{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:00:19Z","timestamp":1791583219610,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007408","name":"Medical Center, University of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Acinic cell carcinoma (AcCC) is diagnostically challenging on fine\u2010needle aspiration because it can mimic several other neoplasms or even normal acinar tissue. Immunopositivity for DOG1, especially circumferential membranous staining, can support the diagnosis of AcCC but is not entirely specific, and it is prone to technical and interpretive challenges on small specimens. <jats:italic>NR4A3<\/jats:italic> (nuclear receptor subfamily 4 group A member 3) translocation and nuclear NR4A3 overexpression were recently described in the majority of AcCCs. Here, the authors evaluate the performance of NR4A3 immunohistochemistry (IHC) and <jats:italic>NR4A3<\/jats:italic> break\u2010apart fluorescence in situ hybridization (FISH) on cell block preparations and compare them with DOG1 IHC in distinguishing AcCC from other entities in the differential diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The authors identified 34 cytology cell blocks with lesional cells, including 11 specimens of AcCC (2 of which derived from 1 patient and showed high\u2010grade transformation) as well as 2 secretory carcinomas, 7 salivary duct carcinomas, 4 mucoepidermoid carcinomas, 3 oncocytomas, 3 renal cell carcinomas, and 6 specimens containing nonneoplastic salivary gland tissue. NR4A3 IHC, DOG1 IHC, and <jats:italic>NR4A3<\/jats:italic> FISH were attempted for all cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NR4A3 IHC had 81.8% sensitivity and 100% specificity for AcCC, whereas <jats:italic>NR4A3<\/jats:italic> FISH had 36.4% sensitivity and 100% specificity, although 4 cases (3 mucoepidermoid carcinomas and 1 salivary gland tissue sample) could not be analyzed because of low cellularity. Notably, no normal acinar tissue specimens showed NR4A3 positivity by IHC or FISH. In addition, DOG1 IHC had 72.7% sensitivity and 92% specificity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NR4A3 IHC is highly specific for the diagnosis of AcCC and is more sensitive than DOG1 IHC and <jats:italic>NR4A3<\/jats:italic> FISH. In addition, NR4A3 IHC performance is not improved by the inclusion of DOG1 IHC. Finally, NR4A3 positivity resolves the perennial problem of distinguishing AcCC from normal acinar tissue.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22338","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T06:36:47Z","timestamp":1598596607000},"page":"104-113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Evaluation of NR4A3 immunohistochemistry (IHC) and fluorescence in situ hybridization and comparison with DOG1 IHC for FNA diagnosis of acinic cell carcinoma"],"prefix":"10.1002","volume":"129","author":[{"given":"John M.","family":"Skaugen","sequence":"first","affiliation":[{"name":"Department of Pathology University of Pittsburgh Medical Center Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja R.","family":"Seethala","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh Medical Center Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simion I.","family":"Chiosea","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh Medical Center Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2871-5409","authenticated-orcid":false,"given":"Michael S.","family":"Landau","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh Medical Center Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"WHO Classification of Head and Neck Tumours. 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