Microvascular density analysis and histological parameters of oral cancer progression.

OBJECTIVES: This study aimed to investigate the role of blood and lymphatic microvascular density in the progression of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The sample was composed of 54 cases of OSCC. The immunoexpression to anti-alpha-smooth muscle actin (α-SMA) and to anti-endoglin (CD105) was used to determine the microvessel density (MVD); anti-podoplanin (D2-40) was used to assess the lymphatic vessel density (LVD); vascular endothelial growth factor (VEGF) was evaluated in malignant cells. The histological differentiation, the worst pattern of invasion (WPOI), tumour thickness and tumour budding (TB) intensity were assessed using haematoxylin-eosin and anti-pan-cytokeratin (AE1/AE3). Patients' age and sex, TNM classification and follow-up time were collected from the medical records. RESULTS: MVD markers presented a similar pattern of expression in blood vessels. However, only α-SMA + MVD was significantly higher among women and in tumours ≤4 cm. LVD was lower in tumours with lymph node metastasis. Regarding the histological parameters, high TB intensity was associated with histological differentiation, advanced clinical stage, greater tumour thickness and reduced disease-free survival. No difference was found in VEGF. CONCLUSIONS: The decrease in OSCC LVD could be related to pathological node involvement, whereas high TB intensity could indicate OSCC progression and worse patient outcomes.

Impact of the COVID-19 pandemic on public University laboratories of oral and maxillofacial pathology: A Brazilian multicenter study.

OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on the number of diagnoses of oral and maxillofacial lesions in public laboratories after one year of COVID-19 outbreak in Brazil. MATERIAL AND METHODS: This is a cross-sectional study. Biopsies submitted to histopathologic examination from March 2019 to February 2020 (pre-pandemic period) and from April 2020 to March 2021 (pandemic period) in nine Brazilian public oral pathology laboratories were retrieved and the number of diagnoses, types of lesion, and percentage changes during both periods were analyzed. RESULTS: There were 7389 diagnoses in the pre-pandemic period and 2728 in the pandemic era, indicating a reduction of 63.08%. The reduction was 64.23% for benign lesions and 49.48% for malignant lesions, with a 50.64% reduction in squamous cell carcinoma. The largest decreases were observed in April 2020 and January 2021. CONCLUSION: An important reduction in the diagnoses of benign and malignant lesions was noted in the Brazilian public oral pathology laboratories during the first year of the COVID-19 pandemic.

Comparison of tobacco and alcohol consumption in young and older patients with oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: To compare the proportion of young (up to 45 years of age) and older (over 45 years of age) oral squamous cell carcinoma (OSCC) patients who report tobacco and alcohol consumption. METHODS: Observational studies reporting tobacco and alcohol consumption among young and older OSCC patients were selected in a two-phase process. Search strategies were conducted on five main electronic databases and complemented by grey literature. The risk of bias was assessed using the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Synthesis of results was calculated with the software R Statistics version 4.0.2 (The R Foundation). RESULTS: From 6675 records identified, 38 studies met the eligibility criteria and were selected for qualitative synthesis and meta-analysis, encompassing 2439 young and 13,393 older patients. Tobacco smoking was reported by 39.5% (confidence interval (CI) = 31.7% to 47.9%, I2 = 78%) of the young patients and 48.4% (CI = 37.8% to 59.2%, I2 = 94%) of the older patients. Alcohol consumption was reported by 30.9% (CI = 22.7% to 40.5%, I2 = 83%) of the young and 45.8% (CI = 35.6% to 56.5%, I2 = 95%) of the older patients (P < 0.05). CONCLUSION: The comparison in the proportion of individuals reporting tobacco and alcohol consumption demonstrated that these habits were more prevalent in the older group (48.4% and 45.8% respectively) than in the young group (39.5% and 30.9%, respectively). CLINICAL RELEVANCE: As a significant proportion of patients with OSCC reported no habits, novel risk factors for OSCC need to be investigated in further research.

