具有内翻生长特征的尿路上皮增生性病变的临床病理学研究

Urothelial hyperplastic lesion with endophytic growth pattern：a clinicopathologic study

目的 研究伴内翻生长特征的尿路上皮增生性病变的临床病理特征,探讨免疫组织化学和多点荧光原位杂交在其鉴别诊断中的作用.方法 收集具有内翻生长特征的尿路上皮病变41例,分为内翻乳头状瘤、内翻生长型尿路上皮癌、旺炽型von Brunn细胞巢,用多点荧光原位杂交方法检测其3、7、17号染色体获得和9p21缺失;免疫组织化学EnVision法标记p53、CK20和Ki-67;并对12例进行随访.结果 （1）内翻乳头状瘤12例,平均1.2 cm,由互相连接的细胞索或巢在固有膜内生长,细胞索相对较细而宽窄一致,细胞巢外呈栅栏状、内为流水状排列,可见鳞状分化,无细胞学上的异型性,无或偶见核分裂象,4例可见少量表面外生乳头,被覆少于6层的正常尿路上皮.（2）内翻生长型尿路上皮癌24例,平均2.1 cm,结构似内翻乳头状瘤,但细胞索较粗并宽窄不一,细胞巢粗大并不规则状,可形成实体结构,瘤细胞轻至中度异形,核分裂象1～8个/10 HPF,3例表面均未见外生性乳头,但表层尿路上皮有明显异型增生,有少量外生乳头者外生成分形态符合低级别或低度恶性潜能.（3）旺炽型yon Brunn细胞巢5例,平均0.9 cm,表面被覆正常或增厚的黏膜组织,固有膜内见巢状分布、大小不等、排列紧密的尿路上皮团伴有囊腔形成,细胞均无异型性,无或偶见核分裂象.多点荧光原位杂交：79.1%（19/24）的内翻生长型尿路上皮癌存在染色体异常阳性,而内翻乳头状瘤和旺炽型von Brunn细胞巢无阳性染色体异常.免疫组织化学：CK20仅在2例内翻生长型尿路上皮癌中弱表达,内翻乳头状瘤和旺炽型von Brunn细胞巢均为阴性;16例内翻生长型尿路上皮癌和1例内翻乳头状瘤中有5%～50%的瘤细胞弱表达p53;内翻生长型尿路上皮癌中1%～5%表达Ki-67,内翻乳头状瘤和旺炽型von Brunn细胞巢均低于1%.随访：2例内翻生长型尿路上皮癌经多次复发后为浸润性癌,行全膀胱切除后仍发生远处转移.内翻乳头状瘤无复发.结论 伴内翻生长特征的尿路上皮增生性病变在良恶性病变中存在形态学上的重叠,但内翻生长型尿路上皮癌在形态及免疫组织化学上有独特特征.多点荧光原位杂交在鉴别诊断中有辅助作用.

Objective To study the clinieopathologie features of urothelial hyperplastie lesion with an endophytic growth pattern and the role of immunohistochemistry and muhitargeted fluorescence in situ hybridization（FISH）in the differential diagnosis.Methods Forty-one cases of urothelial lesions exhibiting endophytic growth patterns were reviewed and reclassified as inverted papilloma.urothelial carcinoma with an endophytic growth pattern,and florid von Brunn nest.The gains of chromosomes 3,7,and 17 and loss of 9p21 was detected by FISH,and performed immunohistochemical staining for CK20,p53,and Ki-67.Follow-up data of 12 cases were obtained.Results （1）Twelve inverted papillomas sized 1.2 cm in average.consisted of anastomosing cords and nests with uniform width distribution involving the lamina propfia,the central portion contained streaming cells with squamous metaplasia,and the periphery showed palisading.No or rare atypia and mitosis were found.Focal exophytic papillary component lined by less than 6 layers of normal urothelium were observed in 4 cases.（2）Twenty-four urothelial carcinomas with an endophytic growth pattern sized 2.1 cm in average,demonstrated the similar architecture with inverted papilloma,but exhibited thick columns and variable thickness ofthe cords,irregular size and shape of large nests with transition into solids.Mild to moderate cytologic atypia was shown,and mitotic figures ranged 1 to 8 per 10 HPFs.Exophytic papillary component was not observed in 3 cases.but the superficial urothelium showed dysplasia,while coexisted exophytie component in other eases was associated with low malignant potential or low grade tumor.（3）Five florid von Brunn nests sized 0.9 cm in average,had normal or hyperplastic urothelium,variable nests with cysts compacted in lamina propria,no cytologic atypia and mitosis.Twenty-one of 24（79.1%）urothelial carcinomas with an endophytie growth pattern displayed abnormally positive results by muhitargeted FISH,whereas all inverted papillomas and florid yon Brunn nests were negative.Immunohistochemically,CK20 Was weakly positive in 2 cases of urothelial carcinoma with an endophytic growth pattern,and negative in all inverted papillomas and florid yon Brunn nests.p53 weakly stained 5%to 50%nuclei of the tumor cells in 16 cafles of urothelial carcinomas with an endophytie growth pattem and 1 inverted papiHoma.1%-5%tumor ceUs expressed Ki-67 in urothelial carcinoma with an endophytic growth pattern,and less than 1%in inverted papiHoma and florid von Brunn nests.Follow-up study revealed that 2 cases of urothelial carcinoma with an endophytic growth pattern had developed invasive carcinoma,underwent cystectomy,and metastasized remotely.No recurrence occurred in cases of inverted papilloma.Conclusions Benign and malignant urothelial lesions with an endophytic growth pattern present histologie overlapping.Urothelial carcinoma with an endophytie growth pattern displays unique characteristics in morphology and immunohistochemistry.Multitargeted FISH analysis is helpful in the differential diagnosis.