Quantitative proteomic study reveals differential expression of matricellular proteins between fibrous dysplasia and cemento-ossifying fibroma pathogenesis.

BACKGROUND: Fibrous dysplasia (FD) and cemento-ossifying fibroma (COF) are the most common gnathic fibro-osseous lesions. These diseases exhibit remarkable overlap of several clinicopathological aspects, and differential diagnosis depends on the combination of histopathological, radiographic, and clinical aspects. Their molecular landscape remains poorly characterized, and herein, we assessed their proteomic and phosphoproteomic profiles. METHODS: The quantitative differences in protein profile of FD and COF were assessed by proteomic and phosphoproteomic analyses of formalin-fixed paraffin-embedded tissue samples. Pathway enrichment analyses with differentially regulated proteins were performed. RESULTS: FD and COF exhibited differential regulation of pathways related to extracellular matrix organization, cell adhesion, and platelet and erythrocytes activities. Additionally, these lesions demonstrated distinct abundance of proteins involved in osteoblastic differentiation and tumorigenesis and differential abundance of phosphorylation of Ser61 of Yes-associated protein 1 (YAP1). CONCLUSIONS: In summary, despite the morphological similarity between these diseases, our results demonstrated that COF and DF present numerous quantitative differences in their proteomic profiles. These findings suggest that these fibro-osseous lesions trigger distinct molecular mechanisms during their pathogenesis. Moreover, some proteins identified in our analysis could serve as potential biomarkers for differential diagnosis of these diseases after further validation.

Diagnosis and management of benign fibro-osseous lesions of the jaws: a current review for the dental clinician.

Benign fibro-osseous lesions of the maxillofacial skeleton constitute a heterogeneous group of disorders that includes developmental, reactive (dysplastic) and neoplastic lesions. Although their classification has been reviewed multiple times in the past, the most common benign fibro-osseous lesions are fibrous dysplasia, osseous dysplasia and ossifying fibroma. For the dental clinician, the challenges involve diagnosis and treatment (or lack thereof). A careful correlation of all clinical, radiologic and microscopic features is essential to establish a proper diagnosis and a clear treatment plan. This article aimed to review the clinical, radiologic and histopathologic characteristics of benign fibro-osseous lesions of the jaws, with emphasis on their differential diagnoses. With a deeper understanding of benign fibro-osseous lesions, clinicians will be better prepared to manage these lesions in their practice.

Can Differences in Vascularity Serve as a Diagnostic Aid in Fibro-Osseous Lesions of the Jaws?

PURPOSE: Different lesions in the fibro-osseous group share microscopic features; thus, establishing a definitive diagnosis based on microscopic features alone can be a challenge. There is a need for additional microscopic tools to aid in differentiating these lesions. This study compared parameters related to vascularity among 3 lesions in the fibro-osseous group: fibrous dysplasia (FD), central ossifying fibroma (COF), and cemento-osseous dysplasia (COD). MATERIALS AND METHODS: This study was a cross-sectional analysis of biopsied lesions retrieved from 3 medical centers over a 14-year period. The primary predictor variables were the vascularity parameters (number, perimeter, and area). The outcome variables were diagnoses of FD, COF, and COD. Diagnosis was based on clinical, microscopic, and radiologic correlations. From each histopathologic slide, 5 representative fields were captured with a computerized digital camera. The number of blood vessels was counted, and the surface area and vascular perimeter were measured by tracing the perimeter of each vessel. Data were statistically analyzed using analysis of variance with logarithmic transformation and a Tukey adjustment. RESULTS: Sixty-six cases were included in the study (26 in FD group, 26 in COF group, and 14 in COD group). The mean number of vessels showed only a tendency to be larger in the FD group compared with the COF and COD groups (5.4 ± 2.6, 3.7 ± 2.3, and 3.6 ± 1.7, respectively), but the results did not reach the threshold for significance. The mean vascular perimeter was 1,385.8 ± 859.2 pixels in the FD group and 742.6 ± 661.8 in COF group after logarithmic transformation (P = .012). The perimeter in the COD group was smaller (941.1 ± 502) compared with that in the FD group, but the difference did not reach the threshold for significance. The mean area was 25,061 ± 24,875.6 in the FD group and 11,773.8 ± 21,734.4 in the COF group after logarithmic transformation (P = .004). The perimeter in the COD group was smaller (13,011.1 ± 8,338.3) compared with the FD group, but the difference did not reach the threshold for significance. CONCLUSION: The vascular content of the FD group was markedly higher than of the COF group. These vascular changes can aid in differentiating these lesions microscopically.

