The evolving molecular characterisation, histological criteria and nomenclature of adenoid ameloblastoma as a World Health Organisation tumour type.

Adenoid ameloblastoma (AA) was recently recognised as a separate tumour type in the most recent World Health Organisation (WHO) classification of head and neck tumours. This decision has been considered controversial by several groups, who have described AA as a subtype of ameloblastoma, a hybrid odontogenic tumour or to fall within the spectrum of other recognised odontogenic tumours, including dentinogenic ghost cell tumour and adenomatoid odontogenic tumour. Here we review the reasons for the WHO decision to classify AA as a separate tumour type. We also critique molecular and histological findings from recent reports published since the WHO classification. While acknowledging that the classification of tumours is constantly evolving, the balance of current evidence suggests that AA should remain a distinct tumour type, and not a subtype of ameloblastoma, pending further molecular characterisation.

Whole-exome sequencing and copy number alterations analysis in a case of expansive florid cemento-osseous dysplasia.

Whole-exome sequencing (WES) analysis of an expansive case florid cemento-osseus dysplasia were reported for the first time. Also, the new potential candidate genes were reported to expand our knowledge about their molecular pathogenesis. Abstract: We report a case of expansive florid cemento-osseus dysplasia in a 32-year-old female patient who presented an expansive tumoral lesion in the anterior mandible. As florid cemento-osseus dysplasia have only been molecularly investigated using targeted-sequencing, fragments of the lesion were collected and subjected to molecular investigation using WES to assess somatic mutations as well as copy number alterations. No gains and losses of chromosomal arms or segments longer than 1 Mb were detected. Our findings revealed a pathogenic stopgain variant at the KIF5C gene, a stoploss variant at MAPK10, and missense SNV at COL6A2 at DCDC1, suggesting potential candidate genes associated with florid cemento-osseus dysplasia.

Tenosynovial giant cell tumor: case report and molecular investigation.

Tenosynovial giant cell tumor is a benign neoplasm arising from the synovium of joints, including the temporomandibular joint (TMJ). Despite its benign nature, these tumors may exhibit aggressive behavior. A 57-year-old woman with a swollen, hardened area in the left TMJ was referred to the university´s clinic. The diagnosis of tenosynovial giant cell tumor was made based on the presence of hyperplastic synovial lining containing mononuclear and giant cells, hemorrhagic areas, hemosiderin deposits, and calcification foci in the biopsy. A low condylectomy was performed, and histopathologic analysis of the surgical piece upheld the diagnosis. Due to histopathologic resemblance with other giant cell-rich lesions (giant cell granuloma of the jaws, brown tumor of hyperparathyroidism, and non-ossifying fibroma) for which signature mutations are known, mutational analysis of KRAS, FGFR1, and TRPV4 genes was conducted. The results revealed wild-type sequences for all the mutations tested, thereby supporting the diagnosis of tenosynovial giant cell tumor.

Familial Melanoma Phenotype With Xeroderma Pigmentosum Group C (XP-C) Genotype - The Putative Role of MC1R Polymorphism as Modifier.

INTRODUCTION: Xeroderma pigmentosum (XP), a rare inherited condition, hallmarked by extreme sensitivity to sun exposure resulting in multiple skin cancers and non-malignant skin alterations is attributed to homozygous inactivating pathogenic variants (PVs) in DNA repair genes, predominantly the XPC gene. OBJECTIVES: Report a unique phenotypic expression of mutant XPC allele that may be compatible with a putative modifier role for MC1R polymorphism. METHODS: A family of 13 siblings, seven of whom were diagnosed with at least one cutaneous melanoma (N = 53) and non-melanoma skin cancers (N = 9) was studied. Of seven melanoma-affected cases, five consented for genetic analysis. CDKN2A revealed no PV in any case and subsequent whole-exome sequencing (WES) identified a rare homozygous missense PV (c.919C>T; p.Arg307Trp) in exon 8 of the XPC gene in all affected individuals. Notably, XPC PV carriers who co-harbored the p.I155T MC1R variant (N = 3) exhibited larger number of tumors, deeper Breslow indexes, higher rates of invasive melanomas and earlier age at diagnosis compared with non MC1R variant carriers (N = 2). CONCLUSIONS: Familial malignant melanoma phenotype may, in fact, be an unusual clinical presentation of XPC, and MC1R may be a genetic modifier of penetrance and phenotype of mutant XPC alleles.

