Synchronous cemento-ossifying fibromas: a systematic review.

BACKGROUND: This systematic review aimed to incorporate published data regarding synchronous cemento-ossifying fibromas (COF), with an analysis of their demographic and clinicopathological characteristics. MATERIAL AND METHODS: Case reports and case series of synchronous COF were searched in PubMed, Web of Science, Scopus, EMBASE, and LILACS according to the PRISMA (2020) statement. Also, a manual search was carried out and the grey literature was assessed. A descriptive statistical analysis was performed. RESULTS: Nineteen studies comprising 20 cases of synchronous COF were included. The mean age at diagnosis was 35 years (±13.8), with a predominance of female patients (n=12/60%). In 13 cases (65%) the mandible and the maxilla were affected simultaneously. In two cases (10%) first-degree relatives (parents or siblings) had been previously diagnosed with COF. The diagnostic hypotheses were reported in 8 cases (40%), with florid cemento-osseous dysplasia, ameloblastic fibroodontoma, calcifying cystic odontogenic tumor, osteoma and cementoblastoma being cited in the differential diagnosis. Among the cases with details about management (n=17), eleven were treated by surgical enucleation and/or excision (64.7%). Follow-up was provided for 10 cases (50%), with a mean period of 44.7±62.19 months. Recurrence occurred in three of informed cases. CONCLUSIONS: Synchronous manifestation of COF is rare. Female patients around the 3rd decade of life are more commonly affected. Bilateral involvement of the mandible and maxilla is the most common clinical presentation.

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.

Cementoblastoma Mimicking Pathology of Endodontic Origin: A Case Report.

Interdisciplinary care in the management of complex pathology is critical to ensure patients receive predictable, evidence-based treatment. The authors report the unique case of a healthy 38-year-old female patient who presented to a private endodontics practice with a radiopaque lesion associated with the root of tooth No. 20. The patient experienced mild and occasional palpation tenderness associated with the tooth. Extraoral examination and intraoral soft tissues presented without any abnormalities. Intraoral radiographs revealed a radiopacity overlying the apex of tooth No. 20. A cone-beam computed tomography scan of the region revealed a well-delineated bulbous radiopaque lesion attached to the lingual aspect of the apical third of the root of tooth No. 20. The lesion could not be distinguished from the root outline and presented with a radiolucent halo along its periphery. The differential diagnosis at the time consisted of cementoblastoma, condensing osteitis, hypercementosis, and periapical cemento-osseous dysplasia. The patient was referred to an oral and maxillofacial surgeon for evaluation and treatment. Tooth No. 20 was subsequently treated with an excisional biopsy and concurrent extraction of the tooth. Histologic examination of the lesion supported the diagnosis of cementoblastoma.

Imaging Characteristics of Embedded Tooth-Associated Cemento-Osseous Dysplasia by Retrospective Study.

BACKGROUND: Since there are many differential diagnoses for cemento-osseous dysplasia (COD), it is very difficult for dentists to avoid misdiagnosis. In particular, if COD is related to an embedded tooth, differential diagnosis is difficult. However, there have been no reports on the characteristics of the imaging findings of COD associated with embedded teeth. The aim of the present study was to investigate the occurrence and imaging characteristics of cemento-osseous dysplasia (COD) associated with embedded teeth, in order to appropriately diagnose COD with embedded teeth. METHODS: The radiographs with or without histological findings of 225 patients with COD were retrospectively analyzed. A retrospective search through the picture archiving and communication system (PACS) of the Division of Oral and Maxillofacial Radiology of Kyushu Dental University Hospital was performed to identify patients with COD between 2011 and 2022. RESULTS: Fifteen COD-associated embedded mandibular third molars were identified in 13 patients. All 13 patients were asymptomatic. On imaging, COD associated with embedded mandibular third molars appeared as masses that included calcifications around the apex of the tooth. On panoramic tomography, COD showed inconspicuous internal calcification similar to that of odontogenic cysts or simple bone cysts, especially in patients with COD only around the mandibular third molar region. Those with prominent calcification resembled cemento-ossifying fibroma, calcifying epithelial odontogenic tumor, calcifying odontogenic cyst, adenomatoid odontogenic tumor, and so on, as categories of masses that include calcifications on panoramic tomography and computed tomography. CONCLUSIONS: The current investigation is the first to report and analyze the imaging characteristics of COD associated with embedded teeth. It is important to consider the differences between COD and other cystic lesions on panoramic tomography, and the differences between COD and masses that include calcifications on CT.

