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This report aimed to describe an uncommon case of verrucous carcinoma of the oral cavity with a unique presentation of proliferative verrucous leucoplakia. An 82-year-old female presented multiple white plaques in the oral cavity, which have been treated as candidiasis without resolution. The biopsy specimen demonstrated a well-defined squamous cell epithelium with verrucous aspects. No cellular or nuclear pleomorphism was observed. The final diagnosis was verrucous carcinoma, and the patient was referred for oncologic treatment. Although unusual, proliferative verrucous leukoplakia may mimic verrucous carcinoma and may even represent a transitional stage of this malignancy. Verrucous carcinoma should be considered in the differential diagnosis of multiple leucoplakias, especially in elderly patients.

Objective The objective of this study was to describe the clinicopathological, molecular, and prognostic features of oral/oropharyngeal diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma. Study Design All cases were retrieved from 7 Brazilian institutions. Immunohistochemical reactions were performed to confirm the diagnoses and to categorize the tumors. In situ hybridization was used to detect Epstein-Barr virus (EBV) and fluorescence in situ hybridization was used to identify gene rearrangements. Results Most cases involved the oral cavity (76.8%). Males and females, with a mean age of 60 years, were evenly affected. Tumors mostly presented as painful swellings. Forty cases represented germinal center B-cell type (58%). Five cases presented double-hit translocation and 3 harbored rearrangement for MYC/BCL2/BCL6. EBV was detected in 3 cases (4.3%). The 5-year overall survival was 44.4%. Female sex, presence of pain and ulcer, microscopic “starry sky pattern” and necrosis, co-expression of c-Myc/Bcl2, and translocation of MYC were associated with a lower survival in univariate analysis (P = .05, P = .01, P = .01, P = .03, P = .05, P = .006, P = .05, respectively). Conclusion Patients affected by oral/oropharyngeal DLBCL have a low survival rate. High-grade B-cell lymphoma (17.7%) and EBV‐positive DLBCL, not otherwise specified (4.3%) account for a small number of cases.

The aim of this study was to correlate the clinical, demographic, and radiographic aspects of 82 cases of florid osseous dysplasia (FOD) from four countries assessed by five reviewers.Retrospective data of patients diagnosed with FOD were obtained from archives of five institutes and analyzed according to clinical and radiographic criteria.A total of 82 cases of FOD were included in the study. In the majority (77.5%) of FOD cases, black women were affected. The disease mainly affected the mandible (100%), and the stage of the lesion was directly correlated with the age (P .05). The rates of convergence showed confluence of assessment in the mandible (posterior), and the highest rate of divergence between the reviewers was in assessing involvement in the maxilla. There were no differences among the characteristics of the lesion provided by the five institutions, except for the variable proportion of black patients affected by the disease.FOD mostly affects the mandible of middle-aged black women, and its stage is correlated with patient age. Although panoramic radiography is used for diagnosis, the divergence in assessment of the maxilla might indicate that this method is not the most suitable to evaluate this area.

Posttransplant lymphoproliferative disorders (PTLDs) comprise a spectrum of complications that affect immunocompromised patients following hematopoietic stem cell transplantation or solid organ transplantation. Its incidence varies depending on the transplanted organ, occurring in approximately 2.3% of kidney transplantations. A 31-year-old woman was referred to the Dental Clinic of the State University of Western Paraná for evaluation of an oral lesion. Her medical history revealed a previous diagnosis of hypertension, Epstein-Barr virus (EBV) seropositivity, and kidney transplantation 12 years prior. She was under standard immunosuppressive therapy. Intraoral examination identified a gingival necrotic lesion with extension to the posterior right lower alveolar bone. An incisional biopsy was performed. Histologic examination showed lymphocytic proliferation of cells with small and hyperchromatic nuclei, atypical mitosis, and cells with large and pale nuclei showing prominent nucleoli permeating connective tissue, muscle fibers, and adipocytes. Correlation of clinical, histologic, and immunohistochemical findings led to a diagnosis of polymorphic EBV-associated PTLD rich in B and T cells.

Aim: In this study we described the causes of mortality in Brazil, its 5 geographic regions, and in the most populated cities of Sao Paulo State in order to contribute for development of prevention and intervention strategies. Methods: Data on causes of death and age distribution of the populations were collected from online public databases and then submitted to the 2001 World Health Organization age standardization of rates for better assessment. Results: Data showed that the main causes of death in Brazil and in all 5 geographic regions were diseases of the circulatory system. Neoplasms were the second most frequent cause of death in Brazil and in 3 regions (South, Southeast and Midwest). However, in the other 2 regions (North and Northeast) the second most common was associated to external causes, being neoplasms the third most often. Additionally, in the South and Southeast the third cause of deaths were from diseases of the respiratory system and from the external causes occupied the fourth position. Analyzing the most populated cities of Sao Paulo State it was observed that all of them have the same profile of the country. On the other hand, as speculated previously, in Piracicaba city, the most common cause of mortality was neoplasm. Conclusions: These findings showed that Brazil has a large spectrum of causes of death and methods to decrease the mortality rates should be implemented in a local scenario rather than a nation-wide approach, where each location has to focus on its most urging problem.

