Department of Pathology, University of California San Francisco (UCSF), San Francisco, CA, 94158, USA.
Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Department of Pathology, Cleveland Clinic, Cleveland, OH, 44195, USA.
Hum Pathol. 2023 Jun;136:56-62. doi: 10.1016/j.humpath.2023.03.007. Epub 2023 Mar 29.
Urothelial carcinoma in situ (uCIS) is typically recognized by overtly malignant cells with characteristic nuclear features; multiple histologic patterns have been described. A rare "overriding" pattern, in which uCIS tumor cells extend on top of normal urothelium, has previously been mentioned in the literature, but not well described. Herein, we report 3 cases of uCIS with "overriding" features. Detailed morphologic evaluation revealed somewhat subtle cytologic atypia: variably enlarged hyperchromatic nuclei and scattered mitotic figures but with abundant cytoplasm and limited to superficial urothelium. Immunohistochemical (IHC) analysis showed a distinctive diffuse positive aberrant p53 pattern, limited to the atypical surface urothelial cells; these cells also showed CK20+, CD44-, and increased Ki-67. In 2 cases, there was a history of urothelial carcinoma and adjacent conventional uCIS. In the third case, the "overriding" pattern was the first presentation of urothelial carcinoma; therefore, next-generation sequencing molecular testing was also performed, revealing pathogenic mutations in TERTp, TP53, and CDKN1a to further support neoplasia. Notably, the "overriding" pattern mimicked umbrella cells, which normally line surface urothelium, can have abundant cytoplasm and more variation in nuclear and cell size and shape, and show CK20+ IHC. We therefore also evaluated umbrella cell IHC patterns in adjacent benign/reactive urothelium, which showed CK20+, CD44-, p53 wild-type, and very low Ki-67 (3/3). We also reviewed 32 cases of normal/reactive urothelium: all showed p53 wild-type IHC in the umbrella cell layer (32/32). In conclusion, caution is warranted to avoid overdiagnosis of usual umbrella cells as CIS; however, "overriding" uCIS should be recognized, may have morphologic features that fall short of the diagnostic threshold of conventional CIS, and requires further study.
尿路上皮原位癌（uCIS）通常通过具有特征性核特征的明显恶性细胞来识别；已经描述了多种组织学模式。以前在文献中提到过一种罕见的“主导”模式，其中 uCIS 肿瘤细胞覆盖在正常尿路上皮之上，但描述不详。在此，我们报告 3 例具有“主导”特征的 uCIS。详细的形态学评估显示出有些微妙的细胞学异型性：细胞核大小不一、染色质深染、散在有丝分裂象，但细胞质丰富，仅限于浅层尿路上皮。免疫组织化学（IHC）分析显示出一种独特的弥漫性异常 p53 模式，仅限于异型表面尿路上皮细胞；这些细胞还显示 CK20+、CD44-和 Ki-67 增加。在 2 例中，有尿路上皮癌和相邻的常规 uCIS 病史。在第 3 例中，“主导”模式是尿路上皮癌的首次表现；因此，还进行了下一代测序分子检测，发现 TERTp、TP53 和 CDKN1a 的致病变异，进一步支持肿瘤发生。值得注意的是，“主导”模式类似于正常排列在表面尿路上皮的伞细胞，可具有丰富的细胞质，并且细胞核和细胞大小和形状的变化更大，并显示 CK20+IHC。因此，我们还评估了相邻良性/反应性尿路上皮的伞细胞 IHC 模式，结果显示 CK20+、CD44-、p53 野生型和 Ki-67 非常低（3/3）。我们还回顾了 32 例正常/反应性尿路上皮：伞细胞层均显示 p53 野生型 IHC（32/32）。总之，应谨慎避免将常见的伞细胞过度诊断为 CIS；然而，应该认识到“主导”uCIS，其形态特征可能达不到常规 CIS 的诊断标准，需要进一步研究。
