NR4A3 immunostain is a highly sensitive and specific marker for acinic cell carcinoma in cytologic and surgical specimens Journal Article


Authors: Viswanathan, K.; Beg, S.; He, B.; Zhang, T.; Cantley, R.; Lubin, D. J.; Shi, Q.; Maleki, Z.; Asiry, S.; Rao, R.; Katabi, N.; Nakaguro, M.; Faquin, W. C.; Sadow, P. M.; Siddiqui, M. T.; Scognamiglio, T.
Article Title: NR4A3 immunostain is a highly sensitive and specific marker for acinic cell carcinoma in cytologic and surgical specimens
Abstract: OBJECTIVES: Salivary gland acinic cell carcinoma (AciCC) has recognizable cytomorphologic features that can overlap with benign and malignant entities, creating a diagnostic challenge. AciCC harbors a t(4;9) translocation increasing nuclear receptor subfamily 4 group A member 3 (NR4A3) expression, detectable by immunohistochemistry (IHC) on surgical resection (SR). NR4A3 IHC cytology data are limited. Here, we examine NR4A3 IHC on smears, cell blocks (CBs), and SRs of AciCC and its mimickers. METHODS: Our cohort comprised AciCC (including high-grade transformation), secretory carcinoma, mucoepidermoid carcinoma (MEC), Warthin tumor, pleomorphic adenoma (PA), cellular PA, carcinoma ex-PA, oncocytic carcinoma, oncocytoma, and nodular oncocytosis. NR4A3 IHC (Santa Cruz Biotechnology and Origene antibodies) was positive if more than 5% tumor cells showed nuclear staining. RESULTS: Among CBs, 90% of AciCC cases and none of the mimickers expressed NR4A3. Among SRs, 100% of AciCC cases showed diffuse NR4A3, whereas one high-grade MEC expressed focal NR4A3. Concordance was 95% with two antibody clones. Sensitivity, specificity, positive predictive value, and negative predictive value were 90%, 100%, 100%, and 94.7% for CBs and 100%, 98.8%, 92.3%, and 100% for SRs, respectively. NR4A3 immunostaining was demonstrable on smears from an AciCC case. CONCLUSIONS: NR4A3 IHC can be a robust diagnostic tool to identify AciCC, especially for cytology specimens. © American Society for Clinical Pathology, 2021. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.
Keywords: acinic cell carcinoma; salivary; oncocytic; nr4a3
Journal Title: American Journal of Clinical Pathology
Volume: 157
Issue: 1
ISSN: 0002-9173
Publisher: Oxford University Press  
Date Published: 2022-01-01
Start Page: 98
End Page: 108
Language: English
DOI: 10.1093/ajcp/aqab099
PUBMED: 34508546
PROVIDER: scopus
PMCID: PMC8742980
DOI/URL:
Notes: Article -- Export Date: 1 February 2022 -- Source: Scopus
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  1. Nora Katabi
    305 Katabi