Department of Pathology and Laboratory Medicine, New York Presbyterian-Weill Cornell Medicine, New York, NY, USA.
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Am J Clin Pathol. 2022 Jan 6;157(1):98-108. doi: 10.1093/ajcp/aqab099.
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.
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.
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.
NR4A3 IHC can be a robust diagnostic tool to identify AciCC, especially for cytology specimens.
唾液腺闰管细胞癌(AciCC)具有可识别的细胞形态学特征,这些特征可能与良性和恶性实体重叠,从而带来诊断挑战。AciCC 存在 t(4;9)易位,导致核受体亚家族 4 组 A 成员 3(NR4A3)表达增加,这种表达可通过手术切除(SR)的免疫组织化学(IHC)检测到。NR4A3 IHC 的细胞学数据有限。在此,我们研究了 AciCC 及其类似物的细胞学涂片、细胞块(CB)和 SR 中 NR4A3 IHC。
我们的队列包括 AciCC(包括高级别转化)、分泌癌、黏液表皮样癌(MEC)、Warthin 肿瘤、多形性腺瘤(PA)、细胞性 PA、PA 后癌、嗜酸细胞瘤、嗜酸细胞瘤和结节性嗜酸细胞瘤。如果超过 5%的肿瘤细胞显示核染色,则 NR4A3 IHC(Santa Cruz Biotechnology 和 Origene 抗体)呈阳性。
在 CB 中,90%的 AciCC 病例和无任何类似物表达 NR4A3。在 SR 中,100%的 AciCC 病例均表现出弥漫性 NR4A3,而 1 例高级别 MEC 则表现出局灶性 NR4A3。两种抗体克隆的一致性为 95%。CB 的灵敏度、特异性、阳性预测值和阴性预测值分别为 90%、100%、100%和 94.7%,SR 分别为 100%、98.8%、92.3%和 100%。从一例 AciCC 病例的细胞学涂片上可显示出 NR4A3 免疫染色。
NR4A3 IHC 可以成为识别 AciCC 的有力诊断工具,特别是对于细胞学标本。