Recently, we discovered the recurrent genomic rearrangement [t(4;9)(q13;q31)] enabling upregulation of the transcription factor Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) through enhancer hijacking as the oncogenic driver event in acinic cell carcinoma (AciCC) of the salivary glands. In the current study, we evaluated the usefulness of NR4A3 immunostaining and NR4A3 fluorescence in situ hybridization (FISH) in the differential diagnosis of AciCC, comparing a total of 64 AciCCs including 17% cases with high-grade transformation, 29 secretory (mammary analog) carcinomas (MASC), and 70 other salivary gland carcinomas. Nuclear NR4A3 immunostaining was a highly specific (100%) and sensitive (98%) marker for AciCC with only 1 negative case, whereas NR4A3 FISH was less sensitive (84%). None of the MASCs or other salivary gland carcinomas displayed any nuclear NR4A3 immunostaining. The recently described HTN3-MSANTD3 gene fusion was observed in 4 of 49 (8%) evaluable AciCCs, all with nuclear NR4A3 immunostaining. In summary, NR4A3 immunostaining is a highly specific and sensitive marker for AciCC, which may be especially valuable in cases with high-grade transformation and in "zymogen granule"-poor examples within the differential diagnostic spectrum of AciCC and MASC.

Center for Digital Health Berlin Institute of Health and Charité Universitätsmedizin Berlin Berlin

Department of Otorhinolaryngology Head and Neck Surgery Augsburg Clinic Center Augsburg

Department of Otorhinolaryngology Head and Neck Surgery University Hospital Erlangen Friedrich Alexander University Erlangen Nuremberg Erlangen

Department of Pathology Charles University Faculty of Medicine in Plzen Plzen Czech Republic

Dermpath Munich Munich

Division of Molecular Genome Analysis German Cancer Research Center Heidelberg Germany

Institute of Pathology

Institute of Pathology Klinikum Augsburg

Am J Surg Pathol. 2019 Dec;43(12):1726-1728. doi: 10.1097/PAS.0000000000001346. PubMed

References provided by Crossref.org

A minority of cases of acinic cell carcinoma of the salivary glands are driven by an NR4A2 rearrangement: the diagnostic utility of the assessment of NR4A2 and NR4A3 alterations in salivary gland tumors

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