Peripheral Cemento-Ossifying Fibroma.

Peripheral cemento-ossifying fibroma (PCOF), a relatively uncommon lesion, reactive in nature is seen as an overgrowth of the gingival tissues often leading to periodontal problems. It is a benign tumor with slow-growing potential commonly affecting the anterior maxilla whose pathogenesis till date is uncertain. It is usually challenging to diagnose peripheral cemento-ossifying fibroma based on clinical observation and examination, hence histopathological examination is mandatory to arrive at an accurate diagnosis. Recurrence of the lesion is common unless and until it is completely excised. We present the report of two cases of peripheral cemento-ossifying fibroma of our department, complaining of a mass in the gingiva of posterior maxilla and mandible.

Central Cemento-Ossifying Fibroma: Primary Odontogenic or Osseous Neoplasm?

Currently, central cemento-ossifying fibroma is classified by the World Health Organization as a primary bone-forming tumor of the jaws. However, histopathologically, it is often indistinguishable from cemento-osseous dysplasias in that it forms osteoid and cementicles (cementum droplets) in varying proportions. It is believed that pluripotent cells within the periodontal membrane can be stimulated to produce either osteoid or woven bone and cementicles when stimulated. If this is true, cemento-ossifying fibroma would be better classified as a primary odontogenic neoplasm arising from the periodontal ligament. Cemento-ossifying fibromas also do not occur in the long bones. The present report compares several entities that fall within the diagnostic realm of benign fibro-osseous lesions and reviews the evidence for reclassifying central cemento-ossifying fibroma as a primary odontogenic neoplasm.

Recurrent cementoblastoma with multifocal growth and cellular atypia: a case report.

BACKGROUND: Cementoblastoma is a rare odontogenic tumor characterized by the formation of osteocementum-like tissue on a tooth root directly by neoplastic cementoblasts. Although it is categorized as benign, it has a high potential for growth with a certain degree of recurrence risk. However, there are only a few studies describing the features of recurrent cementoblastoma. The diagnosis of recurrent cementoblastoma is challenging not only due to its cytological atypia but also because of its large size and multicentric growth pattern. These characteristics suggest a potential for malignancy. CASE PRESENTATION: A 29-year-old woman was transferred to our university dental hospital complaining of swelling of the right mandible. She had a history of enucleation of cementoblastoma associated with the third molar of the right mandible. Five years after the initial treatment, imaging demonstrated well-circumscribed multicentric radiopaque lesions in the same area. Histologically, the lesion consisted of osteocementum-like tissue rimmed with polygonal or plump tumor cells. Several cells were large epithelioid cells with bizarre nucleoli, which may be reminiscent of malignant tumors. Otherwise, there were no apparent malignant findings, including proliferative activity or atypical mitotic figure. Besides, tumor cells were positive for c-FOS, a marker of osteoblastoma and cementoblastoma. Eventually, the patient was diagnosed with recurrent cementoblastoma. CONCLUSIONS: Pathological analyses of this case suggested that the recurrent event in the cementoblastoma altered its growth pattern and tumor cell shape. Moreover, in the case of enucleation surgery, long-term follow-up is important because there is some recurrent risk of cementoblastoma, although it is not high.

Histomorphometric and molecular characterization of stromal and mineralized components in fibro-osseous lesions.

