CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions.

BACKGROUND: Odontogenic lesions constitute a heterogeneous group of lesions. CLIC4 protein regulates different cellular processes, including epithelial-mesenchymal transition and fibroblast-myofibroblast transdifferentiation. This study analyzed CLIC4, E-cadherin, Vimentin, and α-SMA immunoexpression in epithelial odontogenic lesions that exhibit different biological behavior. METHODS: It analyzed the immunoexpression of CLIC4, E-cadherin, and Vimentin in the epithelial cells, as well as CLIC4 and α-SMA in the mesenchymal cells, of ameloblastoma (AM) (n = 16), odontogenic keratocyst (OKC) (n = 20), and adenomatoid odontogenic tumor (AOT) (n = 8). Immunoexpressions were categorized as score 0 (0% positive cells), 1 (< 25%), 2 (≥ 25% - < 50%), 3 (≥ 50% - < 75%), or 4 (≥ 75%). RESULTS: Cytoplasmic CLIC4 immunoexpression was higher in AM and AOT (p < 0.001) epithelial cells. Nuclear-cytoplasmic CLIC4 was higher in OKC's epithelial lining (p < 0.001). Membrane (p = 0.012) and membrane-cytoplasmic (p < 0.001) E-cadherin immunoexpression were higher in OKC, while cytoplasmic E-cadherin expression was higher in AM and AOT (p < 0.001). Vimentin immunoexpression was higher in AM and AOT (p < 0.001). Stromal CLIC4 was higher in AM and OKC (p = 0.008). Similarly, α-SMA immunoexpression was higher in AM and OKC (p = 0.037). Correlations in these proteins' immunoexpression were observed in AM and OKC (p < 0.05). CONCLUSIONS: CLIC4 seems to regulate the epithelial-mesenchymal transition, modifying E-cadherin and Vimentin expression. In mesenchymal cells, CLIC4 may play a role in fibroblast-myofibroblast transdifferentiation. CLIC4 may be associated with epithelial odontogenic lesions with aggressive biological behavior.

Hamartomas, choristomas, and teratomas of the oral cavity: A 49-years cross-sectional study in an oral diagnostic service.

BACKGROUND: To investigate the incidence and demographic profile of hamartomatous, choristomatous, and teratoid lesions in a Brazilian population over a 49 years-period. METHODS: A retrospective cross-sectional study was performed, and data regarding demographic and clinical aspects were obtained from the medical records of a [removed for blind peer review] referral center (1970-2019). The collected data were submitted to descriptive analysis and Pearson's chi-square, Fisher's exact, and Kruskal-Wallis tests (p ≤ 0.05). RESULTS: In a total of 16,412 medical records analyzed, 300 (1.83 %) were hamartomatous, 2 (0.01 %) choristomatous, and 1 (0.01 %) teratoid lesions. Hamartomas were most diagnosed in females and adults. Statistical significance was observed between hamartoma and age group (p < 0.001). Odontoma was the most frequent hamartomatous lesion. In choristomatous and teratoid lesions, there was no occurrence in males. The jaws were the most affected anatomical site by hamartoma. Choristomas were observed on the mandible and tongue, while a teratoid lesion was seen on the floor of the mouth. CONCLUSIONS: Low occurrence of choristomatous and teratoid lesions over hamartomatous lesions and a heterogeneous occurrence profile regarding sex, age group, and anatomic site were observed. Hamartomas are relatively common and benign conditions that may cause damage and require special care during dental treatment. Thus, the dentist needs to be able to identify and treat them appropriately. Likewise, although choristomas and teratomas present no risk to patients and have a lower occurrence than hamartomas, they also require treatment.

The rhythms of histones in regeneration: The epigenetic modifications determined by clock genes.

