Whole-exome sequencing and copy number alterations analysis in a case of expansive florid cemento-osseous dysplasia.

Whole-exome sequencing (WES) analysis of an expansive case florid cemento-osseus dysplasia were reported for the first time. Also, the new potential candidate genes were reported to expand our knowledge about their molecular pathogenesis. Abstract: We report a case of expansive florid cemento-osseus dysplasia in a 32-year-old female patient who presented an expansive tumoral lesion in the anterior mandible. As florid cemento-osseus dysplasia have only been molecularly investigated using targeted-sequencing, fragments of the lesion were collected and subjected to molecular investigation using WES to assess somatic mutations as well as copy number alterations. No gains and losses of chromosomal arms or segments longer than 1 Mb were detected. Our findings revealed a pathogenic stopgain variant at the KIF5C gene, a stoploss variant at MAPK10, and missense SNV at COL6A2 at DCDC1, suggesting potential candidate genes associated with florid cemento-osseus dysplasia.

Lesions Misdiagnosed as Endodontic Pathosis: A Narrative Review.

In daily practice, clinicians come across certain radiographic abnormalities which may or may not be asymptomatic. This abstract discusses radiographic abnormalities encountered by clinicians in daily practice, some of which resemble endodontic lesions. Prompt attention is crucial as these lesions can be benign or malignant. The article emphasizes the importance of differential diagnosis for accurate identification of periapical pathosis.

A Case Series and Literature Review of Craniofacial Fibrous Dysplasia.

Craniofacial fibro-osseous lesions (CFOLs) are a diverse group of relatively rare entities whose etiology ranges from reactive to dysplastic with a potential for malignant transformation. It is distinguished by the replacement of bone with fibrous tissue, that subsequently develops different degrees of calcification. Fibrous dysplasia (FD) is a component of the fibro-osseous lesion spectrum. The clinical spectrum of FD is wide, ranging from minor monostotic lesions affecting a single bone to devastating polyostotic disease involving the entire skeleton. FD produces asymmetry, which impairs face aesthetics. FD leads to bone differentiation, disintegration, and disorganization. It depicts a cellular collagenous stroma lacking mitotic figures and pleomorphism. Blood capillaries are evenly distributed, as are elongated trabeculae of woven or lamellar bone with uneven curves (often referred to as the Chinese letters pattern). Three types of FD patterns can be identified by computed tomography (CT) imaging: a cystic pattern, a homogeneously dense pattern, and a ground-glass pattern. The cornerstone of treatment is surgery, although the method varies depending on the location, size, and symptoms of the lesion. As an alternative to surgery, the use of bisphosphonates to reduce osteoclastic activity is under consideration. In this case series, we present three cases of FD involving the maxilla and mandible. We aim to correlate the clinical presentation, histological features, and radiographic findings, to promote early diagnosis, treatment, and better prognosis of the patient.

Juvenile trabecular ossifying fibroma: A case of extensive lesion of the maxilla.

INTRODUCTION AND IMPORTANCE: Juvenile trabecular ossifying fibroma is a rare benign tumor of childhood affecting the facial bones rarely described in literature. Its aggressive growth and high tendency of recurrence make it a real challenge for diagnosis and care. CASE PRESENTATION: This article presents a case of an extensive juvenile trabecular ossifying fibroma of the maxilla in a 14-year-old boy, which required surgical intervention with immediate bone reconstruction using an autogenous graft (iliac crest). No recurrence has been found after two and a half years of follow-up. CLINICAL DISCUSSION: Common symptoms of juvenile trabecular ossifying fibroma include painless swelling, facial asymmetry, jaw deformity and teeth displacement. Differential diagnosis should consider other forms like psammomatoid ossifying fibroma, osteofibrous dysplasia, fibrous dysplasia, ameloblastoma, odontoma, or even poorly differentiated carcinoma. CONCLUSION: Currently, there is no recommendation or consensus for the treatment of juvenile trabecular ossifying fibroma. The objective of treatment is also to preserve growth and development and conserve the nervous structure and the function, as mastication, vision. Early diagnosis and appropriate care are essential to prevent morphological and functional defects in young patients. Regular and long-term follow-up is essential due to the high recurrence rate.

