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腺样成釉细胞瘤与牙源性影细胞肿瘤的临床病理、免疫组化及分子特征比较分析

Adenoid Ameloblastoma Shares Clinicopathologic, Immunohistochemical, and Molecular Features With Dentinogenic Ghost Cell Tumor: A Comparative Analysis.

作者信息

Xue Jiang, Zhang Wenyi, Zhang Jianyun, Bai Jiaying, Zhang Aobo, Guo Xiaowen, Sun Lisha, Li Tiejun

机构信息

Departments of Oral Pathology.

National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices.

出版信息

Am J Surg Pathol. 2023 Nov 1;47(11):1274-1284. doi: 10.1097/PAS.0000000000002104. Epub 2023 Aug 7.

Abstract

The updated classification of odontogenic tumors by the World Health Organization (WHO) has included adenoid ameloblastoma (AA) as a distinct entity. However, distinguishing between AA and dentinogenic ghost cell tumor (DGCT) can still be challenging due to their significant morphologic similarities. In this study, we aimed to compare the clinicopathologic, immunohistochemical, and molecular characteristics of AA and DGCT to aid in their differentiation and to shed light on their pathologic mechanisms. Thirteen cases of AA and 14 cases of DGCT (15 samples) were analyzed, along with 11 cases of adenomatoid odontogenic tumor (AOT) and 18 cases of conventional ameloblastoma (AM) for comparative purposes. The study found that AA and DGCT shared a similar long-term prognosis. Immunohistochemically, all cytokeratins detected, except CK8/18, were not statistically significant in differentiating AA and DGCT, while there was a statistically significant difference in the immunophenotype of CK7 and CK10/13 between AA and AM. Nuclear β-catenin accumulation were detected in all cases of AA and DGCT, while AOTs and AMs exhibited cytoplasmic β-catenin. Molecularly, CTNNB1 hotspot mutations were found in only 1 case of AA (1/13), but not found in the other 3 types of tumors. BRAF p.V600E mutation was positive in 2/13 (15%) AA, 1/15 (7%) DGCT, and 2/11 (18%) AOT cases. In comparison, conventional AM was positive for BRAF p.V600E mutation in 94% (17/18) of cases, while KRAS mutations were detected in 63% (7/11) of AOT cases. The study suggests that the so-called AA is a rare benign tumor that exhibits clinical, immunohistochemical, and molecular features similar to DGCTs. Based on these findings, AA should not be categorized as a standalone entity solely based on the presence of whorls/morules and cribriform/duct-like structures. Further studies are needed to investigate the pathologic mechanisms of these tumors and to identify potential therapeutic targets.

摘要

世界卫生组织(WHO)对牙源性肿瘤的更新分类已将腺样成釉细胞瘤(AA)列为一个独立的实体。然而,由于腺样成釉细胞瘤和牙本质生成性影细胞瘤(DGCT)在形态学上有显著相似性,区分二者仍具有挑战性。在本研究中,我们旨在比较腺样成釉细胞瘤和牙本质生成性影细胞瘤的临床病理、免疫组化及分子特征,以辅助二者的鉴别诊断,并阐明其病理机制。分析了13例腺样成釉细胞瘤和14例牙本质生成性影细胞瘤(15个样本),并纳入11例腺样牙源性肿瘤(AOT)和18例传统型成釉细胞瘤(AM)作为对照。研究发现,腺样成釉细胞瘤和牙本质生成性影细胞瘤具有相似的长期预后。免疫组化方面,除CK8/18外,所有检测的细胞角蛋白在区分腺样成釉细胞瘤和牙本质生成性影细胞瘤时无统计学意义,而腺样成釉细胞瘤与成釉细胞瘤在CK7和CK10/13免疫表型上存在统计学差异。在所有腺样成釉细胞瘤和牙本质生成性影细胞瘤病例中均检测到核β-连环蛋白积聚,而腺样牙源性肿瘤和成釉细胞瘤表现为细胞质β-连环蛋白。分子水平上,仅在1例腺样成釉细胞瘤(1/13)中发现CTNNB1热点突变,而在其他3种肿瘤类型中未发现。BRAF p.V600E突变在2/13(15%)的腺样成釉细胞瘤、1/15(7%)的牙本质生成性影细胞瘤和2/11(18%)的腺样牙源性肿瘤病例中呈阳性。相比之下,94%(17/18)的传统型成釉细胞瘤BRAF p.V600E突变呈阳性,而63%(7/11)的腺样牙源性肿瘤病例检测到KRAS突变。该研究表明,所谓的腺样成釉细胞瘤是一种罕见的良性肿瘤,其临床、免疫组化和分子特征与牙本质生成性影细胞瘤相似。基于这些发现,不应仅根据漩涡状/桑葚状结构和筛状/导管样结构的存在将腺样成釉细胞瘤归类为一个独立的实体。需要进一步研究来探讨这些肿瘤的病理机制并确定潜在的治疗靶点。

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