Disappearance of histone H3F3A mutation in metastatic giant cell tumor of bone during long term follow up

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive tumor that rarely metastasizes, although a small subset undergoes malignant transformation. H3F3A driver mutations have been recognized as characteristic molecular features of GCTB. We describe a case of a refractory GCTB with disappearance of the H3F3A mutation and that later developed a malignancy within the preexisting tumor. CASE PRESENTATION: A 22-year-old male was diagnosed with GCTB and underwent multiple surgeries for recurrence and lung metastases. The tumor relapsed in the knee, soft tissue, and lungs and required repeated resections. All relapsed tumor tissues were positive for H3F3A mutation. A large lung metastatic tumor developed 35 years after the initial surgery. The specimen from the last lung metastasis showed no significant changes in the morphology and characteristics of GCTB, despite the disappearance of the H3F3A mutation. Subsequently, liver and bone metastases appeared, and chemotherapy was initiated for presumed malignant transformation. Despite treatment, the disease progressed, and the patient died. CONCLUSION: The disappearance of the H3F3A mutation may be associated with malignant transformation in GCTB, whereas our findings suggest that it does not correspond to the tumor's morphological or biological characteristics.