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.

Cemento-ossifying fibroma transforming to osteosarcoma.

Ossifying fibroma is a type of fibro-osseous lesion categorised into cemento-ossifying fibroma and juvenile ossifying fibroma. Malignant transformation of fibro-osseous lesions is documented especially for fibrous dysplasia, but scarcity is seen when we search for malignant transformation of ossifying fibroma. Thus, we are presenting an extremely rare case of cemento-ossifying fibroma transforming into osteosarcoma with long sequential radiographic details.

Familial gigantiform cementoma with recurrent ANO5 p.Cys356Tyr mutations: Clinicopathological and genetic study with literature review.

BACKGROUND: Familial gigantiform cementoma (FGC) is a rare tumor characterized by the early onset of multi-quadrant fibro-osseous lesions in the jaws, causing severe maxillofacial deformities. Its clinicopathological features overlap with those of other benign fibro-osseous lesions. FGC eventually exhibits progressively rapid growth, but no suspected causative gene has been identified. METHODS: In this study, three patients with FGC were recruited, and genomic DNA from the tumor tissue and peripheral blood was extracted for whole-exome sequencing. RESULTS: Results showed that all three patients harbored the heterozygous mutation c.1067G > A (p.Cys356Tyr) in the ANO5 gene. Furthermore, autosomal dominant mutations in ANO5 at this locus have been identified in patients with gnathodiaphyseal dysplasia (GDD) and are considered a potential causative agent, suggesting a genetic association between FGC and GDD. In addition, multifocal fibrous bone lesions with similar clinical presentations were detected, including five cases of florid cemento-osseous dysplasia, five cases of polyostotic fibrous dysplasia, and eight cases of juvenile ossifying fibromas; however, none of them harbored mutations in the ANO5 gene. CONCLUSION: Our findings indicate that FGC may be an atypical variant of GDD, providing evidence for the feasibility of ANO5 gene testing as an auxiliary diagnostic method for complex cases with multiple quadrants.

High-grade osteosarcoma arising in DCIA flap reconstruction after a prior resection of maxillar cemento-ossifying fibroma: A case report.

Cemento-ossifying fibroma is a rare benign odontogenic tumour of the tooth-bearing jaws. Its concomitant occurrence with osteosarcoma, a malignant maxillofacial bone tumour, has never been described before. We present an uncommon case of a 43-year-old woman in whom a cemento-ossifying fibroma in the right maxilla was treated by resection and reconstruction using a deep circumflex iliac artery flap. During surgical prosthetic rehabilitation one-year post-operative, an osteosarcoma extending from the contralateral maxilla was coincidentally discovered in the deep circumflex iliac artery flap. The aim of this case report is to raise awareness on the extremely rare but possible simultaneous and independent occurrence of a cemento-ossifying fibroma and an osteosarcoma.

Comprehensive Genomic Analysis of Cemento-Ossifying Fibroma.

Cemento-ossifying fibroma (COF) of the jaws is currently classified as a benign mesenchymal odontogenic tumor, and only targeted approaches have been used to assess its genetic alterations. A minimal proportion of COFs harbor CDC73 somatic mutations, and copy number alterations (CNAs) involving chromosomes 7 and 12 have recently been reported in a small proportion of cases. However, the genetic background of COFs remains obscure. We used a combination of whole-exome sequencing and RNA sequencing to assess somatic mutations, fusion transcripts, and CNAs in a cohort of 12 freshly collected COFs. No recurrent fusions have been identified among the 5 cases successfully analyzed by RNA sequencing, with in-frame fusions being detected in 2 cases (MARS1::GOLT1B and PARG::BMS1 in one case and NCLN::FZR1 and NFIC::SAMD1 in the other case) and no candidate fusions identified for the remaining 3 cases. No recurrent pathogenic mutations were detected in the 11 cases that had undergone whole-exome sequencing. A KRAS p.L19F missense variant was detected in one case, and 2 CDC73 deletions were detected in another case. The other variants were of uncertain significance and included variants in PC, ACTB, DOK6, HACE1, and COL1A2 and previously unreported variants in PTPN14, ATP5F1C, APOBEC1, HDAC5, ATF7IP, PARP2, and ACTR3B. The affected genes do not clearly converge on any signaling pathway. CNAs were detected in 5/11 cases (45%), with copy gains involving chromosome 12 occurring in 3/11 cases (27%). In conclusion, no recurrent fusions or pathogenic variants have been detected in the present COF cohort, with copy gains involving chromosome 12 occurring in 27% of cases.