Prevalence of oral mucosal lesions in patients with pemphigus vulgaris: A systematic review and meta-analysis.

OBJECTIVE: To assess the prevalence of oral mucosal lesions in patients with Pemphigus Vulgaris. METHODS: Observational studies reporting the prevalence of oral lesions in pemphigus vulgaris patients, without restriction to language and year of publication, were selected in a two-phase process. Search strategies were applied to PubMed, Scopus, Livivo, Web of Science, LILACS, Google Scholar, and OpenGrey databases. Articles assessing the prevalence of oral lesions in patients with conditions other than pemphigus vulgaris were excluded. Risk of bias analysis was performed using the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Synthesis of results was calculated by the software R Statistics version 4.0.2 (The R Foundation). Confidence in cumulative evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: From 1957 studies identified, 40 were included in qualitative synthesis and 38 in meta-analyses. The pooled prevalence of patients with oral lesions solely or concurrent with other mucocutaneous lesions was 90.3%. The prevalence of patients with exclusive oral mucosal lesions was 50.8%. Risk of bias was considered low, and the certainty of evidence was very low. CONCLUSION: Oral lesions were present in approximately nine out of 10 patients with pemphigus vulgaris. The oral mucosa was the most common site of disease onset. Further longitudinal studies are urged to assess the prevalence of oral lesions at different disease stages.

Prognostic and clinicopathological significance of podoplanin immunoexpression in oral and oropharyngeal squamous cell carcinoma: A systematic review.

BACKGROUND: Podoplanin (PDPN) is a glycoprotein associated with epithelial-mesenchymal transition, invasion, and metastasis in several types of malignancies, including oral and oropharyngeal squamous cell carcinoma (OSCC). The aim of this systematic review (SR) was to summarize and critically appraise the available evidence about the association between PDPN immunoexpression and clinicopathological features and its utility as a prognostic marker in OSCC. METHODS: Five electronic databases and three gray literature databases were searched for immunohistochemical studies, which were selected in a two-phase process. RESULTS: From 721 records identified, 22 cohort and seven analytical cross-sectional studies were included. Few studies reported that PDPN expression was associated with poorer survival rates in OSCC: overall survival = 4/12, disease-free survival = 4/7, and cancer-specific survival = 2/4 studies. Positive associations were most frequently reported on lymph node involvement, higher histopathological grade, and advanced clinical stages. CONCLUSION: Within limitations of this SR, PDPN may be associated with lymph node involvement, histopathological grade, and clinical stage of OSCC. Current evidence suggests that PDPN could be a useful prognostic marker for OSCC that needs further exploration.

Prevalence of mucoepidermoid carcinoma among intraoral minor salivary gland tumors: A systematic review and meta-analysis.

This study aimed to synthetize and critically appraise available evidence regarding mucoepidermoid carcinoma (MEC) prevalence among intraoral minor salivary gland tumors (MiSGT). Five main electronic databases and three grey literature databases were searched. The risk of bias (RoB) was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Proportion meta-analyses were performed. From 1321 studies identified, 82 were included in qualitative synthesis and 80 in meta-analyses. Sixteen were classified as high, 33 as moderate, and 33 as low RoB. A total of 12 774 MiSGT were found, of which overall MEC prevalence was 16.5% (95% Confidence Interval [95% CI] = 14.8%-18.4%). Most MiSGT were found in the palate (n = 7115), although MEC pooled prevalence in this anatomic location was only 13.6% (95% CI = 11.7%-15.6%). The retromolar area presented the highest pooled prevalence (58.9%; 95% CI = 47.0%-70.3%), followed by gingiva (28.8%; 95% CI = 22.7%-35.4%) and tongue (27.2%; 95% CI = 21.2%-33.6%). Regarding geographic location, Middle East presented the highest pooled prevalence (20.8%; 95% CI = 14.8%-27.6%), followed by America (20.0%, 95% CI = 17.2%-23%) and Europe (15.6%; 95% CI = 9.2%-23.5%). Among MiSGT, the MEC overall prevalence was approximately 16.5%. Although most MiSGT were found in the palate, the retromolar area was proportionally more affected by MEC.