Role of MDM2, CDK4, BCL2, Parafibromin and Galectin 1 in Differentiating Osteosarcoma from its Benign Fibro-osseous Lesions.

Benign fibro-osseous lesions (BFOLs) are a diverse group of lesions showing considerable degree of overlap with low grade osteosarcoma (LGOS). Further, de-differentiated osteosarcoma (DOS) is usually indistinguishable from conventional high-grade OS (COS) if LGOS foci are not identified. Thus, there is a need for adjunctive immunohistochemical markers to differentiate OS from benign FOLs as well as DOS from COS. This study evaluated the role of immunohistochemical expression of MDM2, CDK4, parafibromin, BCL-2 and Galectin-1 (Gal-1) in accurate characterization of benign FOLs and in differentiating them from OS. From our archives, we retrieved 101 tissue samples which were diagnosed as osteosarcoma (OS) /ossifying fibroma (OF) / fibrous dysplasia (FD) or fibrous hyperplasia (FH) and examined their immunohistochemical staining pattern with the aforementioned antibodies. MDM2 showed 100% specificity for diagnosing OS. CDK4 and Gal-1 showed linear increase in immunoexpression from benign BFOLs to OS. BCL-2 showed equivocal immunopositivity in OF and OS, but the positivity was higher than that observed in FD. The highest immunoexpression for parafibromin was seen in FD followed by OF and OS cases. Thus, MDM2 is most specific, and Gal-1 is most sensitive of all the markers studied in differentiating OS from benign mimics. Combination of these two markers can be used as an adjunct to conventional imaging and microscopy in accurate characterization of these lesions. Further MDM2 overexpression can differentiate DOS and COS.

The importance of clinical and radiological findings for the definitive histopathologic diagnosis of benign fibro-osseous lesions of the jaws: Study of 276 cases.

PURPOSE: Benign fibro-osseous lesions (BFOLs) are heterogeneous intraosseous disease processes sharing overlapping histopathologic features and demonstrate a wide range of biological behavior. The aim of this study is to highlight the importance of clinical and radiological findings for the definitive histopathologic diagnosis of benign fibro-osseous lesions of the jaws. MATERIALS AND METHODS: This is a cross-sectional retrospective study evaluating the three main groups of BFOLs: Cemento-osseous dysplasia, ossifying fibromas, and fibrous dysplasia. Previously diagnosed BFOL cases were searched for thoroughly from the archives of Istanbul University, Institute of Oncology, Department of Tumor Pathology in between 2005 and 2015. Clinical and radiological data of these cases were identified and recorded. The histopathologic features were reevaluated from the H&E-stained slides. RESULTS: A total of 276 BFOL cases were identified and reevaluated for the study. The most common BFOL type was cemento-osseous dysplasia (n = 135), followed by cemento-ossifying fibroma (n = 77), fibrous dysplasia (n = 53) and juvenile ossifying fibroma (n = 11). The female/male ratio was 3.4:1 with a strong predilection for the 4th decade (n = 102). The mandible (n = 209) was the predominantly affected jaw. Prominent osteoblastic rimming around the bony lesion was commonly observed for cemento-ossifying fibroma (n = 60/77), followed by cemento-osseous dysplasia (n = 23/135). Predominant ossification patterns showed some differences among the groups. The most common radiological feature was the mixed radiolucent/radiopaque internal structure. CONCLUSION: Our results document various clinical, radiological and histopathologic findings of BFOLs. Even some histopathologic differences are observed, clinical and radiographic correlation is mandatory prior to the definitive histopathologic diagnosis of BFOLs for the prevention of possible misdiagnoses or inappropriate treatments.

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)

Florid Cemento-Osseous Dysplasia with a Concurrent Glandular Odontogenic Cyst.

The presence of non-odontogenic cysts associated with benign fibro-osseous lesions of the jaws has been well documented. However, literature is scant when describing benign fibro-osseous lesions with associated odontogenic cysts. This case report highlights the presence of a concurrent developmental odontogenic cyst, glandular odontogenic cyst with extensive squamous metaplasia, in a patient with florid cemento-osseous dysplasia (COD). The postulated pathogenesis of these synchronous lesions is discussed along with a review of current literature. Surgical treatment is discouraged for florid COD, however, radiological follow-up is recommended, especially in lesions with associated cysts.

