Primary breast acinic cell-like carcinoma: A report of three cases and a review of the literature.

Acinic cell-like carcinoma (AcCC) of the breast is an extremely rare triple-negative breast carcinoma, analogous to acinic cell carcinoma of the salivary gland in morphology and immunohistochemistry. In this study, we report three new cases of breast AcCC, including clinical characteristics, histological morphology, immunophenotype, ultrastructural characteristics, and results of 1 case of next-generation sequencing. Breast AcCCs predominantly comprised small acinar or glandular structures. Tumor cells were positive for cytokeratin, epithelial membrane antigen, lysozyme, α-1-antichymotrypsin, and S-100 protein, while generally being negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Electron microscopy detected zymogen particles in the cytoplasm of cancer cells. Additionally, FISH assay was performed in one case, and the results were negative for the ETV6::NTRK3 fusion gene, potentially differentiating breast AcCC from secretory carcinoma. Next-generation sequencing in one case revealed two missense mutations of PIK3CA gene (c.3140A > G, p.His1047Arg and c.1624G > A, p.Glu542Lys), as well as an in-frame indels mutation (c.1138_1167del, p.Glu380_Ala389del) and a nonsense mutation (c.1138G > T, p.Glu380*) of TBX3 gene. Breast AcCC is confirmed to be generally similar to its salivary gland counterpart and is considered a distinct lesion. Breast AcCC generally presents relatively indolent biological behavior, although tumor progression and extensive metastasis considerably worsen the disease course. In conclusion, we describe the morphological and immunohistochemical features of three cases, along with the molecular profile of one case, of this rare entity. We also summarize the molecular characteristics of breast AcCC cases reported in the literature to date.