Case of the Week

Editor: Mahmut Akgul (akgulm@amc.edu)

2022-25/June 20

Contributors: Ankur Sangoi

Middle-aged man with no prior history of malignancy presents with hematuria. Cystoscopy showed blue light positive bladder lesion, biopsied.

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7 photo(s) Updated on: June 17, 2022

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Quiz

1. What is the correct diagnosis?

a) Reactive urothelial atypia

b) Urothelial dysplasia

c) BK viral cytopathic atypia

d) Urothelial carcinoma in situ

Even from the original immunohistochemical study of urothelial carcinoma in situ (CIS) in 2001 evaluating p53, CK20, and CD44, a "positive" p53 staining pattern was considered 3 or 4+ nuclear staining intensity within lesional cells. Only few subsequent studies have addressed the concept of "null phenotype" p53 (complete loss of p53 staining) in urothelial neoplasia, unlike within the gynecologic literature where a more descriptive review of p53 staining patterns and recommended reporting diagnostic terminology has been adopted.

Only recently, the concept of null phenotype p53 staining has been shown by molecular confirmation to indeed represent an aberrant staining pattern in urothelial CIS. While the diagnosis of urothelial CIS remains an H&E finding, in some cases an immunopanel of p53, CK20, and CD44 can be helpful, with a urothelial CIS pattern typically showing lesional cells with abnormal p53 (diffuse strong positive or completely negative), positive CK20, and negative CD44. A diagnosis of urothelial dysplasia should be made infrequently, and typically restricted to patients with a known history of urothelial neoplasia, and in which the biopsy shows atypia insufficient for an outright diagnosis of urothelial CIS but beyond that allowable for mere reactive changes. BK viral cytopathic atypia shows nucleomegaly with smudgy chromatin. Chemo/radiation atypia often shows nuclear/cytoplasmic vacuolation and shows radiation-associated stromal changes.

McKenney JK, Desai S, Cohen C, Amin MB. Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens. Am J Surg Pathol. 2001 Aug;25(8):1074-8. doi: 10.1097/00000478-200108000-00013. PMID: 11474293.

Sangoi AR, Chan E, Abdulfatah E, Stohr BA, Nguyen J, Trpkov K, Siadat F, Hirsch M, Falzarano S, Udager AM, Kunju LP. p53 null phenotype is a "positive result" in urothelial carcinoma in situ. Mod Pathol. 2022 Mar 23. doi: 10.1038/s41379-022-01062-2. Epub ahead of print.

About GUPS

The Genitourinary Pathology Society (GUPS) was formed with the vision of advancing the care of patients with urologic diseases through enhancements of best practices, research, and education in the subspecialty of Urological Pathology.

GUPS is an official Companion Society of the United States and Canadian Academy of Pathology (USCAP).

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