Xiao Li, Wang Chao-fu, Zhu Xiong-zeng, Yin Yu-lei, Chen Yan, Lu Chen, Yu Bo
Department of Pathology, Huadong Hospital, Fudan University, Shanghai 200040, China.
Zhonghua Bing Li Xue Za Zhi. 2011 May;40(5):319-23.
To study the clinicopathologic features of urothelial hyperplastic lesion with an endophytic growth pattern and the role of immunohistochemistry and multitargeted fluorescence in situ hybridization (FISH) in the differential diagnosis.
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.
(1) Twelve inverted papillomas sized 1.2 cm in average, consisted of anastomosing cords and nests with uniform width distribution involving the lamina propria, 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 of the 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 exophytic component in other cases 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 endophytic growth pattern displayed abnormally positive results by multitargeted FISH, whereas all inverted papillomas and florid von 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 von Brunn nests. p53 weakly stained 5% to 50% nuclei of the tumor cells in 16 cases of urothelial carcinomas with an endophytic growth pattern and 1 inverted papilloma. 1%-5% tumor cells expressed Ki-67 in urothelial carcinoma with an endophytic growth pattern, and less than 1% in inverted papilloma 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.
Benign and malignant urothelial lesions with an endophytic growth pattern present histologic overlapping. Urothelial carcinoma with an endophytic growth pattern displays unique characteristics in morphology and immunohistochemistry. Multitargeted FISH analysis is helpful in the differential diagnosis.
研究具有内生性生长模式的尿路上皮增生性病变的临床病理特征以及免疫组织化学和多靶点荧光原位杂交(FISH)在鉴别诊断中的作用。
回顾性分析41例具有内生性生长模式的尿路上皮病变,并重新分类为内翻性乳头状瘤、具有内生性生长模式的尿路上皮癌和旺盛型von Brunn巢。采用FISH检测3号、7号和17号染色体的增益以及9p21的缺失,并对CK20、p53和Ki-67进行免疫组织化学染色。获取12例患者的随访数据。
(1)12例内翻性乳头状瘤,平均大小为1.2 cm,由相互吻合的条索和巢状结构组成,宽度均匀,累及固有层,中央部分有呈流水状排列的细胞伴鳞状化生,周边呈栅栏状排列。未见或罕见异型性及核分裂象。4例可见局灶性外生性乳头状成分,由少于6层的正常尿路上皮衬覆。(2)24例具有内生性生长模式的尿路上皮癌,平均大小为2.1 cm,与内翻性乳头状瘤结构相似,但可见粗大的柱状结构及条索厚度不一,大巢状结构大小和形状不规则并可过渡为实性结构。可见轻至中度细胞学异型性,每10个高倍视野核分裂象为1~8个。3例未见外生性乳头状成分,但浅表尿路上皮显示发育异常,其他病例中外生性成分并存时与低恶性潜能或低级别肿瘤相关。(3)5例旺盛型von Brunn巢,平均大小为0.9 cm,尿路上皮正常或增生,巢状结构多样,固有层内有紧密排列的囊肿,无细胞学异型性及核分裂象。24例具有内生性生长模式的尿路上皮癌中21例(79.1%)多靶点FISH检测结果异常阳性,而所有内翻性乳头状瘤和旺盛型von Brunn巢均为阴性。免疫组织化学方面,CK20在2例具有内生性生长模式的尿路上皮癌中呈弱阳性,在所有内翻性乳头状瘤和旺盛型von Brunn巢中均为阴性。p53在16例具有内生性生长模式的尿路上皮癌和1例内翻性乳头状瘤中,5%~50%的肿瘤细胞核呈弱阳性染色。具有内生性生长模式的尿路上皮癌中1%~5%的肿瘤细胞表达Ki-67,内翻性乳头状瘤和旺盛型von Brunn巢中表达率低于1%。随访研究显示,2例具有内生性生长模式的尿路上皮癌发展为浸润性癌,接受了膀胱切除术并远处转移。内翻性乳头状瘤病例无复发。
具有内生性生长模式的良性和恶性尿路上皮病变存在组织学重叠。具有内生性生长模式的尿路上皮癌在形态学和免疫组织化学方面表现出独特特征。多靶点FISH分析有助于鉴别诊断。