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.

Fibrocartilaginous mesenchymoma of pelvis-a potential diagnostic pitfall.

Fibrocartilaginous mesenchymoma (FM) is a rare bone tumor mimicking other fibrocartilaginous lesions on imaging and histologically. Hence, it is difficult to diagnose this entity especially on small biopsies. In this article, we report a case of FM mimicking desmoplastic fibroma on biopsy. A 36-year-old male presented with pain in the left hip. Imaging showed a large expansile lytic lesion involving the acetabulum and pubis. The differential diagnosis was suggestive of giant cell tumor, aneurysmal bone cyst, intraosseous desmoplastic fibroma, and chondrosarcoma. Biopsy revealed a low-grade spindle cell lesion with no evidence of osteoid or chondroid matrix. The lack of cartilaginous nodules in the biopsy prompted a preoperative diagnosis of desmoplastic fibroma. The excised mass showed bland spindle cell proliferation, benign cartilage nodules, and epiphyseal plate-like enchondral ossification suggestive of fibrocartilaginous mesenchymoma. Negative immunostaining for SATB2, CDK4, and MDM2 ruled out low-grade central osteosarcoma. Though GNAS mutations were not performed in this case, rimming of the bony trabeculae at the periphery of the epiphyseal growth plate-like cartilaginous nodule ruled out fibrous dysplasia. The absence of cartilaginous component misleads the diagnosis preoperatively in small biopsies.

Spheno-orbital juvenile psammomatoid ossifying fibroma: a case report and literature review.

Ossifying fibroma (OF) is an uncommon benign fibro-osseous lesion. Based on its clinical, morphological, and radiological features, OF is further divided into cemento-ossifying fibroma (COF), juvenile psammomatoid ossifying fibroma (JPOF), and juvenile trabecular ossifying fibroma (JTOF). JPOF rarely involves the cranial base, with limited reports published on spheno-orbital JPOF. In this paper, we report a case of JPOF of the greater wing of the sphenoid bone and lateral orbital wall in an 11-year-old child and show a surgical video. Although rare, JPOF should be considered in the differential diagnosis of fibro-osseous lesions of the spheno-orbital region.

Multiple calcifying pseudoneoplasms of the neuraxis (MCAPNON): Distinct entity, CAPNON variant, or old neurocysticercosis?

We report a case of multiple calcifying pseudoneoplasms of the neuraxis (MCAPNON) with associated multifocal perivascular microcalcifications and vascular calcinosis. Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a very rare condition that may arise in extra-axial and occasionally, in intra-axial locations. Moreover, it is nearly always a solitary mass with only one case with two lesions reported. While the etiology and pathogenesis of CAPNON remains unclear, the histopathology findings of this entity have been well described. We report a case of a 62-year-old woman with 18 calcifying radiologic lesions involving bilateral cerebral hemispheres. Histologically, these lesions have features similar to that reported for CAPNON, including nodular calcification with fibro-osseous components and peripheral histiocytic reaction. The patient had a poorly documented diagnosis of neurocyticercosis 32 years prior, although without tissue confirmation. The lack of detectable cysticercus serum antibody titers, and absence of residual larval or cyst wall tissue render multifocal calcific involution of that parasite unprovable although still plausible. We also raise the possibility of a blood-brain barrier derangement and/or a metabolic disorder as an alternative etiology. Whether this case of MCAPNON shares the same pathogenesis as the usual solitary CAPNON is unclear.

Florid cemento-osseous dysplasia: review of an uncommon fibro-osseous lesion of the jaw with important clinical implications.

