Squamoid and glycogen-rich-like clear-cell change in low-grade papillary urothelial carcinoma: a clinicopathologic analysis

Abstract

Background: Low-grade papillary urothelial carcinoma (LGPUC) is the most common form of non-muscle-invasive bladder cancer and is typically associated with frequent recurrence but limited progression. While focal squamoid morphology and clear-cell change may occasionally be encountered in LGPUC, their clinicopathologic significance remains poorly defined. Design: We retrospectively reviewed all LGPUC cases diagnosed at a tertiary academic center between 2015 and 2025. Hematoxylin and eosin (H&E)-stained slides were reassessed for squamoid morphology and H&E-suspected glycogen-rich-like clear-cell change. Cases with suspected glycogen-rich-like morphology underwent PAS and PASD staining for histochemical evaluation. Clinicopathologic features and clinical outcomes were analyzed. Results: A total of 514 patients with LGPUC were included. Squamoid morphology was identified in 6 cases (1.2%). Four additional tumors (< 1%) showed focal glycogen-rich-like clear-cell change. During follow-up, recurrence occurred in 1 of 6 patients (16.7%) with squamoid morphology, whereas no progression was observed in this subgroup. One patient with glycogen-rich-like clear-cell change subsequently developed invasive low-grade urothelial carcinoma (pT1). Conventional LGPUC showed recurrence in 57 of 504 patients (11.3%) and subsequent progression in 27 of 504 patients (5.4%). Conclusion: Squamoid morphology is an uncommon finding in LGPUC and was not associated with adverse clinical outcomes in this cohort. Glycogen-rich-like clear-cell change could not be definitively confirmed on corresponding deeper PAS/PASD levels, underscoring the importance of careful histochemical correlation before diagnosing glycogen-rich morphology in LGPUC. These findings suggest that focal squamoid morphology and glycogen-rich-like change should be interpreted cautiously and do not appear to justify tumor upgrading in the absence of conventional high-grade features.