Radiological findings of denosumab treatment for giant cell tumours of bone

Abstract

Giant cell tumours of bone (GCTB) are benign giant cell-rich tumours typically occurring in the epi-metaphysis of skeletally mature patients. Despite their benign classification, GCTB may be locally aggressive with local recurrence as a challenging issue. Denosumab is a human monoclonal antibody that inhibits osteolysis via the RANK-RANK ligand pathway. There is currently no consensus on optimal treatment duration or imaging modality for monitoring patients on denosumab therapy. This review illustrates the radiological findings of GCTB on denosumab treatment seen on plain radiographs, CT, MRI, PET-CT and DEXA, with reference to the current literature. Recognizing imaging features indicative of a positive response to denosumab is important for therapeutic decision-making. Imaging findings with respect to duration of denosumab treatment, tumour upregulation during treatment, tumour recurrence and malignant transformation are discussed. The development of a sclerotic neocortex and varying degrees of matrix osteosclerosis are seen on plain radiographs. Reconstitution of subarticular bone and articular surface irregularity are optimally evaluated on CT which can also quantify tumour density. MRI demonstrates heterogeneous low signal matrix and is useful to assess decrease in size of cystic and/or soft tissue components of GCTB. A fat-suppressed fluid-sensitive MR sequence is important to detect tumour reactivation. Reduction in ¹⁸F-FDG-PET avidity represents an early sensitive sign of response to denosumab treatment. Regardless of imaging modality, close follow-up in a specialist centre and careful evaluation of nonresponders is necessary as local recurrence after cessation of denosumab treatment and malignant transformation of GCTB have been described.

Keywords: CT; Denosumab; Giant cell tumour of bone; Imaging; MRI; PET-CT.

Fig. 1

A 38-year-old female presented with wrist pain and swelling. Plain radiographs at presentation (a) and after 4 weeks on denosumab (b). a At presentation, a Campanacci grade 3 expansile lytic GCTB was found in the distal radius meta-epiphysis, extending up to the subchondral bone plate with destruction of the lateral radial cortex and radial styloid articular surface. b After 4 weeks of denosumab treatment, the cortex has reconstituted laterally with remodelling and irregularity of the distal radial articular surface (arrow). The soft tissue component of the lesion has markedly decreased in size. The distal radius shows an increase in matrix osteosclerosis

Fig. 2

A 17-year-old girl presented with swelling of the middle finger. Plain radiographs at presentation (a) and after 12 weeks on denosumab (b). a At initial presentation, an expansile lytic GCTB is present in the middle finger proximal phalanx with cortical destruction. b After 12 weeks on treatment, the lesion has decreased in size with marginal neocortex formation and matrix sclerosis

Fig. 3

A 20-year-old male with known GCTB of the distal tibial epiphysis. CT sagittal reformat after 8 weeks on denosumab treatment. The GCTB is seen as a mildly expansile, eccentric lytic lesion with the development of marginal sclerosis and irregularity of the tibial articular surface anteriorly (arrow) while on denosumab

Fig. 4

A 15-year-old male presented with swelling of the hard palate, which was first noticed by the dentist. Axial CT of the maxilla at presentation (a) and after 14 weeks on denosumab (b). a CT at presentation shows an expansile lytic GCTB between the roots of the teeth. The cortex was thinned with focal areas of cortical destruction (arrows). No ground glass or chondroid matrix was present in the lesion. The density of the tumour was 52 HU. b Follow-up CT after 14 weeks on treatment shows peripheral sclerosis surrounding the lesion with no cortical defects. The density of the tumour increased to 121 HU. Note that the angulation of the CTs varies slightly

Fig. 5

A 21-year-old male presented with a pathological fracture of the right hip secondary to a GCTB of the proximal femoral epiphysis. He developed histologically confirmed pulmonary metastases 3 months after diagnosis. CT of the chest at baseline (a) and after 6 months on denosumab (b). a Axial CT (lung window) of the chest at baseline demonstrates a right lower lobe pulmonary metastasis (circle). b Axial CT (bone window) of the chest performed 6 months after starting denosumab shows a decrease in size and ossification of the right lower lobe metastasis (within the circle)

Fig. 6

A 17-year-old girl presented with swelling of the middle finger (same patient as Fig. 2). MRI at presentation (a, b) and after 8 weeks on denosumab treatment (c). a Sagittal T1-weighted and b coronal proton density fat-saturated (PD-FS) MR images at presentation demonstrate an expansile, iso-intense T1 and high signal PD-FS GCTB in the proximal phalanx with cortical destruction and soft tissue extension (white arrows). c Coronal T1-weighted MR image after 8 weeks on denosumab shows decreased tumour size and overall lower signal intensity with a low signal intensity sclerotic rim (white arrowheads)

