Giant cell tumor of bone

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Giant cell tumours (GCTs) of bone, also known as osteoclastomas, are relatively common bone tumours, usually benign which are arising from metaphysis and typically ~~found in~~extending into the ~~metaphysis of~~epiphysis of the long bones.

Epidemiology

GCTs are common, comprising 18-23% of benign bone neoplasms and 4-9.5% of all primary bone neoplasms ¹. They almost invariably (97-99%) occur when the growth plate has closed and are therefore typically seen in early adulthood, with 80% of cases reported between the ages of 20 and 50, with a peak incidence between 20 and 30 ¹.

There is overall a mild female predilection, especially when located in the spine, however malignant transformation is far more common in men (M:F of ~3:1) ¹.

Clinical presentation

Presentation is not specific, typically presents insidiously and relates to bone pain, soft tissue mass, compression of adjacent structures or acutely with a pathological fracture.

Pathology

Giant cell tumours are believed to result from an over-expression in RANK/RANKL signalling pathway with resultant over-proliferation of osteoclasts ⁶.

These tumours contain numerous thin walled vascular channels predisposing to areas of haemorrhage and presumably related to the relatively frequent co-existence of aneurysmal bone cysts (ABC) found in 14% of cases^1-2,4.

Macroscopically, giant cell tumours are ~~variable~~ variable in appearance, depending on amount of haemorrhage, presence of co-existent ABC, and degree of fibrosis.

Microscopically they are characterised by prominent and diffuse osteoclastic giant cells and mononuclear cells ( round, oval, or polygonal and may resemble normal histiocytes). Frequent mitotic figures in the mononuclear cells may be seen, especially in pregnant women or those on the oral contraceptive pill (due to increased hormone levels) ¹.GCTs are low grade tumours even in radiologically aggressive appearing lesions.

Approximately 5-10% of GCTs are malignant ¹. Sarcomatous transformation is seen, especially in radiotherapy treated inoperable tumours.

Although rare (3%) lung metastasis are possible- benign metastasising GCT.¹⁰

It is important to realise that features may be difficult to interpret histologically with a relatively wide histological differential diagnosis (e.g. giant cell reparative granuloma, brown tumour, osteoblastoma, chondroblastoma, non-ossifying fibroma, and even osteosarcoma with abundant giant cells)¹ thus making radiology indispensable to the interpretation of these lesions.

Location

They typically occur as single lesions. Although any bone can be affected, the most common sites are ^1-2:

around the knee: distal femur and proximal tibia: 50-65%
distal radius: 10-12%
sacrum: 4-9%
vertebral body

Multiple locations: ≈ 1% (multiple lesions usually occur in association with Paget disease)

Radiographic features

Classic appearance

Four radiographic features are characteristic when a GCT is located in a long bones:

occurs only with a closed growth plate
abuts articular surface: 84-99% come within 1 cm of the articular surface ¹
well defined with non-sclerotic margin (though < 5% may show some sclerosis ⁸)
eccentric: if large this may be difficult to assess

Plain film and CT

General radiographic features include:

narrow zone of transition: a broader zone of transition is seen in more aggressive GCTs
no surrounding sclerosis: 80-85%
overlying cortex is thinned, expanded or deficient
periosteal reaction is only seen in 10-30% of cases
soft tissue mass is not infrequent
pathological fracture may be present
no matrix calcification/mineralisation

MRI

Typical signal characteristics include:

T1
- low to intermediate solid component
- low signal periphery
- solid components enhance, helping distinguish GCT with ABC from pure ABC ^3-4
- some enhancement may also be seen in adjacent bone marrow
T2
- ~~low~~heterogenous high signal with areas of low signal intensity (variable) due to haemosiderin or fibrosis ⁹
- if an ABC component present, then fluid-fluid levels can be seen
- high signal in adjacent bone marrow thought to represent inflammatory oedema ⁴
T1 C+ (Gd): solid components will enhance, helping differentiate from ABCs ⁹

Scintigraphy: bone scan

Most GCT demonstrate increased uptake on delayed images, especially around the periphery, with a central photopenic region (doughnut sign). Increased blood pool activity is also seen, and can be seen in adjacent bones due to generalised regional hyperaemia (contiguous bone activity).

Angiography

If performed, usually in the setting of pre-operative embolisation, angiography usually demonstrates a hypervascular tumour (2/3^rd of cases) with the rest being hypo or avascular.

Treatment and prognosis

Classically, treatment is with curettage and packing with bone chips or polymethylmethacrylate (PMMA). Local recurrence is from the periphery of the lesion and has historically occurred in up to 40-60% of cases. Newer intraoperative adjuncts such as thermal or chemical treatment of the resection margins have lowered the recurrence rate to 2.5-10%¹. Early work on monoclonal antibodies, as an adjuvent treatment, has been impressive in causing high rates of tumour necrosis.⁷ Wide local excision is associated with a lower recurrence rate, but has greater morbidity.