A Brazilian multicentre study of 2,497 isolated cases of odontogenic keratocysts.

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.

Inhibition of cancer stem cells promoted by Pimozide.

Over the past years, studies have described that users of antipsychotics are less likely to develop cancer than the population in general due to cytotoxic properties of this class of drugs on cancer cells. For this reason, Pimozide has been widely studied as a potential anticancer treatment, and satisfactory results in melanoma, central nervous system tumours, osteosarcoma, neuroblastoma, myeloproliferative neoplasms, breast, lung, prostate, ovarian, colorectal, pancreatic, and hepatocellular carcinoma have been showed. Moreover, advantages as clinical use approved by the Food and Drug Administration (FDA), high clinical safety, low side effects, and reasonable price have stimulated the treatment with Pimozide instead of other agents. The action mechanism remains unclear, but three vias associated to cancer stem cell (CSC) hypothesis show that Pimozide: (a) blocks CSC features, as epithelial-to-mesenchymal transition (EMT), through inhibition of Wnt-ß/catenin signalling; (b) acts as an inhibitor of signal transducer and activator of transcription (STAT-3 and 5), pathway which is activated and up-regulated in CSCs; (c) inhibits ubiquitine specific protease (USP1) and WD repeat-containing protein 48 (WDR48), that are proteins responsible to inhibit the differentiation and to maintain the cell in an undifferentiated state. Based on this perspective, the aim of this manuscript is to review the antineoplastic role of Pimozide during tumorigenesis and its potential to revert the process of undifferentiation and proliferation of CSC through different vias.

Calcifying epithelial odontogenic tumours: Collaborative study of 32 cases and review of literature.

OBJECTIVES: To analyse the occurrence of calcifying epithelial odontogenic tumours (CEOT) based on biopsy records from different Brazilian geographic regions and to contrast the data with a review of the literature. MATERIALS AND METHODS: A 2-step study was conducted. Step 1 consisted of a collaborative study of biopsies obtained from 1953 to 2017 at six Brazilian oral and maxillofacial pathology centres. Evaluation of 86,268 biopsy records was performed. Demographic and histopathological diagnosis data were assessed. In Step 2, a review of the literature of case reports and cases series of CEOT identified across five electronic databases was conducted. RESULTS: In the collaborative study, 32 cases of CEOT were evaluated. This figure represented 0.03% of the oral and maxillofacial lesions and 1.7% of all odontogenic tumours across the centres. Women in the fourth decade of life were more affected. CEOT occurred more in the mandible than in the maxilla (ratio 1.9:1). The review of the literature showed that Asian individuals were more affected by this neoplasm. CONCLUSIONS: Useful knowledge on the epidemiology, treatment and follow-up of CEOT has been provided. Demographic data and clinical features of the cases presented in this collaborative study were quite similar to those of studies reported worldwide.

The synergistic effect of tobacco and alcohol consumption on oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVES: This systematic review (SR) aimed to summarise and critically appraise available evidence about the association between the synergistic consumption of alcohol and tobacco and the occurrence of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Observational studies investigating the association between the synergistic consumption of alcohol and tobacco and OSCC occurrence were included. Studies were selected in a two-phase process and searches were conducted on five main electronic databases, complemented by three grey literature databases. RESULTS: From 3260 records identified, 33 articles were included for qualitative analysis, of which 15 were included in the meta-analyses. Overall, the synergistic consumption was positively associated with the occurrence of OSCC (odds ratio [OR] = 5.37; 95% confidence interval [95%CI] = 3.54-8.14). Increased odds for OSCC occurrence were observed regarding the synergistic consumption of alcohol and smoked tobacco (OR = 4.74; 95%CI = 3.51-6.40), alcohol and smokeless tobacco (OR = 7.78; 95%CI = 2.86-21.14), and alcohol, smoked tobacco, and smokeless tobacco (OR = 16.17; 95%CI = 7.97-32.79). CONCLUSIONS: According to the results of this SR, the synergistic consumption of alcohol and tobacco (both smoked and smokeless) significantly increased the odds for the occurrence of OSCC. CLINICAL RELEVANCE: The knowledge provided by this SR may be useful for a better understanding of differences in the effect of synergistic consumption of alcohol and tobacco products in OSCC development. These data might aid healthcare authorities to develop measures for tobacco and alcohol control considering the needs of their population.