Florid cemento-osseous dysplasia (FCOD) is a rare, benign, multifocal fibro-osseous dysplastic process affecting tooth-bearing areas of the jaw, characterized by replacement of normal trabecular bone with osseous tissue and dense acellular cementum in a fibrous stroma. It is one clinicopathologic variant in a spectrum of related non-neoplastic fibro-osseous lesions known as cemento-osseous dysplasias (CODs), thought to arise from elements of the periodontal ligament. Diagnosis primarily relies upon radiographic and clinical findings; unnecessary biopsy should be avoided, as inoculation with oral pathogens may precipitate chronic infection in these hypovascular lesions. Appropriate management of uncomplicated FCOD consists of periodic radiographic follow-up. Accordingly, it is important that both radiologists and clinicians performing endodontic interventions possess familiarity with this entity in order to prevent misdiagnosis and inappropriate intervention, which may result in a protracted clinical course. Lesions are usually asymptomatic in the absence of infection, typically discovered on routine dental radiographs or imaging performed for unrelated indications. Radiographically, the condition typically manifests as widespread non-expansile intraosseous masses of varying internal lucency and sclerosis that surround the root apices of vital teeth or edentulous areas in the posterior jaw. While all CODs share similar microscopic features, FCOD is distinguished by its multifocal distribution, involving two or more quadrants of the maxilla and mandible, often in a bilateral symmetric fashion. The vast majority of cases are sporadic, though few exhibit an autosomal dominant familial inheritance pattern. In this pictorial review, we discuss the radiologic characteristics of this entity, pertinent clinical and histologic features, differential diagnoses, and management options.

Radiologic and Histopathologic Features of Calcifying Pseudoneoplasm of the Neural Axis.

AIM: To describe the radiologic and corresponding histopathologic features of calcifying pseudoneoplasms of the neural axis. METHODS: Two cases of calcifying pseudoneoplasm of the neural axis were retrospectively reviewed. The first case was documented in a 64-year-old woman, who presented with lower back pain with radiation to her left leg. The second case was documented in a 70-year-old man, who presented with headaches. Medical records, radiologic and histologic findings, and related literature were reviewed. RESULTS: In the first case, imaging of the lumbar spine revealed a 3.8 × 2.2-cm calcified lesion at the level of vertebrae L5 and S1. A subsequent excision exposed an extradural lesion at L5. Histopathologic examination showed amorphous and granular calcifying material with occasional fibrohistiocytic and giant cell reaction, consistent with calcifying pseudoneoplasm of the neural axis. In the second case, imaging of the head revealed a 2.4 × 2.6-cm well-circumscribed, lobulated, calcified lesion within the basal frontal lobe. Subsequent resection exposed an intradural mass with a nodular arrangement of amorphous and granular calcifying material associated with fibrohistiocytic and giant cell reaction. Both patients had a favorable postoperative course and failed to show any clinical or radiologic sign of recurrence. CONCLUSION: Calcifying pseudoneoplasm of the neural axis is an uncommon condition with an excellent prognosis but is often misdiagnosed due to its nonspecific clinical presentation and varied findings on radiology.

Juvenile psammomatoid ossifying fibroma with massive mandibular involvement.

Juvenile psammomatoid ossifying fibroma (JPOF) is a histologic variant of an ossifying fibroma. While an ossifying fibroma varies in appearance, it consists of fibrocellular tissue and mineralized material. JPOF is a rare benign lesion; however, it can be extended locally and mimic a malignant tumor. It is considered a specific clinicopathologic entity, due to its occurrence in children and adolescents, the presence of psammomas, and its purported tendency for local aggressive growth and recurrence. It commonly affects the maxilla, nasal cavity, paranasal sinuses, and ethmoid region. This article describes a rare, aggressive case of a large JPOF that led to the total destruction of the mandible.

Ossifying fibroma of the maxilla: A case report with literature review.

Ossifying fibroma is a benign fibro-osseous lesion arising from the periodontal ligament cells. The lesion may progressively enlarge with the mass affecting the mandible or maxilla, resulting in facial deformities and tooth displacement despite its benign nature. Here, we presented a case of an 18-year-old female with ossifying fibroma in the maxilla extending to the maxillary sinus, infraorbital area, and skull base, resulting in considerable facial asymmetry. Since the primary treatment of ossifying fibroma is surgical resection, it is essential to determine the areas where the lesion has expanded, where a 3-dimensional computed tomography scan could play a critical role in providing such information. A complete surgical excision and histopathologic examination in treating this patient are crucial, made possible by a meticulous preoperative radio imaging technique.

Unraveling Cherubism: Examining the Classical "Eye to Heaven" Phenomenon.

