Radiological aspects of Denosumab-treated giant cell tumour of bone

A 35-year-old male is admitted to our institution’s emergency ward with intense pain and tumefaction in the right wrist. The tumefaction growth had begun insidiously but quick progression in the last weeks and worsening of the pain motivated the patient to seek medical attention. No trauma history was reported.

Radiographs of the forearm and wrist were performed and revealed a 10cm lytic expansile lesion in the metaphyseal/epiphyseal region of the right radius, displacing and eroding the lateral cortical surface of the ulna. The margins are ill-defined and the zone of transition is relatively narrow. Despite the aggressive-looking appearance, there is no apparent osteoid matrix or periosteal reaction (Fig. 1).

MRI was performed to better characterize the tumour and its relations to adjacent structures. The tumour is predominantly solid, with intermediate signal on T1SE (Fig. 2A) and T2SE and internal cystic areas (Fig.2B), some with fluid-fluid levels (Fig.2C).

As the lesion was deemed to be of difficult surgical management, the patient was subjected to treatment with Denosumab prior to surgery. Follow-up radiographs (Fig.3-4A) and CT (Fig.4B) revealed marked mineralization of the lesion that now possesses a clear and sharp sclerotic margin. No significant reduction of the lesion size was apparent.

The lesion was submitted to core biopsy and the already suspected diagnosis of giant cell tumour (GCT) of bone was confirmed. Histological confirmation is required to establish the diagnosis[1]. GCTs are typically found after the closure of growth plates and peak incidence occurs in the 3^rd decade[2]. GCTs of bone are usually benign tumours, but local recurrences are common (up to 60%)[3].

 Metastatic involvement (especially to the lungs) and sarcomatous transformation have been reported, but are rare. Histologically, the tumour is characterized by the presence of giant cells in a background of mononuclear stromal cells, with increased osteoclastic activity due to activation of nuclear factor-kappa B ligand (RANKL)[2,4].

These lesions tend to be eccentrically located in metaphyseal/epiphyseal regions, near articular surfaces. The most common radiographic appearance is that of a lytic lesion with well-defined non-sclerotic margins. Some might present with a more aggressive appearance, with cortical thinning, expansible remodelling or cortical bone destruction, as was our case. Typical signal characteristics in MR include low-signal in T1-weighted images, high-signal in T2-weighted images and enhancement of solid components after paramagnetic contrast administration. A low-signal-intensity margin, representing osseous sclerosis or a pseudocapsule, is a common finding. Fluid-fluid levels may be observed, in association with aneurismal bone cyst (ABC) components. These components are common in GCTs (14% of lesions) and, when prominent, contribute to a more aggressive radiographic appearance[5].

For larger and more destructive GCTs wide resection and reconstruction with allografts and/or metal prostheses may be necessary. However, in large lesions, complete resection may be difficult and joint reconstruction can be challenging, with great morbidity. Recent studies support that most patients show objective tumour response to Denosumab which should be assessed by the response criteria by inverse Choi density/size (ICDS)[5-7]. The dynamic response to Denosumab is characterized by a change in lesion density rather than size reduction, inducing internal mineralization, marginal sclerosis and better demarcation of lesions. The changes should be monitored with a combination of radiograph and CT, as the latter allows the use of Hounsfield Units (HU) as an objective measure of response[6-8].

Results from previous studies concluded Denosumab decreased the local staging of GCT, allowing curative surgical resection in approximately 57% of patients. However, it does not prevent recurrence in patients with prior surgical treatment and should not be used as adjuvant therapy[8].

The patient refuses surgery, currently maintaining Denosumab therapy.

Written informed patient consent for publication has been obtained.