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1.
Appl Immunohistochem Mol Morphol ; 29(10): 781-790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320560

RESUMO

A proper antibody panel selection is one of the most important factors to reach an adequate diagnosis in challenging cases. This retrospective study was designed to determine the contribution of immunohistochemistry (IHC) in the primary diagnosis of oral diseases in one of the main services of oral pathology in the State of São Paulo, Brazil, and to identify the most common antibodies used, and recommend diagnostic algorithms based on our experience with challenging lesions. A total of 1698 IHC stains were performed in 401 cases from a total of 28,804 cases received from public dental clinics and private dental practitioners within a period of 13 years, representing a frequency of 1.4% of IHC solicitations. Among these, 112 (28%) were mandatory to reach a final diagnosis and 255 (63.6%) were confirmative. In 34 (8.4%) cases, it was not possible to reach a conclusive/final diagnosis, even with IHC. Regarding the nature of the lesions, 210 (52.3%) were benign, 163 (40.6%) were malignant tumors, 13 (3.2%) were reactive, 10 (2.5%) were premalignant, and 5 (1.2%) were lesions of uncertain malignancy. Small amount of tissue of some incisional biopsies, overlapping features of spindle cell lesions (epithelial, neural, melanocytic, smooth muscle, endothelial, and fibroblastic/myofibroblastic cell differentiation), and overlapping features of salivary gland lesions were the most frequent challenges in which IHC stains were requested. Spindle cell lesions were the most frequent (22%) among all cases that required IHC to reach a final diagnosis. The implementation of IHC for routine practice requires a wide range of markers, proper antibody selection, and knowledge to interpret the subjectivity of staining. The inherent limitation of incisional biopsies was pointed as a reason to inconclusive diagnosis, despite a wide range of antibodies that our laboratory displays.


Assuntos
Imuno-Histoquímica , Neoplasias Bucais , Patologia Bucal , Lesões Pré-Cancerosas , Brasil , Feminino , Humanos , Masculino , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos
2.
Oral Dis ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33901323

RESUMO

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.

3.
Head Neck Pathol ; 15(4): 1119-1126, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33843033

RESUMO

Fatty acid synthase (FASN) expression is closely related to cancer progression, in particular, tumor aggressiveness and poor prognosis. This study aimed to analyse the expression of FASN in carcinomas of the salivary glands and correlate it with Ki-67 expression. We analysed by immunohistochemistry the expression of FASN and Ki-67 on tissue sections from 7 cases of adenocarcinoma, not otherwise specified (AdNOS), 6 cases of polymorphous adenocarcinoma (PAC), 16 cases of acinic cell carcinoma (AcCC), 19 cases of adenoid cystic carcinoma (AdCC), 15 cases of epithelial-myoepithelial carcinoma (EMC); 10 cases of secretory carcinoma (SC), 13 cases of mucoepidermoid carcinoma (MEC), 10 cases of salivary duct carcinoma (SDC) and 7 cases of myoepithelial carcinoma (MC). These carcinomas were classified into aggressive and indolent regarding their biological behaviour. Additionally, MEC and AdCC were also classified according to the histological grade. High expression of FASN was found in SDC (100%), SC (100%), AcCC (68.7%) and AdNOS (57.2%). No association was found between FASN and Ki-67 expression. Aggressive carcinomas showed a higher rate of Ki-67 proliferation (p < 0.001) and greater expression of FASN when compared to indolent carcinomas (p < 0.05). With regards to carcinomas categorized as indolent, FASN expression was much higher in the lesions that presented cell differentiation (SC and AcCC). Also, FASN expression was significantly higher in high-grade AdCC and MEC when compared to low-grade tumors (p < 0.05). We concluded that FASN expression was correlated to tumor aggressiveness and cellular differentiation in salivary gland carcinomas.