The evolutionary establishment of an internal biological clock is a primordial event tightly associated with a 24-h period. Changes in the circadian rhythm can affect cellular functions, including proliferation, DNA repair and redox state. Even isolated organs, tissues and cells can maintain an autonomous circadian rhythm. These cell-autonomous molecular mechanisms are driven by intracellular clock genes, such as BMAL1. Little is known about the role of core clock genes and epigenetic modifications in the skin. Our focus was to identify BMAL1-driven epigenetic modifications associated with gene transcription by mapping the acetylation landscape of histones in epithelial cells responding to injury. We explored the role of BMAL1 in epidermal wound and tissue regeneration using a loss-of-function approach in vivo. We worked with BMAL1 knockout mice and a contraction-resistance wound healing protocol, determining the histone modifications using specific antibodies to detect the acetylation levels of histones H3 and H4. We found significant differences in the acetylation levels of histones in both homeostatic and injured skin with deregulated BMAL1. The intact skin displayed varied acetylation levels of histones H3 and H4, including hyperacetylation of H3 Lys 9 (H3K9). The most pronounced changes were observed at the repair site, with notable alterations in the acetylation pattern of histone H4. These findings reveal the importance of histone modifications in response to injury and indicate that modulation of BMAL1 and its associated epigenetic events could be therapeutically harnessed to improve skin regeneration.

BubR1 and cyclin B1 immunoexpression in pleomorphic adenoma and polymorphous adenocarcinoma of minor salivary glands.

The immunoexpression of BubR1 and cyclin B1 in pleomorphic adenoma (PA) and polymorphic adenocarcinoma (PAC) in minor salivary glands is poorly studied. Thus, a retrospective and observational study was performed to provide a better understanding of the role and immunopositivity patterns of these proteins in these lesions. Sixteen cases of PA and 16 cases of PAC were selected. Parenchyma cells were submitted to quantitative immunohistochemical analysis through the labeling index. Cytoplasmic immunoexpression of BubR1 was observed in neoplastic cells from all analyzed PA and PAC cases. All PA cases and 93.7% of PAC exhibited nuclear immunoexpression of BubR1. Higher cytoplasmic and nuclear immunoexpression of BubR1 was observed in PAC (p = 0.001 and p = 0.122, respectively). Cytoplasmic immunoexpression of cyclin B1 was observed in all cases of PA and PAC, with a higher labeling index in the latter (p < 0.001). There was a significant positive correlation between nuclear and cytoplasmic BubR1 immunoexpressions (p < 0.001) in PA and a significant negative correlation between BubR1 and cyclin B1 cytoplasmic immunoexpressions (p = 0.014) in PAC. The higher cytoplasmic and nuclear immunoexpression of BubR1 in PACs suggests the continuous maintenance of neoplastic cells in the cell cycle and migration. Higher immunoexpression of cyclin B1 supports this lesion's enhanced proliferative and migration ability.

Clinicopathologic analysis of oral dermoid and epidermoid cysts: a Brazilian multicenter study.

Dermoid cysts (DCs) and epidermoid cysts (ECs) are uncommon developmental cysts affecting the oral cavity. This study aims to evaluate patients with oral DCs and ECs and their demographic and clinicopathologic features. A retrospective descriptive cross-sectional study was performed. A total of 105,077 biopsy records of oral and maxillofacial lesions from seven Brazilian oral pathology centers were analyzed. All cases diagnosed as oral DCs and ECs were reviewed, and clinical, demographic, and histopathological data were collected. The series comprised 32 DCs (31.4%) and 70 ECs (68.6%). Most of the DCs occurred on the floor of the mouth (n = 14; 45.2%) of women (n = 17; 53.1%) with a mean age of 34.6 ± 21.6 years. All DCs were lined partially or entirely by stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were observed in the fibrous capsule . Most of the ECs affected the labial mucosa (n = 20; 31.7%) of men (n = 39; 56.5%) with a mean age of 48.0±19.8 years. Microscopically, most ECs (n = 68; 97.1%) were lined entirely by stratified squamous epithelium. Two cysts (2.9%) showed areas of respiratory metaplasia. Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were also observed in the fibrous capsule. Conservative surgical excision was the treatment of choice in all cases. Oral DCs and ECs are uncommon and often clinically misdiagnosed lesions. Clinicians should consider DCs and ECs in the differential diagnosis of soft tissue lesions in the oral cavity, mainly located on the floor of the mouth and labial mucosa.

