Micobacteriose parotidea na AIDS em fase avançada : analise histologica, imunohistoquimica e caracterização por LCR e PCR de especies de Mycobacterium

Orientador : Pablo Agustin VargasTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaDoutorad

Tissue microarray construction for salivary gland tumors study

Objective: To describe and discuss the design, building and usefulness of tissue microarray (TMA) blocks for the study of salivary gland tumors (SGTs). Study Design: Two hundred thirty-eight formalin-fixed, paraffin-embedded SGTs were arranged in blocks of TMA using a manual tissue arrayer. Three representative cores of 1.0, 2.0 or 3.0mm were taken from each original block and their characteristics were analyzed and described. Results: It was created 12 TMA blocks that presented highly representative neoplastic cylinders. However, those neoplasias rich in cystic spaces such as mucoepidermoid carcinoma and Warthin tumor presented more difficulties to be sampled, as the neoplastic tissue available was scarce. Tissue damage and loss during TMA construction was estimated as 3.7%. Conclusion: Representative areas of SGTs, with relatively small loss of tissue, can be obtained with the construction of TMA blocks for molecular studies. However, tumors rich in cystic spaces present more difficulties to be adequately sampled

Oncocytic metaplasia in inflammatory fibrous hyperplasia : histopathological and immunohistochemical analysis

Oncocytic metaplasia (OM) is not a well-known feature in inflammatory fibrous hyperplasia (IFH) lesions, although it may be common, as proposed in our previous study about this lesion. In the present paper, we assessed the histopathological and immunohistochemical features of 18 cases of IFH containing OM areas. All the samples were examined on haematoxylin and eosin stained sections and cytokeratins (AE1/AE3, 34ßE12, CK5, CK7, CK8, CK13, CK14 and CK19), CD15, CD20, CD68, CD45Ro, and LCA primary antibodies were used. The vast majority of IFH occurred in women (n=14) and the most common site of presentation was the buccal vestibule. Oncocytic and salivary duct cells showed uniform immunoreactivity for AE1/AE3, CK7, CK8 and CK19. CD45Ro+ T-lymphocytes were the most common inflammatory cells surrounding the OM areas followed by CD20+ B-lymphocytes. These findings suggest that oncocytic cells present in IFH might develop from salivary duct epithelium, and T-lymphocytes might play an important role in its etiopathogenesis

Childhood Cancer patients and dentist registers from a hospital: a 15-year study / Pacientes com câncer na infância e registos dentários de um hospital: um estudo de 15 anos

Os efeitos colaterais da terapia antineoplásica na mucosa bucal podem afetar a qualidade de vida dos pacientes, principalmente em crianças e adolescentes. Este estudo transversal avaliou a frequência de pacientes de até 19 anos atendidos no Hospital de Câncer de Cascavel - UOPECCAN (Hospital do Câncer de Cascavel) entre 2000-2014, apenas aqueles atendidos pelo dentista da instituição. Neoplasia, tratamento e as manifestações orais foram determinados. Os registros médicos enfocavam sexo, idade, classificação do câncer e tratamento. Exames odontológicos e anos de assistência também foram cobrados. De 100 pacientes que atenderam aos critérios, os resultados foram: masculino (57%), feminino (43%), <1 ano de idade (5%), 1-4 (42%), 5-9 (25%), 10 -14 (23%) e 15-19 (5%). Leucemia (48%), rabdomiossarcoma (10%) e neuroblastoma (7%) foram os mais prevalentes, assim como a quimioterapia (55%). Oito e seis pessoas desenvolveram manifestações orais: mucosite (34%), gengivite (9%), cárie (33%), gengivoestomatite herpética (11%), herpes labial (7%), candidíase (9%) e outro estágio de dentição mista relacionados (esfoliação de dente decíduo e edema - 8%). O setor odontológico aumentou o número de atendimentos ao longo dos anos. O dentista atendeu metade dos pacientes. A maioria deles eram crianças menores de 4 anos. Leucemia e quimioterapia foram mais prevalentes e 86% da amostra desenvolveu manifestação oral. A maioria deles eram crianças menores de 4 anos. Leucemia e quimioterapia foram mais prevalentes e 86% da amostra desenvolveu manifestação oral. A maioria deles eram crianças menores de 4 anos. Leucemia e quimioterapia foram mais prevalentes e 86% da amostra desenvolveu manifestação oral

Histopathological grading systems analysis of oral squamous cell carcinomas of young patients

