Giant cell tumor of bone

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Giant cell ~~tumors~~tumours of bone, also known as osteoclastomas, are relatively common bone ~~tumors~~tumours and are usually benign. They typically arise from the metaphysis of long bones, extend into the epiphysis adjacent to the joint surface, and have a narrow zone of transition.

Epidemiology

Giant cell ~~tumors~~tumours 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. 80% of cases are 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~~:F of ~3:1) ¹.

Clinical presentation

Often they are incidentally identified. They may present insidiously with bone pain, soft tissue mass, or compression of adjacent structures. ~~Pathological~~The pathological fracture may result in an acute presentation.

Pathology

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

These ~~tumors~~tumours contain numerous thin-walled vascular channels predisposing to areas of ~~hemorrhage~~haemorrhage and presumably related to the relatively frequent coexistence of aneurysmal bone cysts found in 14% of cases^1,2,4.

Macroscopic appearance

Macroscopically, giant cell ~~tumors~~tumours are variable in appearance, depending on the amount of ~~hemorrhage~~haemorrhage, the presence of a coexistent aneurysmal bone cyst, and degree of fibrosis.

Histology

Microscopically they are characterized 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.

Giant cell ~~tumors~~tumours are low-grade ~~tumors~~tumours even in radiologically aggressive appearing lesions. Approximately 5-10% are malignant ¹. Sarcomatous transformation is seen, especially in radiotherapy treated inoperable ~~tumors~~tumours. Although rare (~5%), lung metastases are possible and have an excellent prognosis. Hence, this entity has been called benign metastasizing giant cell ~~tumor~~tumour ^10,11.

It is important to realize that features may be difficult to interpret histologically with a relatively wide histological differential diagnosis (e.g. giant cell reparative granuloma, brown ~~tumor~~tumour, osteoblastoma, chondroblastoma, non-ossifying fibroma, and even osteosarcoma with abundant giant cells) ¹, thus rendering 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: 7%
- thoracic spine most common, followed by cervical and lumbar spines

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

Radiographic features

Classic appearance

There are four characteristic radiographic features when a giant cell ~~tumor~~tumour is located in a long bone:

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 radiograph / CT

General radiographic features include:

a narrow zone of transition: a broader zone of transition is seen in more aggressive giant cell ~~tumors~~tumours
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
a pathological fracture may be present
no matrix calcification/mineralisation

MRI

Typical signal characteristics include:

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

Nuclear medicine

On bone scintigraphy, most giant cell ~~tumors~~tumours 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 generalized regional hyperemia (contiguous bone activity).

Angiography (DSA)

If performed, usually in the setting of preoperative embolization, angiography usually demonstrates a hypervascular ~~tumor~~tumour (two-thirds of cases) with the rest being hypovascular 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 thermocoagulation, cryotherapy, or chemical treatment of the resection margins have lowered the recurrence rate to 2.5-10% ¹. Early work on monoclonal antibodies (e.g. denosumab) as an adjuvant treatment targeted at ~~tumor~~tumour necrosis has shown impressive results ⁷. Wide local excision is associated with a lower recurrence rate but has greater morbidity.

Differential diagnosis

There is a relatively wide differential similar to that of a lytic bone 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 giant cell ~~tumor~~tumour; fluid-fluid levels
non-ossifying fibroma: usually younger age group⁴
brown ~~tumor~~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 cyst
desmoplastic fibroma
metaphyseal fibrous defect¹²

