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The aim of the present review was to integrate the available data published on gingival cyst of the adult (GCA), lateral periodontal cyst (LPC), and botryoid odontogenic cyst (BOC) into a comprehensive analysis of their clinical/radiological features. An electronic search was undertaken in July/2017. Eligibility criteria included publications having enough clinical/radiological/histological information to confirm the diagnosis. A total of 146 publications (157 GCAs, 213 LPCs, 96 BOCs) were included. GCA and LPC presented highest prevalence in the sixth/fifth decades; BOC in the sixth/seventh decades. LPCs were larger lesions than GCAs and GCAs appeared at an older age than LPC. There was no statistically significant difference between them for other factors (location, symptoms, recurrence, follow-up time). In comparison with LPC, BOC lesions were larger, appeared more often in mandible and in older subjects, had more often a multilocular appearance, and presented a higher recurrence rate. Recurrence rates: GCA (3.2%), LPC (2.4%), BOC (21.7%). No factor seems to influence the recurrence rate of GCA or LPC. Multilocular radiological appearance seems to affect the recurrence rate of BOCs. Conservative surgical approaches seem to be enough for GCA/LPC. BOC presents a more aggressive behavior than GCA/LPC. Therefore, treatment of this lesion might involve some kind of adjunctive therapy after enucleation., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objective: To integrate the available data published on glandular odontogenic cyst (GOC) into a comprehensive analysis of its clinical/radiological and histopathological features., Methods: An electronic search was undertaken in May/2017. Eligibility criteria included publications having enough clinical/radiological/histological information to confirm the diagnosis., Results: Fifty-eight publications (169 GOCs) were included. The lesion was slightly more prevalent in men than in women. There was a high prevalence in the fifty/sixth decades of life, in the anterior regions, and in mandibles. Lesions were commonly associated with bone expansion (73%) and unilocular radiological appearance (61.5%). GOC was found to be associated with tooth displacement or an unerupted tooth (30.9%), cortical bone perforation (26%), presence of clinical symptoms (24.3%), root resorption (13.9%). Microscopic parameters most commonly were observed in GOCs-in at least 95% of the lesions: presence of hobnail cells, intraepithelial microcysts, epithelial lining with variable thickness. The presence of apocrine snouting was the microscopic parameter less often found (40.4%)., Conclusion: Although the recurrence rate of GOCs is not as high as previously believed, it is a relevant phenomenon (21.6%). Adjunctive procedures after enucleation should be considered. None of the clinical/radiological and histopathological features evaluated had a statistically significant effect on the recurrence rate., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate the association of IL17A G197A polymorphism and serum levels with oral lichen planus (OLP) susceptibility and clinical presentation., Subjects and Methods: Eighty-three individuals diagnosed with OLP and 99 healthy controls (C) were consecutively recruited. All participants had desquamating oral mucosal cells collected and DNA isolated for IL17A (G197A) genotyping. Blood samples of 42 OLP individuals and 23 healthy controls were collected for evaluation of IL17A serum levels., Results: IL17A G197A genotypes were associated with an increased chance of having OLP (GA/AA × GG, OR = 3.44, 95% CI = 1.87-6.33, p < .001). Overall A carriers (GA or AA) were more common in OLP (38.1%) than in C (20.2%; OR = 2.43, 95% CI = 1.53-3.87, p < .001). Serum levels of IL17A were higher among patients with OLP than in healthy controls (reticular, p = .0003; erosive, p < .001), but no difference was found among the disease types., Conclusions: IL17A G197A is associated with a higher susceptibility of developing OLP and these patients seem to present a considerable increase in IL17A serum levels. These findings suggest that Th17 cells, and IL17A in particular, may play a pivotal role in OLP pathogenesis., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objectives: DNA methylation is an important mechanism of gene control expression, and it has been poorly addressed in odontogenic tumours. On this basis, we aimed to assess the methylation pattern of 22 apoptosis-related genes in solid ameloblastomas., Materials and Methods: Ameloblastoma fresh samples (n = 10) and dental follicles (n = 8) were included in the study. The percentage fraction of methylated and unmethylated DNA promoter of 22 apoptosis-related genes was determined using enzymatic restriction digestion and quantitative real-time PCR (qPCR) array. The relative expressions of the genes that showed the most discrepant methylation profile between tumours and controls were analysed by reverse-transcription quantitative PCR (RT-qPCR)., Results: Lower methylation percentages of TNFRSF25 (47.2%) and BCL2L11 (33.2%) were observed in ameloblastomas compared with dental follicles (79.3% and 59.5%, respectively). The RT-qPCR analysis showed increased expression of BCL2L11 in ameloblastomas compared with dental follicles, in agreement with the methylation analysis results, while there was no difference between the expression levels of TNFRSF25 between both groups., Conclusions: On the basis of our results, the transcription of the apoptosis-related gene BCL2L11 is possibly regulated by promoter DNA methylation in ameloblastoma. The biological significance of this finding in ameloblastoma pathobiology remains to be clarified., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The amalgam-associated oral lichenoid lesion (AAOLL) shows clinical and histopathological features similar to oral lichen planus (OLP). Molecular researches to improve knowledge of pathogenesis and clinical behavior of AAOLL are still scarce., Objective: We investigated for the first time the use of loss of heterozygosity (LOH) as a molecular approach for genetic characterization of AAOLL in comparison with OLP and evaluated the cell proliferation index., Materials and Methods: The sample comprised nine AAOLLs, 10 OLPs, and eight NOMs matched by patients' gender and age. LOH was assessed using polymorphic microsatellite markers at chromosomes 9p (D9S157, D9S162, D9S171), 11q (D11S1369), and 17p (TP53, AFM238WF2). Cell proliferation was assessed by immunohistochemical expression of Ki-67 (MIB-1). The association between LOH and Ki-67 was investigated., Results: Loss of heterozygosity occurred in 5/9 AAOLLs and in 2/10 OLPs in at least one marker each, while NOM showed no LOH. Cell proliferation index in AAOLL ranged from 2 to 23%. There was no association between cell proliferation and LOH, independent of the marker., Conclusion: Our study shows that the profile of molecular changes in AAOLL and OLP, evaluated by LOH and Ki-67 expression, is similar. Additional studies including larger samples should be performed to confirm or to refute our findings., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective:  Graft-versus-host disease is a major complication after allogenic hematopoietic stem cell transplantation. Interferon gamma is an important pro-inflammatory cytokine involved in this disease. Cytokine gene polymorphisms are associated with functional differences in cytokine expression and can alter the clinical course of graft-versus-host disease. This study aimed to investigate the association between IFN-γ levels in saliva, blood, and IFNG polymorphisms, as well as the occurrence of acute graft-versus-host disease in allogenic HSCT., Subjects and Methods: Fifty-eight consecutive allogenic hematopoietic stem cell transplantation recipients and their donors were prospectively studied. IFN-g levels in saliva and blood were assessed by ELISA. Samples were collected weekly from 7 days before transplantation (day -7) to 100 days after allogenic HSCT (day +100) or until death. Saliva and/or blood samples were obtained from the recipients and donors to determine IFNG gene polymorphisms., Results:   Increased saliva and blood IFN-g levels were observed in patients that had developed aGVHD. In the saliva, the peak levels of IFN-g could be found one week before aGVHD diagnosis, while in the blood, peak levels of IFN-g could be only observed upon diagnosis. A significant association could be identified between the recipients'IFNG genotypes and the IFN-g levels in their blood, at +14 days after HSCT. No association could be observed between IFNG gene polymorphisms and the aGVHD., Conclusion:  The present study shows that the genetic background of recipients can influence the production of IFN-g. Moreover, as IFN-g levels in the saliva and blood were found to be associated with aGVHD development, this cytokine may be a useful predictor of acute graft-versus-host disease., (© 2012 John Wiley & Sons A/S.)

