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

doi:10.3892/ol.2022.13439

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

Oncol Lett. 2022 Jul 19;24(3):319. doi: 10.3892/ol.2022.13439. eCollection 2022 Sep.

Authors

Eiji Nakata¹, Hotaka Kawai², Tomohiro Fujiwara¹, Toshiyuki Kunisada¹, Hirofumi Inoue³, Mashu Futagawa⁴, Haruyoshi Katayama¹, Takuto Itano¹, Toshifumi Ozaki¹

Affiliations

¹ Department of Orthopedic Surgery, Okayama University Hospital, Okayama 700-8558, Japan.
² Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
³ Department of Pathology, Okayama University Hospital, Okayama 700-8558, Japan.
⁴ Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.

Abstract

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 component. 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 malignant transformation, as well as molecular targeted therapy to improve the clinical outcomes of SMGCTB.

Keywords: denosumab; giant cell tumor of bone; malignant transformation; molecular targeted therapy; p53.

Grants and funding

Funding: No funding was received.