Multinucleated giant cells are commonly encountered in histopathology and are mostly a clue to diagnosis but sometimes pose a diagnostic confusion. The present study elucidates a case series of giant cell lesions (GCL) with emphasis on differential diagnosis and other investigations that contribute towards arriving at a final diagnosis. We also intended to devise an algorithmic approach for the accurate pathological characterization of these lesions. All the cases reported in the department from January 2018 to June 2019 were reviewed by pathologists and the total number of lesions where giant cells were diagnostic or an additional finding were included in this study. Twenty-five cases out of 1000 biopsies were diagnosed based on giant cell morphology. The most frequent lesions were central giant cell granuloma, followed by cherubism, hyperparathyroidism, peripheral giant cell granuloma, tuberculosis, and hybrid lesion. A systematic approach towards differential diagnosis for such cases and a diagnostic algorithm was devised which is being followed as per the reported spectrum of GCL. Radiological, serology, and sometimes ancillary staining techniques are essential for the accurate histopathological diagnosis of giant cell lesions. Our diagnostic algorithm helps narrow down the spectrum of investigations necessary to characterize these lesions, enabling for a swifter and more confident identification of the pathologies.
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