PMC3901337_01
Imaging of the patients right forearm tumor. (A) Initial magnetic resonance imaging (MRI) demonstrating extensive involvement of the soft tissue between the radius and ulna as well as the cortex of the radius by an exclusively solid tumor mass (arrows). (B) Pre-treatment computer tomography (CT) scan with a small area of a split and disrupted cortex of the radius (arrows). (C) MRI directly prior to denosumab therapy with a locally progressive, extensive soft tissue mass following local surgical therapy 18 months previously. Fluid-fluid levels may be seen at this point (arrow). (D) CT scan following five months of denosumab therapy demonstrating almost complete containment of the soft tissue mass by a boney rim (arrow).
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F1
MRI revealed an extensive, deep seated, solid soft tissue tumor with contrast uptake, infiltration of the intra-osseous membranes, biceps tendon, contact with the neurovascular bundle, infiltration of the supinator muscle and deep extensor as well as deep flexor muscles (Figure  1A, B). MRI in February 2011 (Figure  1C) showed a significant increase in the size of a recurrent and progressively symptomatic tumor. As a result of good treatment response, the tumor had become significantly better circumscribed and clearly demarcated by a bony rim (Figure  1D), leading to the feasibility of a complete resection of the tumor. At first presentation in 2009, most of the exclusively solid tumor mass was localized in the soft tissues of the forearm on imaging (Figure  1A), leading to the diagnosis of giant tumor of soft tissue. Retrospectively, careful analysis of the initial CT scans (Figure  1B) showed an area of split and disrupted cortical bone of the radius, which might have initially suggested the diagnosis of an intracortical (solid variant) ABC with a massive extension to the periosteal tissue.
Histopathology of the pre- and post-treatment tumor tissue specimen. (A) Pre-treatment biopsy sample showing giant cell containing soft tissue mass with extensive infiltration of the skeletal muscle (H&E stain; original magnification 50x). (B) Abundant lesional giant cells with numerous nuclei and mononuclear cells in the background (H&E stain; original magnification 100x). Inset shows immunohistochemical expression of RANK (dilution 1:400; R&D Systems, Abingdon, United Kingdom) by the osteoclastic giant cells. (C) Denosumab treatment induced boney containment (asterisk) of the tumor (upper left) (H&E stain; original magnification 25x). (D) Post-denosumab-treatment tumor specimen showing pronounced reduction of the number of giant cells (H&E stain; original magnification 100x).
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F2
A low-grade, giant cell-containing lesion with focal metaplastic bone formation and infiltration of the skeletal muscle was diagnosed on histopathological examination (Figure  2A). Histology of the recovered fragmented tumor revealed similar results to the biopsy (Figure  2B) rendering the diagnosis of an incompletely resected giant cell tumor of soft tissue. The histology of the post-treatment tumor specimen (Figure  2C, D) differed in comparison to the material of the core biopsy and curettage (Figure  2A, B) showing markedly reduced numbers of osteoclasts. There was pronounced metaplastic new bone production with extensive areas of so-called 'blue bone' and lamellar cortical bone at the periphery of the lesion (asterisk Figure  2C).
Resection of the shaft of the proximal radius following the denosumab therapy. (A) Reconstruction using an intercalary fibula-allograft and a custom-made plate. (B) Longitudinal section of the resected specimen demonstrating large intracortical, fully contained by a rim of bone tumor mass (asterisk) with a small intramedullar tumor nodule proximally (black arrow) and an intracortical satellite distally (white arrow).
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F3
Reconstruction was performed using an intercalary fibula-allograft with 3D planning to adjust for radial head rotation and a custom-made plate (Figure  3A). The gross examination of the resection specimen (Figure  3B) revealed an extensive, almost circumferential, intracortical bone tumor mass extending over 4.4 cm of the diaphysis of the radius with a small intramedullary nodule proximally and an intracortical satellite lesion distally.
Fluorescence in situ hybridization conducted on the pretreatment specimen with a custom-designed break apart probe set; the probe cocktail proximal to the USP6 locus is labeled in green and distal in red. The mononuclear nuclei exhibit one fused red/green signal corresponding to a normal 17p USP6 locus (black arrow) and a pair of split green and red signals (white arrows) indicating a rearrangement of the USP6 locus consistent with the diagnosis of aneurysmal bone cyst.
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F4
Finally, the diagnosis of a primary ABC was definitively confirmed by demonstration of a rearrangement of the USP6 gene locus by fluorescence in situ hybridization (FISH) as described previously , utilizing a custom-designed break apart probe set on the original biopsy sample (Figure  4).