Juvenile Trabecular Ossifying Fibroma.

Benign fibro-osseous lesions within the maxillofacial region represent a heterogeneous group of benign entities with overlapping histologic features. Ossifying fibroma, the rarest of these entities, represents a true neoplasm. Juvenile ossifying fibroma (JOF) is considered an aggressive rapidly growing sub-type. It tends to occur in the first or second decades of life. Based on histological and clinical features it can further be classified into two variants, namely juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF). JTOF features a proliferation of cellular fibroblastic tissue admixed with woven bone trabeculae with varying histologic presentations. Correlation with clinical and radiographic features is essential to differentiate it from other fibro-osseous lesions. A case of JTOF of the mandible is exemplified in this Sine Qua Non Radiology-Pathology article.

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.

Periapical cemento-osseous dysplasia: a case report with twelve-year follow-up and review of literature.

AIM: To present a case report describing the long-term behaviour of periapical cemento-osseous dysplasia by observing the radiographic changes that took place over a period of 12 years. A review of the pertinent literature is also presented. SUMMARY: A healthy 26-year-old white female was referred to the Wilford Hall USAF Medical Center Endodontic Department for evaluation of an asymptomatic radiolucency at the apex of the right mandibular lateral incisor. Following a clinical evaluation that included pulp testing, a diagnosis of periapical cemento-osseous dysplasia (PCOD) was made. No treatment was rendered but follow-up visits were recommended. The patient was subsequently re-evaluated 8 times over a period of 12 years. During that time the lesion changed in appearance, displaying the various phases of PCOD. At the same time, lesions affecting the three adjoining incisors appeared and behaved in a similar manner. At the 12-year recall, the right lateral and both central incisors revealed no evidence of PCOD and an almost normal trabecular pattern of bone could be seen. Misdiagnosis and unnecessary treatment of PCOD may be avoided with careful pulp testing and knowledge of its most common locations of occurrence, radiographic appearances (phases) and benign behaviour.

Immunolocalization of bmp2/4, tgfβ-1 and osteonectin in fibro-osseous lesions of the jaws / Imunolocalização de bmp2/4, tgfß-1 e osteonectina em lesões-fibro-óssea benignas

Objetivo: as lesões fibro-ósseas benignas (LFOB) correspondem a um grupo diverso de patologias caracterizadas pela substituição do tecido ósseo por tecido conjuntivo e matriz extracelular mineralizada. Pouco se conhece a respeito da etiologia desse grupo de lesões. Propomo-nos a analisar por meio da técnica imunohistoquímica a expressão de 3 moléculas (osteonectina, TGFβ-1 e BMP 2/4) envolvidas no metabolismo ósseo. Métodos: Trinta e dois casos diagnosticados como osso normal (ON,8), displasia fibrosa (DF,8), displasia cemento-óssea (DCO,8) e fibroma cemento-ossificante (FCO,8) foram selecionados. Resultados: A osteonectina e a BMP2/4 foram positivas em todos os casos. O TGFβ-1 revelou positividade em 1 caso de DCO e FCO. Conclusão: Os achados imunohistoquímicos sugerem que as LFOB tem processos diferentes de produção de tecido ósseo.

Background: Benign fibro-osseous lesions (BFOL) comprise a diverse group of pathologies characterized by the replacement of normal bone by fibrous tissue and a mineralized product. Little is known about the biology of this group of lesions. We have analyzed the immunohistochemical expression of three molecules involved in bone metabolism, namely osteonectin, TGF-b1, and BMP2/4. Methods: Thirty-two cases diagnosed as normal jaw bone (NJB, 8 cases), fibrous dysplasia (FD, 8 cases), cemento-osseous dysplasia (COD, 8 cases), and cemento-ossifying fibroma (COF, 8 cases) were selected. Results: Osteonectin and BMP2/4 antibodies were positive in all cases. TGFb-1 labeling was seen in one case of COD and COF. Conclusion: The immunohistochemistry findings suggest that BFOL have different processes of osseous tissue production.