Immunocompromised patients and coronavirus disease 2019: a review and recommendations for dental health care

Abstract In less than four months, an unprecedented pandemic changed the world scenario, closing institutions and commerce, paralyzing sports championships, blocking frontiers, and putting almost all populations in a house quarantine regimen. Immunocompromised patients are within the high-risk group to severe outcomes from COVID-19. However, there is no clear evidence of the association between impaired immune host status and complications from SARS-CoV-2 infection so far. The virus is transmitted by inhalation or direct contact with infected secretions, and therefore the dental office is a highly susceptible environment for such transmission. Here, we review the literature and discuss immunological COVID-19 related issues. We also make suggestions for immunocompromised patients' support in this new emerging context of clinical dental practice. Until comprehensive findings are published, individuals with impaired immunity should be considered as high-risk. Cross infection control procedures for the clinical care of immunocompromised patients should follow the same guidelines that are being proposed for immunocompetent ones. However, during the active outbreak, people under immunosuppressive conditions should not receive elective procedures, even if they do not have symptoms or exposure history to COVID-19, and in case of emergence, care must be done in a separate airborne room. In the pos-pandemic phase, the dental care general recommendations should be the same for all subjects. Changes in the current guidelines have been proposed to SARS-CoV-2 infection control in order to provide the best and safe dental practice. However, they still need to be validated by future studies.

DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44 Protein Expression

Chromosomal instability, leading to aneuploidy, is one of the hallmarks of human cancers. USP44 (ubiquitin specific peptidase 44) is an important molecule that plays a regulatory role in the mitotic checkpoint and USP44 loss causes chromosome mis-segregation, aneuploidy and tumorigenesis in vivo. In this study, it was investigated the immunoexpression of USP44 in 28 malignant salivary gland neoplasms and associated the results with DNA ploidy status assessed by image cytometry. USP44 protein was widely expressed in most of the tumor samples and no clear association could be established between its expression and DNA ploidy status or tumor size. On this basis, it may be concluded that the aneuploidy of the salivary gland cancers included in this study was not driven by loss of USP44 protein expression.

Resumo Instabilidade cromossômica acarretando aneuploidia é um dos fatores marcantes de neoplasias malignas humanas. USP44 (peptidase específica de ubiquitina 44) é uma importante molécula que exerce um papel regulador no ciclo celular e sua perda pode acarretar em segregação cromossômica deficiente, aneuploidia e desenvolvimento de tumores in vivo. Neste estudo, investigou-se a expressão imuno-histoquímica da proteína USP44 em 28 neoplasias malignas de glândulas salivares, associando-se os resultados com o estado de ploidia do DNA avaliado por citometria de fluxo. A proteína USP44 apresentou ampla expressão na maioria das amostras avaliadas e não foi observada associação entre a expressão protéica e o estado de ploidia do DNA ou extensão do tumor. Baseando-se nos resultados, concluiu-se que a aneuploidia das neoplasias malignas de glândulas de salivares incluídas neste estudo não foi influenciada pela perda de expressão da proteína USP44.

Serotonin transporter gene polymorphisms: a case-control study

Considerable evidence indicates that serotonergic mechanisms, particularly the serotonin transporter, are involved in alcoholism and tobacco use and are influenced by polymorphism of the promoter region of 5HTT (5-HTTLPR). As alcohol and tobacco consumption have been implicated in the pathogenesis of oral cancer, the purpose of this study was to investigate 5-HTTLPR polymorphism in patients with oral squamous cell carcinoma (OSCC) compared with a control group in a sample of Brazilian patients. One hundred and three patients affected by OSCC and 103 volunteers without OSCC were genotyped for 5-HTTLPR. Both groups were matched for age, sex and tobacco use. The chi-squared test was used for statistical analysis (α=0.05). There was no statistically significant difference in 5-HTTLPR genotypes between case and control group (p= 0.408). In conclusion, the present investigation demonstrated that serotonin transporter polymorphisms are not implicated in the OSSC development.

Consideráveis evidências indicam que mecanismos serotoninérgicos, particularmente o transportador de serotonina, estão envolvidos no alcoolismo e no uso de fumo e são influenciados pelo polimorfismo da região promotora do 5HTT (5-HTTLPR). Como o consumo de álcool e fumo está implicado na patogênese do câncer, o objetivo deste estudo foi investigar o polimorfismo 5-HTTLPR em pacientes com carcinoma bucal de células escamosas (CBCE) comparado com um grupo controle em uma amostra de pacientes brasileiros. Cento e três pacientes afetados por CBCE e 103 voluntários sem história de CBCE foram genotipados para 5-HTTLPR. Ambos os grupos foram pareados pela idade, gênero e uso de fumo. O teste do qui-quadrado foi usado para análise estatística. Não houve diferença estatística entre os genótipos dos grupos caso e controle (p= 0,408). Concluindo, a presente investigação demonstrou que os polimorfismos do transportador de serotonina não estão implicados no desenvolvimento do CBCE.

