Persistent, Unexplained Leukocytosis Is a Paraneoplastic Syndrome Associated With a Poor Prognosis in Patients With Urothelial Carcinoma

Abstract

BackgroundWe sought to define the disease characteristics and outcomes of those patients presenting with urothelial carcinoma and a persistently elevated white blood cell (WBC) count. Materials and MethodsWe queried a prospectively maintained institutional database. Patients were included if they had had a histologic diagnosis of urothelial carcinoma and a WBC count of > 20,000 cells/μL on ≥ 2 occasions separated by 30 days. The patients' medical records were reviewed and were excluded from the analysis if an underlying cause for the leukocytosis could be identified. The clinical, histologic, and laboratory data were then collected from the remaining patient cohort. ResultsWe identified a total of 1410 patients with a histologic diagnosis of urothelial carcinoma, 9 (0.6%) of whom met our inclusion criteria. These 9 patients had a median age of 63 years. At their presentation with leukocytosis, all 9 had muscle-invasive disease and 5 had evidence of metastatic disease. Leukocytosis was frequently associated with hypercalcemia (n = 6), thrombocytosis (n = 5), and anemia (n = 9). Chemotherapy was able to achieve a WBC response in 3 of 5 patients, although only 1 patient demonstrated a substantial reduction in tumor volume radiographically. Extirpative surgery was able to provide a response in the laboratory parameters in 2 of 4 patients. However, all studied patients ultimately developed leukocytosis recurrence after systemic or local therapy and experienced rapid disease progression, with a median interval from leukocytosis until death of 71 days. ConclusionParaneoplastic leukocytosis in the setting of urothelial carcinoma is a rare phenomenon but confers a poor prognosis, with a rapid progression to death.