Morphological analysis of cell cannibalism: An auxiliary tool in the prediction of central giant cell granuloma clinical behavior.

Central giant cell granuloma (CGCG) is a benign jaw lesion with variable clinical behavior. Cell cannibalism is a cellular process associated with aggressiveness and invasion in malignant neoplasms. Here, we morphologically investigated cell cannibalism as an auxiliary method to predict CGCG clinical behavior. Cell cannibalism was quantitatively evaluated in 19 cases of peripheral giant cell granuloma (PGCG), 38 cases of CGCG (non-aggressive and aggressive), and 19 cases of giant cell tumor of bone (GCT) stained with hematoxylin and eosin. T-test was performed to assess the differences between the variables analyzed (p ≤ 0.05). Cell cannibalism was identified in 21% of non-aggressive CGCGs and 68.4% of aggressive CGCGs. A significantly higher amount of cannibal multinucleated giant cells (CMGC) was observed in aggressive CGCG compared to PGCG and non-aggressive CGCG (p = 0.042; p = 0.044, respectively). There were no significant differences in the CMGC index between non-aggressive CGCG and PGCG (p = 0.858) and between aggressive CGCG and GCT (p = 0.069). CGGC cases that exhibited rapid growth and tooth displacement and/or root resorption had a higher amount of CMGC (p = 0.035; p = 0.041, respectively). Cell cannibalism can be identified in CGCG through routine anatomopathological examination. The quantification of CMGC can help to predict the clinical behavior of central giant cell granuloma.

Antimicrobial photodynamic therapy in the treatment of oral erythematous candidiasis: a controlled and randomized clinical trial.

OBJECTIVE: To analyze the clinical and microbiological efficacy of antimicrobial photodynamic therapy (aPDT) in patients with erythematous candidiasis (EC). METHODS: This study was a controlled and randomized clinical trial in patients diagnosed with EC, who were allocated into a control group (CG) and experimental group (EG) treated with nystatin oral suspension and aPDT with methylene blue 0.1%, respectively. A clinical index was used to classify the EC lesions from mild to severe and assess the treatment efficacy. Microbiological samples were collected before and after aPDT session and analyzed by counting colony-forming units (CFUs) of Candida and Staphylococcus sp. RESULTS: A total of 41 patients (CG (n = 18); EG (n = 23)) were analyzed in our research. Of these, 16 (94.1%) of the CG and 16 (84.2%) of the EG exhibited complete remission of the lesions. Regarding the degree of the lesion, it was observed that the severe lesions were more difficult to present remission, while all the mild and moderate lesions showed complete regression (p = 0.001). The microbiological analysis showed that Candida albicans and Staphylococcus sp. were the most prevalent microorganisms, and the aPDT group showed a decrease in CFUs of these microorganisms after the first aPDT session (p < 0.05). CONCLUSIONS: aPDT proved to be a clinically and microbiologically effective therapy for treating EC. TRIAL REGISTRATION: Registered at ClinicalTrials.gov; Set 12th, 2019; No. RBR-8w8599. CLINICAL RELEVANCE: aPDT is a promising alternative treatment since it presents satisfactory results and does not cause damage to oral tissues or develop resistance to the treatment.