Background: To analyze the clinicopathological profile of young patients (≤ 40 years) with oral SCC and correlate with a control group (≥ 50 years) by means of histopathological grading systems. Material and Methods: 14 young patients and 14 control patients were selected with similar clinical stage and tumor location. Demographic and clinical data were obtained from patient records and histological sections were evaluated according to four histopathological grading systems. Associations between categories of demographic and clinical data were performed through Chi-square test and Exact Fisher test. The survival analyzes were performed according to the Kaplan-Meier method. Results: The comparison between groups showed a greater association of treatment modalities in younger patients ( p =0.022), they had a higher incidence of local recurrence and regional metastasis ( p =0.018) and lower disease- free survival in 5 years ( p =0.069). There was no difference in 5-year overall survival among the studied groups. There was no difference in histological grading between studied groups according to the four used systems. Conclusions: This study showed that, despite tumors had similar histological grade and more therapeutic modalities were used in the young group, tumors in young patients had a higher incidence of recurrence/metastasis, showing tendency to a more aggressive behavior

Immunoexpression of HOXB7 and HOXB9 in salivary gland tumours

BACKGROUND : Salivary gland carcinomas are uncommon neoplasms and the identification of new prognostic indicators could improve their management. HOXB7 and HOXB9 are members of the class I homeobox-containing genes important for normal embryogenesis and that are dysregulated in several human neoplasms. This study investigated HOXB7 and HOXB9 expression in salivary gland tumourigenesis, they correlation with neoplastic proliferative and angiogenic features, and their importance as prognostic markers. METHODS : A hundred and fifty salivary gland tumours were organized in tissue microarray and expression of CD105, Ki67, HOXB7 and HOXB9 were determined through immunohistochemistry. Reactions were quantified and correlated with clinicopathological parameters. RESULTS : In normal glands HOXB7 was found in basal cells, whereas HOXB9 was seen in serous acinar and scattered ductal cells. Malignancies exhibited an increased vascular density, proliferative index, HOXB7 and HOXB9 expression when compared with pleomorphic adenoma and Warthin tumour. Significant correlation was found between HOXB7 and CD105 (p = 0.004) in adenoid cystic carcinomas, and HOXB7 higher expression significantly correlated with the presence of paresthesia (p = 0.02). No marker exhibited a significant association with survival rates (p > 0.05). CONCLUSION : HOXB7 and HOXB9 were expressed in normal salivary gland and were present in benign and malignant tumours derived from these structures, and HOXB7 significantly correlated with neoangiogenesis in AdCC. These findings suggest that both proteins might play a role in salivary gland tumourigenesis, but they were not significant prognostic determinants in this sample.Grants from the São Paulo State Research Foundation (Brazil), processes numbers 2009/53839-2, 2012/07519-9 and 2012/10781-7, and from the Brazilian Coordination of Higher Education (CAPES/PDSE 2892/13-8).http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1600-07142017-10-31hb2016Oral Pathology and Oral Biolog

Aderencia de Candida albicans, Candida tropicalis e Candida krusei na superficie da lingua de ratos normais e xerostomicos

Orientador: Oslei Paes de AlmeidaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: A adesão de microrganismos às superfícies mucosas do hospedeiro é um pré-requisito importante para a colonização e infecção microbiana. Dentre as espécies de Candida, C.albicans é considerada a mais patogênica e com maior capacidade de aderência às células epiteliais, seguida de C.tropicalis. C.krusei é uma espécie pouco patogênica e com baixa capacidade de aderência, causadora de doença principalmente em indivíduos imunocomprometidos. Muitos dos estudos sobre aderência de Candida são realizados in vitro, havendo poucos estudos in vivo. Este trabalho teve como objetivo principal estudar a aderência de C. albicans, C. tropicalis e C. krusei no dorso da língua de ratos. Foram utilizados 270 ratos divididos em 3 grupos de 90 animais, cada grupo recebendo inóculo de uma das três espécies e sendo composto de 45 animais normais e 45 xerostômicos. A recuperação de Candida a partir da saliva foi realizada nos períodos de 5, 15, 30, 60 minutos e 4, 12, 24, 48 e 72 horas após a inoculação. Logo em seguida os animais foram sacrificados e a língua foi retirada para contagem de leveduras aderidas. A quantificação foi feita a partir do volume de saliva coletado e o número de unidades formadoras de colônias (UFC) recuperadas. A contagem foi realizada em 20 campos da região das papilas verdadeiras da língua dos ratos. Os resultados mostraram que a aderência de Candida ocorre principalmente na queratina mole das papilas verdadeiras, sobre a placa bacteriana presente nesta área. A xerostomia aumentou a quantidade de placa bacteriana nas papilas linguais e facilitou a aderência das três espécies de Candida, aumentando também o número de leveduras recuperadas. C.krusei, C.tropicalis e C.albicans apresentaram valores semelhantes tanto na recuperação como na contagemAbstract: The adhesion of microorganisms to host mucosal surfaces is an important prerequisite for successful microbial colonization and infection. Candida albicans is the most pathogenic of Candida species and has a high ability of adherence to epithelial cells, followed by C.tropicalis. C.krusei is the least pathogenic species, causing candidosis only in immunocompromised host. Candidal adherence is studied mainly in vitro, and there are few in vivo studies. The aim of this study was to determine in vivo C. albicans, C. tropicalis, and C.krusei adhesion to rat tongue. 270 rats were divided in 3 groups of 90 animais, each group having 45 normal and 45 xerostomic rats. Each group received oral innoculation of Candida albicans, Candida tropicalis or Candida krusei suspension and yeasts were recovered from saliva after 5, 15, 30, and 60min, and in 4, 12, 24, 48, and 72h. After saliva recovery the rats were sacrificed and their tongues removed for histological evaluation and yeasts quantification, considering the volume of saliva recovered and the number of colony-forming units (CFU). Histologically, 20 highpower fields of true papillae of the rat tongue were counted and the results showed that the Candida adherence occurred mainly over the bacterial plaque in the "soft keratin" of the papillae. Xerostomia increased the amount of bacterial plaque in the papillae and facilitated the adherence of ali three species, increasing also the number of recovered yeasts. C.krusei, C.tropicalis and C.albicans showed similar values in salivary recovery and histological quantificationMestradoPatologiaMestre em Estomatopatologi