BACKGROUND: Indistinct and analogous histopathological features of various fibro-osseous lesions make establishing a definitive diagnosis a challenge. There is a need for additional molecular and histochemical tools to support and differentiate these lesions in order to establish a concrete diagnosis. MATERIALS AND METHODS: A retrospective analysis of biopsied lesions in formalin-fixed paraffin-embedded sections (10 cases each of fibrous dysplasia, ossifying fibroma, and cement-osseous dysplasia) retrieved from the archives was studied for immunoexpression of osteocalcin (quantitative analysis in osteocytes), collagen characterization using Azan, Picrosirus, and Toluidine blue stain for evaluating intensity and localization of collagen fibers, and morphometric analysis of vasculature (for evaluating mean vessel density as square microns). RESULTS: Positive immunostaining of osteocalcin suggested mutations of the GNAS-1 gene found in fibrous dysplasia indirectly, as it is a negative regulator of bone formation. Osteocalcin immunopositivity was quantitatively measured in the fibro-osseous lesions, with fibrous dysplasia measuring 14.47 ± 3.628 as compared to ossifying fibroma measuring 5.23 ± 1.33, followed by cemento-osseous dysplasia measuring 2.30 ± 1.409. Toluidine blue suggests the presence of oxytalan fibers (resistant to acid hydrolysis) in ossifying fibroma and cemento-osseous dysplasia, pointing toward the pathogenesis of the lesion. Azan stain and Picrosirus (under a polarizing microscope) helped in distinguishing hard tissue characteristics (70% of cases of fibrous dysplasia showed only a magenta component followed by intermixed magenta with a blue component in 20% of cases and only 10% of cases showed magenta with blue borders whereas for ossifying fibroma, 40% of cases depicted magenta with blue borders along with the other 40% with intermixed magenta with blue component). The mean vessel density was also highest in fibrous dysplasia measuring 7.90 ± 1.079 (in Sq. micron area), followed by ossifying fibroma and cemento-osseous dysplasia. CONCLUSION: The diagnosis of fibro-osseous lesions by hematoxylin and eosin alone is confusing and thus should be supported by relatively simple histomorphometric analysis for better treatment outcomes. At the diagnostic stage of fibro-osseous lesions, evaluation of intralesional vessel size, reliable molecular marker, and histochemical nature can aid in differentiating fibrous dysplasia from central ossifying fibroma and cemento-osseous dysplasia alongside, other clinical, radiographic and pathological criteria. These parameters help in the diagnostic decision-making of fibro-osseous lesions.

Giant cemento-ossifying fibroma of the mandible: a rare case.

The World Health Organization classifies cemento-ossifying fibroma (COF) as a fibro-osseous neoplasm included among the nonodontogenic tumors derived from the mesenchymal blast cells of the periodontal ligament, with a potential for forming fibrous tissue, cementum and bone, or a combination of such elements. These are slow-growing lesions, and are more frequent in women, between the third and fourth decades of life. Case reports of massive expansile COFs (measuring more than 10 cm) are rarely reported in the literature. This article aims to describe a case of giant cemento-ossifying fibroma with radiographic and 3D CT features in a 34 year old female patient, who came with the complaint of progressive swelling of the face which had started 6 years earlier.

[Clinical and pathological features and differential diagnosis of fibro-osseous tumors and dysplasias].

Fibro-osseous lesions is a class of diseases with obvious similarities in clinical manifestations and pathological features, which has been attracting the attention of clinicians and pathologists. The latest WHO 2022 Classification (5th edition) included six of these diseases (cemento-osseous dysplasia, segmental odontomaxillary dysplasia, fibrous dysplasia, juvenile trabecular ossifying fibroma, psammomatoid ossifying fibroma and familial gigantiform cementoma) in the " fibro-osseous tumours and dysplasias ", and put forward new ideas on the diagnosis and treatment of these diseases. According to the latest WHO 2022 Classification (5th edition), the clinical and pathological features, diagnosis and differential diagnosis of these six diseases were described.

Extraosseous cemento-ossifying fibroma beneath the left buccal mucosa: a case report.

Cemento-ossifying fibroma (COF) is a benign mesenchymal odontogenic tumor that commonly occurs in the tooth-bearing areas of the maxilla and mandible. This study reports a COF case located under the left buccal mucosa. The classification and differential diagnosis of this COF case were discussed based on the diagnosis and treatment of this case and previous literature.

Expansive focal cemento-osseous dysplasia.

AIM: To present a case of expansive focal cemento-osseous dysplasia and emphasize the importance of differential diagnosis. BACKGROUND: Cemento-osseous dysplasia is categorized into three subtypes on the basis of the clinical and radiographic features: Periapical, focal and florid. The focal type exhibits a single site of involvement in any tooth-bearing or edentulous area of the jaws. These lesions are usually asymptomatic; therefore, they are frequently diagnosed incidentally during routine radiographic examinations. Lesions are usually benign, show limited growth, and do not require further surgical intervention, but periodic follow-up is recommended because occasionally, this type of dysplasia progresses into florid osseous dysplasia and simple bone cysts are formed. CASE REPORT: A 24-year-old female patient was referred to our clinic for swelling in the left edentulous mandibular premolarmolar region and felt discomfort when she wore her prosthetics. She had no pain, tenderness or paresthesia. Clinical examination showed that the swelling in the posterior mandible that was firm, nonfluctuant and covered by normal mucosa. On panoramic radiography and computed tomography, a well defined lesion of approximately 1.5 cm in diameter of mixed density was observed. The swelling increased slightly in size over 2 years making it difficult to use prosthetics and, therefore, the lesion was totally excised under local anesthesia, and surgical specimens were submitted for histopathological examination. The histopathological diagnosis was focal cemento-osseous dysplasia. CONCLUSION: In the present case, because of the increasing size of the swelling making it difficult to use prosthetics, young age of the patient and localization of the lesion, in the initial examination, cemento-ossifying fibroma was suspected, and the lesion was excised surgically; the histopathological diagnosis confirmed it as focal cemento-osseous dysplasia. CLINICAL SIGNIFICANCE: We present a case of expansive focal cemento-osseous dysplasia. Differential diagnosis is essential because ossifying fibroma is a real neoplastic entity.