Immunohistochemical analysis of osteoclastic and osteoblastic activity in ossifying fibroma and juvenile ossifying fibroma: A comparative study.

Cemento-ossifying fibroma (COF) and juvenile ossifying fibroma (JOF) have been considered distinct entities within the category of fibro-osseous lesions. This study aimed to assess osteoblast and osteoclast activity in COF and JOF by investigating bone resorption markers, specifically receptor activator of nuclear factor-kB (RANK), RANK ligand (RANKL), and its inhibitor osteoprotegerin (OPG). A comparative analysis of these markers was performed on all lesions. Immunohistochemistry was employed to evaluate and quantify the expression of these biomarkers in a sample of 20 cases of cemento-ossifying fibroma (COF), 15 cases of psammomatoid juvenile ossifying fibroma (PsJOF), and 10 cases of trabecular juvenile ossifying fibroma (TrJOF). The expression of osteoprotegerin was significantly higher in cemento-ossifying fibroma (33.9±13.0) compared to trabecular juvenile ossifying fibroma (27.3±9.2) and psammatoid ossifying fibroma (25.2±14.9), with the COF showing the highest expression followed by the latter two (p=0.037). There was a higher percentage (80%) of stromal fibroblast cells that showed positive expression of RANKL in cemento-ossifying fibroma (COF) compared to psammomatoid juvenile ossifying fibroma (PsJOF) (33.3%) and trabecular juvenile ossifying fibroma (TrJOF) (30.0%) when considering a positive expression score of 3 (p=0.024). Cemento-ossifying fibroma demonstrated the highest expression of osteoprotegerin and RANKL-positive stromal fibroblast cells, followed by psammomatoid juvenile ossifying fibroma and trabecular juvenile ossifying fibroma. These findings provide valuable insights into the pathogenesis of these lesions.

The True History of Cementoblastoma.

REVIEW OF THE LITERATURE: Cementoblastoma (CB) is unique among odontogenic tumors because its gross pathological anatomy is pathognomonic in most cases, i.e., a rounded calcified growth that is fused to the root of a tooth and completely encapsulated by fibrous tissue. The resulting radiographic appearance is a well-defined, globular mixed radiopaque/lucent or completely radiopaque mass obliterating some details of the root, with a thin radiolucent zone surrounding the central opacity. Although hundreds of publications have covered the clinicopathologic features of CB, almost nothing is known about its true history. Also it seems there is little understanding about how the term "CB" was originally introduced as a pathologic entity. This report covers some overlooked papers on CB dating back to the 19th century, including the first complete description in 1888 and the first radiographic presentation in 1906.

[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.

A Clinical, Radiological and Histopathological Review of 74 Ossifying Fibromas.

BACKGROUND: Ossifying fibroma (OF) is a fibro-osseous lesion of the jaws and craniofacial bones. Accurate diagnosis can be challenging due to significant overlap of clinicopathological features. This study aimed to evaluate the clinical, radiological and histological features that can aid in diagnosis and identify characteristics that allow categorisation into the three subtypes: juvenile trabecular, psammomatoid and cemento-ossifying OF. METHODS: A total of 74 cases of OF were systematically reviewed for their principle features. Of these, 46 cases were evaluated for their radiographic features including size, location and relationship to the teeth. Histological assessment and stereological point counting were performed in 69 cases to assess the pattern, type and proportion of calcification, the nature of the stroma, the border of the lesion and the presence of secondary changes. Fisher's exact test and Chi-squared tests were used to determine associations between clinicopathological parameters and maxillary, mandibular, odontogenic, non-odontogenic and psammomatoid or trabecular lesions. RESULTS: OF showed a female predilection (F: M; 2:1) and a slight bimodal age distribution with peaks in the second (23%) and fourth decades (27%) (Mean age: 32.4 years). 83% of cases presented as an intra-oral swelling, with the mandible being the most common site (73%). Histologically, a range of morphological patterns were seen, with 50% of cases showing mixed trabecular and psammomatoid features. However, there were no significant differences between the variants of OF in terms of age, gender or histological features. CONCLUSION: Histological features of OF cannot be used to differentiate between the subtypes.

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.

Cemento-ossifying fibroma resection combined with heterotopic canine autotransplantation: a case report.

