Case 4 -

Ossifying Fibroma David Parham Arkansas Children's Hospital Little Rock, AR

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Clinical History A seven year-old girl noted increasing pain and discomfort in her left ankle. A radiograph revealed a well-defined, cystic lesion of the talus. Histologic findings A discrete fibro-osseous lesion permeates the bony cortex. The lesion contains a mixture of bony spicules and cementum-like bodies. The bony spicules have curvilinear outlines and comprise woven and lamellar bone. Osteoblasts line the spicules. The cementum-like bodies have irregular to globular outlines and contain a slightly refractive, basophilic material. Some form psammomatoid bodies. Bundles of parallel and whorled fibroblasts form a fibro-collagenous stroma between the bony material. There is no evidence of significant atypia or mitotic activity. Case 4 - Figure 1 - A fibro-osseous lesion contains abundant, refractile, cementum-like bodies ("cementicles") enmeshed within a bland, fibroblastic stroma. Case 4 - Figure 2 - Osteoblasts rim a bony spicule within the fibro-osseous lesion. Differential diagnosis Ossifying fibroma Osteofibrous dysplasia Fibrous dysplasia Adamantinoma of long bones Osteosarcoma Diagnosis Ossifying fibroma Text material In current bone tumor classification, ossifying fibroma does not exist outside of the jaw. The most recent WHO classification of bone tumors contains no mention of ossifying fibroma [7] . The lesion once known as ossifying fibroma of long bone has been replaced by osteofibrous dysplasia, a tumor that arises almost exclusively in the tibia and fibula and predominately affects children up to the age of 15 years [3] . Ossifying fibroma still exists as a jaw tumor that arises with the maxilla and mandible. A pediatric form of this tumor has a predilection for the orbit and shows aggressive clinical features, with recurrences occurring frequently in absence of complete surgical excision [5, 12] . One most frequently considers fibrous dysplasia when dealing when dealing with fibro-osseous lesions of bone. Fibrous dysplasia occurs in all bones, particularly the jaw and long bones, and affects all ages [7] . Monostotic forms of this disease arise six times more commonly than polyostotic forms. The latter are associated with the McCune-Albright syndrome, which is also characterized by precocious puberty, café-au-lait spots, and endocrine tumors [8] . Aggressive surgery is generally not indicated in fibrous dysplasia, which traditionally has been considered to be a developmental lesion instead of a neoplasm. Fibrous dysplasia and ossifying fibroma are classically separated by the absence of an osteoid seam from the curvilinear bony spicules that characterize both lesions. Woven bone typically forms fibrous dysplasia spicules, whereas lamellar bone constitutes the spicules of ossifying fibroma. These features are easily visualized with polarized microscopy. Otherwise the two lesions are quite similar at the histologic level, and there is considerable clinical overlap. Some authors claim that these diagnoses represent a histologic continuum of the same entity [14] . Both fibrous dysplasia and ossifying fibroma may contain cementum-like bodies [13] . In ossifying fibroma, the content of these structures is variable. As a result, the terms "cemento-ossifying fibroma" and "cementifying fibroma" have arisen, but these lesions are now considered to be forms of ossifying fibroma [12] . Normal cementum comprises the material sheathing the roots of teeth. Biologically, cementum appears to be more akin to bone than teeth [6] . Because ossifying fibroma has been banished to the jaw and orbit and fibrous dysplasia may contain cementum, many would consider the present case to be an example to the latter lesion. However, new cytogenetic evidence indicates that these two lesions differ at a genetic level. Sawyer et al. has demonstrated a unique recurring translocation in three juvenile ossifying fibromas of the orbit, the t(X;2)(q26;q33) [11] . To date the genes forming breakpoint fusions of this aberration have not been described. On the other hand, all cytogenetic studies of fibrous dysplasia to date have failed to demonstrate this translocation. Many show no abnormality, although the occasional occurrence of chromosomal deletions, gains, and losses in fibrous dysplasia indicates that these lesions may be clonal in nature [4, 10] . GNAS1 mutations have been demonstrated in fibrous dysplasia but are not seen at the karyotypic level [1] . A constitutional mutation of this gene would be lethal, so these abnormalities are probably mosaic in nature. Recurring gains of chromosome 7, 8, 12, and 21 appear to characterize osteofibrous dysplasia [2, 9] . The current case contains a complex translocation involving X, 2, 7, and 12, with breakpoints located at the t(X;2) found in juvenile ossifying fibroma. These cytogenetic features, combined with the histologic features of ossifying fibroma of jaw, i.e. cementum-like bodies and ossicles lined by a osteoblastic seam, and the unusual location of this lesion, that this case if more consistent with ossifying fibroma than fibrous dysplasia or osteofibrous dysplasia. We should thus reconsider the possibility that ossifying fibroma may occur as a lesion of long bones, instead of purely the jaws. References Alman BA, Greel DA, Wolfe HJ. Activating mutations of Gs protein in monostotic fibrous lesions of bone. J Orthop Res 1996;14:311-5. Bridge JA, Dembinski A, DeBoer J, Travis J, Neff JR. Clonal chromosomal abnormalities in osteofibrous dysplasia. Implications for histopathogenesis and its relationship with adamantinoma. Cancer 1994;73:1746-52. Campanacci M, Laus M. Osteofibrous dysplasia of the tibia and fibula. J Bone Joint Surg [Am] 1981;63:367-75. Dal Cin P, Sciot R, Speleman F, et al. Chromosome aberrations in fibrous dysplasia. Cancer Genet Cytogenet 1994;77:114-7. Dehner LP, O'Sullivan MJ, Strauss BL, Wold LE, McAlister WH. Skeletal system: congenital, developmental, and acquired disorders. In: Stocker JT, Dehner LP, eds. Pediatric Pathology. Philadelphia: Lippincott Williams & Wilkins, 2001:1319-402. Diekwisch TG. The developmental biology of cementum. Int J Devel Biol 2001;45:695-706. Fletcher CDM, Unni KK, Mertens F. World Health Organization Classification of Tumours: Pathology and Genetics of Soft Tissue and Bone. Lyon: IARC Press, 2002. Happle R. The McCune-Albright syndrome: a lethal gene surviving by mosaicism. Clin Genet 1986;29:321-4. Hazelbag HM, Wessels JW, Mollevangers P, van dB, Molenaar WM, Hogendoorn PC. Cytogenetic analysis of adamantinoma of long bones: further indications for a common histogenesis with osteofibrous dysplasia. Cancer Genetics & Cytogenetics 1997;97:5-11. Mertens F, Albert A, Heim S, et al. Clonal structural chromosome aberrations in fibrous dysplasia. Genes Chromosom Cancer 1994;11:271-2. Sawyer JR, Tryka AF, Bell JM, Boop FA. Nonrandom chromosome breakpoints at Xq26 and 2q33 characterize cemento-ossifying fibromas of the orbit. Cancer 1995;76:1853-9. Sciubba JJ, Fantasia JE, Kahn LB. Atlas of Tumor Pathology, Third Series: Tumors and Cysts of the Jaw. Washington, D.C.: Armed Forces Institute of Pathology, 2001. Sissons HA, Steiner GC, Dorfman HD. Calcified spherules in fibro-osseous lesions of bone. Arch Pathol Lab Med 1993;117:284-90. Voytek TM, Ro JY, Edeiken J, Ayala AG. Fibrous dysplasia and cemento-ossifying fibroma. A histologic spectrum. Am J Surg Pathol 1995;19:775-81.