肾嗜酸性空泡状肿瘤7例临床病理学分析

Renal eosinophilic vacuolated tumor:a clinicopathological analysis of seven cases

目的探讨肾嗜酸性空泡状肿瘤(eosinophilic vacuolated tumor,EVT)的临床病理学特点及诊断、鉴别诊断。方法收集2010年1月至2021年12月青岛大学附属医院(6例)和海军第九七一医院(1例)形态学典型、病理诊断无异议的肾EVT,进行组织形态学观察、免疫组织化学染色,并对2例进行全外显子测序。另选取同期诊断的肾嗜酸细胞瘤(RO)22例、嗜酸型嫌色细胞肾细胞癌(eChRCC)17例进行比较。结果男性4例,女性3例。年龄29~61岁(平均年龄42岁)。临床上,7例均系体检发现,瘤体直径1.5~4.5 cm,结节状,边界清楚,切面灰红、灰白色,实性,质软。镜下观察:瘤组织呈巢团状或实性排列,伴有多少不等的腺泡状或小囊状结构,瘤细胞胞质嗜酸,胞质内均可见大而突出的透明空泡,核圆形,核仁明显,4例局部可见核周空晕,1例见灶状分布、胞质稀少、核深染的小细胞成分。所有病例均未见坏死和核分裂象。3例存在水肿性间质。免疫组织化学染色:7例肿瘤均呈CD117、Cathepsin K阳性,波形蛋白、细胞角蛋白(CK)7阴性,CK20散在或斑片状阳性,Ki-67阳性指数1%~4%。全外显子测序显示2例肿瘤均存在MTOR基因突变。统计学分析表明,EVT与RO中Cathepsin K、CD10、S-100A1和Cyclin D1的表达(P<0.05)及EVT与eChRCC中Cathepsin K、CD10、CK7和claudin7的表达(P<0.001)差异有统计学意义。7例随访4~96个月(平均50个月),均未见复发或转移。结论肾EVT是一种在形态学、免疫表型与RO、eChRCC均有重叠、与TSC/MTOR通路密切相关的少见肾肿瘤,嗜酸性胞质内可见大而突出的透明空泡以及存在显著的核仁是该肿瘤的重要组织学特征。联合应用系列免疫组织化学抗体有助于EVT的诊断与鉴别诊断。该肿瘤生物学行为通常惰性,预后良好。

Objective:To investigate the clinicopathological features and differential diagnosis of eosinophilic vacuolated tumor(EVT).Methods:Seven cases of EVT with characteristic morphology and unequivocal diagnosis from the Affiliated Hospital of Qingdao University(6 cases),Qingdao,China and the 971 Hospital of PLA Navy(1 case),Qingdao,China between January 2010 and December 2021 were subject to morphological and immunohistochemical analyses.Additionally,whole exome sequencing(WES)was performed in two cases.Twenty-two cases of renal oncocytoma(RO)and 17 cases of eosinophilic chromophobe renal cell carcinoma(eChRCC)diagnosed at the same time were used as controls.Results:Four males and three females with a mean age of 42 years(range:29-61 years)were included in the study.The tumors were nodular and well-circumscribed,with sizes ranging from 1.5 to 4.5 cm.On cross-section,they appeared gray-red or gray-white,solid,and soft.Tumor cells were arranged in nests,solid sheets,and acinar or small vesicular structures.These cells exhibited eosinophilic cytoplasm with large,prominent clear vacuoles and round nuclei with prominent nucleoli.Perinuclear halos were focally present in four cases,while small tumor cells with sparse cytoplasm and hyperchromatic nuclei were seen in one case.No necrosis or mitosis was noted.Edematous stroma was detected in three cases.All tumors were positive for CD117 and Cathepsin K,but negative for vimentin and CK7.CK20 was positive in scattered individual cells,and Ki-67 positivity ranged from 1%to 4%.Point mutations in MTOR were identified in both patients who were subject to the molecular analysis.Statistical differences in the expression of Cathepsin K,CD10,S-100A1,and Cyclin D1 between EVT and RO(P<0.05)were significant,so were the differences in the expression of Cathepsin K,CD10,CK7 and claudin 7 between EVT and eChRCC(P<0.001).Seven patients were followed up for 4 to 96 months(mean,50 months),with no recurrences or metastases.Conclusions:EVT is a rare renal tumor that shares morphological and immunophenotypic features with RO and eChRCC,and it is closely linked to the TSC/MTOR pathway.The presence of large prominent transparent vacuoles in eosinophilic cytoplasm along with conspicuous nucleoli is its key morphological characteristics.The use of combined immunohistochemical stains greatly aids in its diagnosis.Typically,the tumor exhibits indolent biological behaviors with a favorable prognosis.