Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series.

Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.

Carotid Artery Calcification Detected on Panoramic Radiography Is Significantly Related to Cerebrovascular Accident, Coronary Artery Disease, and Poor Oral Health: A Retrospective Cross-Sectional Study.

Panoramic radiography imaging modality is widely used by dentists for diagnosing dental and jaw conditions. It can also detect carotid artery calcification (CAC), indicative of calcified atherosclerotic plaques in the carotid arteries. This cross-sectional retrospective study at the University of Tennessee Health Science Center investigated the link between CAC identified on panoramic radiograph (PR) and cerebrovascular accident (CVA), coronary artery disease (CAD), and poor oral health. Data from 314 CAC patients collected from 2014 to 2023 included age at diagnosis, gender, and clinical histories of hypertension, hyperlipidemia, diabetes mellitus, CVA, CAD, and the decay, missing, and filled permanent teeth (DMFT) index. These patients were age- and gender-matched with non-CAC patients for analysis. The findings revealed high prevalences of hypertension (86.2%), hyperlipidemia (57.6%), diabetes mellitus (30.7%), CVA (15.5%), and CAD (28.7%) amongst CAC patients and the average DMFT index was 26.6. A comparative analysis of 276 matched controls demonstrated significant differences in hypertension (85.9% vs. 57.6%), hyperlipidemia (58.3% vs. 33.7%), diabetes (32.6% vs. 22.1%), CVA history (14.9% vs. 5.1%), CAD (26.1% vs. 9.8%), and DMFT scores (26.3 vs. 23.7), all indicating strong associations between CAC and these health conditions. The adjusted analysis showed that hypertension (aOR: 3.20 [95% CI: 2.06-5.07]), hyperlipidemia (aOR: 1.70 [95% CI: 1.14-2.50]), CVA (aOR: 2.20 [95% CI: 1.13-4.30]), and CAD (aOR: 2.10 [95% CI: 1.28-3.60]) were significantly associated with CAC. Notably, only 41.7% of the patients received a medical consultation after CAC detection on PR. It is crucial for dentists to refer patients for further evaluation.

Radiographic Orofacial Findings of Systemic Diseases.

This article discusses the orofacial clinicoradiographic features of systemic diseases that manifest in the orofacial region. The systemic diseases discussed are grouped into the following: autoimmune diseases, endocrine diseases, bone diseases, hematologic diseases, syndromes, and malignancies. The radiographic manifestation ranges from radiolucent bony destruction, increased bone density, calcification, thinning of cortical plate, loss of trabeculation, missing teeth, and supernumerary teeth. It is imperative for clinicians to be cognizant of these findings, as they may be the first manifestation of these systemic diseases.

Clinicoradiopathologic Analysis of Odontomas: A Retrospective Study of 242 Cases.

Odontomas are considered hamartomatous lesions and are one of the two most common odontogenic tumors of the jaw. Odontomas are classified as compound or complex. Recently, ameloblastic fibro-odontoma (AFO) and ameloblastic fibro-dentinoma were reclassified as developing odontomas. Though clinically odontomas are usually asymptomatic, they have adverse effects on adjacent teeth such as tooth impaction, delayed eruption, displacement of teeth, over-retention of teeth, and can give rise to odontogenic cysts within the jaw. We sought to evaluate the clinicoradiopathologic presentations of odontomas by collecting and analyzing the clinical, radiographic, and pathologic data of odontomas diagnosed in our institution from 2013 to 2022. Over this 10-year period, there were 242 patients with a histopathological and/or radiographic diagnosis of odontoma. There was no gender predilection and ages ranged from 3 to 101 years (median, 14 years). The second decade of life was the most prevalent (57.4%). There was no jaw predilection; however, the anterior jaw was the most common location. Ninety-four (38.8%) cases presented with clinical findings. The most common finding was tooth impaction (n = 83). Nine (3.7%) cases were histopathologically confirmed to be associated with other lesions such as dentigerous cysts (n = 8) and nasopalatine duct cyst (n = 1). The median age (25 years) of patients diagnosed with odontomas associated with cysts was older than patients with odontomas (14 years) without associated cysts. Compound odontomas were the most common type of odontoma compared to complex and AFOs with 71.4%, 26.6%, and 2%, respectively. The majority of compound odontomas involved the anterior jaw (69.3%) and mandible (54.9%) while the majority of complex odontomas involved the posterior jaw (59.6%) and maxilla (54.7%). The four AFOs were in the posterior jaw and 75% involved the maxilla. The median age (12 years) of patients diagnosed with AFO was the youngest compared to patients diagnosed with compound (13 years) and complex (16 years). In conclusion, we analyzed the clinical, radiographic, and pathologic features of 242 new cases of odontomas. Our study reaffirms that odontomas frequently affect the pediatric population and can disrupt their dentition. Based on the result of this study, our clinical recommendation to prevent problems to adjacent teeth from odontomas is for dentists to be apt in the diagnose of odontomas to ensure that they are surgically removed in a timely manner.