Fig. 7

A 17-year-old female presented with cauda equina symptoms. MRI at presentation (a, b), after 8 months on denosumab (c, d) and after 13 months on denosumab (e, f). a Coronal T1-weighted MR image at presentation illustrates a large sacral GCTB, which is iso-intense to muscle on T1. b Sagittal T1 turbo inversion recovery magnitude (TIRM) MR image at presentation illustrates heterogeneous, predominantly high TIRM signal intensity in the tumour with a soft tissue component anteriorly, epidural and sacral foraminal extension. c Coronal T1-weighted MR image after 8 months on denosumab shows decreased signal intensity in the tumour, corresponding to sclerosis. d Sagittal T1 TIRM MR image after 8 months on denosumab shows the tumour has decreased in signal intensity and in size, which is mainly visible in the reduction of the soft tissue component. e The patient reported increased sacral pain after 13 months on denosumab treatment, and an interval MRI was performed. Coronal T1-weighted MR image demonstrates that tumour size and T1 signal intensity remain more or less unchanged. f Sagittal short tau inversion recovery (STIR) MR image after 13 months on denosumab demonstrates a marked increase in signal intensity of the tumour on the fluid-sensitive sequence, indicative of tumour reactivation. The patient was subsequently found to be pregnant and denosumab therapy was interrupted. Re-biopsy performed 3 months postpartum revealed numerous osteoclastic giant cells supporting the diagnosis of GCTB reactivation. Denosumab therapy was subsequently recommenced with a good clinical response and stable disease on treatment (2 year follow-up to date)

Fig. 8

A 30-year-old female presented with back pain and a newly developed scoliosis. MRI at presentation (a, c) and after 8 weeks on denosumab (b, d). a Sagittal T2 TIRM MR image at baseline shows T12 vertebral collapse secondary to a GCTB with heterogeneous signal intensity and cystic components. b Sagittal T2 TIRM MR image after 8 weeks on denosumab demonstrates decreased size and signal intensity of the tumour, with further loss of height of the vertebral body. c Axial T2-weighted MR image at presentation shows tumour extension into the paravertebral soft tissues and epidural space. There is almost complete obliteration of the spinal canal with minimal remaining CSF posteriorly (white arrow). d Axial T2-weighted MR image after 8 weeks on denosumab shows decreased size and signal intensity of the tumour, with a more defined low signal margin and capacious spinal canal. One of the cystic components shows a fluid-fluid level, likely after haemorrhage (white arrows)

Fig. 9

A 36-year-old man presented with an enlarging mass originating from the left ilium. MRI at presentation (a), after 12 weeks on denosumab (b) and after 20 weeks on denosumab treatment (c). a Coronal T1 TIRM MR image at baseline shows large cystic foci in the left iliac GCTB (arrow). b Coronal T1 TIRM MR image after 12 weeks on treatment demonstrates that the lesion appears smaller and of lower signal intensity, with decreased size of the cystic components (arrow). c Coronal T1 TIRM MR image after 20 weeks on treatment shows further reduction in size and signal intensity of the GCTB and the cysts are barely visible (arrow)

Fig. 10

A 36-year-old female with GCTB of the T10 vertebra. Dynamic contrast-enhanced MRI at baseline (a, b) and follow-up MRI 1.5 years after intralesional resection (c, d). a Axial dynamic contrast-enhanced MR image at baseline demonstrates a region of interest (ROI) drawn in the tumour in Th10 (blue circle) and a ROI in the aorta to reference arterial enhancement (orange circle). b Time intensity curves (X-axis: time in seconds, Y-axis: relative percentage of enhancement) show the tumour (blue line) enhances almost simultaneously with the aorta (orange line) and it shows minor washout over 5 min. c Axial dynamic contrast-enhanced MR image 1.5 years after intralesional resection demonstrates a region of interest (ROI) drawn in a new left paravertebral soft tissue mass at Th10 (blue oval) and a ROI in the aorta to reference arterial enhancement (orange circle). There is a new right paravertebral soft tissue mass (green oval), in keeping with post-surgical spongiosa material as seen on CT (not shown). d Time intensity curves (X-axis: time in seconds, Y-axis: relative percentage of enhancement) show the new left paravertebral mass (blue line) enhances only 5 s after the aorta (orange line) and shows evident washout starting at T = 35 s, indicative of GCTB recurrence. This area was subsequently biopsied under CT guidance and recurrent GCTB was histologically confirmed. The green line represents the area of post-surgical spongiosa material and shows a small relative percentage of enhancement and slow enhancement over time

Fig. 11

A 17-year-old female with a sacral GCTB (same patient as Fig. 7). PET-CT at baseline (a), after 8 weeks on denosumab (b) and after 16 weeks on denosumab (c). a Coronal fused PET-CT at baseline shows marked ¹⁸F-FDG uptake in the sacral GCTB which had an SUV^max of 16.3. No metastases were present. b Coronal fused PET-CT after 8 weeks on treatment demonstrates that the SUV^max had decreased to 4.4. c Coronal fused PET-CT after 16 weeks on denosumab demonstrates a complete response

Fig. 12

A 42-year-old man with a GCTB of the T8 vertebra. Fused axial PET-CT image and a detail from the axial CT (bone window) are shown at baseline (a) and after 16 weeks on denosumab (b). a Fused PET-CT at baseline demonstrates marked ¹⁸F-FDG uptake in a lytic T12 GCTB with an SUV^max of 9. b Fused PET-CT after 16 weeks on treatment shows no increased ¹⁸F-FDG uptake in the GCTB when compared with the adjacent vertebrae, indicative of a good response. The unfused axial CT image illustrates progressive peripheral sclerosis and increased matrix osteosclerosis in the tumour with treatment