Malignant transformation of fibrous dysplasia into osteosarcoma in McCune-Albright syndrome syndrome

A 29-year-old male with a known history of McCune-Albright syndrome with acromegaly and polyostotic fibrous dysplasia had undergone multiple corrective craniofacial procedures. Recent corrective surgery of the mandible was complicated by extensive haemorrhage. Two months after the procedure, rapid enlargement of the jaw was noticed.

CT scan revealed imaging findings consistent with polyostotic fibrous dysplasia and a progressive soft tissue mass with destruction of the mandible, osteoid matrix formation, necrosis, and haemorrhage (Fig. 1a and 1b). On MR imaging, the soft tissue mass appeared heterogeneous with vivid enhancement on contrast-enhanced T1W-images (Fig. 2a-d). Nevertheless, the mass could not be clearly distinguished from pre-existing polyostotic fibrous dysplasia lesions.
18-F-FDG PET-CT revealed increased FDG-uptake by the mandibular lesion and the soft tissue component and a few comparable metabolically active osteolytic lesions at different distant sites (Fig. 3a-e). A calcified pulmonary nodule in the left lower lobe was noted without increased FDG-uptake (Fig. 3f).
Whole-body MR imaging revealed restricted diffusion in the lesion of the mandible (Fig. 4a, b). No restricted diffusion was noticed in the other osteolytic lesions with increased FDG-uptake (Fig. 4c). A biopsy of the mandibular soft tissue mass was performed, and histopathological examination confirmed fibrous dysplasia with malignant transformation to osteosarcoma.

McCune-Albright syndrome is characterized by fibrous dysplasia, café-au-lait macules, and hyperfunctioning endocrinopathies [1]. Fibrous dysplasia is a benign fibro-osseous lesion, which can affect one bone (monostotic) or multiple bones (polyostotic) with a predilection for the craniofacial bones [2]. Fibrous dysplasia is characterized by altering normal osteoblastic activity and replacing normal bone with abnormal fibro-osseous tissue [3]. It is usually a slow-growing lesion, but rapid growth can be seen in young children and prepubertal adolescents. Additionally, rapid growth can be associated with aneurysmal bone cyst or malignant transformation, the latter is estimated to occur in 4% in polyostotic forms and 0.5% in monostotic forms [4-6]. Osteosarcoma is the most common type of malignant transformation from fibrous dysplasia, accounting for 70% of the cases [7].

Fibrous dysplasia shows marked variability in radiographic appearance, which can make it difficult to distinguish fibrous dysplasia from a malignant lesion [8]. Features such as cortical bone destruction, extension in the surrounding soft tissue, and osteoid matrix formation should trigger suspicion of malignant transformation.
The FDG-uptake of fibrous dysplasia lesions may depend on the activity of fibroblasts and an increased FDG-uptake may mimic a malignant lesion [9]. In this case, a few osteolytic lesions with increased FDG-uptake were detected at other locations than the mandible. Therefore, a whole-body MR scan was performed. Although MR imaging usually cannot differentiate fibrous dysplasia from other entities, diffusion-weighted imaging can be a useful tool since ADC values correlate with cellularity [8,10]. However, an overlap between the ADC values of fibrous dysplasia and malignant transformation may exist due to the composition of the tumour matrix and the presence of necrosis. Therefore, no cut off value has been validated as consensus to distinguish these entities [11,12]. In this case, MR imaging demonstrated only restricted diffusion in the soft tissue mass of the mandible. No restricted diffusion in the other FDG-avid osteolytic lesions was observed, which are more likely to be hypermetabolic fibrous dysplasia lesions. However, histopathology is the gold standard, and a biopsy is needed to confirm the diagnosis.
The most common cause to a calcified pulmonary nodule is a healed granulomatous disease or infection. However, a calcified pulmonary metastasis should be included in the differential diagnosis with a history of osteosarcoma. In this case, the calcified pulmonary nodule was unchanged after a short follow-up of 2 months and to distinguish it from a metastasis a long-interval follow-up is needed.