Recurrent frontal bone fibrous dysplasia as a high-grade pleomorphic sarcoma and unfavorable prognosis: Case report and brief review of literature

Malignant transformation of craniofacial fibrous dysplasia into high-grade undifferentiated pleomorphic sarcoma (UPS) is an exceptionally rare but aggressive phenomenon, posing a significant diagnostic and management challenge due to its initially benign appearance and sudden rapid progression.
We report a case of a 34-year-old woman who presented with an 8-year history of progressive, painless right frontal skull swelling, primarily causing cosmetic deformity without neurological symptoms. Initial imaging using CT showed a pathognomonic expansile “ground-glass” lesion (6.8 × 5.2 × 2.4 cm) of the right frontal bone consistent with monostotic FD. The patient was treated with an elective frontal craniotomy with intraoperative contouring and burring of the affected frontal bone through a bicoronal approach.
At the 30-month postoperative visit, repeat CT demonstrated recurrence at the site of the prior procedure in the form of high-grade UPS and pulmonary metastasis; there was no malignant osteoid formation. Molecular studies showed a GNAS mutation (Arg201His), confirming the origin from FD; a TP53 mutation supporting malignant transformation; and negative MDM2 amplification and CDK4 overexpression. The patient was treated with neoadjuvant chemotherapy, radical en bloc resection with craniofacial reconstruction, adjuvant radiation therapy (60 Gy) due to positive margins, second-line systemic therapy (gemcitabine + docetaxel) after progression, and finally, palliative care. 
Ultimately, the decline in function led to death approximately 29 months post-malignant transformation. This case highlights the importance of consistent surveillance of the usually benign FD, as rapid transformation to high-grade sarcoma is associated with poor patient outcomes.