~~Approximately 5-10% of GCTs are malignant~~ ¹~~. Sarcomatous transformation is seen, especially in radiotherapy treated inoperable tumours.~~

~~Although rare (3%) lung metastasis are possible.~~¹⁰

Differential diagnosis

There is a relatively wide differential similar to that of a lytic bony lesion:

chondroblastoma: epiphyseal, usually in skeletally immature patients
chondromyxoid fibroma: metaphyseal, with a well defined sclerotic margin, multiloculated bubbly appearance ³
aneurysmal bone cyst (ABC): younger age group, but may co-exist with GCT; fluid-fluid levels
non-ossifying fibroma: usually younger age group⁴
brown tumour: in the setting of hyperparathyroidism
enchondroma: only really a consideration in lesions of small bones of the hand and foot ³
haemophilic pseudotumour
chondrosarcoma: typically older age group
metastases and multiple myeloma
intraosseous ganglion cysts
desmoplastic fibroma

-<p><strong>Giant cell tumours (GCTs) of bone</strong>, also known as <strong>osteoclastomas</strong>, are relatively common bone tumours, usually benign and typically found in the metaphysis of long bones.</p><h4>Epidemiology</h4><p>GCTs are common, comprising 18-23% of benign bone neoplasms and 4-9.5% of all primary bone neoplasms <sup>1</sup>. They almost invariably (97-99%) occur when the growth plate has closed and are therefore typically seen in early adulthood, with 80% of cases reported between the ages of 20 and 50, with a peak incidence between 20 and 30 <sup>1</sup>.</p><p>There is overall a mild female predilection, especially when located in the spine, however malignant transformation is far more common in men (M:F of ~3:1) <sup>1</sup>.</p><h4>Clinical presentation</h4><p>Presentation is not specific, typically presents insidiously and relates to bone pain, soft tissue mass, compression of adjacent structures or acutely with a pathological fracture.</p><h4>Pathology</h4><p>Giant cell tumours are believed to result from an over-expression in RANK/RANKL signalling pathway with resultant over-proliferation of osteoclasts <sup>6</sup>.</p><p>These tumours contain numerous thin walled vascular channels predisposing to areas of haemorrhage and presumably related to the relatively frequent co-existence of <a href="/articles/aneurysmal-bone-cyst">aneurysmal bone cysts (ABC)</a> found in 14% of cases<sup> 1-2,4</sup>.</p><p>Macroscopically, giant cell tumours are variable in appearance, depending on amount of haemorrhage, presence of co-existent ABC, and degree of fibrosis.</p><p>Microscopically they are characterised by prominent and diffuse osteoclastic giant cells and mononuclear cells ( round, oval, or polygonal and may resemble normal histiocytes). Frequent mitotic figures in the mononuclear cells may be seen, especially in pregnant women or those on the oral contraceptive pill (due to increased hormone levels) <sup>1</sup>.</p><p>It is important to realise that features may be difficult to interpret histologically with a relatively wide histological differential diagnosis (e.g. <a href="/articles/central-giant-cell-granuloma">giant cell reparative granuloma</a>, <a href="/articles/brown-tumour">brown tumour</a>, <a href="/articles/osteoblastoma">osteoblastoma</a>, <a href="/articles/chondroblastoma">chondroblastoma</a>, <a href="/articles/non-ossifying-fibroma-1">non-ossifying fibroma</a>, and even <a href="/articles/osteosarcoma">osteosarcoma</a> with abundant giant cells)<sup>1</sup> thus making radiology indispensable to the interpretation of these lesions.</p><h5>Location</h5><p>They typically occur as single lesions. Although any bone can be affected, the most common sites are <sup>1-2</sup>:</p><ol>
+<p><strong>Giant cell tumours (GCTs) of bone</strong>, also known as <strong>osteoclastomas</strong>, are relatively common bone tumours, usually benign which are arising from metaphysis and typically extending into the epiphysis of the long bones. </p><h4>Epidemiology</h4><p>GCTs are common, comprising 18-23% of benign bone neoplasms and 4-9.5% of all primary bone neoplasms <sup>1</sup>. They almost invariably (97-99%) occur when the growth plate has closed and are therefore typically seen in early adulthood, with 80% of cases reported between the ages of 20 and 50, with a peak incidence between 20 and 30 <sup>1</sup>.</p><p>There is overall a mild female predilection, especially when located in the spine, however malignant transformation is far more common in men (M:F of ~3:1) <sup>1</sup>.</p><h4>Clinical presentation</h4><p>Presentation is not specific, typically presents insidiously and relates to bone pain, soft tissue mass, compression of adjacent structures or acutely with a pathological fracture.</p><h4>Pathology</h4><p>Giant cell tumours are believed to result from an over-expression in RANK/RANKL signalling pathway with resultant over-proliferation of osteoclasts <sup>6</sup>.</p><p>These tumours contain numerous thin walled vascular channels predisposing to areas of haemorrhage and presumably related to the relatively frequent co-existence of <a href="/articles/aneurysmal-bone-cyst">aneurysmal bone cysts (ABC)</a> found in 14% of cases<sup> 1-2,4</sup>.