{"title":"NKX3.1 helps distinguish hyalinizing clear cell carcinoma from other clear cell salivary gland neoplasms.","authors":"Airi Sakyo, Eijitsu Ryo, Shogo Nishino, Kenya Kobayashi, Seiichi Yoshimoto, Go Omura, Chihiro Fushimi, Toshihiko Sakai, Azusa Sakai, Kohtaro Eguchi, Hideaki Takahashi, Kazuki Yokoyama, Yoshitaka Honma, Akiko Mori, Hiroko Kato, Toshiyuki Hatano, Akihiko Yoshida, Fumihiko Matsumoto, Yasushi Yatabe, Taisuke Mori","doi":"10.1016/j.labinv.2024.102205","DOIUrl":null,"url":null,"abstract":"<p><p>Hyalinized clear cell carcinoma (HCCC) is a rare tumor of the minor salivary gland, characterized by pale cytoplasm and EWSR1::ATF1 fusion. Recently, new fusions such as EWSR1::LARP4 and SMARCA2::CREM have also been identified. Histologically, HCCC closely resembles other salivary gland tumors like mucoepidermoid carcinoma and myoepithelial carcinoma, and there are no specific immunohistological markers for its identification. In this study, we investigated potential markers for HCCC based on the characteristics of minor salivary gland acini, from which these tumors may originate. SOX10 is a known marker for serous gland clusters and NKX3.1 for mucus gland clusters. Fluorescence intensity analysis of double staining, objectively evaluated by AI, revealed variations in the positive intensity of cells single positive for NKX3.1 and SOX10, as well as cells positive for both markers, which are commonly observed in normal minor salivary glands. We evaluated NKX3.1 expression by immunohistochemistry in 12 HCCC cases (including 9 EWSR1::ATF1, one EWSR1::LARP4, and one SMARCA2::CREM), 12 myoepithelial carcinoma cases and Tissue micro array (TMA) containing 88 cases of multiple salivary gland tumors using immunohistochemistry. NKX3.1 was expressed in all 12 HCCC cases (100%), with NKX3.1-positive cells ≧90% in four 3 cases, ≧60% one case, ≧30% five 4 cases, and <30% two 4 cases, respectively. SOX10 was negative in 10 cases and weakly positive in 2 cases. This finding mimics the pattern of expression in minor salivary glands and may explain the occurrence of weak NKX3.1 staining and SOX10 positive cases in HCCC. Additionally, in the TMA analysis, NKX3.1 staining was observed in only one HCCC case. These findings indicate that NKX3.1 is a useful marker for distinguishing HCCC from other clear cell salivary gland neoplasms. This study suggests that NKX3.1, along with SOX10 and CK7, can be utilized to improve the accuracy of HCCC diagnosis.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":" ","pages":"102205"},"PeriodicalIF":5.1000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Laboratory Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.labinv.2024.102205","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Hyalinized clear cell carcinoma (HCCC) is a rare tumor of the minor salivary gland, characterized by pale cytoplasm and EWSR1::ATF1 fusion. Recently, new fusions such as EWSR1::LARP4 and SMARCA2::CREM have also been identified. Histologically, HCCC closely resembles other salivary gland tumors like mucoepidermoid carcinoma and myoepithelial carcinoma, and there are no specific immunohistological markers for its identification. In this study, we investigated potential markers for HCCC based on the characteristics of minor salivary gland acini, from which these tumors may originate. SOX10 is a known marker for serous gland clusters and NKX3.1 for mucus gland clusters. Fluorescence intensity analysis of double staining, objectively evaluated by AI, revealed variations in the positive intensity of cells single positive for NKX3.1 and SOX10, as well as cells positive for both markers, which are commonly observed in normal minor salivary glands. We evaluated NKX3.1 expression by immunohistochemistry in 12 HCCC cases (including 9 EWSR1::ATF1, one EWSR1::LARP4, and one SMARCA2::CREM), 12 myoepithelial carcinoma cases and Tissue micro array (TMA) containing 88 cases of multiple salivary gland tumors using immunohistochemistry. NKX3.1 was expressed in all 12 HCCC cases (100%), with NKX3.1-positive cells ≧90% in four 3 cases, ≧60% one case, ≧30% five 4 cases, and <30% two 4 cases, respectively. SOX10 was negative in 10 cases and weakly positive in 2 cases. This finding mimics the pattern of expression in minor salivary glands and may explain the occurrence of weak NKX3.1 staining and SOX10 positive cases in HCCC. Additionally, in the TMA analysis, NKX3.1 staining was observed in only one HCCC case. These findings indicate that NKX3.1 is a useful marker for distinguishing HCCC from other clear cell salivary gland neoplasms. This study suggests that NKX3.1, along with SOX10 and CK7, can be utilized to improve the accuracy of HCCC diagnosis.
期刊介绍：
Laboratory Investigation is an international journal owned by the United States and Canadian Academy of Pathology. Laboratory Investigation offers prompt publication of high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease. Both human and experimental studies are welcome.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
