Clinicopathological and histological analysis of secondary malignant giant cell tumors of bone without radiotherapy

Eiji Nakata, Hotaka Kawai, Tomohiro Fujiwara, Toshiyuki Kunisada, Hirofumi Inoue, Mashu Futagawa, Haruyoshi Katayama, Takuto Itano, Toshifumi Ozaki

Research output: Contribution to journalArticlepeer-review


Giant cell tumor of bone (GCTB) is an intermediate bone tumor that rarely undergoes malignant transformation. Secondary malignant GCTB (SMGCTB) is defined as a lesion in which high‑grade sarcoma occurs at the site of previously treated GCTB. The present study retrospectively reviewed the medical records of patients with GCTB treated at Okayama University Hospital between April 1986 and April 2020. The clinicopathological and histological features of patients with SMGCTB without prior radiotherapy were investigated. A total of three patients (4%) with SMGCTB were detected, and the tumor sites were the distal ulna, distal femur and sacrum. Two of the patients had been treated with curettage and bone graft, and one had been treated with denosumab. In all cases, the lesions were made up of two components, the conventional GCTB component and the malignant compo‑ nent. The Ki67 labeling index was higher in the malignant components of SMGCTB and metastatic lesions compared with that in primary and recurrent conventional GCTB, or the conventional GCTB component of SMGCTB. Moreover, p53 expression was higher in these same components in patients who underwent curettage and bone grafting; however, there was no difference in the patient that received denosumab treatment. In this patient, clinical cancer genomic profiling revealed loss of CDKN2A, CDKN2B and MTAP expression. All three patients developed distant metastasis. The patients with SMGCTB in the ulna and femur died 13 and 54 months after detection of malignant transformation, respectively. The patient with SMGCTB in the sacrum received carbon‑ion radiotherapy to the sacrum and pazopanib; the treatment was effective and the patient was alive at the last follow‑up 3 years later. In conclusion, p53 may be associated with malignant transformation in GCTB. Future studies should investigate the association of between denosumab treatment and malig‑ nant transformation, as well as molecular targeted therapy to improve the clinical outcomes of SMGCTB.

Original languageEnglish
Article number319
JournalOncology Letters
Issue number3
Publication statusPublished - Sept 2022


  • denosumab
  • giant cell tumor of bone
  • malignant transformation
  • molecular targeted therapy
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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