低级别嗜酸细胞性肾肿瘤5例临床病理分析

Low-grade eosinophilic renal tumors: a clinicopathological analysis of 5 cases

目的探讨低级别嗜酸细胞性肾肿瘤(low-grade oncocytic tumor of kidney,LOT)的临床病理特征、免疫表型、分子遗传学特征及鉴别诊断。方法收集5例LOT,采用HE、免疫组化EnVision两步法染色及Sanger测序,分析其临床病理学特征、免疫表型、分子遗传学特征、预后等,并复习相关文献。结果5例LOT中女性4例,男性1例,年龄57~70岁,中位年龄65岁,平均64.8岁。临床表现:仅例1出现尿频伴间断腰痛,其余患者无症状,为偶然发现。影像学特征:B超表现为占位性病变,边界清,内部回声均匀;CT示中心见斑片状低密度影,边缘明显强化。眼观:瘤体呈结节状,最大径2.1~7.6 cm,平均4.04 cm,切面实性。镜检:LOT界清,部分可见厚包膜,肿瘤细胞多构成致密区及稀疏区,新鲜出血灶及蛋白样分泌物常见,可见灶性淋巴细胞聚集、肝板样及肝血窦样结构、厚壁血管、胶原纤维束分割肿瘤细胞形成的假结节及陈旧性出血。肿瘤细胞温和较一致,圆形或多角形,胞质丰富嗜酸性、细颗粒状,核大小一致,圆形、卵圆形,核膜清晰,为2级小核仁,可见核周空晕、双核细胞及核皱缩,未见核分裂象。免疫表型:瘤细胞CK7均弥漫强阳性,CD117均阴性,Ki67增殖指数低。Sanger测序提示4例有mTORC1信号通路突变(3例MTOR,1例RHEB)。患者行局部或根治性肾切除,随访2~52个月,患者均存活、未见复发。结论LOT是一种低级别、嗜酸性且罕见的肾肿瘤,生物学行为惰性,目前随访结果显示局部手术完整切除即可,预后良好,需与其他嗜酸性肾肿瘤等进行鉴别。

Purpose To examine the clinicopathologic,immunohistochemical,and molecular genetic characteristics and differential diagnosis of low-grade oncocytic tumor(LOT)of kidney with CK7 positive and CD117 negative,so as to enhance the understanding of this tumor among pathologists.Methods A total of five cases of renal LOT from the First Affiliated Hospital of Soochow University between December 2016 and February 2023 were included in this analysis.The clinicopathological features,immunophenotype,genetic characteristics,and prognosis were evaluated using HE staing,immunohistochemical staining,and Sanger sequencing.Additionally,relevant literature was reviewed to supplement the findings.Results Among the cohort of five patients,four were female and one was male,aged 57-70 years with a median age of 65 years and an average age of 64.8 years.Clinical presentation revealed that only the first case exhibited frequent urination accompanied by intermittent lumbago,while the remaining cases were asymptomatic and incidentally discovered.Imaging studies demonstrated space-occupying lesions with clear boundaries and even internal echoes on B-ultrasonography,and patchy low-density shadows in the center with obvious edge enhancement on CT.Grossly,the tumor was nodular,with a maximum diameter ranging from 2.1 to 7.6 cm,and an average diameter of 4.04 cm,with a solid section.Microscopically,the boundary of LOT was consistently well-defined,with a thick capsule.The arrangement of tumor cells was observed to be both dense and sparse,accompanied by fresh bleeding foci and proteinoid secretions.Focal lymphocyte aggregation,hepatic plate like and hepatic sinusoid like structures,thick-walled blood vessels,false nodules of tumor cells,and old hemorrhage were also noted.The tumor cells exhibited uniformity in shape,appearing round or polygonal,with eosinophilic and fine granular cytoplasm.The nuclei were of similar size and shape,appearing round or oval with a clear nuclear membrane.The histological features of the tumor included 2-grade small nucleoli,perinuclear halos,binuclear cells,and nuclear shrinkage,but no mitotic figures were detected.The immunophenotypic analysis revealed strongly diffuse expression of CK7 in the tumor cells,while CD117 was negative.The Ki67 proliferation index was low.Sanger sequencing identified mutations in mTORC1 pathway genes in four cases,including three mutations in MTOR and one mutation in RHEB.The patients underwent either local or radical nephrectomy,and were followed up for a period ranging from 2 to 52 months,during which all patients remained free of recurrence.Conclusion The low-grade,eosinophilic,and rare renal tumor known as LOT exhibits inert behavior.At present,the follow-up results show that complete resection of local operation is sufficient,and the prognosis is good.It is important to distinguish this lesion from other eosinophilic renal tumors.