-<p><strong>Giant cell tumors of bone</strong>, also known as <strong>osteoclastomas</strong>, are relatively common bone tumors and are usually benign. They typically arise from the metaphysis of long bones, extend into the epiphysis adjacent to the joint surface, and have a narrow zone of transition.</p><h4>Epidemiology</h4><p>Giant cell tumors 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. 80% of cases are 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>Often they are incidentally identified. They may present insidiously with bone pain, soft tissue mass, or compression of adjacent structures. Pathological fracture may result in acute presentation.</p><h4>Pathology</h4><p>Giant cell tumors are believed to result from an over-expression in the RANK/RANKL signaling pathway with resultant hyperproliferation of osteoclasts <sup>6</sup>.</p><p>These tumors contain numerous thin-walled vascular channels predisposing to areas of hemorrhage and presumably related to the relatively frequent coexistence of <a href="/articles/aneurysmal-bone-cyst">aneurysmal bone cysts</a> found in 14% of cases<sup> 1,2,4</sup>.</p><h5>Macroscopic appearance</h5><p>Macroscopically, giant cell tumors are variable in appearance, depending on the amount of hemorrhage, the presence of coexistent aneurysmal bone cyst, and degree of fibrosis.</p><h5>Histology</h5><p>Microscopically they are characterized 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>Giant cell tumors are low-grade tumors even in radiologically aggressive appearing lesions. Approximately 5-10% are malignant <sup>1</sup>. Sarcomatous transformation is seen, especially in radiotherapy treated inoperable tumors. Although rare (~5%), <a href="/articles/pulmonary-metastases">lung metastases</a> are possible and have an excellent prognosis. Hence, this entity has been called <strong>benign metastasizing giant cell tumor</strong> <sup>10,11</sup>.</p><p>It is important to realize that features may be difficult to interpret histologically with a relatively wide histological differential diagnosis (e.g. <a href="/articles/central-giant-cell-lesions-granuloma">giant cell reparative granuloma</a>, <a href="/articles/brown-tumour">brown tumor</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 rendering 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><ul>
+<p><strong>Giant cell tumours of bone</strong>, also known as <strong>osteoclastomas</strong>, are relatively common bone tumours and are usually benign. They typically arise from the metaphysis of long bones, extend into the epiphysis adjacent to the joint surface, and have a narrow zone of transition.</p><h4>Epidemiology</h4><p>Giant cell tumours 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. 80% of cases are 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>Often they are incidentally identified. They may present insidiously with bone pain, soft tissue mass, or compression of adjacent structures. The pathological fracture may result in an acute presentation.</p><h4>Pathology</h4><p>Giant cell tumours are believed to result from an over-expression in the RANK/RANKL signalling pathway with resultant hyperproliferation 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 coexistence of <a href="/articles/aneurysmal-bone-cyst">aneurysmal bone cysts</a> found in 14% of cases<sup> 1,2,4</sup>.</p><h5>Macroscopic appearance</h5><p>Macroscopically, giant cell tumours are variable in appearance, depending on the amount of haemorrhage, the presence of a coexistent aneurysmal bone cyst, and degree of fibrosis.</p><h5>Histology</h5><p>Microscopically they are characterized 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>Giant cell tumours are low-grade tumours even in radiologically aggressive appearing lesions. Approximately 5-10% are malignant <sup>1</sup>. Sarcomatous transformation is seen, especially in radiotherapy treated inoperable tumours. Although rare (~5%), <a href="/articles/pulmonary-metastases">lung metastases</a> are possible and have an excellent prognosis. Hence, this entity has been called <strong>benign metastasizing giant cell tumour</strong> <sup>10,11</sup>.</p><p>It is important to realize that features may be difficult to interpret histologically with a relatively wide histological differential diagnosis (e.g. <a href="/articles/central-giant-cell-lesions-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 rendering 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><ul>
