Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization

Abstract

Ossifying fibroma and fibrous dysplasia of the jaw are maxillofacial fibro-osseous lesions that should be distinguished each other by a pathologist because they show distinct patterns of disease progression. However, both lesions often show similar histological and radiological features, making distinction between the two a diagnostic dilemma. In this study, we performed immunological and molecular analyses of five ossifying fibromas, four cases of extragnathic fibrous dysplasia, and five cases of gnathic fibrous dysplasia with typical histological and radiographic features. First, we examined the difference between fibrous dysplasia and ossifying fibroma in the expression of Runx2 (which determined osteogenic differentiation from mesenchymal stem cells) and other osteogenic markers. Fibroblastic cells in fibrous dysplasia and ossifying fibroma showed strong Runx2 expression in the nucleus. The bone matrices of both lesions showed similar expression patterns for all markers tested except for osteocalcin. Immunoreactivity for osteocalcin was strong throughout calcified regions in fibrous dysplasia, but weak in ossifying fibroma lesions. Second, we performed PCR analysis with peptide nucleic acid (PNA) for mutations at the Arg 201 codon of the alpha subunit of the stimulatory G protein gene (GNAS), which has reported to be a marker for extragnathic fibrous dysplasia. All nine cases of extragnathic or gnathic fibrous dysplasia were positive for this mutation. On the other hand, none of the five cases of ossifying fibroma showed the mutation. These findings indicate that although fibrous dysplasia and ossifying fibroma are similar disease entities, especially in the demonstration of the osteogenic lineage in stromal fibroblast-like cells, they show distinct differences that can be revealed by immunohistochemical detection of osteocalcin expression. Furthermore, PCR analysis with PNA for GNAS mutations at the Arg 201 codon is a useful method to differentiate between fibrous dysplasia and ossifying fibroma.

MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone

“…18,[35][36][37][38][39][40] Okada et al 41 studied eight cases of low-grade central osteosarcomas retrospectively and showed that proliferative cell activity evaluated by AgNOR and MIB-1 immunohistochemical staining was significantly higher in cases of low-grade central osteosarcoma than in fibrous dysplasia and might be helpful in differentiating low-grade central osteosarcoma from fibrous dysplasia. Pollandt et al 42 showed that Gsalpha gene mutations were a constant finding in cases of monostotic fibrous dysplasia.…”

GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw

“…The details of the 24 studies are summarized in Table 3. 1, Among the 24 studies, the numbers of cases ranged from 1 to 64, various techniques have been used for the detection of GNAS mutations, such as reverse transcription PCR and clone sequencing, conventional PCR and direct sequencing, PCRrestriction fragment length polymorphism, pyrosequencing, PCR with mutation-specific restriction enzyme digestion and so on. A variety of materials were used for the extraction of genomic DNA, including fresh bone biopsy, fresh bone tissue, lesional stromal cell cultures, formalin-fixed, paraffin-embedded tissues and so on.…”

“…In the 13 studies that mentioned the types of the bone involved, 1,13,16,17,19,21,23,27,28,30,31,33,34 the positive rate of GNAS mutation was 84% in the extragnathic bones and 78% in the craniofacial bones.…”

“…1 Ossifying fibroma is a benign tumor thought to arise from the periodontal ligament, 2 which can occur in almost any bone in the craniofacial region, predominantly in the jaws. The clinical course of the tumor varies from indolent to aggressive progression.…”

“…Furthermore, Toyosawa's study also suggest that polymerase chain reaction (PCR) analysis with peptide nucleic acid (PNA) for GNAS mutations at the Arg 201 codon is a useful method to differentiate between fibrous dysplasia and ossifying fibroma. 1 To further explore the role of GNAS gene mutational analysis in differential diagnosis of fibrous dysplasia and ossifying fibroma, we examined both Arg 201 and Gln 227 codon in 30 patients with fibrous dysplasia and 21 with ossifying fibroma in the jaws using PCR and direct sequencing. A meta-analysis was also conducted from the published literature evaluating the GNAS mutations in fibrous dysplasia and ossifying fibroma in both the jaws and extragnathic bones.…”