OralEpitheliumDB: A Dataset for Oral Epithelial Dysplasia Image Segmentation and Classification.

Early diagnosis of potentially malignant disorders, such as oral epithelial dysplasia, is the most reliable way to prevent oral cancer. Computational algorithms have been used as an auxiliary tool to aid specialists in this process. Usually, experiments are performed on private data, making it difficult to reproduce the results. There are several public datasets of histological images, but studies focused on oral dysplasia images use inaccessible datasets. This prevents the improvement of algorithms aimed at this lesion. This study introduces an annotated public dataset of oral epithelial dysplasia tissue images. The dataset includes 456 images acquired from 30 mouse tongues. The images were categorized among the lesion grades, with nuclear structures manually marked by a trained specialist and validated by a pathologist. Also, experiments were carried out in order to illustrate the potential of the proposed dataset in classification and segmentation processes commonly explored in the literature. Convolutional neural network (CNN) models for semantic and instance segmentation were employed on the images, which were pre-processed with stain normalization methods. Then, the segmented and non-segmented images were classified with CNN architectures and machine learning algorithms. The data obtained through these processes is available in the dataset. The segmentation stage showed the F1-score value of 0.83, obtained with the U-Net model using the ResNet-50 as a backbone. At the classification stage, the most expressive result was achieved with the Random Forest method, with an accuracy value of 94.22%. The results show that the segmentation contributed to the classification results, but studies are needed for the improvement of these stages of automated diagnosis. The original, gold standard, normalized, and segmented images are publicly available and may be used for the improvement of clinical applications of CAD methods on oral epithelial dysplasia tissue images.

Depth of invasion of oral squamous cell carcinoma in Nos2-knockout mice correlated to alterations in systemic inflammatory markers following 4NQO treatment.

BACKGROUND: Peripheral blood analysis is a non-invasive and low-cost technique of prognostic value for several diseases, including oral cancer. Considering the role of inducible nitric oxide synthase in tumor-associated inflammation, this study purposed to evaluate the influence of this enzyme on peripheral blood parameters and systemic inflammatory biomarkers during murine oral carcinogenesis. METHODS: A 50 µg/mL solution of 4-nitroquinoleine-N-oxide was provided to 15 C57BL/6J (Nos2+/+ ) and 16 B6.129P2-Nos2tm1Lau /J (Nos2-/- ) for 16 weeks. Animals were followed for 8 weeks after treatment. Blood samples and tongues were collected for hematological and histopathological analyses. Red blood cells, white blood cells, and platelet cell parameters were analyzed. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index were also calculated. The depth of invasion of all carcinomas was measured. RESULTS: Differences were found in several blood parameters. The depth of invasion in Nos2-/- was lower than in Nos2+/+ (p = 0.009), and strong correlations were found between depth of invasion and neutrophil count (ρ = -0.68, p = 0.017), lymphocyte count (ρ = 0.72, p = 0.011), neutrophil-to-lymphocyte ratio (ρ = -0.65, p = 0.025), platelet-to-lymphocyte ratio (ρ = -0.73, p = 0.013), and systemic immune-inflammation index (ρ = -0.67, p = 0.037) in Nos2-/- mice. CONCLUSION: Inducible nitric oxide synthase seems to have an important role in OSCC invasion and progression, which might be associated to alterations in immune-inflammatory cell dynamics evidenced by peripheral blood and systemic inflammatory biomarkers.

Histopathological diagnosis in pediatric stomatology: A 43-year retrospective study of 1,480 cases from a Brazilian institution.

