Is acinic cell carcinoma a variant of secretory carcinoma?: A FISH study using ETV6 'split apart' probes

Aims: Acinic cell carcinomas (ACCs) and secretory carcinomas (SCs) of the breast are rare, low-grade malignancies that preferentially affect young female patients. Owing to the morphological and immunohistochemical similarities between these lesions, they have been proposed to be two morphological variants of the same entity. It has been demonstrated that SCs of the breast consistently harbour the t(12;15)ETV6-NTRK3 translocation. The aim was to determine whether ACCs also harbour ETV6 gene rearrangements and are thus variants of SCs. Methods and results: Using the ETV6 fluorescence in situ hybridization DNA Probe Split Signal (Dako), the presence of ETV6 rearrangements in three SCs and six ACCs was investigated. Cases were considered as harbouring an ETV6 gene rearrangement if > 10% of nuclei displayed 'split apart signals' (i.e. red and green signals were separated by a distance greater than the size of two hybridization signals). Whereas the three SCs displayed ETV6 split apart signals in > 10% of the neoplastic cells, no ACC showed any definite evidence of ETV6 gene rearrangement. Conclusions: Based on the lack of ETV6 rearrangements in ACCs, our results strongly support the concept that SCs and ACCs are distinct entities and should be recorded separately in breast cancer taxonomy schemes.