The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma

Background: Oral squamous cell carcinoma (OSCC) has high morbidity and mortality rates while oral verrucous carcinoma (OVC), an uncommon variant of OSCC, exhibits a distinct biological behavior. CLIC4 protein plays a role in the cell cycle and apoptosis regulation and participates in the myofibroblasts transdifferentiation process, which are the main cells of the tumor stroma. This study analyzed the immunoexpression of CLIC4 and α-SMA in 20 OSCC cases and 15 OVC cases. Material and methods: A semiquantitative analysis of CLIC4 and α-SMA immunoexpression was performed in the parenchyma and stroma. Nuclear and cytoplasmic reactivity was analyzed separately for the CLIC4 immunostaining. The data were submitted to Pearson's chi-square and Spearman's correlation tests (p ≤ 0.05). Results: In the CLIC4 analysis, there was a significant difference in the immunoexpression of this protein between OSCC and OVC stroma (p < 0.001). It was observed a higher expression of α-SMA in the OSCC stroma. There was a positive and significant correlation between CLIC4 and α-SMA immunoexpression in the OVC stroma (r = 0,612; p = 0,015). Conclusions: The decrease or absence of nuclear CLIC4 immunoexpression in the neoplastic epithelial cells and the increase of its expression in the stroma may influence the difference in biological behavior between OSCC and OVC. (AU)

Solitary fibrous tumor: Two cases report with a focus on the differential diagnosis / Tumor Fibroso Solitário: Relato de dois casos com foco no diagnóstico diferencial

Solitary fibrous tumor (SFT) is a neoplasm of fibroblastic/myofibroblastic origin with intermediate biological behavior. We report here two cases of SFT affecting an unusual anatomical site in 58-year-old and 40-year-old female patients and discuss the differential diagnosis of this lesion. In case 01, the lesion showed the clinical appearance of an asymptomatic "blister" with normal color, rubbery consistency, measuring 0.3 cm, and affected the lower lip; while in case 02, a symptomatic red nodular lesion with a soft consistency and measuring 0.5 cm affected the floor of the mouth. Excisional biopsies were performed. Microscopically, two well-delimited benign neoplasms were observed, exhibiting the proliferation of ovoid to spindle-shaped mesenchymal cells, vascular spaces with staghorn arrangement, and the absence of mitosis figures. Immunohistochemistry was performed in case 01 to assist in the diagnosis. Weak and diffuse immunostaining was observed for α-SMA and intense and diffuse immunopositivity for Bcl-2 and CD34. Based on histopathological and immunohistochemical features, a diagnosis of SFT was rendered in both cases. The low occurrence and nonspecific clinical features of oral SFT may make its clinical diagnosis difficult. Also, morphological and immunohistochemical are essential for differential diagnosis with other mesenchymal neoplasms.(AU)

O tumor fibroso solitário (TFS) é uma neoplasia de origem fibroblástica/miofibroblastica com comportamento biológico intermediário. Nesse artigo relatamos dois casos de TFS afetando sítios anatômicos incomuns em pacientes do sexo feminino de 58 anos e 40 anos e discutir os seus diagnósticos. No caso 01 clinicamente a lesão apresentou um aspecto de "bolha" assintomática, coloração normal da mucosa, consistência borrachoide medindo 0,3 cm, em região de lábio inferior, enquanto que no caso 02, como uma lesão sintomática, vermelha, nodular com consistência mole e medindo 0,5 cm afetando o assoalho bucal. As biópsias excecionais foram realizadas. Microscopicamente, observamos duas lesões neoplásicas bem delimitadas exibindo uma proliferação de células mesenquimais variando de ovoides a fusiformes, vasos sanguíneos em formato de "chifre de veado", com ausência de figuras de mitoses. No caso 01 foi realizado análise imuno-histoquímica para auxiliar no diagnóstico. Foi observado uma marcação fraca e difusa de α-SMA e uma intensa e difusa imunopositividade para o Bcl-2 e CD34.Baseado nos achados histopatológicos e imuno-histoquímicos o diagnóstico de TFS foi estabelecido em ambos os casos. A baixa ocorrência e os achados clínicos inespecíficos do TFS oral podem dificultar o diagnóstico clínico. Além disso, as análises morfológicas e imuno-histoquimicas são essenciais para realização do diagnóstico diferencial com outras neoplasias mesenquimais.(AU)_

Effect of Atomic Layer Coating on the Stability of Solid Myoglobin Formulations.

