Giant cell tumor (GCT) of bone accounts for approximately 5% of primary bone tumors and up to 20% of all benign bone tumors. It commonly arises from the epiphyseal-metaphyseal region of long bones, with a predilection for the distal femur, proximal tibia, and distal radius. These tumors predominantly affect individuals with mature skeleton, typically young adults (Male(M): Female(F)= 2:1)¹. Patients present with pain, swelling, and in some cases pathological fracture. The tumor though benign can be locally aggressive, solitary or multifocal (in around 1% of cases when involving the small bones of hands and feet)^1,2,3. Around 3.5-5% of these tumors can show malignant transformation or metastasize to the lungs^1,5. On imaging, the lesion appears large, eccentric, lytic, and intramedullary with well-defined borders and in some cases soft tissue extension can be seen⁴.

On immunohistochemistry (IHC), the multinucleated giant cells share the staining pattern of that of the macrophages (CD68). Whereas the mononuclear tumor cells show nuclear positivity for p63 and H3G34W [6]. More than 90% of GCT of bone harbor a somatic driver mutation in H3 histone family member 3A (H3F3A) with H3F3A G34W mutation being the most common. IHC directed against H3G34W mutation is a highly sensitive and specific surrogate marker. The H3G34W nuclear stain is restricted to the mononuclear tumor cells and is absent in the multinucleated giant cells. A small subset of tumor cases may harbor the alternate G34V, G34R and G34L mutations^2,3,6,11.

A thorough surgical curettage of the tumor or wide local excision is the treatment of choice. However, in cases where the tumor is surgically inaccessible or possesses a high risk of severe surgical morbidity, radiation therapy can be used as an alternative. Additionally, denosumab, a RANK ligand inhibitor has shown promising outcomes in cases where surgical intervention carries increased risk of morbidity, or the disease has advanced locally or metastasized⁵. Denosumab treated tumors can pose diagnostic challenge as the osteoclast-like giant cells can be depleted with increased fibrosis and hyalinization¹.

About 25% of patients experience recurrence within the first three years following treatment. GCT of bone though considered a benign tumor, has the potential to turn malignant and metastasize to the lungs. Patients who have undergone multiple curettages or present with pathological fracture are at increased risk of metastasis. In rare instances GCT of bone may harbor or transform to a sarcoma, which can occur de novo, following recurrence or treatment².