Background Patient-derived xenograft (PDX) involve the direct surgical transfer of fresh human tumor samples to immunodeficient mice. This systematic review aimed to identify publications of head and neck cancer PDX (HNC-PDX) models, describing the main methodological characteristics and outcomes. Methods An electronic search was undertaken in four databases, including publications having used HNC-PDX. Data were analyzed descriptively. Results 63 articles were yielded. The nude mouse was one most commonly animal model used (38.8 %), and squamous cell carcinoma accounted for the majority of HNC-PDX (80.6 %). Tumors were mostly implanted in the flank (86.3 %), and the latency period ranged from 30 to 401 days. The successful rate ranged from 17 % to 100 %. Different drugs and pathways were identified. Conclusion HNC-PDX appears to significantly recapitulate the morphology of the original HNC and represents a valuable method in translational research for the assessment of the in vivo effect of novel therapies for HNC.

Oral leukoplakia (OL) is a white lesion with high potential of recurrence and malignant transformation. The variable clinical and histopathological features of OL may potentially impact both treatment and prognosis. Current literature shows that post treatment rates of recurrence and malignant transformation vary widely. The use of surgical lasers have been proposed with the objective of improving outcomes. We performed a systematic review and a comprehensive meta-analysis dedicated to pooling the rates of recurrence and malignant transformation of OL lesions treated using the main types of surgical lasers available. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 36 articles met the inclusion criteria. Selected studies included OL lesions that were treated by evaporation or excision using Nd:YAG laser, Er:YAG laser, CO2 laser, KTP laser, or diode laser. The results of this systematic review and meta-analysis suggest that surgical laser excision of OL may decrease recurrence rates but have no effect on the malignant transformation of OL when compared with conventional treatments.

A 14-year-old male patient was referred for evaluation of an expansile, slow-growing asymptomatic swelling of unknown duration in the right posterior mandible, which caused facial asymmetry. A panoramic radiograph presented a well-defined radiolucency associated with the crown of an impacted lower second molar, containing small radiopaque foci. The lesion measured approximately 3 cm, causing cortical bone expansion, displacement of mandibular canal, and resorption of the distal root of the adjacent first molar. A panoramic radiograph performed 3 years earlier showed a 0.3 cm radiolucency pericoronal to the lower second molar, with radiographic diagnosis suggestive of hyperplastic pericoronal follicle. The patient underwent incisional biopsy, and the diagnosis of adenomatoid odontogenic tumor (AOT) was rendered out after microscopic identification of epithelial structures forming duct-like spaces and calcification. The present case illustrates a case of AOT in the posterior mandible and its radiographic progression throughout 3 years.

Bisphosphonates are drugs indicated for the treatment of osteoporosis, bone tumors, and bone metastases. However, these patients may eventually develop necrosis of jaw bones recognized as medication-related osteonecrosis of the jaws (MRONJ). Treatment of this complication could be a challenge. The main triggering factor is a dental extraction. A 72-year-old woman with rheumatoid arthritis and using alendronate for several years underwent dental extraction 7 years ago. However, the socket did not heal. The patient remained with MRONJ for 5 years. Clinical evaluation found an area of bone exposure in the inferior alveolar ridge with drainage of purulent secretion. Serratia marcescens was detected, and the antibiotic was replaced. Although improvement was achieved, the bone exposure persisted with subsequent episodes of purulent drainage. Therefore, surgical resection was performed, and the necrotic bone was removed. Total healing was observed, and the patient is in follow-up for 2 years without recurrence.

The aim of this study was to integrate the available data regarding pediatric Burkitt's lymphoma (BL) of the oral cavity. A systematic review was conducted following PRISMA guidelines, through a specific search strategy. Twenty-nine publications were included in this study, resulting in a total of 144 cases. Oral BL was predominantly found in males (75.7%). The mandible was the most involved site (37.5%), and all cases clinically exhibited a swelling. Presence of EBV was observed in 33.3% of the cases, and 4 cases reported HIV-positive patients (33.3%). Chemotherapy was the leading treatment choice for oral BL (94.9%), and the overall 5-year survival was 54.3%. Regarding the quality assessment of the studies, most (19 studies; 65.5%) were classified as an overall moderate risk of bias. In conclusion, the clinicopathological characteristics of oral BL in the pediatric population comprise the sporadic and intermediate subtypes. Despite its aggressiveness, this malignancy presents a moderate overall survival.

Oral submucous fibrosis (OSMF) affects mainly the Indian subcontinent and its manifestations are closely linked with the habit of chewing betel. Immune system cells such as Langerhans cells (LC) and dendritic cells (DC) are linked to the immunopathogenesis of various lesions and have been studied for their ability of recognizing precursor malignant cells and to destroy them. Objective: Verify the distribution of LC and immature DC in OSMF and oral squamous cell carcinoma (OSCC). Study design: Fourteen cases of OSFM, 9 of OSCC associated to OSMF, and 40 of OSCC were retrieved. The original diagnoses were confirmed by 2 oral pathologists, who further classified OSFM in grade I, II, and III. OSCC cases were classified as well, moderately, and poorly differentiated. Immunoreactions against CD1a were performed and the number of positive LC and DC were quantified. Results: Analysis revealed a significant decrease in the number of immature LC and DC in OSCC compared to OSCC-OSMF (P Conclusions: The results suggest that depletion of immature LC and DC would represent an important step for developing OSCC.

