NR4A3 免疫组织化学（IHC）和荧光原位杂交评估及其与 DOG1 IHC 在细针穿刺细胞学诊断涎腺腺样囊性癌中的比较。
Evaluation of NR4A3 immunohistochemistry (IHC) and fluorescence in situ hybridization and comparison with DOG1 IHC for FNA diagnosis of acinic cell carcinoma.
机构信息
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
出版信息
Cancer Cytopathol. 2021 Feb;129(2):104-113. doi: 10.1002/cncy.22338. Epub 2020 Aug 18.
BACKGROUND
Acinic cell carcinoma (AcCC) is diagnostically challenging on fine-needle 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. NR4A3 (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 NR4A3 break-apart 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.
METHODS
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-grade 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 NR4A3 FISH were attempted for all cases.
RESULTS
NR4A3 IHC had 81.8% sensitivity and 100% specificity for AcCC, whereas NR4A3 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.
CONCLUSIONS
NR4A3 IHC is highly specific for the diagnosis of AcCC and is more sensitive than DOG1 IHC and NR4A3 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.
背景
在细针抽吸中，由于腺样细胞癌 (AcCC) 可模拟多种其他肿瘤，甚至是正常的腺组织，因此其诊断具有挑战性。DOG1 的免疫阳性表达，特别是环状膜染色，有助于诊断 AcCC，但并不完全具有特异性，并且在小标本上容易出现技术和解释方面的挑战。最近在大多数 AcCC 中描述了 NR4A3（核受体亚家族 4 组 A 成员 3）易位和核 NR4A3 过表达。在此，作者评估了 NR4A3 免疫组化（IHC）和 NR4A3 断裂分离荧光原位杂交（FISH）在细胞块制备物上的性能，并将其与 DOG1 IHC 进行比较，以区分 AcCC 与鉴别诊断中的其他实体。
方法
作者鉴定了 34 个含有病变细胞的细胞学细胞块，包括 11 个 AcCC 标本（其中 2 个来自 1 例患者，显示高级别转化）以及 2 个分泌癌、7 个唾液腺癌、4 个黏液表皮样癌、3 个嗜酸细胞瘤、3 个肾细胞癌和 6 个包含非肿瘤性唾液腺组织的标本。对所有病例均尝试进行了 NR4A3 IHC、DOG1 IHC 和 NR4A3 FISH。
结果
NR4A3 IHC 对 AcCC 的敏感性为 81.8%，特异性为 100%，而 NR4A3 FISH 的敏感性为 36.4%，特异性为 100%，尽管由于细胞数量少，4 例（3 例黏液表皮样癌和 1 例唾液腺组织样本）无法进行分析。值得注意的是，没有正常的腺组织标本通过 IHC 或 FISH 显示 NR4A3 阳性。此外，DOG1 IHC 的敏感性为 72.7%，特异性为 92%。
结论
NR4A3 IHC 高度特异性地诊断 AcCC，且比 DOG1 IHC 和 NR4A3 FISH 更敏感。此外，加入 DOG1 IHC 并不能提高 NR4A3 IHC 的性能。最后，NR4A3 阳性解决了区分 AcCC 与正常腺组织的长期问题。
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