Orthopedic Oncology cases giant cell tumor

A 40-year-old male presents with complaint of pain and swelling at the right wrist for 3 months. He works as a painter and uses his hands all day. He has been unable to paint due to decreased range of motion and severe pain in the wrist. Aspiration of the wrist is negative for infection. X-rays taken are shown in Figure 8–11A and B.

 

 

 

Figure 8–11 A

 

 

 

Figure 8–11 B

 

Which of the following histopathologic images (Fig. 8–12A through D) is most consistent with the lesion shown in Figure 8–11A and B?

 

 

 

Figure 8–12 A–D

 

Discussion

The correct answer is image (B). Sheets of osteoclast-like giant cells mixed with background mononuclear stromal cells are the key characteristics of giant cell tumor. The nuclei of the stroma cells are similar in size and appearance to the nuclei in the giant cells. This is typical histology of a giant cell tumor of bone.

Which of the following is a true statement regarding this lesion?

1. Despite its benign designation, a small percentage of patients develop lung metastases

2. Curettage and bone grafting is a reliable treatment, and local recurrence rate is close to zero

3. The extent of soft-tissue mass correlates with the tumor’s malignancy potential

4. Fluid–fluid levels evident on MRI within the tumor suggest malignant transformation

Discussion

The correct answer is (A). This is considered a benign but locally aggressive tumor with high rate of local recurrence. A small percentage of patients (fewer than 2%) will develop lung metastases, which are known as “benign pulmonary metastases” because they have a benign histology and generally do not compromise the patient survival as much as malignant metastases. After curettage with high-speed burr, a local adjuvant such as hydrogen peroxide, liquid nitrogen, or sterile water should be used to reduce the high local recurrence rate. These tumors can demonstrate areas of secondary intralesional aneurysmal bone cyst, evident by fluid–fluid levels on cross-sectional imaging and seen on histology.

What is the mechanism of bone destruction in this tumor?

1. Direct destruction of the bone by giant cells

2. pH imbalance caused by tumor cells resulting in alkaline phosphatase dysfunction

3. Secretion of factors by stromal cells which stimulates osteoclast recruitment and subsequent bone resorption

4. Recruitment of tumor cells by high number of giant cells which cause mechanical erosion of bony trabeculae

Discussion

The correct answer is (C). The mechanism of bone destruction in giant cell tumor is an example of a microsystem in which normal bone remodeling via the RANKL signaling pathway is upregulated causing locally increased bone resorption. That is, it is a stimulation by tumor cells of the normal mechanism of bone turnover. Osteoclasts are recruited and activated by cytokines secreted by tumor cells, and osteoclastic bone resorption is mediated by the RANKL pathway. For this reason, agents inhibiting RANKL signaling have been studied in treatment of giant cell tumor. Denosumab, an anti-RANK ligand antibody, has been recently approved for

use in the treatment of this tumor.

 

Objectives: Did you learn...?

 

 

To recognize the imaging and histology of giant cell tumor? Mechanism of tumor-mediated bone destruction?

 

Treatment of giant cell tumor of bone?