Giant cell tumours of bone treated with denosumab: histological, immunohistochemical and H3F3A mutation analyses

Abstract

Denosumab therapy effectively decreases the number of osteoclastic cells in GCTBs. However, the neoplastic cells with H3F3A mutation survive denosumab treatment and undergo dramatic histological changes in response to this agent.

Histomorphometric Analysis of Pre- and Post-Denosumab–Treated Giant Cell Tumor of Bone

“…We analyzed both G34W and SATB2 stains in pre-and post-denosumab-treated GCTB, and our results showed a significant reduction in the number of G34W-positive mononuclear cells in post-denosumab tumors (mean 68.9% in pretreatment to 26.9% in posttreatment) that was statistically significant (P = .001). Results of other 2 studies, 24,25 however, did not show significant difference in the expression of G34W in pre-and posttreatment specimens. The most recent study by Treffel et al 25 found that H3.3 G34W expression (mean index from 55% before denosumab to 47% after denosumab) was statistically significant (P = .06).…”

“…We found a mean of 68.8% G34W-positive cells in the pretreatment specimens as compared with a mean of 26.9% cells in post-denosumab cases. Kato et al 24 also observed decreased number of G34W+ cells in post-denosumab specimens as compared with pretreatment specimens. Traub et al 18 performed immunohistochemical stains RANK and RANKL on 20 pre-and post-denosumab cases of GCTB.…”

“…An eggshell appearance was noted due to woven bone formation at periphery. Like Erdogan et al 19 and Roitman et al, 22 Kato et al 24 also emphasized that changes induced by denosumab may cause potential diagnostic pitfalls. The storiform proliferation of slender spindle cells coupled with collection of foamy histiocytes may result in misinterpretation as non-ossifying fibroma or benign fibrous histiocytoma.…”

“…13 Since then, several studies have been published describing the histological features induced by denosumab, as well as the expression of different immunohistochemical stains in pre-and post-denosumab specimens. [14][15][16][17][18][19][20][21][22][23][24][25] In the study by Thomas et al, 11 37 patients were given denosumab therapy for 6 months. Histologically, elimination of 90% or more of giant cells was seen in all 20 cases who underwent surgery.…”

“…Although analysis of H3F3A on denosumab-treated GCTB either by immunohistochemistry or mutational analysis by sequencing was performed in 3 previous studies, 16,24,25 no study has yet quantified number of positive cells by morphometric analysis that yielded accurate results of positive cells. We analyzed both G34W and SATB2 stains in pre-and post-denosumab-treated GCTB, and our results showed a significant reduction in the number of G34W-positive mononuclear cells in post-denosumab tumors (mean 68.9% in pretreatment to 26.9% in posttreatment) that was statistically significant (P = .001).…”