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Am J Surg Pathol. 2019 May 13. doi: 10.1097/PAS.0000000000001279. [Epub ahead of print]

Nuclear NR4A3 Immunostaining is a Specific and Sensitive Novel Marker for Acinic Cell Carcinoma of the Salivary Glands.

Author information

1
Institute of Pathology.
2
Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, Czech Republic.
3
Dermpath Munich, Munich.
4
Institute of Pathology, Klinikum Augsburg.
5
Center for Digital Health, Berlin Institute of Health and Charité-Universitätsmedizin Berlin, Berlin.
6
Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
Department of Otorhinolaryngology, Head & Neck Surgery, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen.
8
Department of Otorhinolaryngology, Head and Neck Surgery, Augsburg Clinic Center, Augsburg.

Abstract

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.

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