Imaging of Fibro-osseous Lesions and Other Bone Conditions of the Jaws.

This review directs the focus on the imaging features of various fibro-osseous lesions and other bone lesions that can be of similar presentation. Broad diagnosis of "fibrous osseous lesion" may culminate in improper treatment and management. Radiographic discriminating factors between these entities are highlighted and summarized to improve the diagnostic process when encountering these lesions.

When molecular outsmarts morphology: Malignant ossifying fibromyxoid tumors masquerading as osteosarcomas, including a novel CREBZF::PHF1 fusion.

We present two cases of malignant ossifying fibromyxoid tumor (OFMT) which eluded diagnosis due to compelling clinicopathologic mimicry, compounded by similarly elusive underlying molecular drivers. The first is of a clavicle mass in a 69 year-old female, which histologically showed an infiltrative nested and trabeculated proliferation of monomorphic cells giving rise to scattered spicules of immature woven bone. Excepting SATB2 positivity, the lesion showed an inconclusive immunoprofile which along with negative PHF1 FISH led to an initial diagnosis of high-grade osteosarcoma. Next generation sequencing (NGS) revealed a particularly rare CREBBP::BCORL1 fusion. The second illustrates the peculiar presentation of a dural-based mass in a 52 year-old female who presented with neurologic dyscrasias. Sections showed a sheeted monotonous proliferation of ovoid to spindle cells, but in contrast to Case #1, the tumor contained an exuberance of reticular osteoid and woven bone deposition mimicking malignant osteogenic differentiation. NGS showed a novel CREBZF::PHF1 fusion. Both tumors recurred locally less than 1 year post-operatively. As such we reiterate that careful morphologic examination is axiomatic to any diagnosis in our discipline, but this paradigm must shift to recognize that molecular diagnostics can provide closure where traditional tools have notable limitations.

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.

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.

Preserving periodontal tissue in the treatment of a large peripheral ossifying fibroma: a case study.

Peripheral ossifying fibroma (POF) is a reactive, benign gingival enlargement. Its etiology is not fully known. It can be seen in many different sizes in the mouth. The histopathological appearance of POF is mineralized tissue and fibrous proliferation. All relevant soft and hard tissues must be removed to prevent recurrence. Periodontal tissue remaining after excision is important for tooth preservation. With large lesions, the loss of healthy periodontal tissue is also large. Periodontal surgical approaches are important to preserve the remaining periodontal tissue. The positive effects of autogenously obtained titanium-prepared platelet-rich fibrin (T-PRF) and connective tissue graft (CTG) on soft tissue are well known. A 34-year-old woman presented with a fibrous and pedunculated gingival mass in the upper left canine premolar region. The operation was performed with complete excision of the lesion down to the bone along with the surrounding healthy tissue. Periodontal treatment of the large defect created after excision of a large POF lesion was performed with laterally positioned flap, CTG and T-PRF. The periodontal tissue and defect were noted to heal in a healthy manner at the 6-month follow-up. POF is a benign lesion; however, it has a high recurrence rate. Complete elimination of the lesion is crucial to prevent recurrence. Periodontal surgical methods and biomaterials applied after surgical excision are significant to maintain the periodontal health of the remaining teeth and tissues.

Prognostic factors in transnasal endoscopic surgery for paediatric patients with ossifying fibroma of the paranasal sinuses and skull base.

