giant cell tumor of bone

Definition: Giant cell tumor of the bone (GCTB) is a relatively uncommon tumor. Giant cell tumor of the bone (GCTB) is characterized by the presence of multinucleated giant cells (osteoclast-like cells).

Giant-cell tumor of bone (GCTB) are bone tumors that contain a prominent osteoclastlike giant-cell component. Giant cell tumor of bone accounts for 4% to 5% of primary bone tumors. Approximately 1% of cases present as multiple synchronous or metachronous lesions.

Images

 Giant cell tumor of bone

• https://twitter.com/histiocytosisX/status/726076336129847296
• https://twitter.com/histiocytosisX/status/761302607222575104
• https://twitter.com/BellaMicheleang/status/855470482455396352
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 Cytology : https://twitter.com/DrFNA/status/736324581590507520

 Histone3.3G34W IHC identifies the mutation driving 90% of bone giant cell tumors

• https://twitter.com/CaDxPath/status/876674793021489153

Digital case

 JRC:4622 : Lung metastasis of a giant cell tumor of bone.

GCTBs are generally benign, with unpredictable behavior. In most patients, the tumors are slow to develop, but may recur locally in as many as 50% of cases.

Physiopathology

GCTB is a heterogeneous tumor composed of three different cell populations.

The giant cell tumour stromal cells (GCTSCs) constitute the neoplastic cells, which are from an osteoblastic origin and are classified based on expression of osteoblast cell markers such as alkaline phosphatase and ostocalsin.

In contrast, the mononuclear histiocytic cells (MNHCs) and multinucleated giant cells (MNGCs) fractions are secondarily recruited and comprise the non-neoplastic cell population. They are derived from an osteoclast-monocyte lineage determined primarily by expression of CD68, a marker for monocytic precursor cells.

Epidemiology

Giant cell tumor of the bone accounts for 4-5% of primary bone tumors and 20% of benign bone tumors. However, significantly higher incidence rates are observed in asia, where it constitutes about 20% of all primary bone tumors in China.

It is slightly more common in females, has a predilection for the epiphyseal/metaphyseal region of long bones, and generally occurs in the third to fourth decade.

Although classified as a benign tumor, GCTOB has been observed to metastasize to the lungs in up to 5% of cases, and in rare instances (1-3%) can transform to the malignant sarcoma phenotype with equal disease outcome.

Clinical Presentation

Patients usually present with pain and limited range of motion caused by tumor’s proximity to the joint space. There may be swelling as well, if the tumor has been growing for a long time. Some patients may be asymptomatic until they develop a pathologic fracture at the site of the tumor. The symptoms may including muscular aches and pains in arms, legs and abdominal pain. Patients may also experience nerve pain which feels like an electric shock.

Imaging

On x-ray, giant cell tumors of bone (GCTBs) are lytic/lucent lesions that have a epiphyseal location and grow to the articular surface of the involved bone.

Radiologically the tumors may show characteristic ’soap bubble’ appearance.[They are distinguishable from other bony tumors in that GCTs usually have a non-sclerotic and sharply defined border.

Microscopical synopsis

 Most tumors in the long bones.
 expansive lytic lesions involving the metaphysis and extending into the epiphysis
 minority of the tumors confined to the metaphysis
 fibro-osseous lesion
 bone-forming lesion
 fibrohistiocytic regions
 reactive bone formation
 aneurysmal bone cyst-like changes

Types

 solitary giant cell tumor
 mulitcentric giant cell tumor (16951117)

Complications

 rare metastasis
 rare malignant transformation

Differential diagnosis

 giant cell-rich bone lesions (giant cell-rich bone tumors)

• aneurysmal bone cyst
• chondroblastoma
• simple bone cyst
• osteoid osteoma
• osteoblastoma
• giant cell-rich osteosarcoma
• giant cell reparative granuloma (GCRG)
• brown tumor of hyperparathyroidism

Prognosis

5% of giant cell tumors metastasize, usually to lung, which may be benign metastasis, when the diagnosis of giant cell tumor is suspected, a chest x-ray or CT may be needed. MRI can be used to assess intramedullary and soft tissue extension.

Treatment

General treatment regimens have not changed much in the past 30 years, in part due to the lack of randomized clinical trials.

Surgery is the treatment of choice if the tumor is determined to be resectable. Curettage is a commonly used technique.

The situation is complicated in a patient with a pathological fracture. It may be best to immobilize the affected limb and wait for the fracture to heal before performing surgery.

Patients with tumors that are not amenable to surgery are treated with radiation therapy.

However caution is employed since a majority of recurrent tumors with transformations to the malignant sarcoma phenotype have been in patients receiving radiotherapy for their primary benign lesion.

Pharmacotherapy for GCTOB, includes bisphosphonates such as Zoledronate, which are thought to induce apoptosis in the MNGC fraction, preventing tumor-induced osteolysis. Indeed in-vitro studies have shown Zolidronate to be effective in killing osteoclast-like cells.

More recently, humanized monoclonal antibodies such as denosumab targeting the RANK ligand (RANKL) have been employed in treatment of GCTOB in a phase II study. This is based on the notion that increased expression of RANK-ligands by stromal cells plays a role in tumor pathogenesis.

See also : denosumab-treated giant cell tumor of bone

See also

 giant cell tumor of soft tissue (GCTST)

References

 Lau YS, Sabokbar A, Gibbons CL, Giele H, Athanasou N. Phenotypic and molecular studies of giant-cell tumors of bone and soft tissue. Hum Pathol. 2005 Sep;36(9):945-54. PMID: 16153456