Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series

Girolami, Ilaria; Mancini, Irene; Simoni, Antonella; Baldi, Giacomo Giulio; Simi, Lisa; Campanacci, Domenico Andrea; Beltrami, Giovanni; Scoccianti, Guido; D’Arienzo, Antonio; Capanna, Rodolfo; Franchi, Alessandro

doi:10.1136/jclinpath-2015-203248

Cited by 86 publications

(74 citation statements)

References 28 publications

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“…In 11 of the patients (45.8 %), a detailed genotype analysis and immunohistochemical staining was performed [16]. From a surgical point of view, the most interesting findings were a significant reduction in microvascular density of the post-denosumab specimen and a significant overall decrease of the cellular proliferation index [16].…”

Section: Resultsmentioning

confidence: 99%

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series

et al. 2016

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BackgroundThe RANK ligand inhibitor denosumab is being investigated for treatment of giant cell tumor of bone, but the available data in the literature remains sparse and controversial. This study analyzes the results of combining denosumab with surgical treatment and highlights possible changes for the oncologic surgeon in daily practice.MethodsA total of 91 patients were treated surgically for giant cell tumor of bone between 2010 and 2014 in an institution, whereas 25 patients of the total additionally received denosumab and were part of this study. The average age of the patients was 35 years. Eleven patients received denosumab pre- and postoperatively, whereas with 14 patients, the denosumab treatment was applied either before (7 patients) or after (7 patients) the surgery. The average preoperative therapy duration was 3.9 months and the postoperative therapy 6 months by default.ResultsSixteen patients presented a large tumor extension necessitating a resection of the involved bone or joint. In 10 of these patients, the indication for a resection procedure was abandoned due to the preoperative denosumab treatment and a curettage was performed. In the remaining six cases, the surgical indication was not changed despite the denosumab treatment, and two of them needed a joint replacement after the tumor resection. Also with patients treated with curettage, denosumab seems to facilitate the procedure as a new peripheral bone rim around the tumor was built, though a histologic analysis reveals viable tumor cells persisting in the denosumab-induced bone formation.After an average follow-up of 23 months, one histologically proven local recurrence occurred, necessitating a second curettage. A second patient showed a lesion in the postoperative imaging highly suspicious for local relapse which remained stable under further denosumab treatment. No adverse effect of the denosumab medication was observed in this study.ConclusionsDenosumab can be a help to the oncologic surgeon by reconstituting a peripheral rim and switching the stage from aggressive to active or latent disease. But as tumor cells remain in the new-formed bone, the surgical technique of curettage has to be changed from gentle to more aggressive to avoid higher local recurrence rates.

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Section: Resultsmentioning

confidence: 99%

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series

et al. 2016

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“…They demonstrated the osteoclastic arrest and presented histopathologic and immunohistochemical findings but they did not classify these changes. Girolami et al evaluated GCTs' pre-and posttreatment specimens by molecular analysis in addition to immunohistochemistry [20]. They found that denosumab changes the microenvironment of the tumor cells instead of eliminating them.…”

Section: Discussionmentioning

confidence: 99%

Morphologic evaluation of the effect of denosumab on giant cell tumors of bone and a new grading scheme

Erdoğan¹,

Deveci²,

Paydaş³

et al. 2016

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Giant cell tumor (GCT) is a rare, usually benign but locally aggressive neoplasm. Recent studies suggest new approaches in light of the elucidation of molecular pathways in bone. The osteolytic nature of GCT is caused by the receptor for activating nuclear factor-kB ligand (RANKL) associated osteoclasts. Denosumab is a monoclonal antibody that affects GCT through RANKL and it prevents normal and neoplastic osteolysis. The aim of this study is to evaluate the histopathologic alterations due to denosumab treatment and the efficiency of this drug in GCT therapy. Ten patients had been treated with denosumab and were included in the study. Pretreatment biopsies were interpreted as conventional GCTs and posttreatment biopsies of the ten patients' GCTs were classified in accordance with the grading system. Only one patient had tumor remaining after treatment. There is limited data on histopathologic alterations that follow denosumab treatment. The bone pathologist should keep these changes in mind because they mimic different types of bone tumors. Furthermore, there is no widely accepted grading system to evaluate the effect of denosumab in GCT. Our study suggested a scheme that would be helpful to evaluate the efficiency of denosumab treatment in GCT.

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“…Chawla et al [12] reported the interim safety and efficacy of denusumab in an open label multi-centre study involving 29 centres with 282 patients and found that 96% in the surgically unsalvageable group had stable disease without progression. Girolami et al [13] reported that denosumab treatment led to a significant reduction of the GCT proliferative index and tumour angiogenesis. Ueda et al [14] reported that the proportion of patients with an objective tumour response was 88%.…”

Section: Discussionmentioning

confidence: 99%

Neurological Recovery in Two Patients with Cauda Equina Syndrome Secondary to L5 Lumbar Spine Giant Cell Tumour after Treatment with Denosumab without Surgery

et al. 2016

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We report two patients with cauda equina syndrome (CES) secondary to L5 giant cell tumour (GCT) who achieved good neurological recovery after treatment with denosumab without surgery. The first patient was a 26-year-old man with L5 GCT causing CES who regained bowel and urinary control, muscle power improvement from grade 2 to grade 4 and Oswestry disability index (ODI) improvement from 48 to 23 after denosumab treatment. The second patient was a 25-year-old woman with L5 GCT causing CES who regained bowel and urinary control, muscle power improvement from grade 0 to grade 4 and ODI improvement from 42 to 20 after denosumab treatment. The usage of denosumab in the treatment of patients with CES due to GCT allows potential neurological recovery without any surgical intervention. If surgery is not contraindicated, more time is obtained to prepare the patient preoperatively to attain safer surgery and to achieve complete tumour clearance.

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Denosumab treated giant cell tumour of bone: a morphological, immunohistochemical and molecular analysis of a series

Cited by 86 publications

References 28 publications

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone—a case series

Morphologic evaluation of the effect of denosumab on giant cell tumors of bone and a new grading scheme

Neurological Recovery in Two Patients with Cauda Equina Syndrome Secondary to L5 Lumbar Spine Giant Cell Tumour after Treatment with Denosumab without Surgery

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