非典型肾囊肿六例临床病理和分子特征分析

Atypical renal cysts: a clinicopathological and molecular analysis of six cases

目的探讨非典型肾囊肿的临床病理特点和分子遗传学特征。方法收集浙江省人民医院2014年2月至2019年2月间诊治和会诊的6例非典型肾囊肿,观察其临床病理特征以及预后,应用荧光原位杂交(FISH)检测3p丢失以及第7号和17号染色体的三体性。结果6例均为男性,年龄43~63岁(中位年龄52岁)。术前Bosniak分级为Ⅱ级4例、Ⅰ级和Ⅲ级各1例。组织学上,非典型肾囊肿表现为单房或多房性囊肿,被覆复层透明细胞或嗜酸细胞,常见短的乳头样凸起,囊壁或囊肿间隔内无实性或结节状生长。组织学分型:3例为获得性囊性肾病相关性肾细胞癌样(ACKD-RCC样)型,2例为透明细胞型,1例为嗜酸细胞乳头型。2例伴发透明细胞肾细胞癌。免疫组织化学染色,ACKD-RCC样型为局灶CK7+/AMACR+/CD57+,透明细胞型为CK7+/碳酸酐酶Ⅸ(CAⅨ)+,嗜酸细胞乳头状型为CK7+/AMACR+。FISH检测发现1例ACKD-RCC样型表现为第17号染色体三体性,1例透明细胞型表现为3p缺失,其余病例均未见所检测的信号异常。6例术后随访13~70个月(中位随访时间27个月)均未见肾脏肿瘤证据。结论非典型肾囊肿是一组在临床、组织学和免疫表型以及分子遗传学特征上均具有异质性的病变,分子遗传学分析提示某些病例可能是目前已知肾细胞癌类型的前驱病变。广泛的取材和镜下仔细观察囊壁的组织学特征是区分其与广泛囊性变肾细胞癌的关键方法。

Objective To investigate the clinicopathological characteristics and molecular genetics of atypical renal cysts.Methods Six cases of atypical renal cysts were collected from Zhejiang Provincial People′s Hospital,Hangzhou,China,between February 2014 and February 2019.The clinicopathological characteristics and disease progression were analyzed.The 3p deletion and trisomy of chromosomes 7 and 17 were detected using fluorescence in situ hybridization(FISH).Results All of the 6 patients were male,aged 43-63 years(median:52 years).Preoperative Bosniak classification showed 4 cases of gradeⅡ,1 case of gradeⅠand 1 of gradeⅢ.Histologically,atypical renal cysts appeared as unilocular or multilocular cysts,lined by multilayered flattened or cuboidal-shaped clear or eosinophilic cells.They often showed short papillary projections,and lacked solid or nodular growth of the lesional cells within the wall or septa of the cysts.Histologically,these cysts could be classified into three categories:acquired cystic disease-associated renal cell carcinoma(ACKD-RCC)-like(3 cases),clear cell type(2 cases),and eosinophilic papillary type(1 case).Two cases of ACKD-RCC-like atypical renal cysts were accompanied by clear cell renal cell carcinomas.On immunohistochemical staining,ACKD-RCC-like atypical renal cysts were focally CK7+/AMACR+/CD57+,the clear-cell type atypical renal cysts were CK7+/CAⅨ+,and eosinophilic papillary type atypical renal cysts were CK7+/AMACR+.FISH analyses showed that one case of ACKD-RCC-like atypical renal cysts had trisomy 17 and one case of clear cell type had 3p deletion,while no signal abnormality was detected in the other cases.The six patients were followed up for 13 to 70 months(median:27 months),and no evidence of renal cell carcinoma was noted.Conclusion Atypical renal cysts are a group of lesions that are heterogeneous in clinical,histological and immunophenotypical and molecular genetic features.FISH analyses suggest that a subset of the cases may be precursors of currently known renal cell carcinomas.Extensively sampling and careful observation of the histological characteristics of the cyst wall are important for distinguishing atypical renal cysts from extensively cystic renal cell carcinomas.