肾脏杂合性嗜酸细胞/嫌色细胞肿瘤的临床病理学特征

Clinicopathological features of hybrid oncocytic/chromophobe renal cell tumor

目的探讨肾脏杂合性嗜酸细胞/嫌色细胞肿瘤(HOCT)的临床病理、免疫表型特点以及与肾嗜酸细胞瘤(RO)、嫌色性肾细胞癌间的关联性。方法收集2008年1月至2019年6月青岛大学附属医院(5例)和海军第九七一医院(3例)病理确诊为HOCT的临床病理资料,进行组织形态学观察、免疫组织化学染色及随访,并与同期诊断的27例典型RO 和17例嗜酸型嫌色性肾细胞癌(eChRCC)进行免疫组织化学比较。结果 8例中男性3例,女性5例,年龄39~75岁(中位年龄56岁)。均为散发性。7例因体检发现,1例因腰痛就诊。7例获得随访,时间8~96个月(平均37个月),均未见复发或转移。大体检查:7例单发,1例单侧多发。肿瘤直径1.4~5.7 cm,平均3.6 cm,切面灰红、灰黄色,边界清楚。镜下观察:瘤组织边界清楚,6例与周围肾组织直接相邻,2例有纤维性假包膜与周围肾组织分隔,3例瘤组织边缘可见内陷扩张的肾小管,1例瘤组织呈巢团状浸润包膜。瘤组织主要有2种组织学形态:Ⅰ型(4例),由所占比例多少不一的典型RO区与典型eChRCC区混和组成;Ⅱ型(4例),瘤组织具有RO和eChRCC两肿瘤共同的组织形态学特点,3例呈巢团状、梁索状或片状排列,具有显著的水肿性间质,瘤细胞胞质嗜酸,有边界,核小圆形、核周空晕明显;1例多结节状生长,瘤细胞排列成实性片状,水肿性间质不明显,胞质嗜酸、浅染或透明,核小圆形,部分可见明显核周空晕。免疫组织化学染色:所有肿瘤波形蛋白阴性、Ksp-cad弥漫性强度不等阳性,6例(6/8)CD117弥漫阳性,6例(6/8)CK7斑片状或散在着色,S-100A1(4/8)、cyclin D1(6/8)和claudin7(5/8)不同程度阳性表达,但范围和强度较单纯的RO和eChRCC均有缩小和减弱趋势。结论 HOCT是一种兼具RO和eChRCC形态特点的低级别嗜酸性肾肿瘤,联合应用CK7、CD117、Ksp-cad、cyclin D1、claudin7和S-100A1免疫组织化学染色对三种肿瘤的鉴别诊断具有辅助作用。该肿瘤手术切除后预后良好,生物学行为上可视为恶性潜能不能确定的肾上皮性肿瘤。

Objective To investigate the clinicopathological features and immunohistochemical phenotypes of hybrid oncocytic/chromophobe tumor(HOCT)of the kidney and its associations with renal oncocytoma(RO)and eosinophilic chromophobe renal cell carcinoma(eChRCC).Methods A total of 8 HOCT cases were collected from 2008 to 2019 at the Affiliated Hospital of Qingdao University(5 cases)and 971 Hospital of PLA Navy(3 cases),Qingdao,China for morphological studies,immunohistochemical staining and follow-up.The immunohistochemical results of HOCT were compared with those of 27 typical RO and 17 eChRCC.Results Among the 8 patients,3 were male and 5 were female.Their ages ranged from 39 to 75 years(median:56 years).All cases were sporadic.Seven patients were asymptomatic and one suffered from lumbago.During a mean follow-up of 37 months in 7 patients,none of them developed tumor recurrence or metastasis.Seven cases were solitary and one was multiple.The tumor size ranged from 1.4 to 5.7 cm(mean,3.6 cm).The cut surface of the tumors was dark red or yellowish.Histologically,the tumors were well-defined.Six cases were directly adjacent to the surrounding renal tissue,2 cases had pseudocapsule,3 cases showed entrapped renal tubules at the edge of tumor tissue,and one circumscribed with focal infiltrating borders.There were two types of histological morphology:one type(4 cases)was composed of mixed areas of otherwise typical RO and areas resembling chromophobe renal cell carcinoma;another type(4 cases)showed the morphological characteristics of both RO and eChRCC.Three second-type tumors showed nest-like,trabecular,and solid growth patterns with conspicuous edematous stroma.The cell border was conspicuous and the cytoplasm showed an eosinophilic appearance.The nuclei were small and round with clear perinuclear halo.One tumor showed a multi-nodular and solid growth pattern,and the cytoplasm was eosinophilic,hypochromatic or transparent.The nuclei were small and round,and some of them had obvious perinuclear halo.Immunohistochemically,the tumor cells in all 8 cases were positive for Ksp-cad but negative for vimentin.CD117 was diffusely positive in 6/8 cases.CK7 staining showed patchy positivity in 6/8 cases.S-100A1,cyclin D1 and claudin7 showed variable positivity in 4/8,6/8 and 5/8 cases,respectively,but the range and intensity were narrower and weaker than those in RO and eChRCC.Conclusions HOCT is a low-grade eosinophilic renal tumor with morphological characteristics resembling RO and eChRCC.The combined application of immunohistochemical stains of CK7,CD117,Ksp-cad,cyclin D1,claudin7 and S-100A1 may play an auxiliary role in the differentiation of the three tumors.HOCT has a good prognosis after surgical resection and can be regarded as a tumor with uncertain malignant potential.