Objective To carry out a systematic review to address the prevalence and the prognostic potential of translocation (6;9) (MYB-NFIB genes) mutation in head and neck adenoid cystic carcinoma (AdCC). Study Design Articles published were retrieved from multiple databases using specific search strategies. They were screened and articles included had their data extracted by 2 authors who latter assessed the risk of bias of each study. Quantitative analysis was done to determine the incidence of the translocation. Results A total of 1107 articles were initially retrieved with 36 remaining for data extraction. The presence of t(6;9)(MYB-NFIB) translocation varied significantly, especially due to methodologic heterogeneity among studies. The meta-analysis revealed a range from 16% to 100% in the prevalence of the translocation. A total of 11 studies attempted to determine the prognostic importance of the mutation, but no study found any significant association with survival rates and only 3 studies observed a significant association with age, sex, tumor location, and the presence of recurrences and metastases. Conclusions The prevalence of t(6;9)(MYB-NFIB) translocation in head and neck AdCC varies according to the laboratory methods used and the best evidence available demonstrate that t(6;9)(MYB-NFIB) is not a prognostic determinant. Support: CNPq and FAPEMIG.

A 31-year-old woman was referred for evaluation of persistent numbness on the left side of the lower lip, which began during endodontic treatment of the left mandibular first molar. Imaging exams showed a large amount of a radiopaque or hyperdense throughout the left mandibular body in close proximity to the lower alveolar nerve. Histologic analyses identified birefringent crystalloid foreign bodies widespread through soft tissue and bone leading to an inflammatory foreign body reaction, eventually demonstrated to be rich in barium and sulfur by the means of scanning electron microscopy coupled with energy dispersive x-ray detection. This scenario led to the diagnosis of lower alveolar nerve injury due to accidental extrusion of intracanal dressing material composed of calcium hydroxide (CaOH2) paste incorporated with BaSO4. The paresthesia was treated with the combination of citoneurin and prednisone, but no improvement in nerve sensitivity was noticed after 12 months of follow-up examination.

Proliferative verrucous leukoplakia (PVL) is a subtype of oral leukoplakia, which is not commonly associated with risk factors such as alcohol and smoking; it has high rates of recurrence after treatment and has a high risk of malignant transformation. This study described the clinical features of 34 patients with PVL (1991-2016). Of these, the vast majority was female (31%-91.17%) and the mean age was 69.08 years. Regarding risk factors, only 2 patients smoked and 5 consumed alcoholic beverages. The most frequently affected sites were the buccal mucosa and lateral border of the tongue. The average number of site affected with leukoplakia was 3.41 and the development of squamous cell carcinoma occurred in 7 of the patients (20%). PVL starts as an isolated lesion but develops important changes throughout the follow-up period. Therefore, constant clinical monitoring is necessary.

Treatment of benign lip vascular anomalies can be an aesthetic challenge even though several techniques are available to manage these lesions. A difficult case treated with an association of techniques is presented. A 12-year-old boy with an extensive congenital hemangioma in the upper lip was referred with an aesthetic complaint and past history of treatment failures. Sclerotherapy with 5% ethanolamine oleate was proposed. Intriguingly, after 6 sessions of sclerotherapy, the size and the consistency of the lesion remained almost the same, although some color improvement was observed. Therefore, an aesthetic surgery was considered and the patient was referred to a vascular surgeon. After arteriography, 3 sessions of percutaneous embolization with 3% polidocanol foam was performed. Afterward, the patient underwent 2 surgical interventions using diode high-potential laser achieving a satisfactory result. Although uncommon, a refractory vascular lesion may occur and an association of different techniques may be necessary.

Human epididymis protein 4 (HE4) and secretory keukocyte protease inhibitor (SLPI) are members of the WFDC family of proteins and have recently been shown to be expressed in normal salivary glands; however, differential expression in mucoepidermoid carcinoma suggests a potential role in tumorigenesis. Objective: To evaluate the immunoexpression of HE4 and SLPI in mucoepidermoid carcinomas and to correlate expression with tumor grade. Study Design: Forty diagnosed mucoepidermoid carcinoma cases were selected and clinical data collected. Hematoxylin and eosin (H&E)-stained sections were reviewed and immunoexpression of HE4 and SLPI was assessed. Results: The sample was composed mostly of female patients (70%), and the mean age was 42.3 years. Histologic analysis showed that 72.5% of cases were low-grade tumors. Immunohistochemical analysis demonstrated 7.6% and 22.9% positivity for HE4 and SLPI, respectively. Most of the stained cells were mucous type, even though SLPI has also shown positivity in some intermediate and epidermoid cells. A significant correlation was found between SLPI expression and tumor grade, with lower expression in intermediate grades. The correlation between SLPI and HE4 was positive and significant. Conclusions: Although HE4 staining was not prominent, SLPI showed consistent staining in mucoepidermoid carcinomas and should be further investigated to elucidate its role in tumorigenesis.

The aim of this study was to evaluate the macroscopic and microscopic characteristics through polarized light microscopy, scanning electron microscopy and the mineral content of circumpulpal dentin of irradiated (IT) and nonirradiated teeth (NIT), with deep caries that reached the root canal. A total of 25 IT were analyzed macroscopically, and radiographed. Five NIT were used as controls. Two 100-μm cuts for evaluation in a scanning electron microscope and polarized light microscopy were performed on each tooth using precision cutter and sanding. Demographic characteristics and clinical data were collected. The results did not demonstrate distinct morphology of the IT compared with NIT. Mineral content values by weight percentage of calcium (Ca) and phosphate (P) were also similar, corresponding to 66.65% and 33.21% in the IT and 66.60% and 33.29% in the NIT. The Ca/P ratio did not show statistical differences between groups being respectively 2.74 and 2.72, in the IT and NIT (P > .05). Radiotherapy does not change morphologic and mineral content of circumpulpal dentin in IT.

