British Journal of Radiology (2008) 81, e31-e34
© 2008 British Institute of Radiology
doi: 10.1259/bjr/19620568
A rare spontaneous osteosarcoma of the calvarium in a patient with long-standing fibrous dysplasia: CT and MR findings
C REIS, MD
1
E M GENDEN, MD
2
J B BEDERSON, MD
3 and
P M SOM, MD
4
1 Department of Neuroradiology, S. João University Hospital, Porto, Portugal, and the Departments of 2 Otolaryngology, 3 Neurosurgery and 4 Radiology, Mount Sinai School of Medicine, New York University, New York, USA
Correspondence: Dr Carina Reis, Alameda Prof. Hernani Monteiro, Porto, 4204-451 Porto, Portugal. E-mail: reis_carina{at}yahoo.com
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Abstract
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A 52-year-old man with long-standing craniofacial polyostotic fibrous dysplasia (FD) and no history of prior radiation therapy developed a spontaneous right temporal bone osteosarcoma. Such spontaneous sarcomatous degeneration of FD is rare, particularly in the calvarium/skull, where, to our knowledge, only six prior cases have been reported in the literature. We report this case because it is a rare entity with well-documented CT and MR images, and to emphasize the importance of depicting imaging features of sarcomatous degeneration among the complex imaging findings of FD.
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Introduction
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Fibrous dysplasia (FD) represents 2.5% of all osseous and 7% of all benign osseous neoplasms [1–4]. It occurs in monostotic (MFD) and polyostotic (PFD) forms, the latter accounting for 20–25% of the cases [3, 4]. When PFD is associated with endocrinological abnormalities, it is known as McCune–Albright syndrome, often considered a separate entity from classical FD [1, 5]. Spontaneous malignant transformation of FD is estimated to occur in less than 1% of cases, and osteosarcoma is the most common histological type, followed by fibrosarcoma, chondrosarcoma and malignant fibrohistiocytoma [4, 6]. These malignancies are most commonly found in the maxilla and mandible, with rare involvement of the calvarium [3, 7, 8]. Most reported cases of malignant degeneration in FD have occurred after radiation therapy. Although the spontaneous degeneration rate is very low, the recent literature has reported a number of cases of spontaneous transformation, but only six were located in the skull [4, 7, 9–13]. Of the six cases involving the skull, there was no mention of the precise location of the malignancy and there were no illustrations of the cases [7, 10, 11]. We report this case because it is a rare entity with well-documented CT and MR images.
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Case report
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A 52-year-old man who had known PFD for 23 years presented with right-sided hearing loss and a serous otitis. A myringotomy tube was placed. He then developed a right facial paresis that responded incompletely to a short course of prednisone and a concomitant onset of a non-tender mass in the right temporoparietal region. As a result of the long-standing FD, the patient suffered several craniofacial abnormalities including inferior displacement of the right globe and a bony deformity of the right calvarium. He had no prior history of radiation therapy and the remainder of his history and physical examination was unremarkable.
A CT scan showed diffuse FD involvement of the skull base, calvarium, the right ethmoid complex, orbital roof, maxilla and the floor of the anterior cranial fossa. The majority of the disease was sclerotic, although there were scattered areas of cystic components. A distinctly different appearing mass was present in the right temporal squama. Here the bone was both destroyed and expanded, with a "sunburst" type periosteal reaction (Figure 1
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Figure 1. Axial wide-windowed skull CT scan shows diffuse FD involvement of the right orbital roof and lateral wall, and ethmoid complex. The medullary cavity is widened and mostly sclerotic. A different mass is present in the right temporal bone squama that is characterized by destruction, expansion, and "sunburst" periosteal reaction.
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An MR imaging study was then performed to further define any intracranial component. There was non-homogeneously low-to-intermediate T1 weighted signal intensity within the expanded FD bone (Figure 2a). On T2 weighted images, the FD bone overall had a low signal intensity, with scattered areas of high T2 weighted signal intensity corresponding to areas of cystic change. The right temporal tumour was a distinct area of expanded bone with low-to-intermediate signal intensity and streaks of low signal intensity that corresponded to the periosteal reaction seen on CT (Figure 2b). On contrast-enhanced, T1 weighted, fat-suppressed images, there was a mild diffuse enhancement in the FD bone. The temporal mass had intense enhancement, with some dural extension. The tumour also extended down into the mastoid and petrous portions of the temporal bone (Figure 2c).