The effects of atomic layer (ALC) coating on physical properties and storage stability were examined in solid powders containing myoglobin, a model protein. Powders containing myoglobin and mannitol (1:1 w/w) were prepared by lyophilization or spray drying and subjected to aluminum oxide or silicon oxide ALC coating. Uncoated samples of these powders as well as coated and uncoated samples of myoglobin as received served as controls. After preparation (t0), samples were analyzed for moisture content, reconstitution time, myoglobin secondary structure, crystallinity, and protein aggregate content. Samples were stored for 3 months (t3) under controlled conditions (53% RH, 40 °C) in both open and closed vials and then analyzed as above. At t3, the recovery of soluble native (i.e., monomeric) protein depended on formulation, coating type, and drying method and was up to 2-fold greater in coated samples than in uncoated controls. Promisingly, some samples with high recovery also showed low soluble aggregate content (<10%) at t3 and low total monomer loss; the latter was correlated to sample moisture content. Overall, the results demonstrate that ALC coatings can stabilize solid protein formulations during storage, providing benefits over uncoated controls.

Myiasis on the tongue of a patient hospitalized in a psychiatric ward: A case report with a focus on diagnosis and clinical management.

INTRODUCTION: Myiasis is a disease caused by the infestation of fly larvae in the skin, which complete part of their life cycle by feeding on host tissues. OBJECTIVE: To report a rare case of tongue myiasis in a patient admitted to a psychiatric ward, focusing on clinical management. CASE REPORT: A dependent care and mentally challenged 55 years old male patient was hospitalized in a psychiatric ward. After 42 days, during the intraoral examination, it was noted numerous larvae peeking from inside of a wound on the dorsum of the tongue. The clinical diagnosis of myiasis was rendered. For the treatment, manual removal was performed initially and ivermectin (15 mg), metamizole sodium (500 mg/ml), and chlorhexidine digluconate (0.12%) were prescribed. After one week, larvae were no longer observed, and the wound was completely healed. CONCLUSION: Myiasis occurrence is uncommon in the mouth, however, its correct diagnosis and treatment are necessary to avoid further damage to patients, especially those who are hospitalized.

Adverse Reactions Associated with Dermal Fillers in the Oral and Maxillofacial Region: A Venezuelan Experience.

BACKGROUND: Dermal facial fillers are increasingly popular. Published reports on the clinical and histopathologic characteristics related to adverse reactions to dermal fillers in the facial region have been relatively well documented. This study adds to the literature on adverse reactions to injected filler in the oral and maxillofacial region in a South American population. METHODS: A retrospective, descriptive cross-sectional study (2019-2020) was performed. The study population was a dermatology service in Venezuela. Clinical and histopathologic features of patients with adverse effects were documented. RESULTS: A total of 35 cases of adverse reactions associated with cosmetic filler procedures were diagnosed during the analyzed period; of these, six cases (17.1%) involved the oral and maxillofacial region. All cases occurred in women. The mean age at diagnosis was 59.3 years (58-73). In three cases, dermal fillers were used in different locations on the face, while three involved the lips. Five patients exhibited adverse reactions to lip filler. All six cases were histopathologically diagnosed as foreign body reactions to injected material. Four and two cases revealed microscopic features compatible with hyaluronic acid and polymethylmethacrylate, respectively. CONCLUSION: Reflecting the dramatic increase in cosmetic procedures with soft tissue fillers, this study contributed by reporting six cases of foreign body reaction involving the oral and maxillofacial region, confirmed with biopsy and histopathology.