Radiation-related caries (RRC) are rampant caries, which affect up to 25% of patients who undergo head and neck radiotherapy (HNRT). They are characterized by: (1) diffuse brown colorations of the enamel or dentin smooth surfaces; (2) generalized cervical caries; and (3) a tendency to rapidly progress to tooth crown amputation. Herein, we present 2 original cases of patients with RRC with an indolent clinical appearance in the so-called “occult caries” or “hidden caries” pattern, which were demonstrated by means of digital panoramic radiography and cone beam computed tomography. RRC represent advanced fronts of demineralization with the involvement of deep dentin and pulp chamber. In conclusion, advanced RRC may develop under unsuspicious clinical patterns, often leading to late diagnosis and a high potential for tooth destruction; such findings emphasize the importance of systematic clinical and radiographic examination of teeth in populations of patients who are post-HNRT.

Objective This study aimed to provide information regarding the performance of whole slide imaging (WSI) and to validate its use in oral diseases diagnosis, using the intraobserver variability as the primary form of analysis. Study Design Seventy hematoxylin and eosin (H&E)-stained glass slides of oral biopsies were scanned using the Aperio Digital Pathology System at a magnification of 20 x. Two experienced oral pathologists blindly analyzed all H&E-stained sections with a conventional light microscope (CLM) and, after a 3-month washout, with WSI. Clinical information was provided along with the cases in both analyses. Results The intraobserver agreement between CLM and WSI was 97% (κ = 0.9) for both pathologists. The majority of preferred diagnoses were achieved by CLM. Both pathologists had the same discordances in different cases. Challenging cases, and cases with insufficient quantity of tissue for analyses, were considered the main reasons for disagreement rather than the diagnostic methods. Median time taken to make a diagnosis was higher only in CLM for 1 pathologist. Time outliers occurred in discordant cases and in other difficult cases. Conclusions We provide original evidence for the high-performance of WSI for diagnostic purposes in clinical practice, routine pathology, and primary diagnosis in the field of oral pathology.

Plunging ranula (PR) is a mucus extravasation pseudocyst arising from the sublingual glands that forms following mucus escape that herniates through the mylohyoid muscle along the fascial planes into the cervical, submandibular, or submental space. They are rare in children, and surgical management is the most common performed therapy. We report a case of an 11-year-old female patient who sought dental treatment after a 3-year history of swelling in the right sublingual gland and the floor of the mouth, which was asymptomatic. The patient's medical history was unremarkable. Computed tomography image showed a well-defined ovoid lesion with hypoattenuation in the right sublingual gland measuring 4.5 × 4 cm. The initial diagnosis was PR, which was later confirmed by anatomopathologic analysis. Surgical excision of the right sublingual gland was performed intraorally under general anesthesia, followed by floor of the mouth marsupialization. The patient is currently being followed-up with no signs of local recurrence.

Objectives To evaluate the prognostic value of the brain-derived neurotrophic factor (BDNF), its tropomyosin receptor kinase B (TrkB), and 2 downstream targets of TrkB activation in salivary gland carcinomas (SGCs). Study Design Immunohistochemistry was preformed in 128 cases of SGC using antibodies against BDNF, phospho-TrkB, phospho-Akt, and phospho-S6. The slides were scanned and analyzed using the Aperio Scanscope CS Slide Scanner. Results BDNF, pTrkB, and pS6 were more expressed in adenoid cystic carcinoma (ACC) compared to mucoepidermoid carcinoma. In ACC, BDNF expression was associated with the presence of perineural invasion. Carcinoma ex-pleomorphic adenoma (CaExAP), the tumor with the worst prognosis in this study, also demonstrated an elevated expression of BDNF. However, BDNF/TrkB pathway immunoexpression was not associated with clinical outcomes. A direct correlation was observed between BDNF, pTrkB, pAkt, and pS6 expression. The colocalization of BDNF and pTrkB suggest an autocrine mechanism of this pathway in these malignancies. Conclusions Our results indicate that the BDNF/TrkB pathway is more expressed in some histologic types of SGC and might be associated with aggressive behaviors. Yet, these markers had no prognostic value in the present study.

Objectives To evaluate the association between the brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) pathway with disease-specific survival, cell senescence, and "stemness" profile in oral squamous cell carcinoma (OSCC). Study Design Specimens from 87 primary OSCC were arranged into tissue microarray (TMA) blocks. Immunohistochemical analysis for BDNF, TrkB, P-AKT, P-S6, BM1, and p16 were performed. The slides were scanned into high-resolution images using the Aperio Scanscope CS Slide Scanner and evaluated using software for digital analysis. Statistical analysis was performed using the SPSS software. Receiver operating curves were constructed to establish the cut-off values. Results All OSCC cases analyzed were positive for BDNF, TrkB, P-AKT, and pS6. Patients with high BDNF and high P-Akt expression presented, respectively, a 2.83-fold and 2.19-fold significantly higher chance of dying during the follow-up period. An increase in TrkB expression was directly correlated with increased cell senescence measured through p16. The stemness profile, accessed by BM1 expression, was inversely correlated with P-Akt and directly correlated with pS6. Conclusions The increased availability of BDNF influences OSCC prognosis presumably by activating downstream targets such as Akt. Moreover, this pathway seems to have an influence in cell senescence and "stemness" profile. FIPE/HCPA:160437.

