Abstract
Introduction Giant cell tumors of bone (GCTBs) are treated with surgery with or without local
adjuvants. Denosumab is a human monoclonal antibody that has recently emerged to be
effective in treating unresectable and recurrent GCTBs.
Objective In this study, we analyzed the histomorphological changes in GCTB following treatment
with denosumab. The expression of histone mutation H3.3G34W by immunohistochemistry
(IHC) using mutant specific antibody was also determined.
Materials and Methods Of the total 109 GCTBs encountered during the study period, 14 cases with neoadjuvant
denosumab therapy were analyzed retrospectively. The post-treatment changes on histopathology
were examined on routine hematoxylin and eosin-stained sections. IHC was done using
antihistone H3.3G34 antibodies. Statistical analysis was limited to descriptive statistics.
No hypothesis testing was performed.
Results All these cases except three showed fibrosis with areas of hyalinization, prominent
newly formed woven bone along with spindle cells in short fascicles and storiform
pattern. There was complete absence and marked reduction in osteoclast-like giant
cells in six and five patients, respectively. Only three patients showed a substantial
amount of residual osteoclast-like giant cells. IHC with antihistone H3.3G34W antibody
showed unequivocal nuclear positivity in the mononuclear cells in nine cases. The
mononuclear cells rimming and entrapped within the woven bone were also positive on
IHC. The spindle cells in the benign fibrous histiocytoma-like areas and septa of
aneurysmal bone cyst-like areas also retained nuclear staining.
Conclusion Awareness of post-denosumab-related histopathological changes are necessary to avoid
misdiagnosis as fibroosseous lesion and low-grade central osteosarcoma. Expression
of mutant-specific H3.3 G34W antibody suggests that the neoplastic stromal cells are
largely retained after denosumab therapy. The positive staining of cells both within
and those rimming the newly formed woven bone point toward osteoblastic phenotype
of the neoplastic stromal cells.
Keywords
giant cells - denosumab therapy - histomorphological changes - antihistone antibody
- immunohistochemistry
