CD117阴性/CK7阳性低级别嗜酸细胞性肾肿瘤7例临床病理学特征

Clinicopathological features of low-grade oncocytic renal tumor(CD117-negative,cytokeratin 7-positive):report of seven cases

目的:探讨CD117阴性/CK7阳性低级别嗜酸细胞性肾肿瘤(LOT)的临床病理特征,并分析其与杂合性嗜酸细胞/嫌色细胞肾肿瘤(HOCT)、肾嗜酸细胞瘤(RO)和嫌色肾细胞癌(chRCC)的关系。方法:收集中南大学湘雅医院(5例)和湘雅二医院(2例)2012年至2019年病理档案中7例LOT,进行临床资料收集和形态学、免疫组织化学染色结果分析。结果:7例LOT病例均为成人,年龄49~72岁(年龄中位数56.0岁,平均年龄60.7岁),肿瘤最大径2.5~6.0 cm(中位数4.3 cm,平均4.3 cm)。患者男性3例,女性4例,发生于左侧3例,右侧4例。所有肿瘤均为孤立性病变,无Birt-Hogg-Dubé(BHD)综合征或嗜酸细胞瘤病临床病理背景。随访患者5例均无病存活(中位数69.0个月,平均64.6个月,随访时间23~95个月)。镜下观察,所有的LOT均界限清楚(7/7),3例有不完整的包膜。肿瘤主要表现为明显致密的小巢状及纤细的分支薄壁血管围绕瘤巢的生长方式(赋予其器官样结构),但在小巢间常可见到数量不等的腺腔(样)结构(7/7)。肿瘤也常有富含水肿性间质的疏松区,肿瘤细胞在其中呈网状、梁状或单个细胞排列(6/7)。致密区和疏松区常有局灶的出血(5/7)。此外,1例LOT的致密区有局灶的囊肿形成,1例疏松区有局灶骨化。LOT同一肿瘤细胞常有RO和chRCC的杂合/交界细胞学特征:丰富的嗜酸性颗粒状胞质,核卵圆形或圆形,核膜光滑,可见细小的核仁(RO特征)及细微的核周空晕,偶见双核(chRCC特征)。LOT典型的表现为CK7阳性和CD117阴性的免疫表型(7/7)。PAX8(5/7)、P504s(2/7)、波形蛋白(1/7)在LOT中呈不同程度的阳性,而CK20、CD10、FOXI1均阴性。所有肿瘤均保留SDHB免疫染色。结论:LOT是一种罕见的、惰性的嗜酸细胞性肾肿瘤,具有同质性的RO和chRCC的杂合/交界细胞学特征,且与散发性HOCT有一定程度的临床病理重叠。LOT独特的形态学和免疫表型提示其可能是一个独立的肿瘤实体。

Objective To explore clinicopathological features of low-grade oncocytic tumor(LOT)of the kidney and to analyze its relationship to hybrid oncocytic/chromophobe tumor(HOCT)of the kidney,renal oncocytoma(RO),and chromophobe renal cell carcinoma(chRCC).Methods Seven LOTs were identified from the pathologic archives of two hospitals,including Xiangya Hospital(5 cases)and the Second Xiangya Hospital(2 cases)of Central South University between 2012 and 2019.Clinical data of the LOTs were collected.The tumor morphology was analyzed and immunohistochemistry was performed.Results All LOTs occurred in adults,aged from 49 to 72 years(median 56.0 years,mean 60.7 years).The tumor size ranged from 2.5 to 6.0 cm(median 4.3 cm,mean 4.3 cm).There were three male and four female patients.Three cases occurred in the left kidney and four in the right.All the tumors were solitary lesions without the clinicopathologic background of Birt-Hogg-Dubé(BHD)syndrome or oncocytosis.Five patients had available follow-up data(follow-up period 23-95 months,median 69.0 months,mean 64.6 months)and all were alive without disease.Microscopically,all LOTs were well-circumscribed(7/7).Three LOTs were partly encapsulated.The tumors demonstrated a predominant growth pattern comprising prominently compact small nests surrounded by delicately branching thin-walled blood vessels,imparting an organoid architecture(7/7),but variable numbers of glandular or gland-like structures were often seen among the small nests(7/7).There were frequently areas with loose,edematous stroma,and the tumor cells exhibited reticular,trabecular,or single cell arrangements(6/7).Focal hemorrhage was also commonly present in both compact and loose areas(5/7).In addition,focally cystic formation and ossification occurred in the compact area of one case and in the loose area of another case.The tumor cells in LOT showed intermediate cytologic characteristics between RO and chRCC,including abundantly eosinophilic granular cytoplasm,ovoid to round nuclei with mostly smooth contours,discernable small nucleoli(RO features),frequently delicate perinuclear halos,and occasional binucleation(chRCC features).The tumors were typically CK7-positive and CD117-negative(7/7),and variable staining for PAX8(5/7),P504s(2/7),and vimentin(1/7).They were negative for CK20,CD10 and FOXI1.All tumors retained SDHB immunostaining.Conclusions LOT is a rare and indolent oncocytic renal tumor with homogeneously intermediate cytologic features between RO and chRCC.There are some clinicopathologic overlaps between LOT and sporadic HOCT.The distinctive morphology and immunophenotype of LOT suggest that it is potentially a distinct tumor entity.