Wilms tumor 1 protein is not expressed in oral lymphangiomas

Lymphangiomas are benign hamartomatous lesions of lymphatic vessels. Wilms Tumor 1 (WT1) is a transcription factor that is activated in some human neoplasias. WT1 protein expression is observed in endothelial cells during angiogenesis and is a useful marker to distinguish between vascular proliferations and vascular malformations. The purpose of the present study is to report a case series of oral lymphangiomas together with an immunohistochemical investigation of WT1. Seventeen cases of oral lymphangioma were retrieved and reviewed. Immunohistochemical analysis of WT1 protein was performed and pyogenic granuloma samples were used as positive controls. The male/female ratio was 1.125 and most of the lesions occurred in young subjects. While pyogenic granuloma showed positive staining for WT1, the endothelial cells lining the thin-walled dilated lymphatic vessels of lymphangiomas were negative for this protein. The findings strengthen the idea that oral lymphangioma is a vascular malformation characterized by lymphatic dilatation without significant endothelial proliferation.

Os linfangiomas são tumores hamartomatosos benignos dos vasos linfáticos. O Wilms Tumor 1 (WT1) é um fator de transcrição que se encontra ativo em algumas neoplasias humanas. A expressão da proteína WT1 é observada em células endoteliais durante a angiogênese e pode ser um marcador útil para distinguir as proliferações vasculares das malformações vasculares. O objetivo deste estudo foi relatar uma série de casos de linfangiomas orais e avaliar a expressão imunoistoquímica da proteína WT1. Dezessete casos de linfangiomas orais foram recuperados e revisados. A análise imunoistoquímica foi realizada e amostras de granuloma piogênico foram utilizadas como controle positivo. A relação homem/mulher foi de 1,125 e a maioria das lesões acometeram pacientes jovens. Enquanto o granuloma piogênico mostrou uma imunopositividade para WT1, as células endoteliais da fina parede dos vasos linfáticos dilatados apresentaram-se negativas para esta proteína. Tais achados reforçam a idéia de que o linfangioma oral é uma malformação vascular caracterizada por dilatação linfática sem uma proliferação endotelial significativa.

Hypomethylation of tumor suppressor genes in odontogenic myxoma

Odontogenic myxoma (OM) is an ectomesenchymal benign odontogenic tumor characterized by spindle or stellate-shaped cells embedded in an abundant myxoid or mucoid extracellular matrix. DNA methylation is characterized by the addition of methyl groups in cytosines within CpG islands in the promoter gene. DNA methylation can decrease the expression of tumor suppressor genes and contribute to the development of neoplastic lesions. The aim of study was to evaluate the methylation pattern of the tumor suppressor genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53) and RB1 in OM and dental pulp. Methylation was evaluated using methylation-specific polymerase chain reaction (PCR). The transcription was studied in some cases by using reverse transcription quantitative PCR. A higher frequency of unmethylated P27, P53, and RB1 samples was observed in the OM when compared with the dental pulp. OM expressed mRNA of all the genes evaluated. Considering all the samples together, the expression of Rb was higher in the unmethylated samples compared with the partially methylated samples. This investigation revealed hypomethylation of the genes P27, P53, and RB1 in OM. In addition, methylation of tumor suppressor genes was found to be an usual event in normal dental pulp.

O mixoma odontogênico (MO) é um tumor odontogênico benigno de origem mesenquimal caracterizado pela presença de células fusiformes ou estreladas dispostas em abundante matriz extracelular mucóide. A metilação do DNA é caracterizada pela adição de grupos metil em citosinas constituintes de ilhas CpG na região promotora do gene. A metilação pode diminuir a expressão de genes supressores de tumor e contribuir para o desenvolvimento de lesões neoplásicas. O objetivo deste trabalho foi avaliar o padrão de metilação nos genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53), RB1 nos MO e na polpa dental. A metilação foi avaliada pela reação em cadeia da polimerase específica para a metilação. A transcrição dos genes foi estudada em alguns casos pela reação da transcriptase reversa (PCR quantitativa). Uma maior frequência de amostras não metiladas para os genes P27, P53 e RB1 foi observada nos MO quando comparados à polpa dental. Os MO expressaram RNAm de todos os genes avaliados. Considerando todas as amostras juntas, a expressão de Rb foi maior em amostras não metiladas comparadas as amostras parcialmente metiladas. Esta investigação mostrou a hipometilação dos genes P27, P53 e RB1 nos MO. Adicionalmente, a metilação nos genes supressores de tumor é um evento frequente em polpa dental normal.