Cherubism, an infrequent disorder with paramount autosomal importance, predominantly targets the mandible, with occasional involvement of the maxilla. Manifesting in childhood, it typically improves over time but never fully resolves in adulthood. Clinically, it presents as a uniform enlargement of the bones, and when the upper jaw is involved, it can create a cherub-like appearance with exposure to the sclera. As the volume grows, it can cause symptoms such as dental misalignment, delayed tooth eruption, speech difficulties, and tooth loss, in addition to psychological and cosmetic effects that require medical attention. The disorder progresses naturally in youngsters, exhibiting phases of expansion, stabilization, and regression. Cherubism initially is encountered in early childhood, reaches its peak during early years, balances out around puberty, and then steadily recedes after that. We describe the example of a male patient, age 20, who sought correction due to worries about his appearance. He had a bilateral mandibular angle and malar edema. The patient's aesthetic discontent was satisfactorily resolved with surgical intervention, and further pharmaceutical therapy was implemented during follow-up visits.

Maxillofacial Bone Involvement in Fibro-Osseous Lesions: Emphasizing the Significance of Differential Diagnosis.

The World Health Organization's (WHO) 2022 update on the classification of odontogenic and maxillofacial bone tumors has revolutionized diagnostic and treatment paradigms by integrating novel molecular insights. Fibro-osseous lesions of the maxillo-facial bones constitute a heterogeneous group encompassing fibrous dysplasia, Psammomatoid Ossifying Fibroma (PSOF), Juvenile Trabecular Ossifying Fibroma (JTOF), and other variants. Despite histological similarities, their distinct clinical manifestations and prognostic implications mandate precise differentiation. The intricacies of diagnosing fibro-osseous lesions pose challenges for pathologists, maxillofacial surgeons, dentists and oral surgeons, underscoring the importance of a systematic approach to ensure optimal patient management. Herein, we present two cases, fibrous dysplasia and Cemento-Ossifying Fibroma, detailing their clinical encounters and management strategies. Both patients provided informed consent for publishing their data and images, adhering to ethical guidelines.

Benign fibro-osseous lesions: A retrospective study of sixty-four cases from a single institute, Riyadh, Saudi Arabia.

Objective: Benign fibroosseous lesions (BFOLs) encompass a heterogenous collection of bone conditions characterized by replacing normal bone with fibro-collagenous tissue with osteoid or woven bone, and cementicles. Despite their clinical significance, the frequency of BFOLs in Saudi Arabia still needs to be assessed. Methods: This retrospective study investigated the frequency and demographics of BFOLs in Riyadh, Saudi Arabia, by retrieving all cases recorded between January 1984 and January 2013 from a single Oral Pathology Laboratory archive. Results: A total of 64 cases were classified as BFOLs, with a predominance in females (67.2 %) and a median age of 21.5 years. The most prevalent condition identified was fibrous dysplasia (45.31 %), followed by cemento-ossifying fibroma (26.56 %). There were significant sex differences between BFOLs, with a p-value of 0.03. FD was predominantly located in the maxilla (65.5 %), whereas COF was predominantly found in the mandible (82.3 %). Recurrence was observed in 17.2 % of patients with FD, in contrast to no reported recurrence in patients with COF. Conclusion: This study represents the first exploration of BFOL frequency and demographics in Riyadh, Saudi Arabia, highlighting the need for further investigations to comprehensively understand the nature of these lesions in our population.

A Case of an Ossifying Fibroma of the Mandible Suspected as a Static Bone Cavity.

Ossifying fibroma (OF) is a benign fibro-osseous lesion characterized by the proliferation of fibrous connective tissue containing immature bone and/or cementum-like hard tissue. Although the pathogenesis of OF remains unclear, trauma, previous extractions, and periodontitis are considered potential trigger factors. OF is more common in women aged from the second to fourth decades. Clinically, OF is characterized by slow-growing and asymptomatic swelling, often observed incidentally on radiological examinations. OF occurs more frequently in the mandible, particularly above the mandibular canal. Herein, we present a rare case of OF in an 18-year-old man initially misdiagnosed as a static bone cavity. The lesion was first observed as a radiolucent finding below the left mandibular canal on a panoramic radiograph. Later, cone-beam computed tomography (CBCT) imaging revealed the presence of calcifications within the lesion. Additionally, CBCT confirmed the presence of the lesion within the lingual cortical bone, revealing lingual swelling and thinning of the outer cortex. Enucleation was successfully performed under general anesthesia without any postoperative complications. Histopathological examination confirmed the diagnosis of OF, revealing mineralized tissue and proliferating fibrous connective tissue. This case underscores the challenges in diagnosing OF, particularly when it is located below the mandibular canal, emphasizing the importance of thorough imaging and differential diagnosis to avoid misinterpretation as a static bone cavity.

Desmoplastic Ameloblastoma-A Case Report.

Desmoplastic ameloblastoma (DA) is a rare variant of conventional ameloblastoma. It accounts for only 4%-13% of all ameloblastomas. DA was included in the World Health Organization Classification of Head and Neck Tumors (WHO-2005) as a variant of ameloblastoma with specific clinical, imaging, and histological features. The desmoplastic variant of ameloblastoma usually appears in the anterior and premolar regions as a mixed radiolucent and radiopaque lesion, sometimes resembling a benign fibro-osseous lesion.Ameloblastoma is a locally aggressive tumor that may cause recurrence and in rare cases, malignant transformation with repeated postsurgical recurrences. In this paper, we present a case of a 28-year-old female with swelling in the left upper jaw, a biopsy of which turned out to be DA.

Radicular Cyst: A Cystic Lesion Involving the Hard Palate.

A radicular cyst, also known as a periapical cyst or root end cyst, is a type of odontogenic cyst that is typically associated with permanent teeth. The radicular cyst usually is associated with maxillary central incisors followed by mandibular first molars. It occurs as a result of bacterial infection and pulpal necrosis which leads to inflammatory stimulation of the epithelial cell rests of Malassez along the periodontal ligament area of the tooth. Most cases of the radicular cyst are asymptomatic and they are diagnosed accidentally during routine radiographic examination. This article presents a case report of a 42-year-old male with an apical periodontal cyst associated with the maxillary anterior region. Early diagnosis and treatment planning is necessary. This article signifies the role of the surgeon in the early diagnosis and treatment plan of the cyst.

Cemento-osseous dysplasia is caused by RAS-MAPK activation.

Cemento-osseous dysplasia (COD) belongs to the spectrum of benign fibro-osseous lesions occurring exclusively in the tooth-bearing areas of the jaws. Depending on site and extent of involvement, periapical, focal and florid subtypes can be distinguished that share an identical histomorphology. Most cases are asymptomatic and follow a self-limited course requiring no specific treatment. Over time, lesions progressively mineralise while the cellularity decreases. However, the molecular pathogenesis of COD, has not yet been explored. We analysed a series of 31 COD samples by targeted sequencing and detected pathogenic hotspot mutations involving the RAS-MAPK signalling pathway in 5/18 evaluable cases (28%). The mutations were found in the BRAF, HRAS, KRAS, NRAS, and FGFR3 genes. Our findings suggest that COD is driven by RAS-MAPK activation; however, the mechanism underlying the spontaneous growth arrest typically occuring in most of the lesions remains elusive.

Cemento-Osseous Dysplasia of the Jaw: Demographic and Clinical Analysis of 191 New Cases.

Cemento-osseous dysplasia (COD) is a form of benign fibro-osseous lesion of the jaw. We sought to evaluate the demographic and clinical presentations of COD by collecting and analyzing the demographic, clinical, radiographic, and pathologic data of COD diagnosed in our institution from 2017 to 2022. Over this six-year period, the records of 191 patients with COD were reviewed. Most patients were African American and female. Eighty-five patients were diagnosed with florid COD (FLCOD), 63 with periapical COD (PCOD), and 43 with focal COD (FCOD). Twenty-eight (14.7%) patients presented symptoms. The most common symptom was pain. All the symptomatic cases of COD that were histopathologically diagnosed were osteomyelitis in the setting of COD. Symptomatic patients were older (mean of 61.3 years) than the asymptomatic patients (mean of 51.2 years). Due to the radiographic appearance of a radiolucency or a mixture of radiolucency and radiopacity, forty-five asymptomatic patients were biopsied. Most of the asymptomatic patients biopsied were patients with FCOD (n = 19, 54.3%), followed by PCOD (n = 16, 25.8%), and FLCOD (n = 10, 15.2%). FLCOD is the most common form of COD to present with symptoms. Due to the significant overlap in clinical and radiographic presentation with other entities, FCOD and PCOD remain a diagnostic challenge to dentists. In conclusion, we analyzed the demographic and clinical features of 191 new cases of COD, which reaffirms that cemento-osseous dysplasia is a condition that primarily affects middle-aged females of African descent and occurs more frequently in the mandible.

Fibro-Osseous Lesion of the Nose and Paranasal Sinus: A Retrospective Study With Literature Review.

Background Fibro-osseous (FO) lesions are slow-growing benign lesions in the paranasal sinuses. They include osteomas, fibrous dysplasia (FD), and ossifying fibro-ma (OF). Fibro-osseous (FO) lesions are frequently asymptomatic, and they are incidentally found on imaging. They are characterized by different histological, radiological, and clinical variants. Depending on symptoms, size, location, and extension, the treatment strategy varies significantly for these lesions. Objective We aim to compare the age, onset, gender, clinical presentation, postoperative improvement, and complications of a fibro-osseous lesion in the paranasal sinuses. Methods A retrospective analysis was done targeting patients diagnosed with benign fibro-osseous (FO) lesions, and the incidence among 403 patients who underwent functional endoscopic sinus surgery (FESS) at Aseer Central Hospital, Kingdom of Saudi Arabia, was reviewed from January 2013 to January 2022. Results A total of seven patients were found; five patients were diagnosed with osteoma, and two were diagnosed with fibrous dysplasia. There were no ossifying fibroma cases. The patients' mean age was 25.5 ± 12.9 years old. Four (57.1%) patients were males, and three (42.9%) were females, with a male/female ratio of 1.25:1. The most common locations were the frontal sinus and ethmoid sinus, and the two cases of fibrous dysplasia involved almost all facial bones. The endonasal endoscopic approach was chosen to treat all seven patients. Conclusions There are differences in the onset age, location, and complications postoperatively among osteoma and fibrous dysplasia patients. Osteoma most commonly occurs in the frontal sinus, while fibrous dysplasia involved all facial bones in our study. Endoscopic surgery is currently the primary strategy for treatment.

Implant placement in a focal cemento-osseous dysplasia: A modified protocol with a successful outcome.

Cemento-osseous dysplasia (COD) is defined as a condition in which normal bone is replaced by fibrous connective tissue and cementum-like deposits. It is generally asymptomatic and occurs mostly in female patients. Radiologically, it appears as an opaque, lobulated mass. When facing such lesions, it is advised to avoid performing any surgical procedures due to the decreased vascularization and healing potential. The main reported complications being poor healing, sequestrum formation, risk of infection, and fracture of the jaw. Treating posterior mandibular edentulism in presence of a COD can be a challenging situation especially when the patient requires an implant-supported fixed rehabilitation. The aim of this paper is to describe a three-stage modified protocol for implant placement in a compromised site presenting a focal cemento-osseous dysplasia.

Cystic degeneration in cemento-ossifying fibroma: Diagnosis challenge and conservative management - Case report.

INTRODUCTION AND IMPORTANCE: Cemento ossifying fibroma (COF) is an encapsulated lesion that is often found in the mandible of middle-aged females. Cystic degeneration may be associated to several osseous lesion. This particular presentation is not well documented in the jaws. CASE PRESENTATION: Patient presented was referred to oral surgery department for abnormal radiolucency in the right mandible on panoramic X-ray. The patient did not have any specific medical history and reported painful areas in right mandibular region. During diagnosis assessment, ameloblastoma was first considered due to the presence of cystic lesion clusters. But the mixed image in previous X-ray pointed to a fibro-osseous with a change in pathogenesis pathway. Diagnosis buildup was based on previous radiographs, incisional biopsy was proposed to identify the histopathological feature of the lesion before proceeding to further investigation (CBCT) or treatments (decompression or enucleation). COF of the jaws associated to non-specific cystic changes was the histopathological diagnosis. Delay in treatment showed an unexpected outcome with good clinical and bone healing. CLINICAL DISCUSSION AND CONCLUSION: This case shows the importance of previous radiographs, when available, in diagnosis buildup. The fibro-osseous lesion with cystic change may show a good biological response with conservative management. A clinical and radiological surveillance after a conservative treatment may be a better option in treatment of these lesions.

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.