Two similar but distinct types of breast acinar cell carcinoma: evidence from histological, immunohistochemical and molecular features.

Aims: Breast acinar cell carcinoma (AciCC) is a rare breast cancer subtype that exhibits morphological similarities to salivary gland AciCC. However, the molecular profile of breast AciCC differs significantly from that of salivary gland AciCC, suggesting that they may not be related. Whether breast AciCC represents a distinct breast cancer subtype remains controversial.

Methods and results: This study analysed two groups of breast AciCCs. Using comprehensive morphological, immunohistochemical, fluorescence in situ hybridisation and next-generation sequencing analyses, we elucidated the similarities and differences between these two distinct types of 'breast AciCCs' and their salivary gland counterpart. The first, based on morphological and immunohistochemical features, satisfied the 2019 World Health Organization diagnostic criteria for breast AciCC. Notably, NR4A3, a specific marker for salivary gland AciCC, was not expressed in these cases. We propose designating this tumour type as 'carcinoma with acinar cell differentiation'. In contrast, the second group included a case of AciCC in situ, which demonstrated morphological, immunohistochemical and molecular features identical to those of salivary gland AciCC, including NR4A3 protein overexpression and NR4A3 gene rearrangement. This case was considered a precursor of true salivary gland-type AciCC originating in the breast.

Conclusions: This study provides new insights into breast AciCC nomenclature: the widely recognised AciCC name, 'carcinoma with acinar cell differentiation' might be more appropriate. Although true salivary gland-type AciCC requires additional cases for confirmation, our case has clarified that true salivary gland-type AciCC can indeed exist in the breast.