Maxillary cementoblastoma in a child.

Cementoblastoma is a rare benign tumor that almost always occurs in the premolar or molar region and more commonly in the mandible than in the maxilla. We present a unique incisor maxillary cementoblastoma in an 11-year-old child not previously described. To our knowledge, only 2 maxillary cases, both related to canine teeth, were described in the international literature. Thus, the aim of this article was to discuss the clinical presentation, diagnosis, and subsequent treatment of a patient with a cementoblastoma in the anterior maxillary region.

Osseous (cemento-osseous) dysplasia of the jaws: clinical and radiographic analysis.

OBJECTIVES: To explore the demographic characteristics and clinical features among patients with osseous (cemento-osseous) dysplasia (OD/COD) of the jaws and to determine the frequency of particular radiographic characteristics. METHODS: The charts and radiographic reports of 118 patients with OD/COD, obtained from the archives of the University of Toronto discipline of oral and maxillofacial radiology, were reviewed. Demographic and clinical data, radiographic findings and final diagnoses were collected and analyzed to determine typical characteristics. RESULTS: Of the 117 patients for whom age and sex were known, the majority (97 [82.9%]) were female; these female patients had a mean age (± standard deviation) of 44.3 ± 13.4 years. Eighty-three (72.2%) of the 115 patients for whom symptoms were known were clinically asymptomatic. Ninety-three patients (78.8%) had OD/COD at single sites (i.e., periapical OD/COD), and 25 (21.2%) had OD/COD at multiple sites (i.e., florid OD/COD). In addition, 15 (12.7%) of the cases were associated with one or more simple bone cysts, and 13 (11.0%) were associated with osteomyelitis. In most cases, the OD/COD was unilateral, with the lesion being located in the mandible, usually associated only with the posterior teeth. The lesions exhibited well-defined, sclerotic or corticated margins (108 patients [91.5%]) and were surrounded by a radiolucent border. Minimal effects on surrounding structures were observed. As well, 85 (72.0%) of the lesions were in the mixed radiolucent-radiopaque stage, with dense, cementum-like radiopacities. CONCLUSIONS: The majority of cases of OD/COD occurred in women in the fifth decade of life, and most cases were asymptomatic. OD/COD was more likely to present as solitary lesions but also occurred in association with simple bone cysts or osteomyelitis.

[Florid cemento-osseous dysplasia of the jaws]. / Dysplasie cémento-osseuse floride des maxillaires.

INTRODUCTION: Florid cemento-osseous dysplasia is a benign and rare tumor of the jaws. It is more commonly seen in middle-aged black women. Most cases are asymptomatic and are found during routine radiographic examination. OBSERVATIONS: We report two complicated cases of florid cemento-osseous dysplasia, one with facial deformity and the other with chronic osteitis. DISCUSSION: The diagnosis of florid cemento-osseous dysplasia is based on clinical and radiological features. The lesions are commonly bilateral and symmetrical.

Cemento-osseous dysplasia in African-American men: a report of two clinical cases.

Two clinical cases of the unusual occurrence of cemento-osseous dysplasia in men and the clinical, radiographic and demographic findings that formed the basis for their diagnosis and management are presented.

A contraindication to orthodontic and endodontic treatment: periapical cemento-osseous dysplasia.

INTRODUCTION: The dental pulp is completely normal in teeth with periapical cemento-osseous dysplasia. However, orthodontic and endodontic treatments are contraindicated in cases with this injury. OBJECTIVE: Present some biological, clinical and imaging reasons opposing these contraindications and questioning which are the real ones impediments and the reasons for the lack of research on the disease, analyzing cases submitted to orthopedic treatment under controlled and ethically approved conditions. CONCLUSION: The clinician can act safely based in available knowledge and aware of the possible consequences of orthodontic movement in teeth with periapical cemento-osseous dysplasia, as well as in the proper way of making a safe and definitive diagnosis.