Prevalence of oral potentially malignant disorders: A systematic review and meta-analysis.

Oral potentially malignant disorders (OPMD) are chronic conditions, which have a higher risk of transformation to oral squamous cell carcinoma. The aim of this systematic review and meta-analysis was to answer the question: "What is the prevalence of oral potentially malignant disorders among adults?" Studies reporting the prevalence of these conditions (leukoplakia, erythroplakia, oral submucous fibrosis [OSMF], and actinic cheilitis) were selected, only studies in which a clinical assessment and histopathological confirmation were performed were included. Of the 5513 studies, 22 met the inclusion criteria for qualitative and quantitative analyses. The risk of bias (RoB) of the selected studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Seven studies were classified as high risk, 12 as moderate risk, and 3 as low RoB. The meta-analysis showed that the prevalence of OPMD was 4.47% (95% CI = 2.43-7.08). The most prevalent OPMDs were OSMF (4.96%; 95% CI = 2.28-8.62) and leukoplakia (4.11%; 95% CI = 1.98-6.97). OPMDs were identified more commonly in males (59.99%; 95% CI = 41.27-77.30). Asian and South American/Caribbean populations had the highest prevalence rates of 10.54% (95% CI = 4.60-18.55) and 3.93% (95% CI = 2.43-5.77), respectively. The overall prevalence of OPMD worldwide was 4.47%, and males were more frequently affected by these disorders. The prevalence of OPMD differs between populations; therefore, further population-based studies may contribute to the better understanding of these differences.

A multicentre study of oral paracoccidioidomycosis: Analysis of 320 cases and literature review.

OBJECTIVES: To investigate the frequency of oral paracoccidioidomycosis from representative geographical regions of Brazil and to compare the data with a literature review. MATERIALS AND METHODS: A retrospective study was conducted on 108,304 biopsies obtained from 1953 to 2016 at six Brazilian oral and maxillofacial pathology services. Demographic data and clinical and histopathological diagnosis of oral paracoccidioidomycosis were evaluated. A literature review of oral paracoccidioidomycosis studies published in three electronic databases was carried out. Data were analysed descriptively. RESULTS: A total of 320 cases of oral paracoccidioidomycosis were surveyed (0.3% of the oral lesions at the centres studied). The lesions were more frequent among male patients. The gingiva/alveolar ridge was the most affected site. Mean age of affected individuals was 51.3 years (±11.7). The literature review showed a higher incidence of oral paracoccidioidomycosis in the south-east and south regions of Brazil. Male individuals and individuals between 50 and 59 years were most affected. CONCLUSIONS: Oral paracoccidioidomycosis is an uncommon lesion observed in oral biopsy samples. The differences in the relative frequency of oral paracoccidioidomycosis are related to geographical variations. Men between 50 and 59 years are more affected. This study provides helpful information for clinicians in the diagnosis of oral paracoccidioidomycosis.

A multicentre study of 268 cases of calcifying odontogenic cysts and a literature review.