Salivary Duct Carcinoma with Rhabdoid Features of the Parotid Gland with No E-Cadherin Expression: A Report with Anti-HER2 Therapy and Review of the Literature.

Salivary duct carcinoma with rhabdoid features (SDC-RF) is a rare form of salivary gland neoplasm that was recently described. We report a case of SDC-RF of the parotid gland with loss of E-cadherin and decreased ß-catenin expression in a 73-year-old male who presented with right facial/neck swelling and intermittent pain. Morphologically, the tumor presented with a discohesive infiltrate of isolated and cords of pleomorphic round cells containing moderate amount of eosinophilic to fine-vacuolated cytoplasm and hyperchromatic nuclei infiltrating through fibroadipose tissue and salivary parenchyma. Immunophenotypically, the tumor was positive for Cytokeratins Oscar and 7, GATA3, GCDFP, HER2, and an androgen receptor but negative for CK20, S100, p40, Melan A, CDX2, TTF1, ER, SATB2, DOG1, synaptophysin, and chromogranin. Due to its diffuse infiltrating pattern, involvement of the parapharyngeal space, supraclavicular fat pad, dermis, and skin without a defined surgical target, the tumor was deemed unresectable. Anti-HER2 therapy (Herceptin and Pertuzumab) was utilized. At the last follow-up, the patient is alive, with complete locoregional control and brain metastases. An electronic search was performed in the following registries for papers published up to June 2023: PubMed, Embase, and Web of Science. For the database searches, the keywords searched were "salivary gland", "salivary duct carcinoma", and "salivary duct carcinoma with rhabdoid features". Our review of the literature identified 30 cases of SDC-RF that reveal there is a predilection for males (83%), parotid gland (72%), and patients older than the 6th decade of life (83%). Immunophenotypically, all SDC-RF cases except one were positive for AR and GCDFP (97%), 81% were positive for HER2, and loss or decreased expression of E-cadherin in 93% of cases. In conclusion, we described a rare case of SDF-RF of the parotid gland with no E-cadherin expression, decreased ß-catenin expression, and its immunophenotypic profile.

Evaluation of EWSR1/FUS rearrangements by FISH and NKX2.2 immunoexpression in simple bone cysts of the jaw.

OBJECTIVE: Recent studies have identified recurrent rearrangements of EWSR1 or FUS with NFATC2 in extragnathic simple bone cysts (SBCs). We investigated the presence of EWSR1 or FUS rearrangements and the immunophenotypic expression of NKX2.2 and CD99 in a series of SBCs of the jaw. STUDY DESIGN: We retrieved 10 cases of SBC of the jaw from the University of Pittsburgh archives. Of the 10 cases, we were able to evaluate 8 by immunohistochemistry for CD99 and NKX2.2 and 7 by fluorescence in situ hybridization (FISH) for EWSR1 and FUS rearrangement using EWSR1 and FUS break-apart probes. RESULTS: All 8 cases evaluated by immunohistochemistry expressed CD99 but were negative for NKX2.2, and all 7 cases assayed using FISH were negative for EWSR1 and FUS rearrangements. CONCLUSIONS: In contrast to the SBC of extragnathic sites, we found no presence of EWSR1 and FUS rearrangements by FISH in the SBC of the jaw, suggesting that this entity may be etiologically/molecularly distinct and reflects a non-neoplastic reactive process. However, as these lesions tend to be paucicellular, FISH may not be the appropriate technique for identifying EWSR1/FUS fusions. Other techniques should be used to evaluate them in future studies.

A novel STRN3::PRKD1 fusion in a cribriform adenocarcinoma of salivary gland with high-grade transformation.