Inflammatory Fibrous Hyperplasia Associated with Chondroid Metaplasia - Report and Morphological Analysis of Five Cases

Inflammatory fibrous hyperplasia (IFH) is a common reactive lesion in dental prostheses users that may be associated with chondroid metaplasia (CM). Metaplasia is an adaptive cellular process that may be caused by trauma. We reported here five cases of IFH associated with CM and analyzed morphologically the deposition of collagen in these lesions. Patients had a mean age of 58.8 years-old and were ill-fitting dental prostheses users. They presented nodular lesions located in the anterior maxilla. Microscopically, it was observed hyperplastic fibrous connective tissue with chronic inflammatory infiltrate and hyaline cartilage. No morphological differences were observed in collagen deposition under light microscopy, but quantitative analysis revealed a significantly higher collagen deposition at the connective tissue near CM (p = 0.015). IFH associated with CM affects ill-fitting dental prostheses users. The presence of CM is not significant to the lesion prognosis. However, its formation and the higher collagen deposition near it reinforces the IFH reactive origin.

La hiperplasia fibrosa inflamatoria (HFI) es una lesión reactiva común en los usuarios de prótesis dentales que puede estar asociada con la metaplasia cartilaginosa (MC). La metaplasia es un proceso celular adaptativo que puede ser causado por un trauma. El presente informe analizó cinco casos de HFI asociados a MC y se analizaron morfológicamente la deposición de colágeno en estas lesiones. Los pacientes tenían una edad media de 58,8 años y eran usuarios de prótesis dentales mal adaptadas. Se observaron lesiones nodulares localizadas en el la parte anterior del maxilar Microscópicamente se observó tejido conectivo fibroso hiperplásico con infiltrado inflamatorio crónico y cartílago hialino. No se observaron diferencias morfológicas en la deposición de colágeno bajo microscopía óptica, pero el análisis cuantitativo reveló una deposición de colágeno significativamente mayor en el tejido conectivo cerca de MC (p = 0,015). La HFI asociada con la MC afecta a los usuarios de prótesis dentales mal adaptadas. La presencia de MC no es significativa para el pronóstico de la lesión. Sin embargo, su formación y la mayor deposición de colágeno cerca de MC refuerza el origen reactivo de HFI.

Clinicopathologic analysis of oral dermoid and epidermoid cysts: a Brazilian multicenter study

Abstract Dermoid cysts (DCs) and epidermoid cysts (ECs) are uncommon developmental cysts affecting the oral cavity. This study aims to evaluate patients with oral DCs and ECs and their demographic and clinicopathologic features. A retrospective descriptive cross-sectional study was performed. A total of 105,077 biopsy records of oral and maxillofacial lesions from seven Brazilian oral pathology centers were analyzed. All cases diagnosed as oral DCs and ECs were reviewed, and clinical, demographic, and histopathological data were collected. The series comprised 32 DCs (31.4%) and 70 ECs (68.6%). Most of the DCs occurred on the floor of the mouth (n = 14; 45.2%) of women (n = 17; 53.1%) with a mean age of 34.6 ± 21.6 years. All DCs were lined partially or entirely by stratified squamous epithelium (100%). Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were observed in the fibrous capsule . Most of the ECs affected the labial mucosa (n = 20; 31.7%) of men (n = 39; 56.5%) with a mean age of 48.0±19.8 years. Microscopically, most ECs (n = 68; 97.1%) were lined entirely by stratified squamous epithelium. Two cysts (2.9%) showed areas of respiratory metaplasia. Chronic inflammatory cells, melanin pigmentation, multinucleated giant cell reaction, and cholesterol clefts were also observed in the fibrous capsule. Conservative surgical excision was the treatment of choice in all cases. Oral DCs and ECs are uncommon and often clinically misdiagnosed lesions. Clinicians should consider DCs and ECs in the differential diagnosis of soft tissue lesions in the oral cavity, mainly located on the floor of the mouth and labial mucosa.

Biological marker for the establishment of periodontal disease: cross-sectional study in the gingival tissue.

