Flat Urothelial Lesions With Atypia: Interobserver Concordance and Added Value of Immunohistochemical Profiling.
BACKGROUND
Distinguishing urothelial carcinoma in situ (CIS) from other flat lesions of the urinary bladder with cytologic atypia is critically important for the management of patients with bladder neoplasia. However, there is high interpathologist variability in making these distinctions.


OBJECTIVE
The aim of this study is to assess interobserver agreement between general and specialized genitourinary pathologists, and to compare these diagnoses with those rendered after an immunohistochemical panel is performed. We hypothesized that addition of a set of immunohistochemical stains would reduce the number of cases classified within intermediate categories of atypia of uncertain significance and low-grade dysplasia.


METHODS
Two genitourinary pathologists independently assessed haematoxylin and eosin (H&E)-stained sections of 127 bladder biopsies from each of the 4 International Society of Urological Pathology/World Health Organization categories of flat lesions diagnosed by general pathologists. A subset of biopsies from 49 patients was reassessed after staining with a 3-antibody panel (CD44, CK20, and p53) and the results were correlated with patient follow-up.


RESULTS
Based on these immunohistochemistry (IHC) stains, 26 cases (53.1%) were recategorized. Of most clinical importance, 5 of 27 cases (18.5%) originally diagnosed as either atypia of uncertain significance or low-grade dysplasia were recategorized as CIS, and recurrent disease was identified on subsequent biopsies. None of the 10 cases diagnosed as CIS based on H&E stains were recategorized.


CONCLUSIONS
This triad of IHC stains can improve the precision of pathologic diagnosis of histologically atypical urothelial lesions of flat bladder mucosa. We recommend that pathologists apply this set of IHC stains to such lesions they find problematic based on H&E stains.
Department of Pathology, University of Washington, Seattle, WA.
Margaret E
ME
Lawless
Maria S
MS
Tretiakova
Lawrence D
LD
True
Funda
F
Vakar-Lopez
D000368:Aged; D001706:Biopsy; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000473:pathology; D003937:Diagnosis, Differential; D057286:Electronic Health Records; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015588:Observer Variation; D013194:Staining and Labeling / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology