Giant cell tumor - Orthopaedia

Tumor biology and incidence

GCTs of bone are relatively enigmatic lesions which although "benign" can be locally aggressive causing significant bony destruction, can demonstrate metastases to the lung (3%), as well as mets to lymph nodes and malignant transformation (both rare). In the US and Europe GCTs account for nearly 5% of all primary bone tumors and 21% of all benign bone tumors. Interestingly in China they account for 20% of all primary bone tumors.Giant Cell Tumor (GCT) has recently been shown to be of mesenchymal origin. Its associated mononuclear stromal cell of origin is a fibro-osteoblastic cell that produces type I and type II collagen. Some identifying cell characteristics include its receptors for parathormone, its production of alkaline phosphatase. Cells often stain positive for p53, and have alterations in c-myc, N-myc, c-fos oncogenes. Some researchers believe that there is a close genetic relationship between GCT and osteosarcoma. The fusions of mononuclear macrophages result in multi-nucleated giant cells which have receptor sites for calcitonin and lend GCTs its clinical features of pathologic lysis and bony erosion seen on imaging studies.

Age

Most patients are between 20 and 40 years of age; it is extremely rare in patients younger than 13 yrs, and only 10% of cases occur in patients over 65.

Gender

More common in females and faster growing in pregnant women. Female:male ( 1.5:1)

Presentation

A common presentation involves pain in the area of the lesion as well as associated swelling and tenderness to palpation. There is also a 37% incidence of pathologic fracture at presentation. More than 50% of GCTs are located about the knee (distal femur>proximal tibia). The proximal humerus and distal radius are the third and 4th most common sites. GCT has also been described in the Sacrum or around the pelvis and can prove a very difficult entity to treat.Rarely, a patient may present with multi-centric disease which shows a proclivity for the small bones of the hands and feet and can be clinically more aggressive.

Physical findings

Pain and swelling in the area of lesion. Pathologic fracture.

Plain films

Lesions appear mostly lytic, lucent and eccentrically located within the bone. They are often characterized by extensive local destruction, cortical breakthrough and expansion into adjacent soft tissue. When located near the epiphysis GCTs can penetrate through articular surfaces into the adjacent joint. Mineralization of primary GCT is rare although a recurrence or soft tissue GCT commonly demonstrates peripheral calcificationX-Ray Grading system of Campanacci which has no correlation between local recurrence or metastasis Grade 1 (latent): rare stage in which there is a well-defined margin and intact cortex; Grade 2 (active): relatively well-defined margin but cortex is thinned and moderately expanded.Grade 3 (aggressive): indistinct borders, cortical destruction, and soft tissue extensionSite
1) distal femur 2) Proximal tibia 3)proximal humerus 4) Distal Radius 5) Vertebral body, Sacrum Rare: 3% mets to lung, rare lymph node or local mets

Size

Expansile and enlarging.

Tumor effect on bone

Large lytic focus destroying bone and thinning the adjacent cortices.

Bone response to tumor

Bone is unable to form sclerotic margin although a narrow transition zone is commonly observed.

Cortex

Lesion is often expansile and thins the cortices.

Soft tissue mass

Soft tissue extension is a common occurrence.

Bone scan

Depending on the aggressiveness of the GCT bone scan can be cold suggesting a mostly lytic tumor.

CT Scan

Useful to demonstrate cortical breach or to define a suspected pathologic fracture.

MRI

Performed to delineate the extent of the neoplasm. Typically, GCTs have low signal intensity on T1-weighted images and intermediate signal intensity on T2-weighted images. There is usually a homogeneous intensity in this well circumscribed lesion.

Differential Diagnosis

Histological Differential Diagnosis: ABC, brown tumor of hyperparathyroidism, chondroblastoma, osteoblastoma, osteosarcomaIncluded in most differentials: infection, metastatic lesion, EG

Natural history

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Pathology

Gross: Soft, spongy, friable tumor with areas of hemorrhage lending its characteristic yellowish-to-orange discoloration due to hemosiderin.Micro: fairly uniform field of polyhedral to short spindle shaped mono-nuclear stromal cells with a benign nuclear patterns. Several multi-nucleated giant cells are also present.

Diagnosis and treatment

Traditionally GCT was treated with curettage and bone grafting, but this was shown to correlate with a 45% recurrence rate. As a result, adjuvants such as liquid nitrogen, phenol, hydrogen peroxide, or bone cement recurrence rates dropped to 17%. Furthermore, phenol + bone cement led to recurrence rates of 3%. Most orthopaedic surgeons consider aggressive curettage (usually with high speed bur), + bone cement to be the gold standard. Some centers advocate curettage, adjuvant (phenol or liquid nitrogen) + bone cement. Radiation is restricted to difficult lesions of the pelvis and spine where adequate margins are not feasible. Radiation can result in the conversion of GCT to high-grade osteosarcoma, MFH, or malignant GCT which can readily lead to patient death.Wide resection is indicated for lesions of the distal radius and aggressive lesions of the sacrum or spine.

Complications

Local recurrence is a well documented problem which has been reduced due to the use of high speed burr curettage as well as adjuvants and bone cement. Some studies report a 6% rate of post treatment fracture after cryotherapy with liquid nitrogen related to bone necrosis.