膀胱巢状变异型尿路上皮癌4例临床病理分析

Clinicopathologic features of nested variant urothelial carcinoma in urinary bladder

目的探讨膀胱巢状变异型尿路上皮癌（NVUC）的临床病理特征、诊断与鉴别诊断及预后。方法应用常规HE和免疫组化染色及光镜观察4例膀胱NVUC,通过临床随访及结合文献复习进行讨论。结果本组患者男性3例,女性1例,年龄52-62岁,平均57岁;首发症状大多表现为肉眼血尿。组织学上,NVUC癌巢的形态多样,主要呈不规则小巢团状或大巢团状,也可呈条索状、小管状结构。癌细胞相对温和,核异型性很小或无异型性,核/浆比例较典型尿路上皮癌者小;多数染色质纤细,颗粒状,核仁不明显。其中1例肿瘤侵及固有层,2例肿瘤侵及深肌层,1例肿瘤侵及外膜。免疫组化示4例AE1/AE3、CK7、34βE12、p63均弥漫强（＋）,2例CK20（＋）,Ki-67阳性细胞指数20%-40%（平均30%）,p53均（＋）;P504S和uroplakin-Ⅲ均（-）。4例随访时间8-18个月,2例术后复发,均无转移,4例均健在。结论 NVUC是膀胱尿路上皮癌的一种罕见变异型,生物学行为常呈侵袭性。确诊主要依赖正确的形态学观察,免疫组化检查在鉴别诊断中有一定的辅助作用。

Objective To study the clinicopathologic features,diagnosis,differential diagnosis and prognosis of nested variant urothelial carcinoma（ NVUC） in urinary bladder. Methods Four cases of NVUC were reviewed. Routine paraffin sections with HE staining and immunohistochemistry of En Vision method were observed under light microscope.Pathological and clinical data were analyzed with review of literature. Results The patients were 3 males and l female.The age of patients ranged from 52 to 62 years（ average,57 years）. Most of the patients presented with hematuria.Histologically,the tumors showed varied architectures,ranging from predominantly disordered proliferation of small or large nests to cordlike and tubular pattern. The invasion of lamina propria was identified in one case,muscularis propria invasion was identified in two cases,and one case showed infiltration of adventitia. The tumors exhibited overall bland cytology with mild or no atypia. The nuclear / cytoplasm ratio was smaller than typical UC. The tumor cells had granular chromatin with inconspicuous nucleoli. Immunohistochemical study showed that the tumor cells in all cases were strongly positive for AEl /AE3,CK7,34βE12 and P63. CK20 were positive in 2 cases. Ki-67 index ranged from 20% to 40%（ mean 30%）. p53 was positive in all cases. All tumors were negative for P504 S and Uroplakin- Ⅲ. The duration of follow up ranged from 8months to 18 months. Two patients were alive with recurrence,and the other two patients were alive without recurrence and metastasis. Conclusion NVUC of urinary bladder is a rare variant of high-grade UC. The biological behavior of this variant is often aggressive. The correct diagnosis mainly depends on the morphological evaluation. Immunohistochemical study may be helpful in the differential diagnosis.