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

Abstract

Context. Denosumab is a monoclonal antibody against RANK ligand. Its administration in giant cell tumor of bone (GCTB) cases results in elimination of giant cells and new bone formation. Neoplastic stromal cells of GCTB harbor mutation of histone 3.3 and have pre-osteoblastic properties and thus express SATB2. Objectives. To (1) analyze histological changes in post-denosumab–treated GCTB, (2) analyze expression of H3.3G34W and SATB2 in pre- and post-denosumab–treated samples, and (3) to discuss why changes occur in the expression of not only H3.3G34W but also SATB2. Materials and Methods. Hematoxylin and eosin slides of 19 cases of denosumab-treated GCTB were reviewed. Immunohistochemical stains H3.3G34W and SATB2 were performed. The number of positive mononuclear cells were counted and graded. Results. Complete absence of osteoclast-like giant cells (OCLGCs) was noted in most cases along with a fibro-osseous component merging with peripheral shell of reactive bone. Irregular trabeculae of woven bone and osteoid with focal osteoblastic rimming was seen. Spindle cells were arranged predominantly in fascicular pattern. Morphometric analysis of H3.3G34W showed a mean of 68.8% positive stromal cells in pretreatment and a mean of 26.9% positive stromal cells in posttreated specimens with a statistically significant P value (.001). Mean percentage of SATB2-positive stromal cells in the pre- and posttreatment specimens was 36.46% and 20.8%, respectively. Conclusions. Our study validates that denosumab treatment results in marked reduction of OCLGCs with increased osteoblastic activity. Decreased expression of H3.3G34W in posttreatment may be a result of decreased antigenicity of neoplastic mononuclear cells. No significant change in SATB2 expression was noted.

Post-Denosumab-Treated Giant Cell Tumor of Bone: A Retrospective Histomorphological and Immunohistochemical Study

“…There was no significant difference in SATB2 expression of the tumor cells in both the specimens reflecting proosteoblastic properties. 14 In the present study, the pre-treatment biopsy was available in only one case. Hence, a comparative analysis was not studied.…”

“…Similar findings have been observed in other studies as well. 13,14 Majority of GCTBs harbor H3.3G34W mutation, in which few of them have alternate mutation like G34L, G34M, G34R, or G34V substitution. Kato et al and Wu and Hsieh et al detected H3F3A mutation on polymerase chain reaction and genetic sequencing.…”

“…Of the total 109 cases of GCTB encountered during the study period (2018-2020), fourteen (14) cases of Campanacci grade III GCTB who had received neoadjuvant denosumab treatment were analyzed retrospectively to study post-treatment changes. The remaining 95 patients who did not receive denosumab following a histological diagnosis of GCTB were excluded from the study.…”

Giant cell tumor of the bone of maxillary sinus: A rare uncommon manifestation implicated in a new mosaic of disorders?

“…Because G34W mutations happen more frequently than chromosomal abnormalities and can be causative risk factors for chromosomal structural remodeling in DNA synthesis, we hypothesize that the polypoid mass remnant would have differentiating markers in its stroma that would become early precursors for the development of GCTB. (Basu et al, 2021;Noh & Parket al, 2018;Ud Din et al, 2020).…”

Etablierung eines Kollektivs zur histomorphologischen Risikostratifizierung von Riesenzelltumoren mit und ohne Denosumab-Therapie

“…Folglich werden Schlussfolgerungen hinsichtlich Korrelation von untersuchten Parametern und Therapie-Dauer möglich sein (Abbildung 2). H3F3A 11 12…”