OBJECTIVES: the aim of this study was to analyze the prevalence of histopathological diagnoses in oral biopsied tissues obtained from a Brazilian pediatric population. METHODS: an analytical, cross-sectional retrospective study was performed with biopsy files of patients ≤14 years of age from a Brazilian oral pathology laboratory over a 43-year period. Data included sex, age, location, and diagnoses. The prevalence was calculated by means of relative frequency. Associations between sex, age groups and diagnoses were verified with Pearson's chi-square test. RESULTS: from 19,456 oral biopsies, 1480 (7.6%) were obtained from patients aged ≤14 years. Most children were 10-14 years of age (60.1%) and females (55.1%), with an overall M:F of 1:1.2. Children aged 0-9 years and males had a higher frequency of lesions of the oral mucosa, whilst the 10-14 year age group showed a higher frequency of cysts, odontogenic tumors, and salivary gland lesions. The latter was also significantly higher in females. Samples consisted mostly of soft tissue lesions (53%) obtained from the lower lip (30.7%). Intraosseous lesions showed a slight predilection for the mandible (21.2%). Salivary gland lesions (28.8%) was the most common diagnostic category, followed by reactive lesions (18.8%), and cysts (16.1%). Mucocele (33.5%), dentigerous cyst (6.7%), and fibrous hyperplasia (5.9%) were the top three histopathological diagnoses. Malignant lesions affected only 0.9% of this population. CONCLUSION: our results were similar to other retrospective studies. Due to the low frequency of oral biopsies in children, data on the prevalence of oral pathology in this population might aid in the clinical and histopathologic diagnoses.

Vulnerability of the young university population to HIV/AIDS and other sexually transmitted infections

Introduction: Brazilian universities receive annually thousands of young people who experience situations of vulnerability to the human immunodeficiency virus, sexually transmitted infections, and viral hepatitis. Objective: The aim of the present study was to analyze the secondary data obtained from the attendance record of the rapid testing campaign for these health problems at a federal university in the state of Minas Gerais, Brazil, in 2019. Methods: A cross-sectional study was conducted with secondary data of students (n=1,113) obtained from the standard attendance form by the Ministry of Health during the campaigns Fique Sabendo (Be Aware) in the period between November 25 and 29, 2019. Analyses were performed with the support of the Statistical Package for Social Sciences program, with the calculation of absolute and relative frequencies. Pearson's chi-square test (5%) was used for comparison. Results: The results revealed a young, heterosexual, white profile. More than half reported having consumed alcohol and drugs in their lives. Other findings were the non-use of condoms with steady partners (18.1%) and occasional partners (21.3%), oral sex (86.8%), and unprotected sex in the last intercourse (45.6%). Most declared never being tested for human immunodeficiency virus (74.5%), syphilis (67.4%), hepatitis B (76.1%), or hepatitis C (77.0%). Conclusion: The university population is vulnerable to human immunodeficiency virus and other sexually transmitted infections due to the number of sexual partners and discontinued use of condoms with occasional partners. Such vulnerability is increased by the use of alcohol and other drugs

Immunoexpression of PD-L1, CD4+ and CD8+ cell infiltrates and tumor-infiltrating lymphocytes (TILs) in the microenvironment of actinic cheilitis and lower lip squamous cell carcinoma.

OBJECTIVE: Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient.Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. METHODOLOGY: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. RESULTS: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. CONCLUSION: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

Immunoexpression of PD-L1, CD4+ and CD8+ cell infiltrates and tumor-infiltrating lymphocytes (TILs) in the microenvironment of actinic cheilitis and lower lip squamous cell carcinoma

Abstract Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient. Objective: Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. Methodology: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. Results: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. Conclusion: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs.

Differential diagnoses of solitary and multiple pigmented lesions of the oral mucosa: Evaluation of 905 specimens submitted to histopathological examination.

BACKGROUND: The aim was to analyze the frequency, clinical and demographic features of solitary and multiple/diffuse oral pigmented lesions submitted to histopathological examination, and to summarize the features that guide the clinical differential diagnosis. METHODS: Clinical and demographic data were retrieved from biopsy records and descriptive statistics were performed. RESULTS: Nine hundred and five (0.51%) oral pigmented lesions were retrieved among 177 356 specimens, being 95.9% solitary and 4.1% multiple/diffuse lesions. Regardless the overlapping clinical presentation, age, site, association with amalgam restoration, and a nodular appearance may help in the clinical differential diagnosis of solitary oral pigmentations. Patient's habits, site, and systemic signs and symptoms are helpful in the clinical differential diagnosis of multiple/diffuse lesions. CONCLUSIONS: Oral pigmented lesions are a rare diagnosis in oral pathology and solitary lesions are more commonly submitted to biopsy. Some key features help in the differential diagnosis, though biopsy can be warranted in doubtful cases.

