DNA content and clinicopathological features aid in distinguishing ameloblastic carcinoma from ameloblastoma.

BACKGROUND: Ameloblastoma and ameloblastic carcinoma are epithelial odontogenic tumors that can be morphologically similar. In the present study, we evaluated the DNA content and Ki-67 index in the two tumors. METHODS: The paraffin blocks of the tumors were selected to obtain sections for the immunohistochemical reactions and preparation of the cell suspension for acquisition in a flow cytometer. The Random Forest package of the R software was used to verify the contribution of each variable to classify lesions into ameloblastoma or ameloblastic carcinoma. RESULTS: Thirty-two ameloblastoma and five ameloblastic carcinoma were included in the study. In our sample, we did not find statistically significant differences in Ki-67 labeling rates. A higher fraction of cells in 2c (G1) was correlated with the diagnosis of ameloblastoma, whereas higher rates of 5c-exceeding rate (5cER) were correlated with ameloblastic carcinoma. The Random Forest model highlighted histopathological findings and parameters of DNA ploidy study as important features for distinguishing ameloblastoma from ameloblastic carcinoma. CONCLUSION: Our findings suggest that the parameters of the DNA ploidy study can be ancillary tools in the classification of ameloblastoma and ameloblastic carcinoma.

To extract or not extract teeth prior to head and neck radiotherapy? A systematic review and meta-analysis.

PURPOSE: Teeth with poor prognosis are generally recommended to be extracted prior to head and neck radiotherapy (RT) to reduce the risk of developing osteoradionecrosis (ORN), although controversies have been reported. The present systematic review aimed to determine whether tooth extraction prior to head and neck RT may be associated with a reduced risk of developing ORN compared to dental extraction during or after RT. METHODS: The review protocol was registered in PROSPERO (CRD42021241631). The review was reported according to the PRISMA checklist and involved a comprehensive search of PubMed, Scopus, Embase, Cochrane Library, LILACS, and Web of Science, in addition to the gray literature. The selection of studies was performed in two phases by two reviewers independently. The risk of bias of individual studies was analyzed using the Joanna Briggs Institute checklist for cross-sectional studies, and the certainty of evidence was assessed using the GRADE tool. RESULTS: Twenty-eight observational studies were included in the qualitative synthesis, which showed substantial heterogeneity regarding the association between the timing of tooth extraction and ORN development. Twenty-seven of 28 studies were pooled in a meta-analysis that demonstrated a significant association between an increased risk of ORN and post-RT tooth extraction (odds ratio: 1.98; 95% CI: 1.17-3.35; p = 0.01). CONCLUSION: It was confirmed with moderate certainty that dental extractions should be performed prior to the start of head and neck RT to reduce the risk of ORN.

DNA methylation status of MutS genes in ameloblastoma.

OBJECTIVES: Ameloblastoma is an odontogenic epithelial tumour with a low expression of mismatch repair system components. We aimed to investigate the methylation status of the genes MSH2, MSH3 and MSH6 (MutS group) in conventional ameloblastomas. MATERIALS AND METHODS: The ameloblastoma and dental follicle samples (n = 10 each) were collected from 20 different patients. Each ameloblastoma sample was sectioned into two fragments: one was paraffin-embedded while the other one, likewise the dental follicle samples, was fixed in RNAlater and frozen at -196°C. All frozen samples were investigated for the MutS genes methylation levels, using the enzymatic restriction digestion and quantitative real-time PCR (qPCR) assay. The ameloblastoma paraffin-embedded samples were submitted to immunohistochemical reactions for MutS proteins detection and digitally quantification. Correlation analyses were performed between the immunohistochemical results and the respective gene methylation percentage. RESULTS: There are no significant differences between the MutS genes methylation levels in the ameloblastoma and the dental follicle. However, a strong negative correlation was found between MSH2 and MSH6 gene methylation status and their respective proteins expressions evaluated by immunohistochemistry. CONCLUSION: Our results show that the genes methylations is in part responsible for decreasing the expression of MSH2 and MSH6 genes in ameloblastoma.

Surgical Treatment of Ameloblastoma: How Does It Impact the Oral Health-Related Quality of Life? A Systematic Review.

