Malignant transformation of craniofacial fibrous dysplasia: A clinicopathological, immunohistochemical and molecular analysis of 15 cases in one single institution.

Abstract

Objective: Malignant transformation of craniofacial fibrous dysplasia (FD) is not common and its clinicopathological as well as molecular characteristics remain largely unknown with limited literature reports.

Study design: Patients diagnosed with FD including McCune-Albright syndrome (MAS), polyostotic fibrous dysplasia (PFD), and monostotic fibrous dysplasia (MFD), accompanied by malignant transformation at our institution over the past 18 years (2005-2023) were retrospectively screened and analyzed to investigate the epidemiology and clinicopathological features of these tumors.

Results: Three hundred and five patients were diagnosed as FD in our hospital from 2005 to 2023, with 176 females (57.7 %) and 129 males (42.3 %). The average age at diagnosis was 28.35 years, ranging from 7 to 70 years. A total number of 15 (4. 9 %) cases of FD with malignant transformation were selected. Among these 15 patients, the age of the initial diagnosis of FD ranged from 6 to 54 years (mean age 28.87 ± 16.77), and the ages when malignant transformation occurred ranged from 18 to 57 years (mean age 38.53 ± 13.05). Among 15 patients, 12 patients were female (80 %) and 3 were male (20 %). Fifteen cases included MSA in 2 patients, PFD in 4 patients, and MFD in 9 patients. Of the anatomical sites in craniofacial bones, the most common site of the lesion was the maxilla, followed by the mandible. Malignant neoplasm arising in FD were osteosarcoma (12/15), chondrosarcoma (1/15) and high-grade sarcoma of uncertain differentiation (2/15). The 3- and 5-year overall survival rate was 33.3 % (5/15) and 20 % (3/15) respectively. In secondary osteosarcoma from FD, MDM2 and CDK4 positivity were 33.3 % and 41.7 % respectively, and only one case was MDM2-amplified and CDK4-amplified.

Conclusion: Malignant transformation in fibrous dysplasia was an exceedingly rare event and with a female predominance. The overall survival rate was poor. Osteosarcoma was the most common malignant neoplasm arising in FD. MDM2 and CDK4 expression may aid in the diagnosis of secondary osteosarcoma in FD.