Objective: WWOX gene is altered in a variety of neoplasms. Wwox is pro-apoptotic through interaction with p73 and may be involved in chromosomal stability by interaction with p73 and p53. The aims of this study were to characterize WWOX transcription, methylation status and immunoexpression in salivary neoplasms and to determine whether these were associated with p73, p53, cell proliferation and DNA ploidy., Materials and Methods: Seven malignant and 21 benign fresh salivary neoplasms were included. WWOX expression was determined by RT-PCR and sequencing of transcripts, quantitative PCR and immunohistochemistry. Methylation-specific PCR was used to assess the methylation of its first exon. For p73, ΔNp73, p53 and ki67 immunohistochemistry and ploidy analysis, 29 malignant samples from archives were included., Results: No consistent pattern of WWOX exon 1 methylation was found, but aberrant and novel transcripts were observed in 17/28 neoplasms; 55% of tumours showed reduced WWOX RNA. WWOX RNA levels were associated with p53 immunopositivity. Immunohistochemical Wwox expression did not correlate with methylation status, p53 or p73 expression or proliferation. p73, proliferation and DNA ploidy were associated with malignant phenotype., Conclusion: Aberrant WWOX transcription and decreased expression are frequent in salivary neoplasms and WWOX transcription is associated with p53 staining., (© 2011 John Wiley & Sons A/S.)