PURPOSE: This study aimed to analyze the impact of surgical treatment on the quality of life of patients diagnosed with ameloblastoma. METHODS: We searched PubMed, Science Direct, LILACS, EMBASE, and Web of Science, up to February 2021, with no time restriction. We considered only studies published in English that evaluated patients diagnosed with ameloblastoma who underwent conservative or radical surgical treatments using a quality of life (QOL) instrument. RESULTS: Of the 2155 studies identified, ten were included in our sample. Only studies that analyzed QOL of radical surgical treatment were included. No studies that analyzed QOL after conservative surgical treatment were found. Across all studies, 283 patients (122 females and 161 males; mean age: 28.13 years) were surgically treated for ameloblastoma. A total of 69 complications were reported, with the most frequent being infection in both the donor and recipient site (18 cases) and graft loss (8 cases). CONCLUSION: Surgical treatment of ameloblastoma was effective in providing reasonable health-related QOL, as most of the assessed dimensions were found to improve.

Burkitt lymphoma of the head and neck: An international collaborative study.

BACKGROUND: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma with three variants (endemic, sporadic, and immunodeficiency-associated), presenting with specific epidemiological and clinical features. Burkitt lymphoma affects the head and neck region (BLHN) in approximately 10% of cases. The aim of this study was to undertake a comparative analysis of the clinicopathologic and immunohistochemical (IHC) features of BLHN diagnosed in patients from Africa, Guatemala, and Brazil. METHODS: Cases diagnosed as BLHN were collected from the files of six oral pathology laboratory services (Brazil, South Africa, and Guatemala) and one Brazilian pediatric oncology hospital from 1986 to 2020. Clinicopathological and IHC data, and Epstein-Barr virus (EBV) status by in situ hybridization data for each case were reviewed and described. RESULTS: Of the 52 cases, BLHN was predominant in pediatric patients [43 (82.69%)] and males [43 (82.69%)], with a mean age of 11.26 ± 9.68 years (range, 1-39 years). Neck and cervical lymph nodes [14 (26.92%)], and involvement of both maxilla and mandible [8 (15.38%)], were the most common anatomical sites. Clinically, tumor/swelling [40 (31.25%)], cervical lymphadenopathy [14 (10.94%)], pain [12 (9.38%)], and bone destruction [12 (9.38%)] were frequent findings. All cases showed typical morphological characteristics of BL. IHC profiles included positivity for CD20 [52 (100%)], CD10 [38 (79.17%)], Bcl6 [29 (87.88%)], and c-Myc protein [18 (81.82%)]. EBV was positive in 18 cases (62.07%). The Ki-67 index ranged from 90 to 100%. CONCLUSION: The clinicopathological and EBV profile of BLHN in South African, Guatemalan, and Brazilian patients is similar.

Cilostazol and Tocopherol in the Management of Medication-Related Osteonecrosis of the Jaw: New Insights From a Case Report.

Several treatment protocols for medication-related osteonecrosis of the jaw (MRONJ) have been published. Despite the efficacy of surgical therapy of approximately 90% as primary therapy, the role of other agents, such as drug administration, should not be underestimated. Based on previous experience with osteoradionecrosis, the association of pentoxifylline and tocopherol has shown encouraging results in MRONJ patients. Despite the need for long-term use of the combination, compliance has been good. However, studies in breast cancer patients revealed that pentoxifylline can require dose reduction or discontinuation due to nausea and epigastric pain. Cilostazol has been used as a substitute for pentoxifylline in peripheral artery disease. Herein we report a case in which cilostazol replaced pentoxifylline at a dose of 100mg, 2 times/day with tocopherol 500UI, 2 times/day, in a 77-year-old female patient that could not tolerate pentoxifylline for the management of MRONJ. After an uneventful 22 months of follow-up, a cone-beam computed tomography revealed complete bone formation and no signs of recurrence. Cilostazol may be a useful and safe alternative to pentoxifylline as part of MRONJ management protocols.

Intraosseous neurilemoma of the mandible with unusual multilocular presentation: a case report.

This case report describes an intraosseous neurilemoma, observed radiographically as a multilocular lesion, in a 12-year-old patient. Physical examination revealed facial asymmetry, swelling on the right side of the mandibular body, and bone expansion in the region of the base of the buccal sulcus. Panoramic radiography revealed a multilocular radiolucency on the right side of the mandibular body in the periapical region extending from the distal region of the first premolar root to the second molar and adjacent to the third molar. Evaluation of a radiograph obtained 3 years earlier for an orthodontic assessment revealed that the lesion was present, appearing as a unilocular radiolucency near the root of the mandibular right first molar. An incisional biopsy of the multilocular lesion was performed, and Antoni A and Antoni B histologic patterns were identified by microscopic analysis. Immunohistochemical analysis was conducted, and neoplastic cells stained positive for the S-100 protein. The patient underwent conservative surgical excision of the lesion, and no recurrence was observed during 7 years of clinical follow-up. Based on analysis of the present case and previous cases reported in the literature, intraosseous neurilemoma, especially its multilocular variant, is an uncommon neoplasm. In the present case, evaluation of the lesion when it was first radiographically detectable, prior to orthodontic treatment, would have permitted a more limited surgical approach for the excision of a small intraosseous lesion.