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Figure 2. (a) Coronal T1 weighted MR. Right orbit and facial bones FD involvement, obstruction of right-sided paranasal sinuses, and orbit margins deformity with depression of the right eye. (b) Axial T2 weighted image. Low signal intensity in the FD bone, intensity with sparse areas of high signal intensity representing cystic components. Right temporal bone tumour presents as a fusiform low signal intensity area of expanded bone with radiating internal structure corresponding to the "sunburst" seen on CT. There is different and more pronounced enhancement within the tumour than within the FD, seen on axial post-gadolinium fat-suppressed T1 weighted images (c).
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Surgery was performed via a right middle fossa, transzygomatic and transpetrosal approach. A temporal bone resection was performed, with resection of the heavily ossified temporal bone mass. Although stretched and thinned, there was no apparent direct tumour involvement of the overlying temporalis muscle. There was, however, minimal dural invasion. The patient was reconstructed with titanium–methylmethacrylate cranioplasty. Pathology revealed fibrous dysplasia with osteosarcoma.
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Discussion
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In FD there is failure of mature lamellar bone formation, resulting in an immature woven bone which presents a constantly high turnover rate, and therefore usually fails to complete the normal remodelling process [3, 14–16]. The osteoprogenitor cells have an increased rate of proliferation and display markers of early osteoblastic differentiation, but fail to follow normal osteogenic maturation and thereby characteristically lack expression of late osteoblastic markers [14]. This osteoblastic dysfunction is now attributed to specific gene mutations. Thus, FD in now considered a genetic bone disorder, expressing GNAS1 gene mutations in osteoblastic lineage cells [16]. The GNAS1 gene is located at chromosome 20q13.2–13, and encodes the 
-subunit of the stimulatory G protein Gs [3]. Mutations in the GS gene result in replacement of arginine by either cysteine or histidine, and this results in the loss of the guanosine triphosphatase (GTPase) activity of GS- [3]. The inhibition of GTPase allows sustained activation of adenylate cyclase, with overproduction of cyclic adenosine monophosphate (cAMP) and an increase in intracellular interleukin 6 (IL-6) and c-fos proto-oncogene expression, the latter also being increased in osteosarcomas [3]. IL-6 can be related to the increased numbers of osteoclasts and the increased bone resorption found in FD [3]. The mutations occur post-zygotically, giving a somatic mosaic state [14]. Severe disease may imply an earlier mutational event with a larger number or widespread distribution of dysplastic cells [3].
There is no gender predilection for FD, although a female predominance is seen in McCune–Albright syndrome [3, 17]. Caucasians account for more than 80% of the cases of FD [1]. The disease is predominantly diagnosed before the fourth decade of life [3], and the craniofacial bones are the most frequent involved bones in PFD (40–50%) [18]. The occipital and temporal bones are rarely involved [1] and bilateral bone involvement can be uncommonly found in advanced stages [18]. Strict follow-up of patients with FD is warranted not only for the possibility of malignant degeneration, but also because of disease progression, especially in the fronto-orbital region [19]. Sarcomatous degeneration of FD can be difficult to detect in an earlier phase, and must be suspected in the setting of increasing pain, aggressive growth or elevated levels of serum alkaline phosphatase [1, 6].
CT remains the "gold-standard" imaging modality for FD, allowing characterization of the three main imaging patterns of expanded bone. The cortical bone tends to remain intact, with the changes of FD being most noted in the medullary bone, where there can be a mixed sclerotic/lucent form, the classical homogeneous "ground-glass" form, and/or the cystic form [20]. CT findings of a soft tissue mass with aggressive periosteal reaction especially if a "sunburst" pattern is present should raise the suspicion of sarcomatous degeneration [21].
MRI can also be utilized to diagnose FD, which tends to have low T1 weighted and T2 weighted signal intensities because of the predominance of fibrous tissue and osteoid, with low water content [3]. If cysts are present, high T2 weighted signal intensity is usually present [3]. FD has a rich microvascular circulation accounting for its often significant enhancement on post-contrast MR images [3]. Haemorrhage can also occur in FD. MR may also better characterize any soft tissue extent of a sarcomatous degeneration, and the signal depends on bone content of the tumour, being primarily low on T1 and intermediate on T2, and presents with a distinct pattern from the adjacent FD bone.