Cribriform adenocarcinoma of salivary gland (CASG) is a rare form of salivary gland neoplasm that mostly arises from minor salivary glands. We report a case of CASG with high-grade transformation harboring a novel STRN3::PRKD1 fusion. A 59-year-old male presented with a palatal mass. Morphologically, the tumor consisted of two components: solid high-grade and glandular low-grade areas. The solid high-grade area comprised solid nests of high-grade carcinoma with central necrosis arranged in lobules delineated with prominent stromal septa. The glandular low-grade area comprised of cribriform and microcystic architecture in a hyalinized and hypocellular stroma. Immunophenotypically, the tumor was positive for S100 but negative for p40 and actin. However, due to the high-grade component, tissue was sent for salivary gland NGS fusion panel analysis to confirm the diagnosis. The current case illustrates high-grade transformation in CASG. Furthermore, identification of a STRN3::PRKD1 fusion expands the genetic spectrum of CASG.

The Role of Dental Practitioners in the Management of Oncology Patients: The Head and Neck Radiation Oncology Patient and the Medical Oncology Patient.

This narrative review addresses the role of a dentist in the management of oncology patients, highlighting the oral complications that arise in head and neck radiation oncology patients and medical oncology patients. The prevention and management of these complications are discussed.

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.

MAML2-Rearranged Primary Central Mucoepidermoid Carcinoma of the Mandible as an Incidental Finding: A Case Report and Review of the Literature of Molecularly Confirmed Cases.

This report presents an extremely rare case of MAML2-rearranged primary central mucoepidermoid carcinoma (MEC) of the mandible that was discovered as an incidental finding. Our review of the literature identified 36 cases of MAML2-rearranged intraosseous lesions of the jaw (30 central MECs, 5 odontogenic cysts with mucous prosoplasia, and 1 glandular odontogenic cyst). Given the therapeutic indications for a diagnosis of MEC (a malignant neoplasm), MAML2 rearrangement should be confirmed in suspected cases of central MEC.

Clinicopathologic Study of Sialadenoma Papilliferum of the Minor Salivary Glands: A Series of 8 New Cases With BRAF V600E Mutation-specific Immunohistochemical Analysis.

Introduction. Sialadenoma papilliferum (SP) is a rare benign neoplasm that usually arises in the minor salivary glands. Recently, it was demonstrated that SP shares similar molecular genetic alterations (BRAF V600E or HRAS mutations) with its morphologic analog, syringocystadenoma papilliferum. Methods. We sought to perform clinicopathologic and immunophenotypic (BRAF V600E and SOX10) analyses on 8 new cases of SP. Results. The cases were from 4 males and 4 females, with ages ranging from 28 to 81 years (average: 64 years). The common locations were the hard palate (n = 3) and buccal mucosa (n = 3). Histopathologically, 7 cases were classic and 1 case was oncocytic. BRAF V600E immunohistochemistry (IHC) was positive in all classic SP, involving both the exophytic and endophytic components, but negative in the oncocytic SP. SOX10 was positive in the endophytic ductal cells of the evaluated classic SP but was negative in the oncocytic SP. Conclusions. We report 8 new cases of this rare salivary gland neoplasm, using BRAF V600E and SOX10 IHC to further support the following points: (1) the functional role of BRAF V600E mutation, RAS/mitogen-activated protein kinase signaling pathway in the pathogenesis of classic SP of salivary glands by IHC; (2) the analogous relationship between SP, syringocystadenoma papilliferum, and papillary seromucinous adenocarcinoma with sinonasal papilloma-like surface component (PSASP-like surface); (3) endophytic ductal component in classic SP arises from the intercalated ducts and not the excretory ducts; and (4) oncocytic SP is distinct from classic SP.

MAML2-Rearranged Mucoepidermoid Carcinoma of the Parotid Gland: A Report in a 20-Month-Old Toddler.

Malignancies of salivary gland origin are rare in children. Mucoepidermoid carcinoma (MEC) is the most common histologic type of salivary gland neoplasm in pediatrics. We report a rare case of parotid MEC in a 20-month-old female patient. The tumor was composed of nests of epidermoid cells with nuclei appearing vesicular, pleomorphic, and hyperchromatic with an admixture of mucous cells and cystic spaces within a prominent connective tissue stroma. Immunohistochemically, the epidermoid cells showed cytokeratin 7 and P63 positivity, and mucous cells were positive for mucicarmine. Molecularly, this case was positive for MAML2 rearrangement by FISH. To our knowledge, this is one of the youngest cases of MEC of the parotid gland reported in the English literature.

