Distinguishing nested variants of urothelial carcinoma from benign mimickers by TERT promoter mutation

Minghao Zhong, Wei Tian, Jian Zhuge, Xiaoyong Zheng, Tiangui Huang, Dongming Cai, David Zhang, Ximing J. Yang, Pedram Argani, John T. Fallon, Jonathan I. Epstein

Research output: Contribution to journalArticlepeer-review


Nested variant of urothelial carcinoma (NVUC) is an uncommon variant with minimally atypical cytology, which may overlap with benign urothelial lesions such as von Brunn nests, cystitis cystica, cystitis glandularis, and nephrogenic adenoma. Because of the tumor's deceptively bland appearance, these cancers can potentially be misdiagnosed as benign lesions, leading in some cases to a significant delay in correct diagnosis and appropriate treatment. Prior studies suggest that Ki67 and p53 are useful markers in distinguishing NVUC from benign lesions. However, the overlap in the rates of immunoreactivity has prevented pathologists from using these markers as reliable adjunct markers in differentiating NVUC from mimickers. In addition, large nested variant urothelial carcinoma (LNVUC), a relatively new entity, shares features of both the NVUC and papillary urothelial carcinomas with an inverted growth pattern. They also mimic benign lesions, such as proliferation of von Brunn nests and inverted urothelial papilloma. With the recent demonstration of a strong association of TERT promoter mutations and urothelial carcinoma, we hypothesized that TERT promoter mutations would be a useful marker to distinguish NVUC and LNVUC from other benign urothelial lesions. We have therefore sequenced the TERT promoter region of 20 cases of NVUC, 10 cases of LNVUC, 5 cases of von Brunn nests, 3 cases of cystitis cystica, 3 cases of cystitis glandularis, and 3 cases of nephrogenic adenoma. We found that 17 of 20 cases of NVUC and 8 of 10 cases of LNVUC had TERT promoter mutation: C228T; no mutation was found in any of the benign mimickers (0/14). This result strongly suggests that TERT promoter mutation is a useful adjunct biomarker to distinguish NVUC and LNVUC from benign mimickers.

Original languageEnglish (US)
Pages (from-to)127-131
Number of pages5
JournalAmerican Journal of Surgical Pathology
Issue number1
StatePublished - Jan 20 2015


  • Benign mimickers
  • Nested variants of urothelial carcinoma
  • TERT promoter mutation

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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