Influence of bisphosphonates on clinical features of osteoradionecrosis of the maxilla and mandible.

BACKGROUND AND PURPOSE: Osteoradionecrosis (ORN) is one of the most severe adverse effects of radiotherapy (RT) to the head and neck region. Medication-induced osteonecrosis of the jaw has been reported among patients using bisphosphonates. However, the impact of RT on osteonecrosis in patients using bisphosphonates has not yet been described. Therefore, the aim of this study was to compare ORN characteristics between patients who use and do not use bisphosphonates. MATERIALS AND METHODS: This retrospective study evaluated 96 patients with ORN of the jaw. Patients were divided into group I (patients who did not receive bisphosphonates, n = 83) and group II (patients who did receive bisphosphonates, n = 13). Clinical data were obtained from medical charts. RESULTS: Osteoradionecrosis more often involved the mandibular jaw than the maxillary jaw for both patient groups. However, maxillary involvement was more common among patients who received bisphosphonates than those who did not (p = 0.014). There was also a trend toward earlier development of ORN in the group that received bisphosphonates (p = 0.21). CONCLUSIONS: Bisphosphonate use appears to contribute to earlier development of ORN. Long-term prospective studies are needed to understand the pathogenesis of ORN in patients treated with combined radiation and bisphosphonate therapy.

Clinical predictors of malignancy in palatal salivary gland tumors.

OBJECTIVES: To establish a predictive clinical index of malignancy risk in palatal salivary gland tumors (PSGT). MATERIALS AND METHODS: One hundred cases of PSGT were evaluated. Clinical data were retrieved from the patient's files. Representative clinical photographs of each tumor were evaluated to identify clinical features suggestive of a malignant tumor. Features significantly associated with malignancy were included in a binary logistic regression model. RESULTS: Malignant tumors were more common in the hard palate, in women and in older patients. Features associated with a malignant diagnosis included pain (p = .017), irregular surface (p = .004), bluish/purple coloration (p < .001), ulceration (p = .005), and telangiectasia (p = .015). After multivariate logistic regression, pain (OR: 4.017; 95% CI: 1.198-13.471; p = .024) and color alteration (OR: 7.243; 95% CI: 2.068-25.363; p = .002) were independently associated with malignancy. Including these factors in a predictive index, the proportion of malignant tumors in patients presenting none, one and two factors were 25% (95% CI: 0.13-0.40), 67% (95% CI: 0.48-0.83), and 85% (95% CI: 0.42-0.99), respectively. CONCLUSION: Pain and color alteration might be independent predictors of malignancy in PSGT, which could support the decision to perform an incisional or excisional biopsy.

Odontogenic keratocyst: The role of the orthodontist in the diagnosis of initial lesions.

Odontogenic keratocysts (OKCs) are locally infiltrative odontogenic cysts that are usually diagnosed during routine radiographic examinations. Therefore, it is critical that dental practitioners, in particular orthodontists, recognize and diagnose OKCs to recommend appropriate treatment. This report describes a patient whose OKC was not initially identified during orthodontic pretreatment. In addition, this report discusses the clinical and radiographic features of OKCs, as well as the differential diagnoses of these lesions.

Tissue microarray use for immunohistochemical study of ameloblastoma.

BACKGROUND: Ameloblastoma is a locally aggressive odontogenic tumor with high rates of recurrence. To better understand the molecular basis of ameloblastoma, tissue microarray (TMA) may represent a useful tool. However, despite TMA has been considered a high-throughput technique for different human neoplasms, it remains to be validated in the ameloblastoma context. Therefore, the objective of this study was to validate TMA for immunohistochemical study of ameloblastoma, determining its most appropriate design. METHODS: Forty cases of ameloblastoma were manually distributed in two TMA blocks assembled in triplicate containing 1.0- and 2.0-mm cores (20 cases each). Immunohistochemistry for cytokeratins 14 and 19, and Bcl-2 and Ki-67 was performed, and semiquantitative analysis was performed. Results obtained with TMA sections were compared to their corresponding conventional whole-section slides (CWSS). RESULTS: Kappa statistical test demonstrated that both 1.0- and 2.0-mm cores assessed as duplicate or triplicate significantly correlated with CWSS, with higher levels obtained using Ki67 (k = 0.98, 0.97, 0.88, 0.87) and CK19 (k = 0.62, 0.58, 0.85, 0.85). There was no significant difference between 1.0- and 2.0-mm cores, and between duplicate and triplicate values. 1.0-mm TMA showed a higher index of core loss (33.74% vs. 4.99%). CONCLUSION: Using a manual arrayer, it was demonstrated that 1.0-mm TMA arranged in duplicate is a valid method for ameloblastoma immunohistochemical study with satisfactory levels of agreement between TMA cylinders and CWSS.

