Cytologic features of micropapillary variant urothelial carcinoma in urinary tract cytology: Case series and review of literature

Background The micropapillary variant of urothelial carcinoma (MPVUC) is rare and aggressive. Surgical specimens often show atypical micro-clusters (AMCs) of cells with hyperchromatic, pyknotic, peripheral, irregular nuclei with variable nuclear to cytoplasmic ratios. We reviewed urinary tract cytology (UTC) from patients with MPVUC and hypothesized that AMCs would be present similar to those in surgical specimens. Methods The archives were searched from 2000 to 2020 for patients with surgical cases with either MPVUC or conventional high-grade urothelial carcinoma (HGUC) and with prior abnormal UTC. Two pathologists reviewed UTC cases and controls in a blinded manner for AMCs, with quantitation of none, low, moderate, and high. Interrater reliability was compared by quadratic weighted Cohen's Kappa test. The association between numerical average score and MPVUC status was determined by logistic regression. Results Five patients with invasive MPVUC, one patient with a noninvasive micropapillary component, and 15 control patients with conventional HGUC were included. All patients had prior or concurrent abnormal UTC samples. Increasing category of quantities of AMCs on cytology was associated with micropapillary status (OR 7.9, 95% CI 2.7-118, p = .045), with moderate agreement between raters (Cohen's Kappa 0.54, 95% CI 0.19-0.89, p = .004). Conclusions In patients with MPVUC on surgical specimen, AMCs were frequently observed on cytology. Similar atypical clusters were observed in patients with nonmicropapillary HGUC, albeit at lower frequency. However, given the WHO recommendation to diagnose micropapillary only if an invasive micropapillary component is present, a specific diagnosis of MPVUC on UTC cannot be based solely on the presence of AMCs.