FD imaging features, although fairly typical, can be mimicked by other entities and therefore require biopsy or even genetic and/or immunohistochemical testing [5]. Ossifying fibroma resembles FD on imaging, and even pathology might fail to make this distinction [20, 22]. Paget's disease tends to occur in older patients, involvement is usually bilateral, and there tends to be less bone thickening and a poorer medullary/cortical distinction than noted in FD [23]. Hyperparathyroidism has associated hypercalcaemia and neurofibromatosis can be easily differentiated by additional gene testing and its often unique clinical/imaging features. Rarely, chondroblastoma and chondrosarcoma may simulate FD, but in chondrosarcoma there are usually areas of arc-like or curvilinear enhancement [20]. Aneurysmal bone cyst is usually associated with pain and tenderness (uncommonly related to FD), and characteristically osteolytic- and multicystic-presenting fluid–fluid levels [24, 25]. Metastatic lesions from prostate may be seen as sclerotic, almost ground-glass appearing regions on imaging, but history and involvement of the cortices are distinguishing features from FD. Untreated metastatic breast carcinoma invariably is a mixed sclerotic/lytic process with areas of bone destruction [20]. Intraosseous meningiomas can mimic FD although irregularity of the inner table of the skull on CT and dural thickening on contrast-enhanced MR may be seen in most cases, favouring the diagnosis of meningioma [26, 27].
Surgery for routine FD is often reserved for extreme and specific cases, as blood loss at surgery can be substantial. Surgery can be utilized to correct bone deformities, relieve pain, and/or to address specific neurovascular encroachment [28, 29]. Surgery, when possible, is the primary treatment of any malignant transformation [3]. Medical treatment with bisphosphonates may improve function and decrease pain in some patients with FD. Pamidronate, a second generation bisphosphonate, acts as an inhibitor of osteoclastic activity decreasing bone resorption and, thus, reducing overall bone turnover [3, 4, 30]. This results in increased bone density and slows spread of FD into adjacent normal bone [4].
The time interval between the diagnosis of FD and the development of malignancy is usually long, with a mean of 15.5 years [6]. Our patient developed a right temporal osteosarcoma after 23 years of known FD diagnosis, with no previous radiation therapy. Reports concerning prognosis after curative surgery indicate that there is no significant difference between patients who develop spontaneous or radiotherapy-related osteosarcoma, with a mean of survival of 5 and 3.5 years respectively [6].
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Conclusions
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Imaging follow-up is of utmost importance in patients with FD. CT remains the "gold-standard" imaging modality for FD diagnosis, and allows early visualization of sarcomatous degeneration. MR adds anatomic detail including neurovascular compromise, and extent of soft-tissue involvement by sarcomatous degeneration.
The depiction of early signs of sarcomatous degeneration is of great value in order to minimize the extension of surgical resection, particularly in craniofacial FD involvement. This implies a good knowledge of the natural history of FD and experience of the early signs of malignant degeneration.
Received for publication October 2, 2006.
Accepted for publication October 31, 2006.
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References
|
|---|
- Song J-J, Jung H-H, Lee H-M, Hwang S-J. Monostotic fibrous dysplasia of temporal bone: report of two cases and review of its characteristics. Acta Otolaryngol 2005;125:1126–9.[CrossRef][Medline]
- Marshman LAG, David KM, O'Donovan DG, Chawda SJ. Fibrous dysplasia of the cervical spine presenting as a pathological fracture. Br J Neurosurg 2004;18:527–33.[CrossRef][Medline]
- DiCaprio MR, Enneking WF. Fibrous dysplasia. Pathophysiology, evaluation, and treatment. J Bone Joint Surg Am 2005;87: 1848–64.[Abstract/Free Full Text]
- Ricalde P, Horswell BB. Craniofacial fibrous dysplasia of the fronto-orbital region: a case series and literature review. J Oral Maxillofac Surg 2001;59:157–68.[CrossRef][Medline]
- Sakamoto A, Oda Y, Iwamoto Y, Tsuneyoshi M. A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to GSa mutation at the Arg201 codon polymerase chain reaction-restriction fragment length polymorphism analysis of paraffin-embedded tissues. J Mol Diagn 2000;2:67–72.[Abstract/Free Full Text]
- Kaushik S, Smoker WRK, Frable WJ. Malignant transformation of fibrous dysplasia into chondroblastic osteosarcoma. Skeletal Radiol 2002;31:103–6.[CrossRef][Medline]
- Yabut SM, Kenan S, Sissons HA, Lewis MM. Malignant transformation of fibrous dysplasia. A case report and review of the literature. Clin Orthop Relat Res 1988;228:281–7.[Medline]
- Ohmori K, Matsui H, Kanamori M, Yudoh K, Yasuda T, Terahata S. Malignant fibrous histiocytoma secondary to fibrous dysplasia. A case report. Int Orthopaed 1996;20:385–8.