Assuntos
Carcinoma/metabolismo , Carcinoma/patologia , Ácido Graxo Sintases/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo
4.
Virchows Arch ; 479(3): 585-595, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33713188

RESUMO

The role of digital pathology in remote reporting has seen an increase during the COVID-19 pandemic. Recently, recommendations had been made regarding the urgent need of reorganizing head and neck cancer diagnostic services to provide a safe work environment for the staff. A total of 162 glass slides from 109 patients over a period of 5 weeks were included in this validation and were assessed by all pathologists in both analyses (digital and conventional) to allow intraobserver comparison. The intraobserver agreement between the digital method (DM) and conventional method (CM) was considered almost perfect (κ ranged from 0.85 to 0.98, with 95% CI, ranging from 0.81 to 1). The most significant and frequent disagreements within trainees encompassed epithelial dysplasia grading and differentiation among severe dysplasia (carcinoma in situ) and oral squamous cell carcinoma. The most frequent pitfall from DM was lag in screen mirroring. The lack of details of inflammatory cells and the need for a higher magnification to assess dysplasia were pointed in one case each. The COVID-19 crisis has accelerated and consolidated the use of online meeting tools, which would be a valuable resource even in the post-pandemic scenario. Adaptation in laboratory workflow, the advent of digital pathology and remote reporting can mitigate the impact of similar future disruptions to the oral and maxillofacial pathology laboratory workflow avoiding delays in diagnosis and report, to facilitate timely management of head and neck cancer patients. Graphical abstract.


Assuntos
COVID-19 , Carcinoma in Situ/patologia , Tecnologia Digital , Interpretação de Imagem Assistida por Computador , Neoplasias Maxilares/patologia , Microscopia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Telepatologia , Biópsia , Diagnóstico Diferencial , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fluxo de Trabalho
5.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 131(4): 452-462.e4, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33610538

RESUMO

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.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Brasil , Feminino , Herpesvirus Humano 4 , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética
6.
Head Neck Pathol ; 15(3): 757-768, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33394374

RESUMO

Neuroblastoma is the most common extracranial solid cancer of infancy, occurring mainly in the adrenal gland, with high metastatic potential. However, involvement of the head and neck region is rare. Here, we present two cases of metastatic neuroblastoma of childhood, in which a mandibular swelling was the first sign of disseminated disease. Case 1 describes a 4-year-old boy with a 2-week history of painful swelling in the left mandibular region, body soreness and weakness. Panoramic radiography and computed tomography showed a destructive lesion in the left mandibular ramus. Case 2 describes a 3-year-old boy with a 1-month history of swelling in the right mandibular area. Panoramic radiograph and cone-beam computed tomography showed a destructive lesion in the right body and ramus of the mandible, displacing tooth germs, with the destruction of vestibular and lingual bone cortices. In both cases, microscopic analyses revealed a diffuse proliferation of small, round, and blue cells with hyperchromatic nuclei and scant cytoplasm. While Case 1 was more undifferentiated, Case 2 presented eosinophilic areas suggestive of neuropil. A large immunohistochemical panel was performed, showing expression of neural markers such as CD56, neuron-specific enolase (in Case 2), chromogranin, and synaptophysin. Both lesions presented a high proliferation index (Ki67 > 70% and 80%, respectively). Positron emission tomography-computed tomography revealed ipsilateral adrenal primary lesions in both cases, with multiple bone metastatic lesions. Besides the mandible, multiple sites of the axial and appendicular skeleton were affected. Treatment consisted of induction chemotherapy, adrenalectomy, consolidation chemoradiotherapy, and post-consolidation therapy.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias Mandibulares/secundário , Neuroblastoma/secundário , Pré-Escolar , Humanos , Masculino
7.
Front Oral Health ; 2: 751162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35048062

RESUMO

Objectives: DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1, DNMT3A, DNMT3B, and H3K9ac in the dental follicle (DF), ameloblastoma (AME), and ameloblastic carcinoma (AC), correlating these expressions with the recurrence and aggressive behavior in ameloblastoma. Study Design: Immunohistochemical reactions were performed in 10 human DFs, 38 ameloblastomas, and 6 AC samples. Another 59 ameloblastomas assembled in a tissue microarray were used to compare the immunoexpression with the clinical, radiographic, and histopathological characteristics and the presence of BRAFv600e mutation. Each slide was digitized as a high-resolution image and quantified by Aperio ScanScope Nuclear V9 software. All statistical analyzes were performed using GraphPad Prism statistical software. Results: DNMT3B expression was higher in ameloblastomas than in the DFs, while the AC overexpressed all proteins. The ameloblastomas with BRAFv600e mutation, vestibular/lingual, or vestibular/palatine bone cortical disruption and maxilla involvement showed DNMT1 overexpression, while recurrent cases had high DNMT3B levels. Conclusions: DNA methylation and histone modification might play a role in the development, clinical aggressiveness, and recurrence rates of ameloblastoma, such as the progression to AC. Further investigation about gene methylations in ameloblastomas is needed to better understand its relationship with aggressiveness and recurrence.