OBJECTIVES: To investigate the frequency of calcifying odontogenic cysts (COCs) that have been submitted for microscopic examination from representative geographic regions of Brazil and to compare it with literature data. MATERIALS AND METHODS: A retrospective study was conducted on biopsies obtained from 1953 to 2016 at 10 Brazilian oral and maxillofacial pathology centres. A total of 198,350 biopsy specimens were analysed. Demographic data and histopathological diagnosis were evaluated descriptively and statistically. In addition, a literature review of case series was carried out in four electronic databases. RESULTS: A total of 268 cases of COC were surveyed, representing 0.1% of the oral lesions at the centres studied. Female patients in their second decade of life and the maxilla were more affected. The mean lesion size of symptomatic individuals was larger than that of cases without symptoms (p = 0.026). The literature review showed a higher frequency in Asia and Europe, mainly affecting men in the third decade of life. CONCLUSIONS: COC is a rare lesion. Novel data on the clinicopathological features of 268 cases have been added to the literature. Data regarding gender and age of the Brazilian patients reported herein contrast with findings of case series and retrospective studies reported elsewhere.

Evaluation of Mandibular Bone After Dental Extraction in Rats Treated With Antiresorptive Drugs.

PURPOSE: Zoledronic acid (ZOL) and denosumab (Dmab) are commonly used to treat bone pathologies. Because these drugs suppress bone metabolism, this study sought to compare their effect on bone repair after tooth extraction. MATERIALS AND METHODS: Four-week-old male Wistar rats were randomly assigned to 1 of 3 groups: ZOL 0.125 mg/kg, Dmab 0.25 mg/kg, or saline solution 10 mL/kg (control). After 1 week of treatment, the first left molar was extracted; the rats were euthanized at 28 days. The jaws were removed and photographed for macroscopic analysis of wound healing and then subjected to tomographic and histologic analyses. Immunohistochemistry was carried out against the receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG). RESULTS: No difference in wound healing, presence of inflammatory infiltrate and bone sequestration, or osteocyte expression of RANKL and OPG was found among groups. Tomographic analysis showed that the ZOL group had less alveolar resorption and more complete alveolar repair compared with the other groups. There was a statistically significant difference in the OPG marker in the control (P = .008) and ZOL (P = .05) groups when comparing the extracted and non-extracted sides. CONCLUSION: Systemic use of ZOL can improve alveolar bone healing; however, the potential risk for the development of osteonecrosis should be considered. Higher expression of OPG seems to be associated with the control of osteoclastogenesis during bone repair.

Comparative evaluation of the GP5+/6+, MY09/11 and PGMY09/11 primer sets for HPV detection by PCR in oral squamous cell carcinomas.

The aim of this study was to evaluate the use of GP5+/6+, MY09/11 and PGMY09/11 primer sets for the detection of human papillomavirus (HPV) DNA by single step polymerase chain reaction (PCR) and nested PCR in formalin-fixed and paraffin-embedded (FFPE) tissues from oral squamous cell carcinomas (OSCCs). DNA extracted from FFPE tissues were tested for amplification of the human beta globin gene with PCO3/4 primers. Positive samples for this gene were tested for HPV DNA using single step PCR with GP5+/6+, MY09/11 and PGMY09/11 primer sets. All negative samples at single step PCR with MY09/11 and PGMY09/11 were subjected to a further PCR with GP5+/6+ primers using the non-amplified product in the previously reactions (nested PCR) as samples. Among 26 samples, 23 were positive for the human beta globin gene and were considered viable for HPV DNA detection by PCR. Single step PCR with GP5+/6+ and MY09/11 primers and MY/GP+ nested PCR did not amplify HPV DNA in any samples. PGMY09/11 primers detected HPV DNA in 13.0% of OSCC cases and this rate was raise to 17.4% with the use of PGMY/GP+ nested PCR. According to our results the PGMY/GP+ nested PCR is the most appropriate primer set for the detection of HPV DNA using FFPE samples from OSCC.

Immunohistochemical expression of matrix metalloproteinases in ameloblastomas and pericoronal follicles.