BACKGROUND: The present study investigated the expression of COX-2, EMMPRIN, HIF-1α, and GLUT-1 in the gingival tissue to verify if there is a correlation between the immunoexpression of these proteins and the changes caused by the inflamed infiltrate present in the gingival tissues. MATERIAL AND METHODS: A morphological analysis of epithelial changes (hyperplasia, exocytosis, spongiosis, and hydropic degeneration) was performed, as well as a semiquantitative analysis of the immunoexpression of COX-2, EMMPRIN, HIF-1α, and GLUT-1 in the epithelium and connective tissue of 60 specimens of gingival tissue. RESULTS: Epithelial immunoexpression to COX-2 was observed in three cases, while EMMPRIN, HIF-1α, and GLUT-1 were strongly expressed in the basal layer of the epithelium and gradually decreased until the upper layers. In the connective tissue, COX-2 immunoexpression showed a statistically significant association (p < 0.001) with the gingival inflammatory infiltrate. In connective tissue, EMMPRIN and HIF-1α exhibited intense immunopositivity, while GLUT-1 was negative in most cases. CONCLUSION: COX-2 expression may constitute a biological marker of gingival tissues since its epithelial immunoexpression may indicate a greater propensity for the establishment of periodontal disease.

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

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

Intraosseous rhabdomyosarcoma of the maxilla with TFCP2 fusion: A rare aggressive subtype with predilection for the gnathic bones.

Rhabdomyosarcomas (RMS) are malignant tumors with skeletal muscle differentiation extremely rare in intraosseous sites. We reported a rare case of an aggressive intraosseous RMS found in the maxilla of a 17-year-old female patient with five months of evolution. Computed tomography revealed a large osteolytic lesion extending from tooth 21 to 27, causing buccal and lingual cortical plate perforation. Microscopically, the lesion showed a proliferation of spindle-shaped cells with elongated nuclei and eosinophilic cytoplasm, arranged in an interlaced fascicle pattern. The nuclei ranged from vesicular with distinct nucleoli to hyperchromatic. A focal component of plump to epithelioid cells with a moderate amount of eosinophilic cytoplasm was seen at the periphery of the tumor. The immunohistochemical analysis revealed positivity for desmin, MyoD1, and myogenin (scattered cells). S-100, SOX10, HMB45, ß-catenin, and CD34 were negative. Ki-67 was positive in 30% of tumor cells. Fluorescence in situ hybridization (FISH) analysis showed the presence of a FUS-TFCP2 fusion. The diagnosis was intraosseous RMS with TFCP2 fusion. Surgical excision followed by chemo- and radiotherapy was carried out; however, the patient died of disease nine months after the treatment. Because of the rarity and non-specific signs and symptoms, the clinical diagnosis of intraosseous RMS is difficult and often overlooked. Therefore, careful histopathological evaluation, supported by immunohistochemical and molecular analysis, is essential to correct diagnosis. Early surgical excision with tumor-free margins and prolonged follow-up are strongly recommended.

DNA damage through oxidative stress is an important event in oral leukoplakia.

OBJECTIVE: To evaluate the oxidative DNA damage, through 8-hydroxy-2'-deoxyguanosine (8-OHdG), and its repair by base excision repair pathway [Redox factor-1 (Ref-1); X-ray Repair Cross Complementing-1 (XRCC-1)] in different epithelial dysplasia degrees in oral leukoplakia. DESIGN: Forty-four cases of oral leukoplakia and 10 normal oral mucosa were quantified for 8-OHdG, Ref-1, and XRCC-1 through immunohistochemistry. RESULTS: Cytoplasmic 8-OHdG and nuclear XRCC-1 were significantly associated with multiple synchronous lesions (p = 0.048; p = 0.034, respectively). Nuclear Ref-1 was significantly associated with oral leukoplakia on the tongue (p = 0.027). A significantly gradual cytoplasmic 8-OHdG expression increase was observed between normal oral mucosa and epithelial dysplasia (p < 0.05). Nuclear Ref-1 expression was significantly lower (p < 0.01) in non-dysplasia/mild dysplasia, while its cytoplasmic expression was significantly higher in non-dysplasia/mild dysplasia compared to moderate/severe dysplasia and normal oral mucosa (p = 0.03; p < 0.0001, respectively). A significantly higher cytoplasmic XRCC-1 expression was observed in non-dysplasia/mild and moderate/severe dysplasia compared to normal oral mucosa (p < 0.0001; p < 0.0001, respectively). All epithelial dysplasia degrees showed a correlation between nuclear and cytoplasmic expression of these proteins (p < 0.05). CONCLUSIONS: 8-OHdG formation may not play a role in the development of multiple synchronous oral leukoplakias. However, it is related to the severity of the epithelial dysplasia. The subcellular level of Ref-1 implies different roles according to the degree of epithelial dysplasia. Cytoplasmic XRCC-1 expression indicates a possible failure of the DNA repair mechanism and occurs in early morphological stages of epithelial dysplasia.

