Increased TNF-alfa, IL-6 and decreased IL-1beta immunohistochemical expression by the stromal spindle-shaped cells in the central giant cell granuloma of the jaws

Abstract

Objectives: the exp ress ion of the osteoclastogenic cytokines TNF-α, IL-6 and IL-1β were immunohistochemically evaluated in periph eral (PGCG) and central (CGCG) giant cell granulomas of the jaws in order to determine diff erences between these two lesions and between the two distinct tumor cell populations (multinucleated giant cells, MGCs and stromal sp indle-sh aped cells). Study Design: Paraffin-embedd ed tiss ue sections from 40 PGCG and 40 CGCG were immunohistochemically stained using antibodies against TNF-α, IL-6 and IL-1β. The percentage of positively stained cells and the staining intensity were ass ess ed to provide a combined immunoreactivity score value. Results: TNF-α, IL-6 and IL-1β were exp ress ed in all lesions. The CGCG compared to the PGCG sh owed significantly increased exp ress ion of TNF-α and IL-6 and decreased exp ress ion of IL-1β by the sp indle-sh aped cells and increased exp ress ion of IL-1β by the MGCs. The MGCs demonstrated in comparison to the stromal sp indlesh aped cells significantly increased exp ress ion of all three cytokines in both PGCG and CGCG. Conclusions: The proinflammatory cytokines TNF-α, IL-6 and IL-1β seem to be involved in the growth process of PGCG and CGCG of the jaws. A poss ible alteration in the sy nthesis or/and activity of these cytokines by the stromal sp indle cells in the CGCGs may enhance osteolys is through the stimulation of osteoclast progenitor cells, given the fact that the intraoss eous lesions cause bone resorption. Key words: Giant cell granuloma, giant cell tumor, multinucleated giant cells, jaw, TNF-alpha, IL-6, IL-1beta, immunohistochemistry.

Peripheral and central giant cell lesions: etiology, origin of giant cells, diagnosis and treatment

“…It is a well-defined lesion with exophytic growth. Additionally, it may be pedunculated, sessile or it may not present areas of ulceration (2,11,12,20,27,31,34) . It may develop at any age, predominantly in the first to sixth decade of life, especially from 31 to 41 years of age.…”

“…Although PGCL arise in soft tissues, the "cup-shaped" resorption of the subjacent alveolar bone may be occasionally observed (27,31) . Thus, it may be difficult to determine whether the increased volume originates from a PGCL or a CGCL that ruptured the cortical bone and invaded the gingival soft tissues (2,3,21) .…”

“…Although there is not enough evidence that this lesion promotes reparative process, it was denominated reparative giant cell granuloma (2,(25)(26)(27)(28)(29)(30) . Based on differences in their histological pattern and clinical behavior, Jaffe separated maxillary CGCL from long bone giant cell tumor.…”

“…The differentiation mechanism would be through RANK-RANKL interaction, similarly to giant cells from PGCL, as described previously (13,14,16,21,27) . The proliferation component of CGCL is the mesenchymal stromal cells that are able to differentiate into fibroblast / osteoblast lineages.…”

“…It is debatable whether the lesions that have a greater number of giant cells with multiple nuclei and densely cellular stroma are more aggressive and more likely to relapse after surgical treatment (13,14,21,27) . By means of histomorphometric analysis, Reddy et al (30) revealed significant differences in the number of giant cells in aggressive and non-aggressive lesions, although there was no statistically Recently, a strong expression of nuclear factor of activated T cells (NFATc1), a factor of osteoclastogenesis probably involved in bone resorption, has been observed in giant cells from CGCL, cherubism and brown tumor of hyperparathyroidism (10,18) .…”