Malignancy in Giant Cell Tumor of Bone: A Review of the Literature

Abstract

Background: Primary and recurrent giant cell tumor of bone is typically benign; however, rarely giant cell tumor of bone can undergo malignant transformation. Malignancy in giant cell tumor of bone may be primary (adjacent to benign giant cell tumor of bone at first diagnosis) or secondary (at the site of previously treated giant cell tumor of bone). Malignant giant cell tumor of bone has a poor prognosis; it is important to distinguish malignant from benign lesions to facilitate appropriate management. The true incidence of malignant giant cell tumor of bone is not known, probably owing to inaccurate diagnosis and inconsistent nomenclature. We have analyzed current data to provide a robust estimate of the incidence of malignancy in giant cell tumor of bone.

Methods: A literature search was performed to source published reports of primary and secondary cases of malignant giant cell tumor of bone. Studies that reported a denominator were used to estimate the incidence of malignancy.

Results: We identified 4 large series of patients with malignant giant cell tumor of bone that provided data on 2315 patients with giant cell tumor of bone. Across these studies, the cumulative incidence of malignancy was 4.0%; the cumulative incidence of primary malignancy was 1.6% compared with 2.4% for secondary malignancy. Our analyses confirmed that most malignant giant cell tumor of bone is secondary and occurs following radiation. In addition, data from 8 small series showed that 4.8% of patients with giant cell tumor of bone who received radiation therapy developed secondary malignancy.

Conclusions: Malignant giant cell tumor of bone is rare, and its identification is hindered by a lack of clear diagnostic criteria. For optimal care of patients with giant cell tumor of bone, we recommend: comprehensive histologic sampling to ensure accurate diagnoses; watchful follow-up, particularly for patients treated with radiation; and timely treatment of local recurrence.

Keywords: bone tumors; clinical features; diagnosis; incidence; prognosis; rare disease.

Figure 1.

Histologic differences between benign giant cell tumor of bone (GCTB), giant cell-rich osteosarcoma, and malignant GCTB. (A) Benign GCTB consists of two cell types: stromal mononuclear spindle cells and multinucleated giant cells (GCs). Arrow shows a GC. (B) Giant cell-rich osteosarcoma consists of GCs, oval or spindle mononuclear cells with atypical nuclei, fibrovascular stroma, and new woven bone. (C) Malignant GCTB consists of a GC tumor component with mononuclear cells with typical nuclei, side by side with a pleomorphic malignant spindle cell component (T). Panels A and B are reproduced with permission from Dr Palmerini. Panel C has been adapted with permission from Bertoni et al.