Cemento-ossifying fibroma (COF) is a mesenchymal benign odontogenic tumor, which may lead to impacted or ectopic permanent teeth. Autotransplantation of teeth is a surgical process, in which a tooth is transplanted from one position to another in the same individual. This method can effectively restore the patient's mastication and aesthetics and is feasible in replacing missing teeth. This study reports a case of simultaneous COF resection combined with heterotopic canine autotransplantation to repair dentition defect, which effectively promotes the restoration of bone continuity and stability and achieves immediate and long-term aesthetic function requirements.

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.

Ossifying Fibroma of Non-odontogenic Origin: A Fibro-osseous Lesion in the Craniofacial Skeleton to be (Re-)considered.

In the cranio-facial skeleton, a heterogeneous group of well characterized fibro-osseous lesions can be distinguished. Whereas fibrous dysplasia can affect any skeletal bone, ossifying fibroma and cemento-osseous dysplasia exclusively develop in the cranio-facial region, with most subtypes restricted to the tooth bearing areas of the jaws. Herein we present a series of 20 fibro-osseous lesions that developed mostly in the frontal bone and in the mandible, presenting as expansile intramedullary tumors with a unique histologic appearance and an indolent clinical course. We provide evidence that these tumors are distinct from the categories included in the WHO classification and are therefore currently unclassifiable. The definition of cemento-ossifying fibroma as an odontogenic neoplasm developing only in close proximity to teeth should be re-considered and incorporate also extragnathic lesions as shown here.

Fibroma ossificante trabecular juvenil: um relato de caso / Juvenile ossifying fibroma: a case report

Objetivo: o fibroma ossificante trabecular juvenil (FOJT) é uma lesão fibro-óssea incomum, benigna, porém de comportamento agressivo. Ocorre, frequentemente, em crianças e adolescentes, com maior acometimento em maxila e mandíbula. O presente relato aborda os aspectos clínicos, imaginológicos, histopatológicos, imuno-histoquímicos e o tratamento de um caso de FOTJ. Além de discutir suas similaridades com o osteossarcoma de baixo grau e as alternativas para o seu diagnóstico. Relato de caso: paciente do sexo masculino, com 12 anos de idade, apresentando aumento de volume em mandíbula no lado esquerdo, perda de função mastigatória e de fala, com tempo de evolução de seis meses. Radiograficamente, a lesão apresentava aspecto unilocular, com limites definidos e de padrão misto. O tratamento consistiu em cirurgia de enucleação total da lesão, seguida de curetagem sob anestesia geral. A histopatologia e a ausência de marcação para MDM2 e CDK4 na imuno-histoquímica confirmaram o diagnóstico de FOTJ e excluíram o de osteossarcoma de baixo grau. No controle pós-operatório de 20 dias, o paciente relatou melhora da parestesia, da função mastigatória e da fala e ausência de dor. Não se observou recidiva no acompanhamento de 1 ano após a cirurgia. Considerações finais: a similaridade dos aspectos clínico, imaginológico e microscópico entre FOJT e osteossarcoma de baixo grau pressupõe o estudo imuno-histoquímico com os arcadores MDM2 e CDK4, minimizando equívocos no diagnóstico e orientando de forma mais eficiente o plano de tratamento adotado.(AU)

Objective: juvenile Trabecular Ossifying Fibromas (JTOF) are uncommon benign fibro-osseous lesions with a local aggressive behavior. They frequently occur in children and adolescents involving the jaw bones. This report addresses the clinical, imaging, histopathological, and immunohistochemical aspects and the treatment of a case of JTOF. In addition, it discusses similarities between JTOF and low-grade osteosarcomas and alternatives for their diagnosis. Case report: male patient, 12 years old, with a tumor in his left mandible, loss of masticatory function and speech, with a 6-month time course. Radiographically, the lesion had an unilocular aspect, with defined borders and a mixed image pattern. Treatment consisted surgical enucleation, followed by bone curettage, under general anesthesia. Histopathology presented fibrous stroma interspaced with bone trabeculae without signs of cellular malignancy. MDM2 and CDK4 markers in immunohistochemistry, confirmed the diagnosis of JTOF and excluded low-grade osteosarcoma. At the 20-day postoperative follow-up, the patient reported improvement in paresthesia, masticatory function and speech, and the absence of pain. Evaluation 1 year after surgery showed no signs of local recurrence. Final considerations: the similarity of clinical, imaging, and microscopic aspects between JTOF and low-grade osteosarcoma prompts an immunohistochemical study including MDM2 and CDK4 markers in order to improve final diagnosis and guide the treatment plan more efficiently.(AU)