Evaluation of CD3 and CD20 Lymphocytes and Mast Cells in the Microenvironment of Central Giant Cell Granuloma, Peripheral Giant Cell Granuloma, and Giant Cell Tumor of Bone

<b>Objective</b>: Giant cell lesions (GCLs) share similar histopathologic features. The influence of immune involvement on the biology of giant cell lesions remains largely elusive. This study aimed to evaluate and compare lymphocyte and mast cell infiltration and distribution among three giant cell lesions. <b>Study design</b>: A total of 30 FFPE tissue blocks, comprising 10 PGCGs, 10 CGCGs (aggressive and nonaggressive), and 10 GCTs (aggressive and nonaggressive) of bone, were subjected to IHC staining for CD3 and CD20 lymphocyte markers and toluidine blue staining for mast cells. The mean count of positively stained cells was calculated and categorized into three scores, along with a group for negative cases. Statistical analysis was conducted to assess significance at <i>p</i> < 0.05. <b>Result</b>: Lymphocyte infiltration was observed across all lesions. CD3⁺ and CD20⁺ cell counts were significantly elevated in PGCGs, followed by CGCGs, and were lowest in GCTs of bone. In contrast, mast cell counts were high in GCTs of bone and CGCGs and low in PGCGs. Aggressive giant cell lesions of bone showed a significantly low number of CD3⁺ and CD20⁺ cells (Mann-Whitney U test; <i>p</i> = 0.05, 0.004) and a high number of mast cells (Mann-Whitney U test; <i>p</i> < 0.001) compared with nonaggressive lesions of bone. PGCGs and nonaggressive CGCGs showed comparable CD3 expression, with no significant difference between them (<i>p</i> = 0.59). CD20 levels were higher in nonaggressive CGCGs but did not reach statistical significance (Mann-Whitney U test; <i>p</i> = 0.07). Mast cell density was significantly lower in PGCGs compared with intraosseous nonaggressive CGCGs. <b>Conclusions</b>: The present study shows that GCTs of bone, CGCGs, and PGCGs possess distinct immune microenvironmental profiles. Aggressive lesions demonstrate reduced lymphocyte infiltration and increased mast cell density, a pattern particularly evident in GCTs of bone. This imbalance may contribute to their aggressive behavior by enabling them to escape host immune regulation.