- Huvos AG, Higinbotham NL, Miller TR. Bone sarcomas arising in fibrous dysplasia. J Bone Joint Surg 1972;54-A:1047–56.[Abstract/Free Full Text]
- Ruggieri P, Sim FH, Bond JR, Unni KK. Malignancies in fibrous dysplasia. Cancer 1994;73:1411–24.[CrossRef][Medline]
- Taconis WK. Osteosarcoma in fibrous dysplasia. Skeletal Radiol 1988;17:163–70.[Medline]
- Deyong X, Hongmei L, Alai Z, Weihua F, Xihe S, Fanlu M. Spontaneous malignant transformation of fibrous dysplasia. Chin Med J 1996;109:941–5.[Medline]
- Present D, Bertoni F, Enneking WF. Osteosarcoma of the mandible arising in fibrous dysplasia. A case report. Clin Orthopaed Rel Res 1986;204:238–44.[Medline]
- Cohen MM. Fibrous dysplasia is a neoplasm (editorial comment). Am J Med Genet 2001;98:290–3.[CrossRef][Medline]
- Perdigão PF, Pimenta FJGS, Castro WH, De Marco L, Gomez RS. Investigation of the GSa gene in the diagnosis of fibrous dysplasia. Int J Oral Maxillofac Surg 2004;33:498–501.[CrossRef][Medline]
- Ippolito E, Bray EW, Corsi A, De Maio FE, Ulrich G, Robey PG, et al. Natural history and treatment of fibrous dysplasia of bone: a multicenter clinicopathologic study promoted by the European Pediatric Orthopaedic Society. J Pediatr Orthop 2003;12:155–77.[CrossRef]
- Lustig LR, Holliday MJ, McCarthy EF, Nager GT. FD involving the skull base and temporal bone. Arch Otolaryngol Head Neck Surg 2001;127:1239–47.[Abstract/Free Full Text]
- Som PM, Brandwein MS. Tumors and tumor-like conditions. In: Som PM, Curtin HD, editors. Head and neck imaging, 4th edn. St Louis: Mosby, 2003: 331–3.
- Yavuzer R, Bone H, Jackson IT. Fronto-orbital fibrous dysplasia. Orbit 2000;19:119–28.[CrossRef][Medline]
- Sakai O, Curtin HD, Hasso AN, Swartz JD. Otosclerosis and dysplasias of the temporal bone. In: Som PM, Curtin HD, editors. Head and neck imaging, 4th edn. St Louis: Mosby, 2003: 1253–6.
- Haque F, Fazal ST, Ahmad SA, Abbas SZ, Naseem S. Primary osteosarcoma of the skull. Australas Radiol 2006;50:63–5.[CrossRef][Medline]
- Baumann I, Zimmermann R, Dammann F, Maassen MM. Ossifying fibroma of the ethmoid involving the orbit and the skull base. Otolaryngol Head Neck Surg 2005;133:158–9.[CrossRef][Medline]
- Tehranzadeh J, Fung Y, Donohue M, Anavim A, Pribram HW. Computed tomography of Paget disease of the skull versus fibrous dysplasia. Skeletal Radiol 1998;27:664–72.[CrossRef][Medline]
- Shah GV, Doctor MR, Shah PS. Aneurysmal bone cyst of the temporal bone: MR findings. AJNR Am J Neuroradiol 1995;16:763–6.[Abstract]
- Marcol W, Mandera M, Malinowska I, Pajak J, Wlaszczuk E. Aneurysmal bone cyst of the orbit. Pediatr Neurosurg 2006;42:325–7.[CrossRef][Medline]
- Politi M, Romeike BFM, Papanagiotou P, Nabhan A, Struffert T, Feiden W, et al. Intraosseous hemangioma of the skull with dural tail sign: radiologic features with pathologic correlation. AJNR Am J Neuroradiol 2005;26:2049–52.[Abstract/Free Full Text]
- Daffner RH, Yakulis R, Maroon JC. Intraosseous meningioma. Skeletal Radiol 1998;27:108–11.[CrossRef][Medline]
- Horgan MA, Delashaw JB, Dailey RA. Bilateral proptosis: an unusual presentation of fibrous dysplasia. Br J Neurosurg 1999;13:335–7.[CrossRef][Medline]
- Papay FA, Morales L Jr, Flaharty P, Smith SJ, Anderson R, Walker JM, et al. Optic nerve decompression in cranial base fibrous dysplasia. J Craniofac Surg 1995;6:5–10.[Medline]
- Liens D, Delmas PD, Meunie PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia bone. Lancet 1994;343:953–4.[CrossRef][Medline]
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Abstract
Introduction
