Giant cells with multiple nuclei are frequently observed in histopathological examinations and are often crucial for diagnosis, though they can occasionally lead to diagnostic challenges. This study highlights a series of cases involving giant cell lesions (GCL), focusing on the differential diagnosis and the additional diagnostic methods used to reach a conclusive diagnosis. The aim was to develop a diagnostic approach to more accurately characterize these lesions. We reviewed all cases from January 2018 to June 2019 in the department, including those where giant cells were either a primary or secondary finding. Of 1000 biopsies, 25 cases were identified based on the presence of giant cell morphology. The most common lesions included central giant cell granuloma, cherubism, hyperparathyroidism, peripheral giant cell granuloma, tuberculosis, and hybrid lesions. A step-by-step approach for differential diagnosis was created, and a diagnostic algorithm was established, which is now in use for GCL cases. The use of radiological imaging, serological tests, and sometimes special staining techniques is crucial for accurate histopathological diagnosis. This proposed algorithm streamlines the diagnostic process, helping to quickly narrow down the necessary investigations for effective diagnosis.
