HMGA 2 is a specific immunohistochemical marker for pleomorphic adenoma and carcinoma ex‐pleomorphic adenoma

Aims Accurate classification of salivary gland neoplasms may be challenging, owing to morphological overlap, particularly in small biopsies. Recurrent translocations involving the high‐mobility group AT ‐hook 2 ( HMGA 2) gene are present in a subset of pleomorphic adenomas ( PA s) and carcinoma ex‐pleomorphic adenomas ( CA ex‐ PA s). The aim of this study was to evaluate immunohistochemical HMGA 2 expression in 225 salivary gland tumours, including 56 PA s, 37 CA ex‐ PA s, and 132 potential histological mimics, to determine its diagnostic utility. Methods and results HMGA 2 expression was identified in 19 PA s (33.9%) and nine CA ex‐ PA s (24.3%). Expression was strong and diffuse throughout all PA s, and in four of nine positive CA ex‐ PA s. In five CA ex‐ PA s, HMGA 2 showed weak‐to‐strong multifocal staining within the carcinomatous component, and strong diffuse HMGA 2 expression in the residual PA . Among histological mimics, six de‐novo salivary duct carcinomas (28.5%), three epithelial–myoepithelial carcinomas (33.3%) and one case each of myoepithelioma and basal cell adenoma expressed HMGA 2. Fluorescence in‐situ hybridization for HMGA 2 rearrangement performed on a subset of tumours that showed diffuse HMGA 2 expression in PA s and CA ex‐ PA s was frequently associated with rearrangement of the HMGA 2 locus, whereas cases of de‐novo salivary duct carcinoma, or CA ex‐ PA with limited or no HMGA 2 expression, had an intact HMGA 2 locus. Conclusions HMGA 2 expression is a highly specific (96.2%), but low‐sensitivity (29.8%), marker for PA and CA ex‐ PA when compared with histological mimics, and is frequently associated with rearrangement of the HMGA 2 locus.