Histone modification, such as histone 3 lysine 9 acetylation (H3K9ac), is a major posttranslational epigenetic mechanism related to physiologic process of repairing, replication, and gene expression. Changes in H3K9ac immunoexpression have been recently reported in some human pathologies, for example in oral squamous cell carcinoma, but it has not yet been described in ameloblastoma. Objectives: To report H3K9ac immunoexpression in ameloblastoma, correlating it with dental follicles. Study Design: Ten dental follicles and 38 ameloblastoma cases with 3-µm sections in silanized slides underwent immunohistochemical reactions for H3K9ac antibody (C5B11 – Cell Signaling) in order to determine the immunoexpression profile, mean positivity and staining intensity. All samples were digitalized into high-resolution images using the Aperio Scanscope CS Slide Scanner and evaluated using software for digital analysis. Results: The respective mean values of positivity and intensities (weak, medium and strong) were 71.79%, 17.93%, 38.60%, and 15.26% for dental follicles, whereas 67.84%, 18.69%, 34.08%, and 15.07% for ameloblastoma. Conclusions: Although other human pathologies show H3K9ac immunoexpression changes in relation with normal tissues, the ameloblastoma development and progression may be not correlated with epigenetic changes involving histone 3 acetylation.

Leiomyomas are benign smooth muscle tumors that are uncommon in the oral cavity. The purpose of this study was to present the clinicopathologic features of a series of 8 cases of oral leiomyomas from 2 Brazilian and 1 Argentinian oral pathology service. The patients’ age at diagnosis varied from 28 to 67 years, and similar frequency in male and female patients was observed (1:1). The most commonly involved sites were lip and palate. The tumors manifested as slow-growing, asymptomatic, solitary swelling. Microscopic analysis revealed similar pattern in all cases with bundles or fascicles of spindle-shaped cells. The most common histologic subtype was angioleiomyoma. Immunohistochemical evaluation revealed positivity for smooth muscle markers. All patients underwent excision of the tumor, and no recurrence was observed. Although diagnosis is usually done on histologic analysis, immunohistochemistry is a useful tool to differentiate oral leiomyomas from other spindle cell lesions. Support: FAPEMIG.

Although controversial, the World Health Organization has recently categorized ameloblastic fibrodentinoma (AFD) as part of the spectrum of odontomas, pointing out that it may be a “developing odontoma.” The aim of this presentation is to report the case of a 9-year-old girl with a painless swelling in the posterior right mandible. Intraoral examination revealed a firm and slightly tender swelling on palpation. Panoramic radiograph showed a massive well-defined radiolucency affecting the mandibular body and ascending ramus presenting the so-called "soap bubble pattern" and root resorption. The diagnosis of AFD was provided by incisional biopsy. Primary treatment was performed by an intraoral approach and conservative surgical excision. After 9 months of treatment and follow-up, a discreet radiolucency with sclerotic borders was detected near the condylar neck and managed by another conservative surgery via retromandibular approach. No recurrence was noticed after a 3 years of follow-up.

Osteosarcoma is the most frequent primary malignant bone tumor, but osteosarcomas of the jaws are uncommon and account for only 2% to 10% of all cases diagnosed. The aim of this study is to present 3 new cases of osteosarcoma affecting the gnathic bones. The mandible was affected in 2 cases, whereas the maxilla was involved in 1. Age ranged from 10 to 25 years, and all patients were female. An asymptomatic expansive swelling was the chief complaint in all cases. Microscopically, a diffuse proliferation of pleomorphic cells with presence of osteoid material and variable number of atypical mitotic features were observed. Ki67 staining showed a proliferative index of approximately 15%, and positivity for D2-40 and CDK4 were also observed. All patients are currently under oncological treatment. Support: FAPEMIG.

Emerging evidence indicates that bromodomains comprise a conserved class of epigenome readers involved in cancer development and inflammation. Bromodomains are associated with epigenetic modifications of gene transcription through interactions with lysine residues of histone tails. Particularly, the bromodomain and extra-terminal domain (BET) family member BRD4 has been found to be involved in the control over oncogenes, including c-MYC, and in the maintenance of downstream inflammatory processes. The objective of this study was to evaluate the effect of pharmacologically displacing BRD4 in mucoepidermoid carcinoma (MEC) cells. We assessed the presence of BRD4 levels in a panel of human MEC tissue samples in conjunction with histological grading and clinical information. In vitro studies were carried out using human MEC-derived cell lines. The BET inhibitor iBET762 was administered to MEC cells to assess the impact of disrupted BRD4 signaling on colony forming capacities and cell cycle status. The activation of cellular senescence induced by iBET762 was determined by immunohistochemical staining for p16ink4. Flow cytometry was used to identify populations of cancer stem cells in MEC-derived cell lines. We found that primary human MECs and MEC-derived cell lines are endowed with high BRD4 expression levels compared to those in normal salivary glands. We also found that, by displacing BRD4 from chromatin using the BET inhibitor iBET762, MEC cells lose their colony forming capacities and undergo G1 cell cycle arrest and senescence. Finally, we found that targeted displacement of BRD4 from chromatin results in depletion of cancer stem cells from the overall MEC cell populations. Our findings indicate that bromodomain-mediated gene regulation constitutes an epigenetic mechanism that is deregulated in MEC cells and that the use of BET inhibitors may serve as a feasible therapeutic strategy to manage MECs.