Surgical Therapy for Bisphosphonate-Related Osteonecrosis of the Jaw: Six-Year Experience of a Single Institution.

PURPOSE: Bisphosphonates are drugs commonly used to treat osteoporosis, hypercalcemia of malignancy, and bone metastases. In some cases, its administration has been associated with osteonecrosis of the jaws. The management of medication-related osteonecrosis of the jaw (MRONJ) has not been completely elucidated, and its treatment can vary from no or limited surgery to more extensive surgery. The objective of the present study was to evaluate the efficacy of surgical therapy for patients presenting with MRONJ. PATIENTS AND METHODS: A retrospective study was conducted that evaluated all MRONJ cases resulting from bisphosphonate use and treated by surgery from 2006 to 2012. All patients underwent surgery under general anesthesia. RESULTS: A total of 33 patients with 46 MRONJ sites were evaluated. Most of the patients were women, with an age range of 39 to 83 years (mean 65.6 ± 10.6). Complete healing of the MRONJ region was observed in 40 of the 46 sites (87%), with partial improvement (symptom control and reduction of the exposed bone area) observed in 3 sites (6.5%), for a 93.5% clinical benefit rate. Of the remaining regions, 2 showed no significant changes, and 1 presented with a worse aspect compared with the patient's preoperative condition. Such cases were located in the posterior mandible region. The number of applications and type of bisphosphonate did not influence the treatment response. CONCLUSION: The surgical approach to treating MRONJ showed a high rate of clinical control. Therefore, surgery should be considered as a therapy for some cases of this condition.

Report of intraosseous intravascular papillary endothelial hyperplasia associated with an odontogenic cyst in the maxilla and literature review.

Intravascular papillary endothelial hyperplasia (IPEH) represents an uncommon reactive endothelial hyperplastic proliferation. A 46-year-old man experienced increased volume in the right maxilla, elevation of the nasal ala, and swelling of the hard palate with a reddish hue for 3 months. Computed tomography revealed an expansive hypodense region and cortical bone destruction associated with an impacted supernumerary tooth and an endodontically treated tooth. Under the differential diagnoses of a radicular cyst, dentigerous cyst, and ameloblastoma, an exploratory aspiration and incisional biopsy were performed. This revealed the formation of blood vessels of various diameters lined by endothelium, forming intravascular papillae positive for CD-34. The definitive diagnosis was IPEH, and the patient was treated by embolization and surgery. Histological analysis confirmed the presence of IPEH associated with an odontogenic cyst. After 12 months of follow-up, no recurrence was observed. Also, we reviewed case reports of IPEH affecting the maxilla and mandible. Fourteen intraosseous cases were reported in the maxilla and mandible, with a preference for males and affecting a wide age range. Complete surgical excision was the treatment of choice, and recurrences were not reported. The pathogenesis of IPEH is controversial and may originate from trauma or inflammatory processes. To the best of our knowledge, this is the first report of an association of IPEH with an odontogenic cyst. The importance of IPEH in the differential diagnosis of intraosseous lesions in the jaws is emphasized, and preoperative semiotic maneuvers are needed to prevent surgical complications.

Malignant tumors affecting the head and neck region in ancient times: Comprehensive study of the CRAB Database.

In the modern world, cancer is a growing cause of mortality, but archeological studies have shown that it is not exclusive to modern populations. The aim of this study is to examine the epidemiologic, social, and clinicopathologic features of head and neck cancers in ancient populations. To do this, we extracted all records that described malignant lesions in the head and neck region available in the Cancer Research in Ancient Bodies Database (CRAB). The estimated age, sex, physical condition of the remains (skeletonized, mummified), anatomic location of tumors, geographic location, chronology, tumor type, and methods of tumor diagnosis were collected. One hundred and sixty-seven cases were found, mostly originating from Europe (51.5%). Most records were of adults between 35 and 49 years of age (37.7%). The most involved site was the skullcap (60.4%), and the most common malignancies were metastases to the bone (65.3%) and multiple myeloma (17.4%). No primary soft tissue malignancies were registered. The results of our study indicate that head and neck cancers were present in ancient civilizations, at least since 500,000 BCE. The available data can help to improve the current understanding of the global distribution of head and neck cancer and its multidimensional impacts on populations in the contemporary world.