</p><p>Macroscopically, giant cell tumours are variable in appearance, depending on amount of haemorrhage, presence of co-existent ABC, and degree of fibrosis.</p><p>Microscopically they are characterised by prominent and diffuse osteoclastic giant cells and mononuclear cells ( round, oval, or polygonal and may resemble normal histiocytes). Frequent mitotic figures in the mononuclear cells may be seen, especially in pregnant women or those on the oral contraceptive pill (due to increased hormone levels) <sup>1</sup>. <span style="line-height:13.8666658401489px">GCTs are </span><span style="line-height:1.6">low grade tumours even in radiologically aggressive appearing lesions. </span></p><p>Approximately 5-10% of GCTs are malignant <sup>1</sup>. Sarcomatous transformation is seen, especially in radiotherapy treated inoperable tumours.</p><p>Although rare (3%) lung metastasis are possible- benign metastasising GCT.<sup>10</sup></p><p>It is important to realise that features may be difficult to interpret histologically with a relatively wide histological differential diagnosis (e.g. <a href="/articles/central-giant-cell-granuloma">giant cell reparative granuloma</a>, <a href="/articles/brown-tumour">brown tumour</a>, <a href="/articles/osteoblastoma">osteoblastoma</a>, <a href="/articles/chondroblastoma">chondroblastoma</a>, <a href="/articles/non-ossifying-fibroma-1">non-ossifying fibroma</a>, and even <a href="/articles/osteosarcoma">osteosarcoma</a> with abundant giant cells)<sup>1</sup> thus making radiology indispensable to the interpretation of these lesions.</p><h5>Location</h5><p>They typically occur as single lesions. Although any bone can be affected, the most common sites are <sup>1-2</sup>:</p><ol>
+<li>vertebral body</li>
~~-<li>low signal intensity (variable) <sup>9</sup>~~
+<li>heterogenous high signal with areas of low signal intensity (variable) due to haemosiderin or fibrosis <sup>9</sup>
-</ul><h5>Scintigraphy: bone scan</h5><p>Most GCT demonstrate increased uptake on delayed images, especially around the periphery, with a central photopenic region (<a href="/articles/doughnut-sign-bone-scans">doughnut sign</a>). Increased blood pool activity is also seen, and can be seen in adjacent bones due to generalised regional hyperaemia (<a href="/articles/contiguous-bone-activity">contiguous bone activity</a>).</p><h5>Angiography</h5><p>If performed, usually in the setting of pre-operative embolisation, angiography usually demonstrates a hypervascular tumour (2/3<sup>rd</sup> of cases) with the rest being hypo or avascular.</p><h4>Treatment and prognosis</h4><p>Classically, treatment is with curettage and packing with bone chips or polymethylmethacrylate (PMMA). Local recurrence is from the periphery of the lesion and has historically occurred in up to 40-60% of cases. Newer intraoperative adjuncts such as thermal or chemical treatment of the resection margins have lowered the recurrence rate to 2.5-10%<sup>1</sup>. Early work on monoclonal antibodies, as an adjuvent treatment, has been impressive in causing high rates of tumour necrosis.<sup>7</sup> Wide local excision is associated with a lower recurrence rate, but has greater morbidity.</p><p>Approximately 5-10% of GCTs are malignant <sup>1</sup>. Sarcomatous transformation is seen, especially in radiotherapy treated inoperable tumours.</p><p>Although rare (3%) lung metastasis are possible.<sup>10</sup></p><h4>Differential diagnosis</h4><p>There is a relatively wide differential similar to that of a lytic bony lesion:</p><ul>
+</ul><h5>Scintigraphy: bone scan</h5><p>Most GCT demonstrate increased uptake on delayed images, especially around the periphery, with a central photopenic region (<a href="/articles/doughnut-sign-bone-scans">doughnut sign</a>). Increased blood pool activity is also seen, and can be seen in adjacent bones due to generalised regional hyperaemia (<a href="/articles/contiguous-bone-activity">contiguous bone activity</a>).</p><h5>Angiography</h5><p>If performed, usually in the setting of pre-operative embolisation, angiography usually demonstrates a hypervascular tumour (2/3<sup>rd</sup> of cases) with the rest being hypo or avascular.</p><h4>Treatment and prognosis</h4><p>Classically, treatment is with curettage and packing with bone chips or polymethylmethacrylate (PMMA). Local recurrence is from the periphery of the lesion and has historically occurred in up to 40-60% of cases. Newer intraoperative adjuncts such as thermal or chemical treatment of the resection margins have lowered the recurrence rate to 2.5-10%<sup>1</sup>. Early work on monoclonal antibodies, as an adjuvent treatment, has been impressive in causing high rates of tumour necrosis.<sup>7</sup> Wide local excision is associated with a lower recurrence rate, but has greater morbidity.</p><h4>Differential diagnosis</h4><p>There is a relatively wide differential similar to that of a lytic bony lesion:</p><ul>

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