Background Diffuse large B-cell lymphoma, NOS (DLBCL NOS) is the commonest extranodal non-Hodgkin lymphoma diagnosed in the oral and maxillofacial region. However, few studies are currently available and its prognostic determinants remain undefined. Purpose To analyse the available data on oral DLBCL NOS and to describe its clinicopathological features, identifying potential prognostic factors. Methods An electronic systematic search was performed using multiple databases with a specific search strategy in April 2018. All reports describing DLBCL NOS involving the oral cavity and jaw bones with sufficient clinicopathological information were assessed. Results Sixty-three publications were included in the study, comprising 122 cases. Oral DLBCL NOS was found predominantly in elderly males (61.5%), and most often presented as an asymptomatic swelling of the gingiva. Patients commonly were HIV-negative (36.1%), with few reports describing EBV-positive cases (four cases/3.3%). Only eight cases presented B symptoms and most cases were classified as stage I or II (48.4%). CHOP therapy was the main treatment option (24.5%) and the overall 5-year survival rate achieved 83%. Males and advanced Ann Arbor stage patients presented significantly lower survival rates in the univariate analysis, but no significance was found in the multivariate model. Conclusion Oral DLBCL NOS is an aggressive malignancy, but with a high survival rate.

The presence of a translocation involving MYB and NFIB genes have been described in adenoid cystic carcinoma (AdCC) from different anatomical regions. However, the exact frequency of this genetic event and its prognostic impact for patient survival remain obscure. The aim of this study was to carry out a systematic review to address the prevalence and the prognostic potential of t(6;9)(MYB-NFIB) in head and neck AdCC. Quantitative analysis was done to determine the prevalence of the translocation. A total of 1,107 articles were initially retrieved with 36 remaining for data extraction. The prevalence of t(6;9)(MYB-NFIB) varied significantly (16%-100%), especially due to methodological heterogeneity among studies. A total of 11 studies attempted to determine the prognostic importance of the translocation, but no study found any significant association with survival rates; only three studies observed a significant association with age, sex, tumour location and the presence of recurrences and metastases. The prevalence of t(6;9)(MYB-NFIB) in head and neck AdCC varies according to the laboratorial methods used, and the best evidence available demonstrates that t(6;9)(MYB-NFIB) does not seem to be a prognostic determinant.

Whole slide imaging (WSI) systems are being increasingly used in educational and professional settings, highlighting the value of digital microscopy and favouring its acceptance for use in primary diagnosis. There has been a reluctance to introduce diagnostic applications due to a lack of validation and regulation of these devices. This study aims to provide information regarding the performance of WSI and to validate it for use in the diagnosis of oral diseases, using the intraobserver variability as the primary form of analysis. Seventy (n = 70) H&E-stained glass slides of oral biopsies were scanned using the Aperio Digital Pathology System at a magnification of × 20. Two experienced oral pathologists blindly analysed all H&E-stained sections with a conventional light microscope (CLM) and, after 3-month washout, with WSI. Clinical information was provided along with the cases in both analyses. The intraobserver agreement between CLM and WSI was 97% (κ = 0.9) for both pathologists. The majority of preferred diagnoses were by CLM. Both pathologists had the same discordances in different cases. Challenging cases and cases with insufficient quantity of tissue for analyses were considered the main reasons for disagreement rather than the diagnostic methods. Median time taken to make a diagnosis was higher only in CLM for one pathologist. Time outliers occurred in discordant cases and in other difficult cases. This study provides evidence of a high performance of WSI for diagnostic purposes in clinical practice, routine pathology and primary diagnosis in the field of oral pathology.

Non-Hodgkin lymphomas are a group of disorders involving malignant monoclonal proliferation of lymphoid cells, which appear at extranodal sites in approximately 40% of the cases, particularly in the gastrointestinal tract. Intraosseous lymphomas of the head and neck region are extremely rare and can mimic other diseases such as periodontitis or periapical pathologies. This report presents an additional case of intraosseous lymphoma that was previously misdiagnosed as periapical disease. In addition, a literature review was made based on PubMed, and all cases of periapical lymphoma were analyzed. After the diagnosis of lymphoma, the current patient was treated with 6 cycles of chemotherapy and showed satisfactory outcome. The literature review displayed 29 cases of lymphoma affecting the periapical region, and in 51.7% of them endodontic treatment was performed previously to the diagnosis of lymphoma. Although lymphoma is uncommon in the oral cavity, some symptoms can assist the dentist to suspect malignant conditions, mainly in cases presenting numb chin syndrome.

Objective The aim of this study was to analyze the expression pattern of proteins in the HGF/c-MET/PI3K signaling pathway in salivary gland tumors (SGTs) and to correlate the findings with the proliferative index and clinical parameters. Study Design We assembled tissue microarrays (TMAs) of 108 cases of SGTs, including 69 cases of pleomorphic adenoma (PA), 24 cases of adenoid cystic carcinoma (AdCC), and 15 cases of mucoepidermoid carcinoma (MEC). An immunohistochemical analysis of hepatocyte growth factor (HGF), MET phosphorylation (p-MET), protein kinase B (AKT) phosphorylation (p-AKT), and Ki-67 proteins was performed. Results Benign and malignant SGTs presented similar scores of HGF-positive cells (P = .36), whereas, malignant SGTs exhibited higher levels of p-MET (P = .001) and p-AKT (P = .001) than benign SGTs. No correlation of HGF, p-MET, or p-AKT expression was observed with clinical parameters. PA had a lower proliferative index than either AdCC (P = .001) or MEC (P = .001). Conclusions The salivary gland carcinomas exhibited increased activation of the HGF pathway, as evidenced by the phosphorylation of the MET receptor, and increased activation of the PI3K pathway, as indicated by p-AKT. These data suggest that the HGF/c-MET/PI3K signaling pathway is active in SGTs, especially in malignant neoplasms.

