Concurrent Polyostotic Fibrous Dysplasia and Osteosarcoma: A Diagnostic Dilemma in the Era of FDG PET/CT Imaging

INTRODUCTION

Fibrous dysplasia (FD) is a benign fibro-osseous disorder that accounts for approximately 5% of benign bone lesions. It is characterized by defective maturation of lamellar bone, with persistence of immature woven bone. FD may present as either monostotic or polyostotic disease.^[1] The condition results from postzygotic activating mutations in the Guanine nucleotide-binding protein (GNAS) gene, which encodes the stimulatory G-protein alpha subunit (Gsα).

FD is oft en an incidental radiological finding, as patients are usually asymptomatic. Diagnosis is typically established by correlation of clinical and imaging features; biopsy is rarely required except in symptomatic patients or when atypical imaging features raise concern. Malignant transformation of FD is uncommon, with osteosarcoma being the most frequently reported subtype.^[1] Unlike FD, osteosarcoma arises from a distinct and complex molecular profile without involvement of GNAS mutations.

The coexistence of histologically proven FD and osteosarcoma in the same patient is extremely rare and presents significant diagnostic and therapeutic challenges. Distinguishing between primary osteosarcoma and secondary osteosarcoma arising from FD is oft en difficult. We report a case of concurrent FD and osteosarcoma in a 17-year-old male. The case illustrates the diagnostic pitfalls of ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F FDG PET/CT), which demonstrated nonspecific FDG uptake in FD lesions, complicating interpretation when CT and magnetic resonance imaging (MRI) findings suggested FD.

CASE REPORT

A 17-year-old male presented with pain in the left lower limb. Plain radiographs revealed a large, ill-defined, predominantly sclerotic lesion with lytic areas in the metadiaphyseal region of the proximal left tibia. The lesion demonstrated a wide zone of transition, osteoid matrix, and soft -tissue ossification extending into adjacent proximal muscles. These features are consistent with osteosarcoma. In addition, multiple lytic, ground-glass opacities were identified within the intramedullary regions of the right femur and tibia, suggesting polyostotic FD.

¹⁸F-FDG PET/CT demonstrated a metabolically active, ill-defined lytic–sclerotic lesion in the proximal left tibia involving the growth plate and epiphysis. A heterogeneously enhancing extraosseous soft -tissue component infiltrated the tibialis posterior muscle, with associated periosteal reaction. Multiple metabolically active, well-defined, ground-glass intramedullary lesions were also noted in the right femur and tibia. Correlative MRI showed multiple T1- and T2-hypointense lesions with STIR (Short Tau-Inversion Recovery) hyperintensity and postcontrast enhancement in both lower limbs [Figure 1]. Given the intense metabolic activity and multifocal disease with suspected osteosarcoma, biopsy was performed from both limbs.

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Figure 1:

(a) Maximum intensity projection of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scan with multiple FDG avid ground glass skip lesions in the right femur and tibia (green arrow), FDG avid expansile lesion with extraosseous component in the left proximal tibia (blue arrow), (b,c) Non specific uptake noted in multiple intramedullary ground glass nodules with enhancement in right femur (green arrow) and tibia (red arrow) likely fibrous dysplasia and characteristic appearence of osteosarcoma in left proximal tibia (blue arrow). (d) Hypointense lesions on T1W MRI coronal image (upper row); non specific STIR hyperintensity in left tibia (blue arrow) (middle row); and contrast enhancement in T1W axial image in FD of right tibia (red arrow) and in osteosarcoma involving left tibia (blue arrow) (lower row).

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Histopathology confirmed osteosarcoma in the left tibia. The right tibial lesion showed features of FD without evidence of malignancy, thereby downstaging the disease to localized osteosarcoma with concurrent FD. The patient is currently under evaluation for neoadjuvantchemotherapy.

DISCUSSION

FD is a benign bone disorder caused by activating GNAS mutations, leading to replacement of normal marrow and cancellous bone with fibrous stroma and irregular woven bone trabeculae.^[2] It is congenital but not inherited, typically manifesting during the first three decades of life, and oft en stabilizes in adulthood. FD is characterized by irregular trabeculae lacking osteoblastic rimming.^[2]

Most cases are monostotic, while roughly 20% are polyostotic.^[3] The femur, tibia, pelvis, ribs, and craniofacial bones are the most commonly affected sites. Polyostotic FD may be associated with endocrine abnormalities, such as in McCune–Albright syndrome. Clinical presentation varies from incidental findings to pain, deformity, fractures, or functional impairment. Asymptomatic lesions require only periodic imaging surveillance, whereas symptomatic or radiologically atypical lesions warrant further investigation.

FD poses a diagnostic challenge on ¹⁸F-FDG PET/CT. Because of their hypercellular stroma and active osteoblastic remodeling, FD lesions frequently exhibit increased FDG uptake, as documented in literature. This uptake may mimic malignancy, particularly when radiological features are atypical or when concurrent osteosarcoma is present.^[4]

In the present case, the patient had biopsy-proven osteosarcoma of the left tibia. PET/CT also revealed metabolically active lesions in the right femur and tibia. Despite their FDG avidity, these lesions had imaging features more typical of FD. CT-guided biopsy confirmed FD, excluding malignant transformation.

Malignant transformation of FD is rare, occurring in < 1% of cases.^[5] Secondary osteosarcomas tend to occur later in life, oft en in the context of long-standing FD, Paget’s disease, or following radiation therapy. They are associated with poorer prognosis.^[6] The suspicion of malignant change is usually raised by new-onset pain, swelling, or rapid progression. Clinical radiographs demonstrating cortical destruction, periosteal reaction, or soft -tissue extension. Illustrated in the case shown above involving the left tibia.

A well-recognized limitation of PET/CT is the overlap of standardized uptake value (SUV) between benign FD and malignant lesions.^[7,8] The SUV_max alone is insufficient for diagnosis, as FD can demonstrate uptake equal to or greater than that of low-grade osteosarcoma.^[9] Morphologic CT features, lesion stability on follow-up, and MRI correlation are essential adjuncts. Biopsy remains the gold standard for atypical or suspicious FD lesions.

This case highlights the importance of a multidisciplinary approach,^[10] incorporating nuclear medicine, radiology, pathology, and surgeons to distinguish FD from malignancy. Timely differentiation is critical, as secondary osteosarcoma carries a worse prognosis and requires prompt treatment.

CONCLUSION

¹⁸F-FDG PET/CT is a valuable tool in bone tumor evaluation but must be interpreted with caution in FD. High FDG uptake is not diagnostic of malignancy. Biopsy remains indispensable in lesions with atypical features or new symptoms. Awareness of this overlap is essential to avoid both overtreatment of benign FD and missed diagnoses of malignant transformation.