Nuclear hypochromasia: Shedding light on the “lightness” of high‐grade urothelial carcinoma

Abstract

Background The Paris system (TPS) has provided a standardized classification for reporting urinary cytology, specifically high‐grade urothelial carcinoma (HGUC). While hyperchromasia is well described in HGUC, there exists little data on nuclear hypochromasia in HGUC. Our focus was to investigate the incidence of hypochromasia in HGUC and if it should become a criterion for HGUC. Design All cases of HGUC at our institution for a 3‐year interval (2017–2019) using TPS were reviewed. Each case had a single ThinPrep slide and concurrent biopsy or resection specimen to confirm the diagnosis within 30 days. The presence of hypochromasia was evaluated, and cases with hypochromasia were stratified based on the tumor cell percentage. Cases with hypochromasia in 5% or greater of the tumor cells were considered “positively identified” for hypochromasia. Results We reviewed 117 cases of HGUC and identified nuclear hypochromasia in 12 cases (10.2%) within 5% or greater of the tumor cells. These 12 cases were further assessed based on if tumor cells showed hypochromasia in 5%–49% of the sample, or greater than 50% of the sample. Hypochromasia in 5%–49% of tumor cells was present in 8/117 cases (6.8%); whereas in 50% or greater samples 4/117 cases (3.4%) showed hypochromasia. No cases were identified where hypochromasia was noted in less than 5% of the tumor cells. Conclusion TPS and use of hyperchromasia as a feature of HGUC is affirmed. However, hypochromasia, while not diagnostic in isolation, is present in a sub‐set of patients with HGUC (10.2%) and should be considered as a variance noted in the nuclei of HGUC.

A comparison between conventional and the Paris systems of reporting urinary cytopathology with a literature update

“…The study by Stern and Siddiqui 41 elaboratively discusses the issues with hypochromatic HGUCs. Notably, 6.8% and 3.3% of total urothelial cells in urine samples of their 177 cases exhibited hypochromatic nuclei.…”

Are we on track for diagnosing high‐grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria

“…Cytomorphological features that may be present include cellular pleomorphism, prominent nucleoli, dense or vacuolated cytoplasm, mitoses, and necrosis 8 . There have been reports of cases of HGCs with hypochromasia as well as HGCs with extremely dark or inky chromatin that are also recognized as features of HGUC 11–15 …”

“…8 There have been reports of cases of HGCs with hypochromasia as well as HGCs with extremely dark or inky chromatin that are also recognized as features of HGUC. [11][12][13][14][15] Awareness of the variance in urothelial carcinoma differentiation on histology may help in the quick recognition of the nonconventional malignant urothelial cells on cytology, especially in paucicellular specimens. Recognized subtypes include squamous, glandular, trophoblastic, Mullerian, nested, large nested, tubular and microcystic, micropapillary, plasmacytoid, sarcomatoid, lipid-rich, lymphoepithelioma-like, clear cell (glycogen rich), giant cell, and poorly differentiated urothelial carcinoma.…”

Nuclear membrane irregularity in high‐grade urothelial carcinoma cells can be measured by using circularity and solidity as morphometric shape definitions in digital image analysis of urinary tract cytology specimens

“…The field of urine cytology was revolutionized with the introduction of The Paris System for Urine Cytology (TPS), originally published in 2016 and now in its second edition. [1][2][3][4] TPS standardized the diagnostic criteria and reporting system for urinary tract cytology specimens to focus on the diagnosis of high-grade urothelial carcinoma (HGUC). This focus improved the specificity of the classification of HGUC and increased the utility of urine cytology in diagnosis and monitoring of HGUC.…”