8.
Cytopathology ; 31(6): 555-563, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32681691

RESUMO

INTRODUCTION: The aim of this study was to perform an audit of oral and maxillofacial specimens submitted for cytological diagnosis to verify the importance of this complementary examination. METHODS: A retrospective analysis of our institutional cytopathology database was performed over an 18-year period. Clinical information and cytological data were collected. Associations between independent variables and outcomes were assessed using the Pearson χ2 test or Fisher's test, with a 5% significance level. When available, the histological diagnosis was compared with cytological diagnosis to identify the percentage of agreement and the specificity, sensitivity and accuracy of cytology in identifying malignant neoplasms. RESULTS: A total of 1082 cases were identified, which included 65 different cytological diagnoses. Exfoliative cytology (EC) was performed in 312 cases (29.1%) and fine needle aspiration cytology (FNAC) in 770 cases (70.9%). EC was mainly employed to diagnose oral infectious diseases (P < 0.001) and FNAC to diagnose neoplasms, cystic, reactive and miscellaneous lesions (P < 0.001). Cell-block was performed in 555 FNAC cases (51.3%). Panoptic, Papanicolaou and haematoxylin-eosin staining were performed in FNAC and periodic acid-Schiff in EC (P < 0.001). In 211 cases (19.5%), the histological diagnosis was available and the percentage agreement with the cytological diagnosis was 41.2%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy to identify malignant neoplasms were 84.6%, 100%, 100%, 77.8% and 90.0%, respectively. CONCLUSIONS: EC was mainly performed for diagnosis of infectious diseases and FNAC for diagnosis of salivary gland tumours, odontogenic lesions, reactive lesions and cervical metastasis.


Assuntos
Citodiagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Patologia Bucal/normas , Neoplasias das Glândulas Salivares/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/normas , Criança , Pré-Escolar , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Boca/diagnóstico por imagem , Boca/patologia , Neoplasias das Glândulas Salivares/patologia , Manejo de Espécimes , Adulto Jovem
9.
Front Physiol ; 11: 549, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581840

RESUMO

The aim of this study was to analyze the relationship between alveolar bone deformation and ß-catenin expression levels in response to the mechanical load changed by dental extraction in adult rats. Twenty-four male rats (Rattus norvegicus albinus), Wistar linage, at 2 months of age, were used. The right upper incisor tooth was extracted, and euthanasia occurred in periods 5 (n = 6), 7 (n = 6), and 14 (n = 6) days after Day 0. In the control group (n = 6), the dentition was maintained. The euthanasia occurred within 14 days after day 0. After euthanasia, the rats of all groups had their left jaw with tooth removed and separated in the middle. The pieces were undergone routine histological processing and then the immunohistochemical marking were performed to label expression of the primary ß-catenin antibody, which was evaluated by qualitative and quantitative analysis. One head by each group (control and experimental) was submitted to computerized microtomography. After the three-dimensional reconstruction of the skull of the rat in each group, the computational simulation for finite elements analysis were performed to simulate a bite in the incisors. In finite element analysis, the strain patterns were evaluated after the application of bite force. The results were analyzed considering the areas in which changes in the amount of deformations were detected. The action of the bite force in the experimental condition, resulted in a uniform distribution of the amount of deformations, in addition to lower amount of deformation areas, differentiating from the control group. Comparing with the control group, the levels of ß-catenin signaled in the lingual bone of the middle third of the alveolar bone were raised in the periods of 5 and 14 days. The increased ß-catenin positive staining intensity was concentrated on osteocytes and gaps of osteocytes. The findings of the present study were in accordance with our hypothesis that the condition of dental extraction can cause the expression of ß-catenin and alter the regimes of bone deformation.

10.
Oral Dis ; 26(3): 711-715, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31917876

RESUMO

We present the frequency of cases of isolated odontogenic keratocysts submitted to microscopic examination at 10 Brazilian referral centres in Oral and Maxillofacial Pathology. In a retrospective (1953-2017) analysis, data on clinicoradiographic features and treatment of these lesions were collected and analysed descriptively. Among the 258,867 cases retrieved, 2,497 (0.96%) were isolated odontogenic keratocysts. In summary, an overview of individuals affected with isolated odontogenic keratocysts is reported herein. This lesion showed predilection for the posterior mandible of young adult men.


