alterations. A review of the literature on previous and current genomic profiles indicates that MCAs are similar to triple-negative breast cancer (TNBC). In our opinion, patients with breast MCA should receive precise clinical treatment similarly to invasive breast carcinoma of no special type, with careful consideration of tumor grade, stage, immunophenotype, and genomic profile, and we believe that PI3K-targeted therapies may play a valuable role in treating this rare tumor.