Giant cell tumor of the bone: aggressive case initially treated with denosumab and intralesional surgery

Abstract

Giant cell tumor of the bone (GCTB) is a locally aggressive benign tumor, which has historically been treated with wide surgical excision. We report a case of a 29-year-old male with histology-proven GCTB of the distal ulna. The initial imaging study was a contrast-enhanced magnetic resonance imaging (MRI) examination of the left wrist, which was from an outside facility performed before presenting to our institution. On the initial MRI, the lesion had homogenous T2-hyperintense and T1-hypointense signal with expansive remodeling of the osseous contour. A radiographic study performed upon presentation to our institution 1 month later showed progression of the lesion with atypical imaging characteristics. After confirming the diagnosis, denosumab therapy was implemented allowing for reconstitution of bone and intralesional treatment. The patient was treated with five doses of denosumab over the duration of 7 weeks. Therapeutic changes of the GCTB were evaluated by radiography and a post-treatment MRI. This MRI was interpreted as suspicious for worsening disease due to the imaging appearance of intralesional signal heterogeneity, increased perilesional fluid-like signal, and circumferential cortical irregularity. However, on subsequent intralesional curettage and bone autografting 6 weeks later, no giant cells were seen on the specimen. Thus, the appearance on the MRI, rather than representing a manifestation of lesion aggressiveness or a non-responding tumor, conversely represented the imaging appearance of a positive response to denosumab therapy. On follow-up evaluation, 5 months after intralesional treatment, the patient had recurrent disease and is now scheduled for wide-excision with joint prosthesis.

Radiological findings of denosumab treatment for giant cell tumours of bone

“…Decreased T2-weighted MR signal has previously been described [4,11,21,33] with demonstrable signal change from 7 weeks [11] after commencing denosumab treatment.…”

“…MRI findings of increased intralesional heterogeneity, cortical thickening and irregularity following short-term (7 weeks) denosumab therapy have previously been described and misinterpreted as disease progression [11]. These MR features are not uncommonly seen with denosumab treatment and represent an appropriate response to treatment.…”

“…Intralesional osteosclerosis has been documented on plain radiographs as early as 2 weeks [11] after commencing denosumab, with varying degrees of internal matrix consolidation seen on plain radiographs increasing with treatment duration [4,11,14,21,22].…”

“…GCTB may be locally aggressive, with local recurrence forming a challenging issue. The reported local recurrence rate varies widely and lies between 10 and 50% for intralesional resection (curettage) and 5% for wide resection [9][10][11][12][13]. Treatment with denosumab becomes an option in histologically confirmed GCTB where surgical resection may result in severe morbidity (such as joint reconstruction or amputation), or in patients who have an unresectable tumour (such as in the spine or sacrum) [3,10,12].…”

“…Imaging features on plain radiographs, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography-CT (PET-CT) will be discussed. Recognizing imaging features indicative of a positive tumoural response to denosumab in various tumour locations and on different imaging modalities is important for therapeutic decision-making [11]. There are currently no guidelines for optimal duration of denosumab treatment, and imaging findings with respect to the time on treatment are discussed.…”