To determine the effects of radiotherapy on salivary BPIFA expression and to investigate the role of BPIFA in the development of known radiotherapy side effects.Unstimulated whole-mouth saliva was collected from 45 cancer patients (1 week before treatment, during the treatment, and 1 week after completion of radiotherapy) and from 20 controls. BPIFA1 and BPIFA2 expression was detected by western blotting and analyzed along with clinicopathologic data and side effects from the radiotherapy.A facial radiation field was associated with lower salivary flow during and after radiotherapy and correlated with side effects, mainly mucositis. Salivary BPIFA1 expression levels were similar between the control group and the patient group before treatment. On the other hand, BPIFA2 levels were higher in the patient group before treatment compared with the control group. BPIFA concentration was modified by radiotherapy as BPIFA1 levels increased (P = .0081) and BPIFA2 decreased (P .0001). Higher levels of BPIFA1 were associated with the presence of mucositis (P = .0363) and its severity (P = .0500).The present study found that levels of BPIFA1 and glycosylated forms of BPIFA2 are affected by radiotherapy, suggesting that these proteins may play a role in the oral microenvironment in irradiated patients with head and neck cancer.

Hodgkin lymphoma (HL) is a malignant lymphoproliferative disease that originates from alterations in germinal center B cells. HL generally affects cervical and supraclavicular nodes, and the most common clinical presentation is adenopathy. It can be symptomatic and detected by the patient or asymptomatic and identified during a physical examination. This article reports the case of a 17-year-old girl who was diagnosed with HL during dental treatment, highlighting the importance of a complete physical examination in dental practice.

Made available in DSpace on 2018-12-11T16:51:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-02-16 Paracoccidioidomycosis is a common deep fungus infection in South America, particularly in Brazil. It is acquired through inhalation and primary involvement of lungs. Subsequently, dissemination may occur and oral mucosa is frequently affected and actually, in most of the cases the diagnosis is established because of the oral lesions. Thus, the role of the dentist is fundamental to correct diagnosis. However, the involvement of intestine is rarely reported. The current case describes a 36-year-old man who presented abdominal pain and intestinal constipation, being suspected and then confirmed as paracoccidioidomycosis after already be diagnosed with this disease by a dentist through oral manifestations. Oral Diagnosis Department Semiology and Oral Pathology Areas Piracicaba Dental School University of Campinas (UNICAMP), Av. Limeira, 901 Department of Tropical Diseases School of Medicine São Paulo State University (UNESP), Av. Prof. Montenegro, s/n Faculdade de Odontologia de Piracicaba Departamento de Diagnóstico Oral – Semiologia, Av. Limeira 901 Department of Tropical Diseases School of Medicine São Paulo State University (UNESP), Av. Prof. Montenegro, s/n

Oral squamous cell carcinomas (OSCC) can arise from potentially malignant disorders, such as leukoplakia. The immune system plays an important role recognizing tumour precursor cells. However, due to immunoediting mechanisms cancer cells are able to escape immune system surveillance. Objective Evaluate the profile of dendritic (Langerhans and plasmacytoid) and T cells in OSCC and oral epithelial dysplasia (OED) and correlate these findings with clinical data. Materials and Methods Fifty cases of OSCC and 48 of OED were immunostained for CD1a and CD83 dendritic Langerhans cells (DLC), plasmacytoid dendritic cells (pDC) CD303 and CD8 followed by quantitative analysis. Results Analysis revealed a significant decrease in the number of mature CD83 DLC in OSCC compared with OED. CD303 positivity was significantly increased in the OSCC group when compared to OED. CD8 positive lymphocytes were significantly decreased in OSCC compared with OED lesions. No statistical correlation was found with clinical data. Conclusion The number of mature dendritic cells (DC) was decreased in OSCC compared with OED lesions suggesting that either these cells might have migrated to lymph nodes to present the tumour antigens and activate the immune system or cytokines secreted by the tumour microenvironment are inhibiting the adequate maturation of DLC. The numbers of pDC was significantly increased in the OSCC group compared with the OED group. This suggests they may play an important role in the defence against tumours although it is not clear whether this is promoting or inhibiting malignant progression. This article is protected by copyright. All rights reserved.

Objective Glandular odontogenic cyst (GOC) is an uncommon developmental cyst. Its molecular pathogenesis is unclear, and deep sequencing may help identify causative low-frequency variants in tumors. We investigated in GOC mutations in 50 genes commonly altered in human cancers. Study Design Targeted next-generation sequencing was used to interrogate a panel of approximately 2800 mutations in GOC. Results Six missense single nucleotide variations (SNVs) were reported. Three SNVs ( TP53 rs1042522, KDR rs1870377, and KIT rs3822214) are listed as “common single-nucleotide polymorphisms” at the UCSC Genome Browser. The other SNVs ( PIK3CA p.Glu689Lys, PIK3CA p.Ala708Thr, and TP53 p.Leu289Phe) are predicted to have deleterious or damaging effects on proteins, but they showed very low frequency in our samples and could not be further validated by orthogonal methods. Conclusions No pathogenic SNV was detected in this cohort of GOCs. Further studies with larger gene panels or whole exome sequencing are needed to find the genetic basis of GOC.