HMGA2 Immunoexpression is frequent in salivary gland pleomorphic adenoma: immunohistochemical and molecular analyses of PLAG1 and HMGA2 in 25 cases.

The main oncologic events in pleomorphic adenoma (PA) are the translocations of Pleomorphic adenoma gene 1 (PLAG1) on chromosome 8q12 and High-mobility group AT-hook 2 (HMGA2) on chromosome 12q14.3 with various fusion partners. These translocations result in the transcriptional up-regulation of PLAG1 and HMGA2 proteins. We carried out a preliminary evaluation of PLAG1 translocation by fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC) and HMGA2 IHC on twenty-five archived formalin-fixed paraffin-embedded tissues of PAs and its clinicopathologic features. Only eight cases were successfully hybridized and 50% of the interpretable cases were considered positive for PLAG1 translocation. PLAG1 IHC was only positive in 2 (8%) of the 25 cases stained, including one of the positive PLAG1 translocation cases. HMGA2 IHC was positive in 12 (48%) of the 25 cases stained including 2 (50%) of the 4 cases identified with PLAG1 translocation by FISH, 3 (75%) of the 4 cases negative for PLAG1 translocation by FISH and 7 (41%) of the 17 cases with failed hybridization. Overall, 15 (60%) of the 25 PA cases demonstrated PLAG1 and/or HMGA2 alterations confirmed either by FISH or IHC. In conclusion, PLAG1 and HMGA2 alterations were confirmed either by FISH or IHC in this cohort and HMGA2 alteration is a common event in PAs of salivary gland.

NR4A3 (NOR-1) Immunostaining Shows Better Performance than DOG1 Immunostaining in Acinic Cell Carcinoma of Salivary Gland: a Preliminary Study.

OBJECTIVES: Acinic cell carcinoma of salivary gland harbours recurrent and specific chromosomal rearrangement [t(4;9)(q13;q31)], resulting in the translocation of secretory calcium-binding phosphoprotein gene cluster at 4q13 to nuclear receptor subfamily 4 group a member 3 at 9q31. This upregulates the transcription factor nuclear receptor subfamily 4 group A member 3, which can be detected by immunohistochemistry. The purpose of this pilot study is to evaluate the performance of nuclear receptor subfamily 4 group A member 3 immunostaining on whole-slide acinic cell carcinoma tissue, in comparison with discovered on GIST-1 immunostaining. MATERIAL AND METHODS: We retrieved 6 cases of acinic cell carcinoma (AciCC), including 5 conventional low-grade and 1 dedifferentiated high-grade. Immunohistochemistry (IHC) for nuclear receptor subfamily 4 group A member 3 (NR4A3) and discovered on GIST-1 (DOG1) were performed at the University of Pittsburgh Medical Centre in Pittsburgh, Pennsylvania on all retrieved cases. RESULTS: The result shows that NR4A3 IHC shows better performance than DOG1 IHC: 5 of the 6 (83.3%) AciCC cases (including the dedifferentiated high-grade) demonstrated strong diffuse nuclear staining for NR4A3, also five AciCC cases (including the dedifferentiated high-grade) demonstrated weak to moderate membranous staining with variable distribution for DOG1. Moreover, only 3 (50%) cases showed complete membranous staining with DOG1. CONCLUSIONS: This pilot study showed that nuclear receptor subfamily 4 group A member 3 immunostaining is a sensitive marker for acinic cell carcinoma and of better utility than discovered on GIST-1 immunostaining in making a diagnosis of acinic cell carcinoma.

Clear Cell Odontogenic Carcinoma of the Mandible Harboring EWSR1 Rearrangement: Report of a Massive Jaw Tumor and Review of Diagnostic Considerations.

