Hypochromatic large urothelial cells in urine cytology are indicative of high grade urothelial carcinoma

Abstract

In this study, we have examined 67 cytology specimens from patients from 2014 to 2016. The ratio man to women was 4:1 with a median age of 75 years (range: 55-87 years). Thin-Prep processed urinary cytology specimens demonstrated large urothelial cells, with cytologic features of malignancy, thus including hypochromatic nuclei with occasional peripherally accentuated chromatin rim. The cytological diagnosis of High Grade Urothelial Carcinoma (HGUC) was made in 55 patients while 12 specimens were classified as Atypical Urothelial Cells (AUC). This cases represent the 15% of the HGUC and the 4% of the AUC cases diagnosed in our department between 2016 to 2018. Of note, is the fact that in AUC cases, hypochromatic irregular urothelial cells were the only type of cells with malignant features observed in the specimen, and therefore, according to the Paris System criteria, the absence of nuclear hyperchromasia precludes a diagnosis of suspicious high grade urothelial carcinoma (SHGUC) or High Grade Urothelial Carcinoma (HGUC). Subsequent biopsy diagnosis of high grade urothelial carcinoma confirmed the cytological diagnosis of HGUC in 55 patients but also in all 12 patients with a AUC cytologic diagnosis. Our study series support the hypothesis that malignant urothelial cells with hypochromatic nuclei seen in urine cytologic specimens can be diagnostic for HGUC based on their very large nuclei, high nuclear cytoplasmatic ratio (N/C) >0.7, irregular nuclear outlines and coarse (frequently peripheral) chromatin in the absence of hyperchromasia.

Comparison of diagnostic performances of urine cytology before and after the use of the paris system criteria: An institutional experience from Turkey

“…It has been reported that nuclei of HGUC cells may be even hypochromatic, and they may resemble umbrella cells and do not demonstrate an increased N/C ratio. [ 19 20 ] In their study with digital image analysis, McIntire et al . showed that N/C ratio cut-off values for SHGUC and HGUC were lower than 0.7 and they advocated reducing the N/C ratio below the current threshold suggested in TPS.…”

Diagnostic Agreement for High-Grade Urothelial Cell Carcinoma in Atypical Urine Cytology: A Nationwide Survey Reveals a Tendency for Overestimation in Specimens with an N/C Ratio Approaching 0.5

“…Several studies have investigated the performance and use of cytomorphological features for diagnosing HGUC. All four TPS criteria were reported to be crucial indicators in urine cytology diagnosis although the sensitivity, specificity, and risk of malignancy varied in different studies or clinical scenarios [12][13][14][15]. None of the four cytological features can be regarded as a single conclusive criterion for diagnosing HGUC.…”

Impact of the Paris system for reporting urine cytopathology on predictive values of the equivocal diagnostic categories and interobserver agreement

“…Coarse chromatin alone was more specific than other individual features. [42631] Digital image analysis has been shown to support N/C ratio cutoff of 0.5 as a criterion for AUC. [32] A recently published study utilizing digital image analysis found that the average N/C ratio for HGUC was 0.57 and for SHGUC was 0.53, proposing reduction of the N/C ratio criterion to a cutoff below 0.7.…”