Recurrent rearrangements of the PLAG 1 and HMGA 2 genes in lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma

Purpose Lacrimal gland tumours constitute a wide spectrum of neoplastic lesions that are histologically similar to tumours of the salivary gland. In the salivary gland, pleomorphic adenoma ( PA ) is frequently characterized by recurrent chromosomal rearrangements of the PLAG 1 and HMGA 2 genes, a genetic feature retained in carcinoma ex pleomorphic adenoma (ca‐ex‐ PA ) that makes it possible to distinguish ca‐ex‐ PA from de novo carcinomas. However, whether PLAG 1 and HMGA 2 gene rearrangements are found in lacrimal gland PA and ca‐ex‐ PA is not known. Methods Twenty‐one lacrimal gland PA s and four ca‐ex‐ PA s were retrospectively reviewed and subjected to break‐apart fluorescence in situ hybridization ( FISH ) for rearrangements of the PLAG 1 gene. Cases without PLAG 1 abnormalities were subjected to HMGA 2 break‐apart FISH . Immunohistochemical staining for PLAG 1 and HMGA 2 protein was performed and correlated with gene status. Results Sixteen of 21 PA s showed rearrangement of PLAG 1 and were all positive for PLAG 1 protein. Two of the remaining five PA s showed rearrangement of HMGA 2 and were the only cases positive for HMGA 2 with immunohistochemistry. The three FISH ‐negative PA s expressed PLAG 1 protein. All four ca‐ex‐ PA s showed rearrangement of PLAG 1 and expressed PLAG 1 protein. None of the de novo carcinomas showed rearrangement of either of the two genes or expression of the two proteins. Conclusion Rearrangement of PLAG 1 and HMGA 2 and expression of the corresponding proteins are frequent and specific findings in lacrimal gland PA and ca‐ex‐ PA . The mechanism for PLAG 1 overexpression in FISH ‐negative PA s is yet to be clarified.