摘要目的:探讨膀胱大巢状变异型尿路上皮癌（large nested variant of urothelial carcinoma, LNUC）的临床病理特征、诊断和鉴别诊断。方法:回顾性分析浙江省人民医院病理科2014年1月至2018年12月间诊治的5例膀胱LNUC的临床病理资料，行免疫组织化学EnVision法染色和基因测序，并复习相关文献。结果:5例均为男性，平均年龄63岁（48~81岁），肿瘤平均直径3.4 cm（1.7~4.7 cm）。镜下观察，浸润性的中等至大的癌巢呈规则的圆形、球茎样、椭圆形，至不规则的融合状、分支状、哑铃状排列，伴有轻度的间质反应。5例癌巢中均可见局灶的中央坏死和微囊变性。4例瘤细胞为低级别，1例局灶高级别，核分裂象少见。5例均可见表面尿路上皮肿瘤（3例低级别乳头状癌，1例高级别乳头状癌，1例原位癌）。3例可见伴随的小巢状变异型尿路上皮癌，2例可见伴随的普通型浸润性尿路上皮癌。4例分别可见神经侵犯和淋巴管血管内癌栓。4例行膀胱前列腺根治切除，pTNM分期：2例为pT3aN0M0期，各1例分别为pT4aN0M0和pT4aN1M0期；1例行经尿道膀胱切除，pT分期为pT2期。免疫组织化学染色结果：细胞角蛋白（CK）7、p40均为阳性（5/5），GATA3阳性4例，CK20阳性2例，Ki-67阳性指数平均为18%。3例行TERT基因启动子突变检测：1例为突变型（C228T），2例为野生型。5例术后均接受辅助化疗，随访2~11个月，1例死于其他疾病，各1例出现远处和盆腔淋巴结转移，2例无疾病生存。结论:LNUC具有"欺骗性"的低级别组织学特征和侵袭性的生物学行为，准确的认识其独特的浸润方式可助于诊断和鉴别诊断。LNUC并不偶然的与小巢状变异型尿路上皮癌并存，提示两者可能为同一种尿路上皮癌亚型的不同表现形式。

abstractsObjective:To investigate the clinicopathologic features, diagnosis and differential diagnosis of large nested variant of urothelial carcinoma (LNUC) of urinary bladder.Methods:The clinical and pathologic data of five cases of LNUC of urinary bladder diagnosed between January 2014 and December 2018 at the Department of Pathology, Zhejiang Provincial People′s Hospital were analyzed by immunohistochemistry (IHC) and Sanger sequencing. The relevant literature was reviewed.Results:All five patients were male with a mean age of 63 years (range, 48 to 81 years). The mean tumor size was 3.4 cm (range, 1.7 to 4.7 cm). Histologically, the invasive LNUC tumor cells formed medium to large sized nests of varying shapes, from regular round, bulbous, oval to irregularly fused, branched, dumbbell shaped glands, with mild stromal reaction. In all five cases, focal central necrosis and microcystic changes in the tumor nests were identified. Cytologically, the tumor cells were low grade in four cases; the remaining case was overall low grade with focal high grade areas. Mitoses were scarce. All cases possessed surface urothelial tumors, including three low-grade papillary carcinomas, one high-grade papillary carcinoma and one carcinoma in situ. Three of the LNUC were accompanied by small nested variant of urothelial carcinoma and two by conventional high grade invasive urothelial carcinoma. Perineural involvement and angiolymphatic invasion were each noted in four tumors. Radical cystectomy was performed in four cases with TNM stages as followings: pT3aN0M0 in two cases, pT4aN0M0 and pT4aN1M0 in one case each. The remaining case had transurethral bladder resection and was of pT2 stage. By IHC, all five cases were positive for CK7 and p40; four were positive for GATA3; two were positive for CK20; and the mean Ki-67 proliferation index was 18%. TERT promoter mutation status were successfully performed in three cases, with one showing mutation (C228T) and two were wild type. All patients received postoperative chemotherapy. At a follow-up of 2 to 11 months, one patient died of unrelated causes, two patients developed metastases, and two were alive with no evidence of disease.Conclusions:LNUC is a histologic subtype of urothelial carcinoma with deceptively benign features but aggressive behavior, and appreciation of its unique infiltration patterns can aid in diagnosis and differential diagnosis. LNUC tends to coexist with small nested variant of urothelial carcinoma, suggesting these may represent different manifestations of the same urothelial carcinoma subtype.