BACKGROUND: Ameloblastoma (AM) is a benign odontogenic neoplasm characterized by local invasiveness and recurrence. We compared the immunohistochemical expression of matrix metalloproteinases in different clinical types of AM as well as in normal odontogenic tissue. METHODS: Thirteen cases of solid AMs, five cases of unicystic AM and eight pericoronal follicles (PF) were selected and subjected to immunohistochemical investigation for matrix metalloproteinase-1, matrix metalloproteinase-2 and matrix metalloproteinase-9 expressions. RESULTS: The expressions of MMP-1 and MMP-2 were very high in the cytoplasm of cells throughout the entire epithelium and in fibroblasts from the adjacent connective tissue. MMP-9 expression was observed in the same location although with weaker staining. The Kruskal-Wallis test showed statistically significant differences in the epithelial expressions of MMP-1 and MMP-2; there was lower expression among solid AMs when compared with unicystic AM and PF. Compared to both types of AM, higher stromal expression of MMP-9 was found in PF. CONCLUSION: MMP-1, MMP-2 and MMP-9 seem to be associated with AM tumour behaviour as well as physiological tissue remodelling within PF.

A Rare Case of Labial Myiasis caused by Dermatobia hominis.

INTRODUCTION: The aim of this article is to present a rare case of myiasis caused by Dermatobia hominis. Myiasis is a disease caused by invasion of tissues of animals and humans by larval stages of dipterous (2-winged) flies. There are few reports of oral myiasis in the literature, mostly related to Cochliomyia hominivorax larvae. We present a case of a 53-year-old man with painful swelling of the left lower lip that was confirmed to be myiasis caused by D. hominis. Though more common in tropical and subtropical regions of North and South America, myiasis should be considered in the differential diagnosis of subcutaneous masses among residents or travelers in endemic areas.

A Rare Case of Mucoepidermoid Carcinoma ex Pleomorphic Adenoma arising in Minor Salivary Gland: Histopathological and Immunohistochemical Analysis.

Mucoepidermoid carcinoma ex pleomorphic adenoma (MCxPA) is a rare salivary gland tumor predominantly found in major salivary glands. A case of MCxPA involving the soft tissue and bone of the retromolar region of a 26-year-old man is presented. The histopathological features revealed a neoplasm with predominance of pleomorphic adenoma (PA) elements, and presence of mucoepidermoid carcinoma malignant epithelial cells in several areas. Histochemical and immunohistochemical studies were positive for periodic acid Schiff, alcian blue, cytokeratins 7, 13, 14, and 19, Bcl-2, c-erbB-2, FGF-2 and maspin in the malignant areas. The patient underwent a partial resection of the left side of the mandible with neck dissection and MCxPA diagnosis was confirmed.

Immunohistochemical analysis of matrix metalloproteinases (1, 2, and 9), Ki-67, and myofibroblasts in keratocystic odontogenic tumors and pericoronal follicles.

BACKGROUND: Keratocystic odontogenic tumor (KCOT) is a benign tumor that arises sporadically or associated with nevoid basal cell carcinoma syndrome (NBCCS). Its locally aggressive behavior contrasts with its cystic histological appearance. To better understand the interaction between tumor cells and the stroma, the present study aimed to evaluate and compare the immunohistochemical expression of matrix metalloproteinases (MMP-1, -2, and -9), the cellular proliferation index (Ki-67), and the presence of myofibroblasts (MFs) in KCOTs. METHODS: Eleven cases of isolated KCOT (G1) and 12 cases of KCOT associated with NBCCS (G2) were selected for an immunohistochemical investigation of the proteins MMP-1, MMP-2, MMP-9, Ki-67, and α-smooth muscle actin (α-SMA) in MFs. A group of 6 pericoronal follicles (G3) was included as a normal odontogenic tissue control. RESULTS: Significant differences between the G3 and G1/G2 groups regarding the expression of MMP-1, MMP-9 (in connective tissue), and Ki-67 were observed. In KCOT, there was a positive correlation between the Ki-67 antigen and MMP-1 and between MFs and MMP-1 in the parenchyma. No statistical differences were found between G1 and G2 groups. CONCLUSIONS: MMP-1, MMP-9, and proliferative activity appear to play important roles in KCOT pathogenesis. The increased proliferative activity with KCOT was associated with elevated MMP-1 production in the parenchyma, which influenced the growth of the lesion in association with an increased number of MFs.