原发性颅内DICER1突变型肉瘤7例临床病理学分析  

Primary intracranial DICER1-mutant sarcoma:a clinicopathological analysis of seven cases

作　　者：区丽琼 奚少彦[1] 付凌怡 张文光[2] 贤欣仪 刘艳辉 云径平[1] 曾敬[1] 胡婉明 Ou Liqiong;Xi Shaoyan;Fu Lingyi;Zhang Wenguang;Xian Xinyi;Liu Yanhui;Yun Jingping;Zeng Jing;Hu Wanming(Department of Pathology,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Department of Neurosurgery,Jiangmen Central Hospital,Guangdong Province,Jiangmen 529000,China;Department of Pathology,Jiangmen Central Hospital,Guangdong Province,Jiangmen 529000,China)

机构地区：[1]中山大学肿瘤防治中心病理科,广州510060 [2]广东省江门市中心医院神经外科,江门529000 [3]广东省江门市中心医院病理科,江门529000

出　　处：《中华病理学杂志》2024年第12期1231-1237,共7页Chinese Journal of Pathology

摘　　要：目的探讨原发性颅内DICER1突变型肉瘤(primary intracranial DICER1-mutant sarcoma)的临床病理特征、免疫表型、分子特征及鉴别诊断,以提高病理医师对该类肿瘤的认识。方法收集2021—2023年中山大学肿瘤防治中心病理科经二代测序确诊的7例原发性颅内DICER1突变型肉瘤进行回顾性分析,收集同期10例胶质肉瘤、4例FET::CREB颅内间叶性肿瘤、4例恶性脑膜瘤、3例恶性孤立性纤维性肿瘤、3例恶性外周神经鞘膜瘤、3例滑膜肉瘤及3例横纹肌肉瘤,共30例作为对照。结果7例患者中,男性6例,女性1例;年龄10~32岁(中位年龄23岁)。组织形态多为梭形或多形肉瘤样,6例出现了嗜酸性小球结构,3例伴横纹肌或横纹肌母样细胞分化。免疫组织化学结果显示3例(3/7)灶性表达结蛋白,3例(3/7)ATRX缺失表达,4例(4/7)具有p53突变型表达模式。此外,4例(4/7)出现了SALL4的灶性或弥漫表达,而对照病例30例均未见SALL4蛋白表达。二代测序结果显示7例原发性颅内DICER1突变型肉瘤病例中均存在DICER1基因体细胞突变,其中5例DICER1基因突变位点均为p.E1813D。截至2024年5月,7例患者均存活。结论原发性颅内DICER1突变型肉瘤是一种罕见肿瘤,需要熟悉其形态学特点、免疫组织化学标志物、分子特征及鉴别诊断,提高对该肿瘤的认识,避免误诊。Objective To investigate the clinicopathological features,immunophenotype,molecular characteristics,and differential diagnosis of primary intracranial DICER1-mutant sarcoma in order to better understand this tumor type.MethodsA retrospective analysis was conducted on 7 cases of primary intracranial DICER1-mutant sarcoma diagnosed in the Department of Pathology,Sun Yat-sen University Cancer Center,Guangzhou,China between 2021 and 2023 using next-generation sequencing.At the same time,10 gliosarcomas,4 intracranial FET::CREB fusion-positive mesenchymal tumors,4 malignant meningiomas,3 malignant solitary fibrous tumors,3 malignant peripheral nerve sheath tumors,3 synovial sarcomas and 3 rhabdomyosarcomas(total 30 cases)were selected as control.ResultsAmong the 7 patients with primary intracranial DICER1-mutant sarcoma,6 were male and 1 was female,aged 10-32 years(median,23 years).The tissue morphology was predominantly spindle or pleomorphic sarcoma-like,with 6 cases exhibiting eosinophilic globules,and 3 cases showing rhabdomyoblastic or rhabdomyosarcoma-like cell differentiation.Immunohistochemistry revealed focal desmin expression in 3 cases(3/7),ATRX loss in 3 cases(3/7),and p53 mutant pattern in 4 cases(4/7).Additionally,4 cases(4/7)showed focal or diffuse SALL4 expression,whereas the control cases(30 cases)did not exhibit SALL4 protein expression,suggesting that SALL4 may possess certain auxiliary diagnostic value.Next-generation sequencing confirmed that all 7 cases of primary intracranial DICER1-mutant sarcoma harbored mutations in the DICER1 gene,with 5 cases having the mutation site at p.E1813D.Until May 2024,all 7 patients were alive.ConclusionsPrimary intracranial DICER1-mutant sarcoma is a rare tumor.Understanding its morphological characteristics,immunohistochemical and molecular markers and differential diagnosis is crucial to avoid misdiagnosis and to improve diagnostic accuracy of this tumor.

关 键 词：中枢神经系统肿瘤 肉瘤 预后 DICER1 人类婆罗双树样基因4(SALL4) 

分 类 号：R739.41[医药卫生—肿瘤]