Clear cell odontogenic carcinoma (CCOC) is a low-grade malignant neoplasm that affects the jaws. We report an 18 cm massive case of mandibular CCOC in a 43-year-old female. The tumor was composed of nests and cords of round to polygonal monomorphic clear cells separated by prominent stromal hyalinization. Immunohistochemically, the tumor cells showed focal cytokeratin 5/6 positivity and intracytoplasmic PAS-positive granules and were negative for S100 and after diastase treatment (PAS-D). Molecularly, this case was positive for EWSR1 rearrangement by FISH. The following should be included in the histopathological differential diagnosis: hyalinizing clear cell carcinoma of the salivary gland, clear cell variant of central mucoepidermoid carcinoma, clear cell variant of calcifying epithelial odontogenic tumor, and metastatic renal cell carcinoma. CCOC is a rare entity, with only 79 cases reported in the mandible. This case highlights the propensity for CCOC to exhibit invasiveness, destructive nature, and facial disfigurement if left untreated.

A clinicopathologic study of secretory carcinoma of minor salivary gland: a series of 4 cases and diagnostic considerations.

OBJECTIVE: Secretory carcinoma (SC) of salivary gland is a recently described low-grade malignant neoplasm of the salivary gland, characterized by rearrangement of the ETV6 gene. SC of salivary gland shares striking morphologic, immunophenotypic, and molecular similarity to SC of breast. STUDY DESIGN: We report the clinicopathologic features of 4 ETV6-rearranged SCs of minor salivary gland and histopathologic diagnostic considerations. RESULTS: Two cases were located in the lip, 1 in the soft palate, and 1 in the mandibular vestibule. No patient presented with regional or distant metastases at diagnosis. All cases were positive for S100 protein and mammaglobin, and all cases were negative for p63. All cases were positive for ETV6 rearrangement. CONCLUSIONS: SC of the minor salivary glands are rare. Because of its shared histopathologic features with other salivary gland tumors, positivity for ETV6 gene rearrangements is recommended before rendering a diagnosis of SC of salivary gland.

Dental status and risk of odontogenic complication in patients undergoing hematopoietic stem cell transplant.

PURPOSE: Dental evaluation and management prior to hematopoietic stem cell transplant (HSCT) plays a vital role in identifying and treating infections that may be life-threatening. The purpose of this study is to describe the dental management of patients undergoing pre-HSCT examination with the Dental Service at Memorial Sloan Kettering Cancer Center (MSKCC) and to report on odontogenic complications. METHODS: Patients referred for evaluation as part of the standard preparation for HSCT were included. Following clinical and radiological examination, patients were assigned to one of three groups based on risk of odontogenic infection, and treatment was provided as indicated. Patients were followed, and their medical records were reviewed for odontogenic complications during the transplant admission. RESULTS: Of the 375 patients evaluated, 350 patients underwent HSCT: allogeneic 143 (40.9%) and autologous 207 (59.1%). The distribution of primary cancer diagnosis was as follows: multiple myeloma 104 (29.7%), leukemias 95 (27.1%), Hodgkin's lymphoma 28 (8.0%), non-Hodgkin's Lymphoma 99 (28.3%), and other conditions 24 (6.9%). The median time from dental evaluation to transplant was 29 days. The median Decayed, Missing, Filled Teeth Index was 17. The median Community Periodontal Index was 1. Based on dental status, 145 patients (41.4%) were classified as low risk, 133 (38%) as moderate risk and 72 (20.6%) as high risk of odontogenic infection. One hundred fourteen patients (32.6%) required dental treatment prior to HSCT, and 100 of these (28.6%) completed treatment. Two (0.57%) patients had odontogenic complications. CONCLUSIONS: With conservative pre-HSCT dental treatment based on an infection risk classification system, a low odontogenic complication rate was observed.

MYB-NFIB Translocation by FISH in Adenoid Cystic Carcinoma of the Head and Neck in Nigerian Patients: A Preliminary Report.

Adenoid cystic carcinoma (AdCC) is a relatively rare malignancy of head and neck sites such as the salivary glands, lacrimal gland, sinonasal region, and pharynx and may arise in other exocrine glands. The oncologic event in AdCC is the translocation between MYB proto-oncogene transcription factor (MYB) and nuclear factor I/B (NFIB) resulting in t(6;9)(q22-23;p23-24). We carried out a preliminary evaluation of MYB-NFIB translocation by fluorescence in-situ hybridization on seven archived formalin-fixed paraffin-embedded tissues of AdCC of Nigerian patients and its clinicopathologic features. Only 3 of the 7 cases were successfully hybridized, all featuring MYB-NFIB translocations with a range of 14.7-83.3% of translocated cells in 60 cells examined. The 3 translocation positive cases were located in the maxillary sinus, buccal mucosa and parotid. Their morphologic appearances were cribriform-solid (1) & cribriform (2) and classified as grades III (1) & I (2), respectively. These patients may potentially benefit from MYB-targeted anti-neoplastic therapy.