Clonality analysis of giant cell lesions of the jaws

Despite the importance of clonality to understand the pathogenesis and progression of tumors, it has not been investigated yet in giant cell lesions of the jaws. The aim of this study was to analyze the clonality of peripheral giant cell lesions (PGCL) and central giant cell lesions (CGCL) of the jaws. Six samples of PGCL and 5 samples of CGCL were analyzed in this study using the polymorphic human androgen receptor locus (HUMARA) assay. Three out of the 5 samples of the CGCL and 3 out of 6 samples of PGCL exhibited a monoclonal pattern. Our findings demonstrate that some giant cell lesions of the jaws are clonal, which indicate that these lesions may have a common genetic mechanism of development. Further studies are necessary to better elucidate the molecular mechanisms involved in the pathogenesis of such lesions.

Apesar da importância que a clonalidade das lesões tem para o entendimento da patogênese e progressão dos tumores, ainda não foi feita essa investigação em lesões de células gigantes dos maxilares. O objetivo desse trabalho foi analisar a natureza clonal de lesões periféricas de células gigantes (LPCG) e de lesões centrais de células gigantes (LCCG). Foram analisadas nesse estudo 6 amostras de LPCG e 5 amostras de LCCG, sendo todas elas provenientes de pacientes do sexo feminino. Para essa investigação foi utilizado o método baseado na região polimórfica do exon um do gene humano para oreceptor de andrógeno (HUMARA). Três das 5 amostras de LCCG e 3 das 6 amostras de LPCG exibiram um padrão monoclonal. Nossos resultados demonstram que algumas lesões de células gigantes dos maxilares apresentam uma natureza monoclonal indicando que essas lesões podem ter um mecanismo genético comum de desenvolvimento. Outros estudos são necessários para uma maior compreensão dos mecanismos moleculares envolvidos na patogênese dessas lesões.

A clinical case of peripheral ameloblastoma

The peripheral ameloblastoma (PA) is a rare, benign, extraosseous odontogenic soft tissue tumour that is confined to the gingiva or alveolar mucosa. The PA presents the same histological characteristics of intraosseous ameloblastoma, although it is less aggressive than this classical subtype. We report a clinical case of PA of the alveolar mucosa in the right posterior maxilla, highlighting the importance of histological examination to the diagnosis.

Helicobacter pylori in the oral mucosa of patients submitted to allogeneic haematopoietic stem cell transplantation / Helicobacter pylori na mucosa oral de pacientes submetidos ao transplante de células-tronco hematopoiéticas

This study was designed to investigate the impact of haematopoietic stem cell transplantation (HSCT) on Helicobacter pylori colonization of the oral mucosa by nested polymerase chain reaction (nested-PCR). Forty six consecutive patients submitted to HSCT and 46 healthy volunteers were included in the study. Oral swabs were taken from the oral mucosa of the patients and control group. The medical records of the patients were reviewed and the following information was retrieved: gender and age of the patient, donor gender, primary disease, stem cell source (bone marrow or blood stem cells), leukocyte, neutrophil and platelet counts, and chronic graft versus host disease (cGVHD) of salivary glands. The results demonstrated an increased frequency of H. pylori in the oral mucosa of HSCT patients compared to controls (rho = 0.002). The presence of H. pylori in the oral mucosa was not related to the severity of cGVHD. The median counts of platelet/mm³, leukocytes/mm³ and neutrophils/mm³ in the group of HSCT patients positive for H. pylori were not statistically different from those of the patients negative for it. In conclusion, the present study shows increased frequency of H. pylori in the oral mucosa of HSCT patients compared to non-transplanted healthy volunteers.

O objetivo do estudo é investigar o impacto do transplante de células-tronco hematopoiéticas (TCTH) na colonização da mucosa bucal pela Helicobacter pylori através do "nested-PCR". Quarenta e seis pacientes submetidos ao TCTH e 46 indivíduos saudáveis foram incluídos no estudo. Raspados de mucosa bucal foram realizados nos pacientes do grupo de estudo e grupo controle. Os dados médicos dos pacientes foram revisados e as seguintes informações foram coletadas: gênero e idade do paciente, gênero do doador, doença primária, fonte de células-tronco (medula óssea ou células-tronco sanguíneas), número de leucócitos, neutrófilos e plaquetas, doença do enxerto contra o hospedeiro crônica (DECHc) de glândulas salivares. Os resultados demonstram aumento na freqüência de H. pylori na mucosa bucal de pacientes submetidos ao TCTH comparado com grupo controle (r = 0.002). A presença da H. pylori na mucosa bucal não teve relação com a severidade da DECHc. As medianas de número de plaquetas/mm³, leucócitos/mm³ e neutrófilos/mm³ no grupo de pacientes TCTH positivos para H. pylori não foram estatisticamente diferentes das medianas dos pacientes negativos. Concluindo, o presente estudo mostra um aumento da freqüência da H. pylori na mucosa bucal de pacientes submetidos ao TCTH quando comparada com a de um grupo de voluntários não transplantados saudáveis.