BACKGROUND: Ossifying fibroma of the paranasal sinuses and skull base in paediatric patients is difficult to operate and can recur easily after surgery. This study aimed to analyse factors associated with recurrence after transnasal endoscopic resection of ossifying fibroma in paediatric patients. METHODS: This retrospective observational study included 34 patients under 17 years of age who underwent transnasal endoscopic resection of ossifying fibroma of the paranasal sinuses and skull base from 2005 to 2021 at a single tertiary medical centre. Clinical indicators such as age; surgical history; pathological type; intraoperative bleeding; and orbit, anterior skull base, sphenoid bone, sella turcica, clivus, or frontal sinus involvement were subjected to univariate analysis using the χ2 test, to investigate whether any of these factors affected recurrence. RESULTS: All 34 patients underwent transnasal endoscopic resection. The follow-up period was 6-120 months (mean: 48.0 months). Five patients experienced local recurrence during the follow-up period (14.7%). Results of χ2 tests indicated that a history of previous surgery, the amount of intraoperative bleeding, and sphenoid and/or sella turcica and clivus involvement were significantly associated with recurrence (P < 0.05). Age; pathological stage; and orbit, anterior skull base, and frontal sinus involvement were not associated with recurrence (P > 0.05). CONCLUSIONS: The increased risk of recurrence after transnasal endoscopic resection of nasal-skull base ossifying fibroma should be considered during endoscopic surgery in paediatric patients with a history of previous surgery, intraoperative bleeding tendency, and sphenoid and/or sella turcica and clivus involvement. These patients require careful postoperative follow-up.

Ossifying Fibromyxoid Tumor of the Genitourinary Tract: Report of 4 Molecularly Confirmed Cases of a Diagnostic Pitfall.

Ossifying fibromyxoid tumors (OFMTs) are rare mesenchymal neoplasms which typically present in the superficial subcutaneous tissues and have not been reported to arise in visceral organs. We now report 4 molecularly confirmed cases of OFMT involving the genitourinary tract. All patients were males, ranging in age from 20 to 66 years (mean: 43 y). One case each arose in the kidney, ureter, perirenal soft tissue, and penis. All neoplasms demonstrated bland epithelioid to spindled cells set in a variably fibrous to fibromyxoid stroma, and only 1 had a peripheral shell of lamellar bone. All cases appeared well-circumscribed on gross/radiologic examination, though the primary renal neoplasm permeated between native renal tubules. By immunohistochemistry, S100 protein was negative in all 4 cases, while desmin was positive in 2 cases. In 2 cases, the Illumina TruSight RNA Fusion Panel demonstrated a PHF1::TFE3 and EP400::PHF1 fusion, respectively. In the remaining 2 cases, PHF1 gene rearrangement was confirmed by fluorescence in situ hybridization analysis. Due to unusual clinical presentation, lack of S100 positivity, and only occasional bone formation, the correct diagnosis was challenging in the absence of molecular testing. In summary, OFMT may rarely present primarily in the genitourinary tract. Given their nonspecific morphology and immunophenotype, molecular analysis is crucial to establish the correct diagnosis.

A large-cohort study of 2971 cases of epulis: focusing on risk factors associated with recurrence.

BACKGROUND: To analyze the clinicopathological features of different histological subtypes of epulis, and evaluate the risk factors associated with recurrence. MATERIALS AND METHODS: A retrospective study including 2971 patients was performed. The patients' sex, age, location, size, histological subtypes, recurrence information, oral hygiene habits, periodontitis symptoms and smoking history were retrieved from the patient medical records and follow-up information. RESULTS: Among the 2971 cases, focal fibrous hyperplasia (FFH) was the most common lesion (60.92%), followed by peripheral ossifying fibroma (POF) (29.32%), pyogenic granuloma (PG) (8.08%) and peripheral giant cell granuloma (PGCG) (1.68%). The peak incidence of epulis was in the third and fourth decade of life, with a mean age of 45.55 years. Female predominance was found in all types of lesions with a female to male ratio of 1.71:1. PG had the highest recurrence rate (17.18%), followed by POF (12.98%), FFH (9.55%) and PGCG (8.82%). Histological subtypes were significantly correlated with the recurrence of epulis (P = 0.013). Regular supportive periodontal therapy (P = 0.050) had a negative correlation with recurrence, whereas symptoms of periodontitis (P < 0.001) had a positive correlation with the recurrence of epulis. CONCLUSIONS: Controlling the periodontal inflammation and regular supportive periodontal therapy might help reduce the recurrence of epulis.

Genomic Profiling of the Craniofacial Ossifying Fibroma by Next-Generation Sequencing.

BACKGROUND: Ossifying fibroma (OF) of the craniofacial skeleton is a fibro-osseous lesion characterized by various patterns of bone formation in a cellular fibroblastic stroma. The molecular landscape of OF remains mostly unknown. There are a few known pathogenic abnormalities in OF, including HRPT2 mutations in conventional OF and SATB2 translocations in juvenile psammomatoid OF. On the other hand, conflicting reports exist regarding MDM2 gene amplification and chromosomal copy number alterations (CNA) in OF. METHODS: Surgically removed biopsies and curettage specimens from OF patients were obtained. Clinical, radiographic, and pathologic features of tumors were reviewed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded blocks of tumor tissue. Capture-based DNA next-generation sequencing targeting the coding regions 529 cancer genes and select introns was performed. RESULTS: We identified 17 OF cases from 8 male and 8 female patients with mean age of 22 years (range 1-58 years). Nine case occurred in the gnathic bones and 8 in the extragnathic craniofacial bones. These cases included 3 juvenile psammomatoid OF, 6 conventional OF and 8 juvenile trabecular OF. Large-scale CNAs were present in 6 of 17 cases. Seven cases (41%) had focal amplifications including FOSB (n = 2, 11%), FOS (n = 4, 23%), COL1A1 (n = 4, 23%) and TBX3 (n = 5, 29%). Three cases (17%) had pathogenic CDC73 mutations. No cases showed focal MDM2 amplification. CONCLUSIONS: Here, we provided a comprehensive molecular characterization of OF that reveals a heterogeneous genetic profile with occasional large-scale CNAs (n = 6, 35%). FOS, FOSB, and TBX3 genes that regulate AP-1 transcriptional complex are frequently altered in OF (n = 7, 41%), chiefly in juvenile trabecular OF. These genes encode transcription factors that act as downstream effectors of the MAP kinase signaling pathway. MDM2 amplification is an exceedingly rare event in OF, if present at all, so identification of this event should continue to raise concern for low-grade gnathic osteosarcoma. In summary, our findings suggest that OF represents a heterogeneous group of tumors at the genetic level but dysregulation of the AP-1 pathway may play a role in pathogenesis of juvenile trabecular OF.

[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.

Expanding the molecular signatures of malignant ossifying fibromyxoid tumours with two novel gene fusions: PHF1::FOXR1 and PHF1::FOXR2.

AIMS: Ossifying fibromyxoid tumor (OFMT) is a rare enigmatic tumor of uncertain differentiation that can be classified as typical, atypical, and malignant subtypes based on cellularity, nuclear grade, and mitotic activity. The majority of OFMTs, regardless of the risk of malignancy, harbor genetic translocations. We report two malignant OFMTs, including one with evidence of dedifferentiation, with novel genefusions. METHODS AND RESULTS: Case 1 was a 63-year-old male with a dedifferentiated OFMT arising in the right wrist, while case 2 was a 41-year-old male with a malignant OFMT presenting as a posterior mediastinal mass. Case 2 showed multifocal expression with EMA and synaptophysin, while desmin and S100 were absent in both tumors. NGS sequencing studies detected PHF1::FOXR1 and PHF1::FOXR2 gene fusions in cases 1 and 2, respectively. Despite aggressive regimens, both progressed with wide spread metastases resulting in death within six years of diagnosis. CONCLUSIONS: We expand the genetic spectrum of OFMTs with two novel gene fusions, PHF1::FOXR1 and PHF1::FOXR2. These cases confirm the previously reported tendencies for OFMTs with rare variant fusions to demonstrate malignant behavior, unusual morphology, and non-specific immunophenotype.

Gingival and alveolar mucosal reactive hyperplastic lesions: a retrospective clinical and histological study of 996 cases.

BACKGROUND: gingival/alveolar mucosal reactive hyperplastic lesions (GRHL), including fibrous hyperplasia (FH), pyogenic granuloma (PG), peripheral ossifying fibroma (POF) and peripheral giant cell lesion (PGCL), are a common group of oral diseases. The aim of the present study was to access the frequency and distribution of the clinical and histological features of these disorders in a Brazilian population. MATERIAL AND METHODS: all specimens diagnosed as GRHL in three Oral Pathology laboratories were selected for the study. Clinical information was retrieved from the laboratory biopsy forms and hematoxylin and eosin stained histological slides were reviewed for analysis of the histological characteristics. RESULTS: final sample was composed of 996 specimens, including 463 FH (47%), 280 PG (28%), 183 POF (18%) and 70 PGCL (7%). Females were more affected by FH, PG, and POF, and most cases affected adults with mean ages ranging from 40 to 53 years. FH, PG, and POF were more common in the upper gingiva/alveolar mucosa. Most PG, POF and PGCL were pedunculated, in contrast with FH (p<0.001). PG, FH and POF were mostly red or normal mucosal in color, while PGCL were mostly red/purple (p<0.001). PGCL were larger, followed by POF, FH and PG (p<0.001). Some histological features were characteristically found in some conditions, but they were also encountered in other lesions with variable frequencies. CONCLUSIONS: Oral medicine specialists, oral pathologists and periodontists are usually the professionals in contact with patients presenting GRHL and it is of upmost relevance that they should be familiarized with their clinical and histological profile.

Immunohistochemical Characterization of Gingival Fibromas.

PURPOSE: Gingival fibromas (GFs) are fibrous lesions of the gingiva that are not well defined in the literature. They are histologically similar to peripheral ossifying fibromas (POFs), both being characterized as cellular proliferations of dense fibrous tissue, with POFs differing in that they demonstrate foci of calcification. This study aims to expand upon the immunohistochemical characterization of GFs, and to confirm their osteoblastic phenotype. METHODS: Formalin fixed, paraffin embedded GFs, POFs and fibroepithelial polyps (FEPs) of the gingiva were examined. Immunohistochemical staining was performed for special AT-rich sequence binding protein 2 (SATB2), runt-related transcription factor 2 (RUNX2), osteocalcin and alpha-smooth muscle actin (αSMA). Sections were evaluated by light microscopy and the immunohistochemical staining patterns were assigned immunoreactive scores (IRS) based on percentage of stained cells and intensity of staining. RESULTS: GFs, POFs, and FEPs of the gingiva expressed osteoblastic markers SATB2, RUNX2 and osteocalcin. GFs and POFs expressed αSMA while FEPs of the gingiva did not. GFs and POFs had similar staining patterns of SATB2, RUNX2 and αSMA. DISCUSSION: These findings demonstrate that GFs and POFs exhibit a similar immunohistochemical profile, and supports a theory that GFs are osteoblastic lesions possibly related to POFs.

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.

Clinical and pathological features and differential diagnosis of fibro-osseous tumors and dysplasias / 中华口腔医学杂志

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.

Peripheral ossifying fibroma: A 20-year retrospective studywith focus on clinical and morphological features

Background: Peripheral Ossifying Fibroma (POF) is a reactive hyperplastic lesion that exclusively occurs in thegingiva and is characterized by the deposition of dystrophic calcification, cementum-like tissue, and immatureand mature bone within the connective tissue. The objective of the present study was to perform a retrospectiveanalysis of clinicopathologic features of POF.Material and Methods: Clinical and histopathological data were obtained from biopsy records and histopathological reports from a Brazilian reference service in Oral Pathology (1999 - 2020). Morphological analysis wasperformed to evaluate features related to the mesenchymal component, inflammatory infiltrate, ulceration, andmineralized tissue.Results: A total of 270 POFs were diagnosed during the study period. A higher frequency was observed in females(71.9%) between the third (22.9%) and fourth (23.3%) decades of life. The anterior upper gingiva (29.1%) wasthe most affected region. Mature (86.7%) and immature (52.6%) bone tissue were the most frequent. There was asignificant association between immature bone deposition and lesions with size ≤ 1.7 cm (p = 0.041); immaturebone and cement-like tissue deposition with an evolution time ≤ 16 months (p < 0.001); deposition of immaturebone and mesenchymal hypercellularization (p < 0.001); deposition of dystrophic calcification and the presenceof ulceration (p < 0.001).Conclusions: The clinical characteristics corroborate the findings in the literature. The heterogeneous distributionand quantity of mineralized tissues found in the analyzed cases support the theory that the different mineralizedtissues constitute a spectrum of clinical maturation of POF. (AU)

Peripheral ossifying fibroma: A 20-year retrospective study with focus on clinical and morphological features.

BACKGROUND: Peripheral Ossifying Fibroma (POF) is a reactive hyperplastic lesion that exclusively occurs in the gingiva and is characterized by the deposition of dystrophic calcification, cementum-like tissue, and immature and mature bone within the connective tissue. The objective of the present study was to perform a retrospective analysis of clinicopathologic features of POF. MATERIAL AND METHODS: Clinical and histopathological data were obtained from biopsy records and histopathological reports from a Brazilian reference service in Oral Pathology (1999 - 2020). Morphological analysis was performed to evaluate features related to the mesenchymal component, inflammatory infiltrate, ulceration, and mineralized tissue. RESULTS: A total of 270 POFs were diagnosed during the study period. A higher frequency was observed in females (71.9%) between the third (22.9%) and fourth (23.3%) decades of life. The anterior upper gingiva (29.1%) was the most affected region. Mature (86.7%) and immature (52.6%) bone tissue were the most frequent. There was a significant association between immature bone deposition and lesions with size ≤ 1.7 cm (p = 0.041); immature bone and cement-like tissue deposition with an evolution time ≤ 16 months (p < 0.001); deposition of immature bone and mesenchymal hypercellularization (p < 0.001); deposition of dystrophic calcification and the presence of ulceration (p < 0.001). CONCLUSIONS: The clinical characteristics corroborate the findings in the literature. The heterogeneous distribution and quantity of mineralized tissues found in the analyzed cases support the theory that the different mineralized tissues constitute a spectrum of clinical maturation of POF.

Immunohistochemical evaluation of IL-1ß, IL-6, TNF-α and IL-17 cytokine expression in peripheral giant cell granuloma and peripheral ossifying fibroma of the jaws.

OBJECTIVE: To examine and compare the immunohistochemical expressions of IL-1ß, IL-6, IL-17 and TNF-α in peripheral giant cell granuloma (PGCG) and peripheral ossifying fibroma (POF). DESIGN: The study included 20 POF and 20 PGCG cases diagnosed at the Pathology Department of Eskisehir Osmangazi University Medical Faculty. Hematoxylin & Eosin-stained slides obtained from each biopsy specimen were re-evaluated, and IL-1ß, IL-6, IL-17 and TNF-α antibodies were investigated immunohistochemically. While staining in stromal cells was examined in POF cases, staining in both stromal spindle cells and multinucleated giant cells was evaluated in PGCG cases. An immunoreactivity score was established for each case by evaluating the staining percentage and intensity for each individual case. The significance level was set at 5% (p < 0.05). RESULTS: The level of IL-6 and TNF-α expressions in the multinucleated giant cells in PGCG lesions was found higher than that in stromal cells (p < 0.005 and p < 0.000, respectively). In PGCG lesions, there was no significant difference between giant cells and stromal cells in terms of IL-1ß and IL-17 expression levels. There was no significant difference between PGCG and POF lesions in terms of IL-1ß and IL-6 expression. TNF-α expression levels were significantly higher in spindle cells of PGCG lesions than that of POF lesions (p < 0.00). However, IL-17 expression levels were significantly lower in PGCG lesions than in POF lesions (p < 0.05). CONCLUSION: The study results showed that TNF-α expression was significantly higher in PGCG lesions and IL-17 expression in POF lesions. IL-1ß, IL-6, IL-17 and TNF-α are involved in the pathogenesis of both PGCG and POF lesions.