Objective: To investigate the clinicopathologic and immunohistochemical features associated with invasive low-grade papillary urothelial carcinoma (LGPUC), an uncommon entity not previously described in published studies. Methods: A multicenter effort originally identified 36 cases diagnosed as invasive LGPUC by urologic pathology subspecialists; after re-review, 23 cases were included. Results: The average patient age was 69 years (range 46-82); 20 patients were men and 3 were women. Stage pT1 disease was present in 19 (83%) of 23 and pT2 disease in 4 patients. Of the 23 cases, 13 (57%) showed a single focus of invasion and 10 multiple foci. The invasive front showed rounded, variably sized nests in 17 cases (74%) and irregular nests with retraction artifact in 6. Additional findings in the noninvasive component included inverted growth in 23, apoptotic debris in 5, focal brisk mitotic activity in 4, dispersed chromatin in individual cells in 4, and a single atypical cell in 2. Immunohistochemical stains showed focal p53 nuclear stain in 23, patchy full-thickness cytokeratin 20 stain in 20, full-thickness CD44 expression in 17, and retention of E-cadherin in 23 cases. Clinical follow-up was available for all patients. The subsequent diagnosis included papilloma in 1 patient (4%), LGPUC in 5 (22%), and high-grade papillary urothelial carcinoma in 8 (35%) of the 23 patients, with 5 demonstrating invasion. Of the latter patients, 2 developed metastatic disease. Conclusion: Given the risk of progressive disease in these patients, especially the limited stage pT1 disease in most patients, additional studies investigating the molecular properties and outcomes associated with this uncommon lesion are warranted.
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