Clinical characteristics and evolution of giant cell tumor occurring in paget's disease of bone.

Patients with Paget's bone disease (PDB) have an increased risk of developing giant cell tumor (GCT). This study was performed to evaluate the clinical characteristics and evolution of GCT complicating PDB and to compare these clinical characteristics to those observed in two large PDB cohorts, the PDB Italian Registry and the PRISM study. A systematic literature' review identified 117 patients complicated by GCT, which involves the skeletal sites affected by PDB (110 patients) or the extraskeletal tissues adjacent to affected bones (7 patients). In contrast with GCT not PDB-related, four-fifths of PDB-GCT patients (83.2%) were Caucasian and one-fourth of them (24.8%) had multifocal GCTs. Compared to PDB patients without GCT, PDB-GCT patients showed a higher male/female ratio (2.1 vs. 1.2) and more severe disease (age at PDB onset 52.1 ± 12.1 vs. 63.3 ± 10.6 years; number of affected sites 6.1 ± 2.9 vs. 2.34 ± 1.6; prevalence of polyostotic PDB 93.3% vs. 60.6%). Mortality rate of PDB-GCT patients was higher than those occurring in GCT not PDB-related (about 50% vs. 0-5% at 5 years) or in PDB patients without GCT (Log Rank= 29.002). Moreover, up to 98% of PDB-GCT cases had elevated total alkaline phosphatase levels at neoplasm diagnosis, suggestive of active PDB. Importantly, PDB-GCT patients from southern Italy (45.6% of all GCT patients) showed a higher prevalence of multifocal GCT (51.7%) and of positive familial history for PDB (70.8%) and GCT (65.0%). Indirect evidence finally suggests a decline in the incidence of GCT in PDB patients. The occurrence of GCT in PDB is associated with severe disease and reduced life expectancy of affected patients. The increased prevalence of familial diseases in PDB-GCT patients from southern Italy suggests a founder effect. The observed changes over time in the incidence of GCT in PDB could be related to the improved clinical management and/or living conditions of patients. © 2014 American Society for Bone and Mineral Research.