嗜酸型嫌色性肾细胞癌的临床病理学特点及鉴别诊断

Clinicopathological features and differential diagnosis of eosionphilic chromophobe renal cell carcinoma

目的探讨嗜酸型嫌色性肾细胞癌(eosionphilic chromophobe renal cell carcinoma,eChRCC)的临床病理特点,以及与肾嗜酸细胞瘤(renal oncocytoma,RO)、经典型嫌色性肾细胞癌(classic chromophobe renal cell carcinoma,cChRCC)在形态学、免疫表型及临床预后方面的差异。方法收集2006年10月至2019年2月青岛大学附属医院(13例)和海军第九七一医院(4例)病理确诊的17例eChRCC临床病理资料,进行组织学观察、免疫组织化学分析,并与同期诊断的RO 27例、cChRCC 30例进行比较。结果17例eChRCC中男性7例,女性10例,中位年龄54岁(40~75岁)。临床上,15/17例系体检发现。病理学检查:瘤体直径1.8~10.0 cm(平均5.7 cm),切面15例为实性,1例囊实性、1例囊性,多呈灰红、灰黄色,质软。镜下观察:瘤组织主要呈实性片状伴有多少不等的腺泡状结构(12例),3例以管囊状结构为主,以腺泡状和微囊状结构为主各1例,瘤细胞胞质嗜酸性,16例细胞间有清楚程度不等的边界,核小圆形或不规则,14例至少局部可见明显的核周空晕,9例散在或小灶状分布体积大多边形的淡染细胞,4例有小灶状细胞稀少的疏松水肿区,7例可见瘤组织灶状(4例)侵及肾实质、肾被膜外脂肪(2例)、肾窦侵犯(1例)。免疫组织化学染色:所有肿瘤均呈上皮细胞膜抗原(EMA)和claudin-7弥漫中度以上阳性,细胞角蛋白7(CK7,12/17)、CD117(15/17)和Ksp-cad(14/17)在大多数肿瘤阳性表达,cyclin D1(4/17)、AMACR(3/17)、CD10(4/17)、S100A1(1/17)和RCC(1/17)很少表达,所有病例对波形蛋白、碳酸酐酶Ⅸ(CAⅨ)、HMB45及Melan A均不表达,Ki-67阳性指数1%~5%。17例均获得随访,随访时间7~154个月,15例患者生存且无疾病进展证据,2例分别于术后31和38个月因肺/肝转移死亡。结论eChRCC形态学和免疫表型与RO均有重叠,瘤组织实性片状、腺泡状排列,瘤细胞间有边界、出现核周空晕以及缺乏显著的疏松水肿区是该肿瘤的重要组织学特征,瘤组织内散在或灶状分布多少不一的淡染细胞对eChRCC的诊断具有重要提示作用。免疫组织化学CK7、CD117、claudin-7和Ksp-cad阳性,cyclin D1和S100A1阴性有助于该肿瘤的诊断及鉴别诊断。eChRCC手术完整切除后预后极好,极少数病例可以出现远期转移,其累积生存率和cChRCC无明显差异,但较RO预后差。

Objective To investigate the clinicopathological characteristics of eosionphilic Chromophobe renal cell carcinoma(eChRCC),and differences in morphology,immunophenotype and clinical prognosis betweeneChRCC,renal oncocytoma(RO)and classic Chromophobe renal cell carcinoma(cChRCC).Methods The clinicopathologic data of 17 patients diagnosed as eChRCC from the Affiliated Hospital of Qingdao University(13 cases)and 971 Hospital of PLA Navy(4 cases)from October 2006 to February 2019 were collected.Immunohistochemical analysis was carried out to compare the immunophenotypes between 17 cases with ChRCC,27 cases with RO and 30 cases with cChRCC.Resuls Among the 17 patients,seven were males and ten were females,and the age ranged from 40 to 75 years(median 54 years).Clinically,15 cases of 17 were found accidentally by physical examination.The tumor size ranged from 1.8 cm to 10.0 cm(average 5.7 cm)and the cut surface of 15 cases were solid,one case was solicl and cystic,and one was cystic.Most showed gray to red,and partially soft,gray to yellow appearances.Microscopically,most tumors presented solid growth pattern with vary number of alveolar structures(12 cases).Some were predominately characterized by cystic structure(3 cases),alveolar structure(1 case)and microcapsule structure(1 case).There were boundaries with varying degrees of clarity between tumor cells in 16 cases.The cytoplasm of tumor cells was eosinophilic and the nuclei were small round or irregular with focal perinuclear haloes in 14 cases.Large polygonal cells with light-stained cytoplasm appeared focally in 9 cases,and edematous areas with scarce tumor cells were found in 4 cases.Among 7 cases,4 cases focally invaded peripheral renal parenchyma,2 cases invaded adipose tissues outside the renal capsule,and 1 case presented invasion of renal sinus.Immunohistochemically,all cases were moderate to strong positive for EMA and claudin-7.CK7,CD117 and Ksp-cad were highly expressed with the expression rates of 12/17,15/17,14/17,respectively.Cyclin D1,AMACR,CD10,S100A1,and RCC were rarely expressed with the expression rates of 4/17,3/17,4/17,1/17 and 1/17,respectively.On the contrary,all cases were negative for vimentin,CAⅨ,HMB45 and Melan A.The Ki-67 proliferation index of the 17 cases was 1%‒5%.Follow-up data were available for all 17 patients from 7 to 154 months.Among them,15 patients were alive without tumor recurrence or metastasis,one patient died of pulmonary metastasis after 31 months of surgery and one patient died of hepatic metastasis after 38 months of surgery.Conclusion eChRCC has overlapping morphology and immunophenotype with RO.eChRCC is characterized by solid nest or alveolar structure,distinct border between tumor cells,perinuclear halos and lacking of interstitial looseness and edema.Scattered large polygonal cells with light-stained cytoplasm in tumor tissue play a significant role in the diagnosis of eChRCC.The positive expression of CK7,CD117,claudin-7 and Ksp-cad,and negative expression of cyclin D1,S100A1 are helpful to the diagnosis and differential diagnosis of eChRCC.The prognosis of eChRCC after complete surgical resection is excellent and few cases may have long-term metastasis.There is no significant difference in prognosis between eChRCC and cChRCC,but eChRCC shows better outcome than RO.