Objective: Microchimerism has been extensively investigated in autoimmune diseases, which display similarities with graft-vs-host disease. This study was conducted to investigate the presence of microchimerism in minor salivary glands of hematopoietic stem cell transplanted patients, one of the targets of graft-vs-host disease., Methods: Labial salivary glands biopsy specimens from 11 stem cell transplanted patients were analysed. The samples were grouped in control (five specimens from a female-to-female transplantation) and study group (five glands from male-to-female transplantation). One male transplanted patient was used as a positive control. Fluorescence in situ hybridization with Y-chromosome probe and immunofluorescence with anticytokeratin AE1/AE3 and CD45 were used to identify Y-chromosome positive glandular epithelial cells from allogeneic hematopoietic stem cell transplanted patients., Results: In the study group, all samples were positive to Y-chromosome and cytokeratin AE1/AE3, in agreement with the pattern exhibited by male labial salivary gland. None of the samples from control group were positive to Y-chromosome despite being positive to cytokeratin AE1/AE3. Positivity to CD45 was not relevant., Conclusion: Microchimerism in the labial salivary glands of sex-mismatched stem cell transplanted patients is a real phenomenon. Further studies are necessary to elucidate the impact of this phenomenon on the clinical status of stem cell transplanted patients., (© 2010 John Wiley & Sons A/S.)

Background: Glycoprotein B (gB) has been implicated in determining the pathogenicity and clinical outcomes of human cytomegalovirus (HCMV) disease., Objective: The purpose of this study was to assess the prevalence of gB genotypes in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the relationship between it and cytokine levels in saliva and blood samples. The impact of these parameters on patients' survival was also investigated., Methods: Samples were obtained from 63 patients receiving an allo-HSCT. HCMV gB genotyping was carried out by multiplex nested PCR. The cytokine levels were assessed using ELISA assay., Results: A single or mixed genotype infection was detected in the saliva and blood of 36/63 and 52/63 subjects, respectively. Patients with gB2 in their saliva showed lower IL-10 levels in comparison with patients without gB2. Reduced blood levels of IFN-γ and IL-1β were also found in recipients with the HCMV gB4 genotype compared with patients without it. Decreased IL-1β and increased IL-10 blood levels were associated with lower survival. However, HCMV gB genotypes have no impact on patient outcome., Conclusion: Decreased IL-1β and increased IL-10 levels in the blood are associated with lower survival. HCMV genotypes are associated with different cytokine levels in saliva and blood., (© 2011 John Wiley & Sons A/S.)

Objective: The purpose of this study was to investigate the use of saliva for the identification of human cytomegalovirus (HCMV) in allogeneic hematopoietic stem cell transplant patients by real time PCR compared with blood., Materials and Methods: Saliva and blood samples were sampled weekly in 30 allogeneic hematopoietic stem cell transplant patients until 100 days after transplant. Total genomic DNA, extracted from saliva and whole-blood samples, was used for HCMV real time PCR. Nonparametric tests were performed, and P value

Central giant cell lesion (CGCL) is a reactive bone lesion that occurs mainly in the mandible, characterized by the multinucleated osteoclast-like giant cells in a background of oval to spindle-shaped mononuclear cells. The etiology is unknown and occurs more commonly in young adults. Cherubism, a rare disease found predominantly in females has histologic characteristics indistinguishable from those of CGCL and is caused by mutations mostly present in exon 9 of the SH3BP2 gene. In this study, we investigated four cases of CGCL and one case of cherubism. DNA was extracted from peripheral blood and tumor tissue and all coding and flanking regions of the SH3BP2 amplified by PCR and directly sequenced to identify underlying mutations. Two novel mutations were found; a heterozygous missense mutation c.1442A>T (Q481L) in exon 11 in one sporadic case of CGCL and a heterozygous germline and tumor tissue missense mutation c.320C>T (T107M) in exon 4 in one patient with cherubism. These findings open a new window to investigate the possible relationship between the pathogenesis of the cherubism and CGCL.

