Central giant cell granuloma: A clinicopathological and immunohistochemical study of macrophages, blood vessels, lymphatic vessels and regulatory proteins.

OBJECTIVE: This study seeks to investigate immunohistochemical parameters that could distinguish non-aggressive Central giant cell granuloma (CGCG) from aggressive CGCG, two groups of lesions which differ in their clinical and radiographic features and prognosis. MATERIAL AND METHODS: 12 cases of non-aggressive CGCG and 11 cases of aggressive CGCG were investigated and associated the immunohistochemical expression of macrophages (CD68 and CD163), blood vessels (CD34 and CD105), lymphatic vessels (D2-40) and regulator proteins (p63 and Ki-67). Clinical and radiographic features were also studied. RESULTS: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (p > 0.05). With respect to non-aggressive CGCG, there were no significant correlations, while in aggressive CGCG there was a significant positive correlation between CD68 and CD163 (p = 0.031), between CD34 and D2-40 proteins (p = 0.04), whereas a significant negative correlation was observed between CD105 and CD68 (p = 0.040). However, regardless of aggressiveness of CGCG, there was a significant positive correlation between CD68 and CD163 (p = 0,04). Among the clinical and immunohistochemical aspects, only the symptomatology was a significant risk factor for the occurrence of aggressive CGCG (OR = 12.00/p = 0.016). CONCLUSION: Macrophages and angiogenesis contribute to their maintenance and development of CGCG. In addition, immunohistochemistry used here was not able to differentiate their aggressiveness. However, symptomatology was proved to be a risk factor for the occurrence of aggressive CGCG. It is possible that clinical features, particularly symptomatology, represent the most appropriate parameter to attempt to distinguish GCCG.

Potential role of Hedgehog signaling pathway and myofibroblastic differentiation in central giant cell granuloma-A preliminary study.

OBJECTIVE: This study investigated components of the Hedgehog (HH) signaling pathway (SHH, GLI1), cyclin D1, and smooth muscle actin (SMA) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. MATERIAL AND METHODS: Twelve cases of non-aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. RESULTS: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (P > .05). All cases of CGCG showed significantly higher expression of SMA compared with the other proteins (P < .01). A positive correlation (P = .04) was only observed between SHH and GLI1 for all cases of CGCG. Furthermore, a positive correlation between SHH and GLI1 in non-aggressive CGCG (P = .04) and between GLI1 and cyclin D1 in aggressive CGCG (P = .03) were observed. There was also a negative correlation between the expression of SHH and SMA in non-aggressive CGCG (P = .031). CONCLUSIONS: This study provided insights into the activation of the HH signaling pathway in CGCG. In addition, the activation of this pathway (SHH and GLI1) might play some role in the differentiation of stromal myofibroblasts, although these markers including Cyclin D1 and SMA do not indicate aggressiveness of the CGCG. Furthermore, this myofibroblastic differentiation process would occur at the expense of maturation of these lesions.