SATB2 and MDM2 Immunoexpression and Diagnostic Role in Primary Osteosarcomas of the Jaw.

Primary osteosarcomas of the jaw (OSJ) are rare, accounting for 6% of all osteosarcomas. This study aims to determine the value of SATB2 and MDM2 immunohistochemistry (IHC) in differentiating OSJ from other jawbone mimickers, such as benign fibro-osseous lesions (BFOLs) of the jaw or Ewing sarcoma of the jaw. Certain subsets of osteosarcoma harbor a supernumerary ring and/or giant marker chromosomes with amplification of the 12q13-15 region, including the murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) genes. Special AT-rich sequence-binding protein 2 (SATB2) is an immunophenotypic marker for osteoblastic differentiation. Cases of OSJ, BFOLs (ossifying fibroma and fibrous dysplasia) of the jaw, and Ewing sarcoma of the jaw were retrieved from the Departments of Oral Pathology and Oral Medicine, Faculty of Dentistry, Obafemi Awolowo University and Lagos State University College of Medicine, Nigeria. All OSJ retrieved showed histologic features of high-grade osteosarcoma. IHC for SATB2 (clone EP281) and MDM2 (clone IF2), as well as fluorescence in situ hybridization (FISH) for MDM2 amplification, were performed on all cases. SATB2 was expressed in a strong intensity and diffuse staining pattern in all cases (11 OSJ, including a small-cell variant, 7 ossifying fibromas, and 5 fibrous dysplasias) except in Ewing sarcoma, where it was negative in neoplastic cells. MDM2 was expressed in a weak to moderate intensity and scattered focal to limited diffuse staining pattern in 27% (3/11) of cases of OSJ and negative in all BFOLs and the Ewing sarcoma. MDM2 amplification was negative by FISH in interpretable cases. In conclusion, the three cases of high-grade OSJs that expressed MDM2 may have undergone transformation from a low-grade osteosarcoma (LGOS). SATB2 is not a dependable diagnostic marker to differentiate OSJ from BFOLs of the jaw; however, it could serve as a valuable diagnostic marker in differentiating the small-cell variant of OSJ from Ewing sarcoma of the jaw, while MDM2 may be a useful diagnostic marker in differentiating OSJ from BFOLs of the jaw, especially in the case of an LGOS or high-grade transformed osteosarcoma.

BRAF V600E mutation-specific immunohistochemical analysis in ameloblastomas: a 44-patient cohort study from a single institution.

PURPOSE: The aim of this study is to investigate the presence and prevalence of BRAF V600E mutation in ameloblastomas using anti-BRAF V600E monoclonal antibody (VE1 clone) and to identify any clinicopathologic correlation with BRAF V600E mutation in ameloblastoma. MATERIALS AND METHODS: The pathology files of the Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, Lagos State University College of Medicine, Lagos, Nigeria, were searched for the diagnosis of ameloblastoma from 2016 to 2020. Archived non-decalcified formalin-fixed paraffin-embedded tissue underwent immunohistochemistry using anti-BRAF V600E antibody at the University of Pittsburgh, Pennsylvania. Clinicopathologic data such as age at diagnosis, gender, jaw bone involved (mandible or maxilla), tumor location (anterior or posterior) and histologic subtype were collected. The clinicopathologic parameters were analyzed using Chi-square test and Fisher's exact test according to the BRAF status. RESULTS: Forty-four cases of ameloblastoma were retrieved. The male to female ratio was 1.32:1. The average age of patients at diagnosis was 33.3 years. Thirty-nine cases were located in the mandible and 5 cases in the maxilla. Only cases in the mandible were positive for anti-BRAF V600E antibody (n = 15/39; 38.5%). There was a significant correlation between BRAF V600E expression in mandibular tumors and histologic subtype (p = 0.02); however, no significance was observed for gender, age and tumor location. CONCLUSION: BRAF V600E mutation preferentially occurs in mandibular ameloblastomas, especially in non-plexiform ameloblastomas. These patients may benefit therapeutically from the use of BRAF inhibitors.