Objective Although radiation-related caries (RRC) are a well-known toxicity of head and neck radiotherapy, a clinical classification system for RRC has not yet been clinically validated. Therefore, the aim of this study was to assess whether the International Caries Detection and Assessment System (ICDAS) and the Post-Radiation Dental Index (PRDI) were viable methods for the assessment of RRC. Study Design Clinicopathologic data and intraoral digital photographs of 60 patients (833 teeth) affected by RRC were assessed and classified according to the ICDAS and PRDI criteria. Results A total of 814 (97.7%) teeth presented RRC lesions ranging from early stage to complete tooth destruction. Mean scores for the whole sample were 5 for ICDAS and 3 for PRDI, indicating that RRC were diagnosed predominately in late stages. ICDAS and PRDI criteria underestimate the clinical expressivity of RRC by not including the whole qualitative clinical spectrum of RRC, such as enamel cracks, delamination, dental crown amputation, surface color alterations, and atypical lesions topography (incisal/cuspal caries). Conclusions ICDAS and PRDI may not be considered viable for the assessment of RRC. The development of a specific clinical classification system is urgently needed to help clinicians recognize the peculiar patterns of RRC, particularly in incipient cases.

Objective The aim of this study was to compare the expression of proliferative markers and apoptosis-associated proteins in the oral mucosa adjacent to bone sequestrum associated with osteonecrosis (ON) of the jaws and florid osseous dysplasia (OD). Study Design Oral mucosal samples derived from surgical procedures performed for treatment of ON and OD (10 cases each) were retrieved. Histologic analysis was done on hematoxylin and eosin–stained slides; immunohistochemical reactions against epidermal growth factor (EGF), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), Bcl-2 protein, interleukin-6 (IL-6), and Ki-67 antigen were performed with the immunoperoxidase technique. Results The epithelium was hyperplastic in 60% and 22% of ON and OD samples, respectively. Cytoplasmic EGF and KGF expression; Bcl-2, VEGF, and IL-6 expressions; and the mean epithelial proliferative index were not statistically different between the 2 groups. Membranous EGF expression was more evident in samples showing hyperplastic epithelium. Conclusions Exposure to bisphosphonates did not alter the expression of KGF, EGF, VEGF, Bcl-2, IL-6, and the epithelial proliferating index in comparison with inflamed oral mucosa not exposed to bisphosphonates.

Background Hyaline ring granuloma (HRG) of the oral cavity is an uncommon disorder considered to be a foreign-body reaction resulting from implantation of food vegetable particles. Microscopically, it is characterized by the presence of structures of hyaline rings in an inflamed fibrous tissue background, which contains multinucleated giant cells. Material and methods We present the case of a 4-year-old boy diagnosed with a mandible osseous HRG, which showed clinical and tomographic aspects suggestive of an aggressive bone tumor. Results The patient underwent surgical exploration and histopathologic analysis showed fragments composed predominantly of widespread dense connective tissue with an acute and chronic inflammatory infiltrate containing multinucleated giant cells and scattered areas of eosinophilic material associated with hyaline rings, strongly suggestive of vegetable particles. The eosinophilic material was positive for periodic acid-Schiff (PAS) and resistant to diastase digestion. These features led to diagnosis of osseous HRG. Scanning electron microscopy (SEM) analysis was performed for illustrative purposes and the multiple structures resembling vegetable particles were characterized in more detail. Conclusions Although rare, this case highlights the importance of the clinician's awareness regarding the existence of an osseous counterpart of HRG. Key words:Agenesis of the corpus callosum, child, hyaline ring granuloma, intraosseous, mandible, pulse granuloma.

Objectives: Several medical and dental schools have described their experience in the transition from conventional to digital microscopy in the teaching of general pathology and histology disciplines; however, this transitional process has scarcely been reported in the teaching of oral pathology. Therefore, the objective of the current study is to report the transition from conventional glass slide to virtual microscopy in oral pathology teaching, a unique experience in Latin America. Study Design: An Aperio ScanScope® scanner was used to digitalize histological slides used in practical lectures of oral pathology. The challenges and benefits observed by the group of Professors from the Piracicaba Dental School (Brazil) are described and a questionnaire to evaluate the students’ compliance to this new methodology was applied. Results: An improvement in the classes was described by the Professors who mainly dealt with questions related to pathological changes instead of technical problems; also, a higher interaction with the students was described. The simplicity of the software used and the high quality of the virtual slides, requiring a smaller time to identify microscopic structures, were considered important for a better teaching process. Conclusions: Virtual microscopy used to teach oral pathology represents a useful educational methodology, with an excellent compliance of the dental students. Key words:Digital microscopy, virtual microscopy, dental education, virtual slides, oral pathology.

The purpose of this study was to quantify and compare the density of dendritic cells (DCs) in cervical lymph nodes (LNs) and palatine tonsils (PTs) of AIDS and non-AIDS patients.Factor XIIIa, CD1a and CD83 antibodies were used to identify migratory DCs by immunohistochemistry in LNs and PTs of 32 AIDS patients and 21 HIV-negative control patients. Quantification was performed by the positive pixel count analytical method. AIDS patients presented a lower density of factor XIIIa(+) cells (P0.001), CD1a(+) cells (P0.05) and CD83(+) cells (P0.001) in cervical LNs and PTs compared to the non-AIDS control group.Overall depletion of DCs in lymphoid tissues of AIDS patients may be predictive of the immune system's loss of disease control.