Epstein-barr Virus (ebv)-associated posttransplant lymphoproliferative disorder appearing as mandibular gingival ulcers

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.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 cells1214e80e8

Brazilian Multiethnic Association Study of Genetic Variant Interactions among <i>FOS, CASP8</i>, <i>MMP2</i> and <i>CRISPLD2</i> in the Risk of Nonsyndromic Cleft Lip with or without Cleft Palate

Associations of CRISPLD2 (cysteine-rich secretory protein LCCL domain containing 2) and genes belonging to its activation pathway, including FOS (Fos proto-oncogene), CASP8 (caspase 8) and MMP2 (matrix metalloproteinase 2), with nonsyndromic orofacial cleft risk, have been reported, but the results are yet unclear. The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) in FOS, CASP8 and MMP2 and to determine their SNP-SNP interactions with CRISPLD2 variants in the risk of nonsyndromic cleft lip with or without cleft palate (NSCL±P) in the Brazilian population. The SNPs rs1046117 (FOS), rs3769825 (CASP8) and rs243836 (MMP2) were genotyped using TaqMan allelic discrimination assays in a case-control sample containing 801 NSCL±P patients (233 nonsyndromic cleft lip only (NSCLO) and 568 nonsyndromic cleft lip and palate (NSCLP)) and 881 healthy controls via logistic regression analysis adjusted for the effects of sex and genomic ancestry proportions with a multiple comparison p value set at ≤0.01. SNP-SNP interactions with rs1546124, rs8061351, rs2326398 and rs4783099 in CRISPLD2 were performed with the model-based multifactor dimensionality reduction test complemented with a 1000 permutation-based strategy. Although the association between FOS rs1046117 and risk of NSCL±P reached only nominal p values, NSCLO risk was significantly higher in carriers of the FOS rs1046117 C allele (OR: 1.28, 95% CI: 1.10–1.64, p = 0.004), TC heterozygous genotype (OR: 1.59, 95% CI: 1.16–2.18, p = 0.003), and in the dominant model (OR: 1.50, 95% CI: 1.10–2.02, p = 0.007). Individually, no significant associations between cleft risk and the SNPs in CASP8 and MMP2 were observed. SNP-SNP interactions involving CRISPLD2 variants and rs1046117 (FOS), rs3769825 (CASP8) and rs243836 (MMP2) yielded several significant p values, mostly driven by FOS rs1046117 and CASP8 rs3769825 in NSCL±P, FOS rs1046117 in NSCLO and CRISPLD2 rs8061351 in NSCLP. Our study is the first in the Brazilian population to reveal the association of FOS rs1046117 with NSCLO risk, and to support that CRISPLD2, CASP8, FOS and MMP2 interactions may be related to the pathogenesis of this common craniofacial malformation

MutSa expression predicts a lower disease-free survival in malignant salivary gland tumors:an immunohistochemical study

Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutS? (hMSH2-hMSH6) and MutS? (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutS?high and MutS?high based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutS?high expression had lower disease-free survival compared to MutS?low cases. A 10.26-fold increased risk of presenting local recurrence was observed. Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutS? overexpression predicts a poor clinical outcome in malignant SGT