Objective: This study was designed to investigate the effect of allogeneic haematopoietic stem cell transplantation (HSCT) on cytomegalovirus (CMV) shedding in the saliva by nested polymerase chain reaction (nested PCR) and its impact on patient survival., Patients and Methods: One hundred and twenty-four HSCT patients and 124 healthy volunteers were included in the study. Oral swabs were taken before, after 100 days and 1 year of HSCT at the buccal mucosa. Nested PCR was used to detect CMV in the saliva. Time of death after HSCT was displayed, by means of the Kaplan-Meier method, for the following parameters: age and gender of the patient, donor gender, primary disease, stem cell source, platelet number, chronic graft vs host disease (cGVHD) of salivary glands and oral mucosa, and oral CMV shedding. Cox proportional hazards model was used for multivariate survival analysis., Results: While none of the individuals in the control group showed positive swabs for CMV, the frequency of positive CMV oral swabs in patients at day + 100 after HSCT (45.2%) was statistically higher than before (7.2%) and 1 year after HSCT (17.5%). The presence of CMV was not associated with cGVHD and did not have any impact on post-transplant survival., Conclusions: The present study shows that oral CMV shedding occurs after HSCT, especially at day +100 post-transplant. Identification of CMV in the saliva might be important for the early diagnosis of CMV infection in allo-HSTC.

Aim: To investigate the accuracy of histological diagnosis of oral hemangioma, oral vascular malformation and oral pyogenic granuloma according to immunohistochemical evaluation of the human erythrocyte-type glucose transporter protein (GLUT-1), and to observe the immunoexpression of this protein in oral varix., Materials and Methods: Immunohistochemistry for GLUT-1 was performed in 93 histologically diagnosed cases of oral benign vascular lesions: 17 vascular malformations, 19 hemangiomas, nine varix, and 48 pyogenic granulomas. Descriptive analyses were performed., Results: None of the cases of the oral benign vascular lesions evaluated were immunopositive to GLUT-1. The 19 cases histologically diagnosed as oral hemangioma that showed negative staining to GLUT-1 were reclassified as oral pyogenic granuloma or oral vascular malformations. The histological evaluation itself is not enough to obtain the correct diagnosis of oral HEM as none of the sample cases were true hemangioma. All sample cases with initial vascular malformation or pyogenic granulomas classification were negative to GLUT-1, demonstrating the accuracy of histological diagnosis of these lesions itself. Oral varix showed negative staining to GLUT-1 in blood vessels., Conclusions: GLUT-1 is an useful, effective and important auxiliary marker for the diagnosis of oral benign vascular lesions., Clinical Relevance: This study showed that histological diagnosis alone is not sufficient to correct diagnoses of oral hemangioma. Moreover, immunohistochemistry to GLUT-1 is a useful and easy diagnostic method that may be used to avoid such misdiagnosis. Accurate diagnosis of these oral lesions has an important clinical relevance allowing: (1) correct management, (2) adequate communication among the multidisciplinary team (dentist, dermatologist, pediatrist, radiologist, pathologist, and surgeon), (3) understanding of the biological behavior of the lesions, and (4) facilitate the development of new therapeutic modalities. Thus, supporting the use of this marker in medical and dentistry communities is warranted.

Background: Recurrent aphthous stomatitis (RAS) is characterized by recurrent episodes of oral ulceration in an otherwise healthy individual. Some reports in the literature indicate that RAS may have immunological, psychological, genetic and microbiological bases. The purpose of the present study was to investigate the possible association between interleukin-1beta (IL-1beta) +3954 (C/T) genetic polymorphism and RAS in a sample of Brazilian patients., Subjects and Methods: Sixty-two consecutive subjects affected by minor and major forms of RAS and 62 healthy volunteers were genotyped at IL-1beta (+3954). The chi-squared test was used for statistical analysis., Results: A significant increase in the high production of IL-1beta genotype CT was observed in the group with RAS (P = 0.01). After stratifying RAS patients according to the mean number of lesions per episode, a significant difference was only observed between patients with >or=3 lesions in each episode and control., Conclusion: There is an increased frequency of polymorphism associated with high IL-1beta production in RAS patients.