Biomarkers involved in the proliferation of the odontogenic keratocyst, glandular odontogenic cyst and botryoid odontogenic cyst.

INTRODUCTION: Odontogenic cysts are a heterogeneous group of lesions with varied clinical behavior. OBJECTIVE: To analyze the expression of the epidermal growth factor receptor (EGFR), Cyclin D1, and transcription factor SOX2 in the odontogenic epithelium evaluating the cell cycle control and cystic expansion. METHODS: This was a cross-sectional study including 40 cases, 20 odontogenic keratocysts (OKC), 10 botryoid odontogenic cysts (BOC), and 10 glandular odontogenic cysts (GOC). RESULTS: All cases of OKC, BOC, and GOC were positive for EGFR in all layers of the cyst lining. The highest expression of nuclear Cyclin D1 was observed in the suprabasal layer of OKCs and in the basal and suprabasal layers of GOC and BOC (p < 0.001). In addition, SOX2 was only expressed in the suprabasal layer of OKCs. CONCLUSION: The high expression of EGFR in the cyst membrane suggests that EGF stimulates epithelial proliferation in BOCs, and the high expression of SOX2 in OKCs may be related to the presence of stem cells in the lesion. Cyclin D1 is related to cell cycle disruption in G1-S contributing to stimulates epithelial proliferation of OKCs and GOCs and BOCs.

Angina bullosa haemorrhagica: A 14-year multi-institutional retrospective study from Brazil and literature review

Background: Angina bullosa haemorrhagica (ABH) is characterized by the recurrent appearance of blood blisters on the oral mucosa, mainly in adults' soft palate. In general, the blisters rupture spontaneously, lacking the necessity for biopsy. We report the clinical features of 23 ABH cases, emphasizing the clinical behavior and the management of these conditions. Material and Methods: A retrospective descriptive cross-sectional study was performed. A total of 12,727 clinical records of oral and maxillofacial lesions from four dental services in Brazil were analyzed. Clinical data were collected from the clinical records and evaluated. Results: The series comprised 12 males (52.2%) and 11 females (47.8%), with a mean age of 56.8 ± 14.6 years (ranging: 24-82 years) and a 1.1:1 male-to-female ratio. Most of the lesions affected the soft palate (n = 15, 65.2%). Clinically, the lesions presented mainly as an asymptomatic (n = 17, 73.9%) blood-filled blister that ruptured after a few minutes or hours, leaving an erosion. The masticatory trauma was the most frequent triggering event. No patient had coagulation disorders. A biopsy was performed in only four cases (17.4%). Treatment was symptomatic with a favorable outcome. Conclusions: ABH is still poorly documented in the literature, and its etiology remains uncertain. ABH mainly affects the soft palate of elderly adults and has a favorable evolution in a few days. The therapeutic approach is often focused only on the relief of symptoms. However, it can share some clinical features with more serious diseases. Therefore, clinicians must recognize these lesions to avoid misdiagnosis.(AU)