Synchronous ossifying fibromas of maxilla and mandible.

Ossifying fibroma is a benign neoplasm composed of fibrocellular tissue and mineralized material of varying appearance, which is most commonly seen in the posterior region of the mandible as a solitary lesion. We report an unusual case of synchronous ossifying fibroma of maxilla and mandible. To the best of our knowledge, only 13 similar cases have been previously reported.

Can the prophylactic use of pentoxifylline and tocopherol before dental extractions prevent osteoradionecrosis? A systematic review.

PURPOSE: This systematic review aimed to determine whether the pentoxifylline and tocopherol (PENTO) protocol effectively reduce the risk of osteoradionecrosis (ORN) in patients undergoing tooth extraction after head and neck radiotherapy. METHODS: We searched PubMed, SCOPUS, LILACS, EMBASE, Web of Science, and Cochrane databases up to August 2022. We considered only studies that included patients diagnosed with head and neck cancer undergoing tooth extraction with PENTO prophylaxis after radiotherapy. RESULTS: Of the 642 studies identified, 4 were included. Across the included studies, 387 patients had 1871 teeth extracted while on PENTO prophylaxis. The interval of the PENTO protocol differed among the studies included. Overall, a total of 12 (3.1%) patients had ORN, whereas at the individual tooth level analysis the ORN rate was 0.9%. CONCLUSIONS: Insufficient evidence exists to promote using the PENTO protocol before dental extractions to prevent ORN.

Rhabdomyosarcoma with TFCP2 Rearrangement or Typical Co-expression of AE1/AE3 and ALK: Report of Three New Cases in the Head and Neck Region and Literature Review.

BACKGROUND: Rhabdomyosarcoma (RMS) harboring EWSR1/FUS-TFCP2 fusions has been recently described as a distinct form of RMS with an aggressive course and predilection for the craniofacial bones, especially the jaws. METHODS: We report three new cases of this rare entity, two from Brazil and one from Guatemala, with detailed clinicopathologic, immunohistochemical, and molecular descriptions. Additionally, we explored the English-language literature searching RMS with TFCP2 rearrangement or typical immunophenotype with co-expression of AE1/AE3 and ALK in the head and neck region. RESULTS: Case 1 is a 58-year-old male with a 3-month history of painful swelling in the anterior maxilla. Case 2 is a 22-year-old male presenting with right facial swelling and proptosis. Case 3 is a 43-year-old female with a rapidly growing tumor located in the zygomatic region. Imaging examinations revealed highly destructive intraosseous masses in the first two cases, and a soft tissue tumor with bone invasion in case 3. Microscopically, all cases showed a hybrid spindle and epithelioid phenotype of tumor cells which expressed desmin, myogenin and/or Myo-D1, AE1/AE3, and ALK. FISH confirmed molecular alterations related to TFCP2 rearrangement in Cases 1-2. In case 3, there was no available material for molecular analysis. The patients were subsequently referred to oncologic treatment. Additionally, we summarized the clinicopathologic, immunohistochemical, and molecular features of 27 cases of this rare RMS variant in the head and neck region reported in the English-language literature. CONCLUSION: RMS with TFCP2 rearrangement is a rare and aggressive tumor with a particular predilection for craniofacial bones, especially the jaws. Knowing its clinicopathologic and immunohistochemical profile can avoid misdiagnosis.

Synchronous jawbone diseases: a multicenter retrospective study.

The aim of this study is to report an original case series of synchronous jawbone diseases. Data of patients seen over 13 years were extracted from the files of three Oral Radiology and Pathology diagnostic centers in Brazil. The clinical, radiographic, and laboratory characteristics were tabulated and analyzed by the authors; the patients were described according to lesion type. Seventy-two synchronous jawbone diseases were included in this study. Florid osseous dysplasia, Gorlin-Goltz syndrome, and cherubism were the most frequent disorders reported in this case series. In addition, the posterior mandible area was the main site of manifestation. Florid osseous dysplasia and Gorlin-Goltz syndrome represented two-thirds of our samples. With the utilization of adequate demographic, clinical, and radiologic information, it is possible to diagnose most of the synchronous lesions of jawbones. Sometimes, however, we need complementary exams, such as histopathologic and biochemical analysis or dosing of calcium, phosphorus, and alkaline phosphatase.