-</ul><p>Multiple locations: ≈1% (multiple lesions usually occur in association with <a href="/articles/paget-disease-bone">Paget disease</a>).</p><h4>Radiographic features</h4><h5>Classic appearance</h5><p>There are four characteristic radiographic features when a giant cell tumor is located in a long bone:</p><ul>
+</ul><p>Multiple locations: ≈1% (multiple lesions usually occur in association with <a href="/articles/paget-disease-bone">Paget disease</a>).</p><h4>Radiographic features</h4><h5>Classic appearance</h5><p>There are four characteristic radiographic features when a giant cell tumour is located in a long bone:</p><ul>
~~-<li>narrow zone of transition: a broader zone of transition is seen in more aggressive giant cell tumors</li>~~
+<li>a narrow zone of transition: a broader zone of transition is seen in more aggressive giant cell tumours</li>
~~-<li>pathological fracture may be present</li>~~
+<li>a pathological fracture may be present</li>
~~-<li>low to intermediate solid component</li>~~
+<li>low to intermediate signal solid component</li>
~~-<li>solid components enhance, helping distinguish giant cell tumors with an <a href="/articles/aneurysmal-bone-cyst">aneurysmal bone cyst (ABC)</a> from a pure ABC <sup>3,4</sup>~~
+<li>solid components enhance, helping distinguish giant cell tumours with an <a href="/articles/aneurysmal-bone-cyst">aneurysmal bone cyst (ABC)</a> from a pure ABC <sup>3,4</sup>
~~-<li>high signal in adjacent bone marrow thought to represent inflammatory edema <sup>4</sup>~~
+<li>high signal in adjacent bone marrow thought to represent inflammatory oedema <sup>4</sup>
-</ul><h5>Nuclear medicine</h5><p>On bone scintigraphy, most giant cell tumors demonstrate increased uptake on delayed images, especially around the periphery, with a central photopenic region (<a href="/articles/doughnut-sign-on-bone-scan">doughnut sign</a>). Increased blood pool activity is also seen, and can be seen in adjacent bones due to generalized regional hyperemia (<a href="/articles/contiguous-bone-activity">contiguous bone activity</a>).</p><h5>Angiography (DSA)</h5><p>If performed, usually in the setting of preoperative embolization, angiography usually demonstrates a hypervascular tumor (two-thirds of cases) with the rest being hypovascular 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 thermocoagulation, cryotherapy, or chemical treatment of the resection margins have lowered the recurrence rate to 2.5-10% <sup>1</sup>. Early work on monoclonal antibodies (e.g. denosumab) as an adjuvant treatment targeted at tumor necrosis has shown impressive results <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 bone lesion:</p><ul>
+</ul><h5>Nuclear medicine</h5><p>On bone scintigraphy, most giant cell tumours demonstrate increased uptake on delayed images, especially around the periphery, with a central photopenic region (<a href="/articles/doughnut-sign-on-bone-scan">doughnut sign</a>). Increased blood pool activity is also seen, and can be seen in adjacent bones due to generalized regional hyperemia (<a href="/articles/contiguous-bone-activity">contiguous bone activity</a>).</p><h5>Angiography (DSA)</h5><p>If performed, usually in the setting of preoperative embolization, angiography usually demonstrates a hypervascular tumour (two-thirds of cases) with the rest being hypovascular 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 thermocoagulation, cryotherapy, or chemical treatment of the resection margins have lowered the recurrence rate to 2.5-10% <sup>1</sup>. Early work on monoclonal antibodies (e.g. denosumab) as an adjuvant treatment targeted at tumour necrosis has shown impressive results <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 bone lesion:</p><ul>
~~-<a href="/articles/aneurysmal-bone-cyst">aneurysmal bone cyst (ABC)</a>: younger age group, but may co-exist with giant cell tumor; fluid-fluid levels</li>~~
+<a href="/articles/aneurysmal-bone-cyst">aneurysmal bone cyst (ABC)</a>: younger age group, but may co-exist with giant cell tumour; fluid-fluid levels</li>
~~-<a href="/articles/brown-tumour">brown tumor</a>: in the setting of <a href="/articles/hyperparathyroidism">hyperparathyroidism</a>~~
+<a href="/articles/brown-tumour">brown tumour</a>: in the setting of <a href="/articles/hyperparathyroidism">hyperparathyroidism</a>

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