Assuntos
Cistos Odontogênicos/patologia , Tumores Odontogênicos/patologia , Brasil , Humanos , Masculino , Mandíbula/patologia , Estudos Retrospectivos , Adulto Jovem
11.
Pathol Res Pract ; 214(6): 907-913, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29559247

RESUMO

Ameloblastoma is a locally aggressive neoplasm with a poorly understood pathogenesis. Therefore, the aim of this study is to investigate whether COX-2 expression is associated with ameloblastoma microvascular density (MVD) and with tumor aggressiveness. Sixty-three cases of primary ameloblastomas arranged in tissue microarray were submitted to immunohistochemistry against cyclooxigenase-2 (COX-2) and CD34. Clinicopathological parameters regarding sex, age, tumour size, tumour duration, tumour location, treatment, recurrences, radiographic features, vestibular/lingual and basal cortical disruption and follow-up data were obtained from patients' medical records and correlated with the proteins expression. The results on BRAF-V600E expression were obtained from our previous study and correlated with COX-2 and CD34 expressions. Log-rank univariate analysis and multivariate Cox regression model were done to investigate the prognostic potential of the molecular markers. Twenty-eight cases (44.4%) exhibited cytoplasmic positivity for COX-2, predominantly in the columnar peripheral cells, with a mean MVD of 2.2 vessels/mm2. COX-2 was significantly associated with recurrences (p < 0.001) and BRAF-V600E expression (p < 0.001), whereas lower MVD was associated with the use of conservative therapy (p = 0.004). Using univariate and multivariate analyses, COX-2 was significantly associated with a lower 5-year disease-free survival (DFS) rate (p < 0.001 and p = 0.012, respectively), but not with a higher MVD (p = 0.68). In conclusion, COX-2 expression in ameloblastomas is not associated with MVD, but it is significantly associated with recurrences and with a lower DFS.


Assuntos
Ameloblastoma/patologia , Biomarcadores Tumorais/análise , Ciclo-Oxigenase 1/biossíntese , Neoplasias Maxilomandibulares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ameloblastoma/mortalidade , Criança , Ciclo-Oxigenase 1/análise , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Maxilomandibulares/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
12.
J Oral Pathol Med ; 47(4): 417-424, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29453876

RESUMO

BACKGROUND: Fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) have been investigated in different human neoplasms and were shown to play important roles in the pathogenesis of these diseases; however, very few are known regarding their prognostic importance in the context of ameloblastoma. Therefore, the aim of this study was to investigate whether the expression of FGF2 and FGFR1 is associated with ameloblastoma clinical behavior. METHODS: Fifty-eight cases of ameloblastoma arranged in tissue microarray were submitted to immunohistochemistry against FGF2 and FGFR1. Clinicopathological parameters regarding sex, age, tumor size, duration and location, treatment, recurrences, radiographic features, cortical disruptions, and follow-up data were obtained from patients' medical records and correlated with the molecules expression. Univariate and multivariate Cox regression analyses were used to investigate the prognostic potential of the biomarkers. RESULTS: Forty-four cases (75.9%) exhibited cytoplasmic positivity for FGF2 in central and peripheral epithelial cells, 46 of 58 (79.3%) showed FGFR1 cytoplasmic positivity predominantly in the columnar peripheral cells, and 43 cases (74.1%) were positive for both. Expression of FGF2 and FGF2 + FGFR1 was associated with tumor recurrences (P = .05). However, univariate and multivariate analyses did not demonstrate a significant influence of FGF2, FGFR1, or FGF2 + FGFR1 in the 5-year disease-free survival (DFS) rate (P = .27, P = .33, and P = .25, respectively). CONCLUSION: Cytoplasmic expression of FGF2 and FGF2 + FGFR1 is associated with ameloblastoma recurrence, but FGF2 and FGFR1 are not determinants of a lower DFS.


Assuntos
Ameloblastoma/metabolismo , Fator 2 de Crescimento de Fibroblastos/biossíntese , Neoplasias Maxilomandibulares/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/biossíntese , Adulto , Ameloblastoma/terapia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Maxilomandibulares/terapia , Masculino , Prognóstico , Estudos Retrospectivos
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