Objective: Investigate the frequency of herpes simplex virus type 1 (HSV-1) reactivation in the oral cavity of seropositive patients with previous history of recurrent herpes labialis (recrudescent group) compared with those without any history of recrudescent lesions (asymptomatic HSV-1 infection). In addition, the relation between recrudescence and the presence of the virus in the saliva was assessed., Materials and Methods: Fourteen individuals with previous history of herpes labialis (recrudescent group) and 11 HSV-1 seropositive asymptomatic volunteers were included in the study. Swabs were performed periodically in all subjects and the presence of HSV-1 DNA was identified by nested PCR., Results: All the 25 subjects enrolled in the study, revealed at least one positive swab for HSV-1. The frequency of HSV-1 positivity in the group with recrudescent herpes labialis was not statistically different from the other group. Ten subjects of the recrudescent group presented with herpes labialis at least once during the study., Conclusions: HSV-1 shedding in the oral cavity occurs independently of herpes labialis recrudescence.

Objective: Considering that hMSH2, hMLH1 and p53 are important in maintaining genomic stability of the oral mucosa epithelium, the purpose of the present study was to investigate the immunolocalization of these proteins in the epithelium of the oral mucosa of patients submitted to bone marrow transplantation (BMT) compared with controls., Materials and Methods: Twenty-one samples of lip biopsies from BMT recipients were retrieved. Twenty samples of normal lower labial mucosa associated with mucocele in non-transplanted patients were included as control group. The streptavidin-biotin complex stain was used to detect the human DNA mismatch repair proteins hMSH2, hMLH1 and p53 protein., Results: The main findings demonstrated that the mean number of suprabasal epithelial cells positive for MSH2 was statistically higher than the control group. The immunostaining of hMLH1 and p53 at the basal and suprabasal epithelial layers were statistically higher in the oral labial mucosa of the BMT patients compared with controls., Conclusion: The present study shows that oral epithelial cells of BMT patients show increased immunolocalization of the DNA repair related proteins.

Cysticercosis is a condition in which a human acts as the intermediate host of the pork tapeworm Taenia solium. Although cysticercosis is a common disease in some regions of the world and can occur in any body site, oral lesions are rare. This paper reviews the natural history of the disease and reports on seven cases of oral cysticercosis.

Objectives: Peripheral giant cell lesion (PGCL) and central giant cell lesion (CGCL) of the jaws have a distinct clinical behaviour. Whether such biological differences are supported by a distinct pattern of proliferation markers or cell cycle associated proteins expression is not known. Therefore the purpose of the present study was to compare the immunohistochemical expression of p53, MDM2, Ki-67, PCNA and the histochemical expression of argyrophilic nuclear organiser region (AgNOR) on PGCL and CGCL of the jaws., Materials and Methods: Paraffin wax blocks of 14 cases of PGCL and 12 cases of CGCL were retrieved. A biotin-streptavidin amplified system was used for identification of the antigens. The AgNOR number was also evaluated., Results: Ki-67 immunoreactivity was greater in the mononuclear cells of PGCL compared to CGCL. PCNA and AgNOR staining were similar in PGCL and CGCL. Prominent MDM2 immunoreactivity was observed in all tissues investigated. By contrast, there was no p53 immunoreactivity., Conclusions: Although CGCL present a more aggressive clinical behaviour, it has a decreased proliferative activity compared to PGCL. Finally, p53, MDM2, PCNA, Ki-67 immunohistochemical expression and AgNOR histochemical expression do not reflect their distinct biological behaviour.

Objective: To study the nature of multinucleated and mononuclear cells from peripheral giant cell granuloma (PGCG)., Materials and Methods: Formalin-fixed, paraffin-embedded sections of 40 cases of PGCG were immunohistochemically stained for vimentin, alpha I-antichymotrypsin, CD68, S-100 protein, lysozyme, leucocyte common antigen (LCA), factor VIII-related antigen and muscle cell actin. Six cases of PGCG were also studied by transmission electron microscopy., Results: Vimentin, alpha I-antichymotrypsin and CD68 were expressed in both the mononuclear and multinucleated giant cells. Dendritic mononuclear cells, positive for S-100 protein, were noted in 67.5% of the lesions, whereas lysozyme and leucocyte common antigen were detected in occasional mononuclear cells. Ultrastructural examination showed mononuclear cells with signs of phagocytosis and sometimes interdigitations with similar cells. Others presented non-specific characteristics and the third type exhibited cytoplasmic processes and occasional Birbeck granules. Some multinucleated giant cells showed oval nuclei, abundant mitochondria and granular endoplasmic reticulum whereas others presented with irregular nuclei and a great number of cytoplasmic vacuoles., Conclusions: Immunohistochemical and ultrastructural results suggest that PGCGs of the jaws are composed mainly of cells of the mononuclear phagocyte system and that Langerhans cells are present in two thirds of the lesions.