Revisiting the metallothionein genes polymorphisms and the risk of oral squamous cell carcinoma in a Brazilian population / Revisando los polimorfismos de los genes de metalotioneína y el riesgo de carcinoma oral de células escamosas en una población brasileña

Background: Metallothioneins (MTs) gene polymorphisms have been associated with the ability of free radicalscavenging and detoxification of heavy metals leading to cancer development. Our aim was to revisit, in a Brazil-ian population, single-nucleotide polymorphisms (SNPs) of the MT gene family previously associated with oralsquamous cell carcinoma (OSCC).Material and Methods: A case-control investigation with 28 OSCC patients and 45 controls was conducted, usingconventional risk factors (tobacco use and alcohol consumption) as covariates. SNPs genotyping for rs8052334(MT1B), rs964372 (MT1B), and rs1610216 (MT2A) was performed by PCR-RFLP, and SNPs for rs11076161(MT1A) were analyzed by TaqMan assay.Results: The only SNP associated with increased risk for OSCC was the MT-1A AA genotype (OR = 4.7; p = 0.01).We have also evidenced for the first time a significant linkage disequilibrium between the SNPs of MT-2A andMT-1A in this population with the highest frequency (30%) of the unfavorable haplotype G/A/C/T (rs1610216 /rs11076161 / rs964372 / rs8052334) of MT gene polymorphisms (OR = 6.2; p = 0.04). Interestingly, after removingthe effects of conventional risk factors, we have uncovered the significance of the AA genotype of the rs11076161with increased odds of 19-fold higher towards OSCC development.Conclusions: This is the first demonstration that a significant linkage disequilibrium among gene polymor-phisms of the MT family may affect susceptibility to oral cancer, which is conditioned by the G/A/C/T haplotype(rs1610216/rs11076161/rs964372/ rs8052334) and the MT-1A gene polymorphism has a potential clinical utility forthe OSCC risk assessment.(AU)

A retrospective study of 30 basal cell adenomas of the salivary gland in a Brazilian population and literature review.

PURPOSE: The present study aimed to provide the clinicopathological data of Brazilian patients with basal cell adenoma (BCA). METHODS: Records of BCA cases were retrospectively gathered from the Brazilian National Cancer Institute database between 1996 and 2006. All cases were histopathologically reviewed, and the clinicopathological data were collected from the patients' medical files. In addition, an English literature review about this tumor is also presented. RESULTS: Of 1127 salivary gland tumors identified, 30 were BCAs (2.7%). Women were more affected than men (70.0% vs. 30.0%), and the majority (60.0%) were elderly (> 65 years old). The parotid gland was the most frequent location affected (93.3%), followed by the upper lip (3.3%) and submandibular gland (3.3%). Fine-needle aspiration was the main procedure applied to establish a preoperative diagnosis of tumor; however, the results were not always consistent. Histopathologically, the trabecular pattern was the most common type seen (50.0%) among our BCA samples. Most patients underwent superficial or partial parotidectomy. Frey's syndrome was reported only in one case during the follow-up. No recurrence was noted in the present series. The literature review revealed a total of 213 reported cases of BCA in the period investigated. CONCLUSIONS: This is the first case series of BCA reported in Brazil. As occurred in other previously reported series, the clinicopathological data of BCAs are similar and confirm that this type of tumor is rare, develops predominantly in the parotid gland, frequently affects older women, has an indolent behavior, and the affected patients have an excellent prognosis.

The role of the histones H3K9ac, H3K9me3, HP1γ, and H3K36me3 in oral squamous cell carcinoma loco-regional metastasis and relapse.

Molecular markers with unequivocal significance in predicting cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) has not yet been identified. Histones are DNA-binding proteins that can regulate gene expression, and some studies have shown that such proteins are implicated with tumor development and progression. This study aimed to investigate the expression of some histone modifications in OSCC and their roles in cervical lymph node metastasis. To address this goal, H3K9ac, H3K9me3, HP1γ, and H3K36me3 expression levels were investigated immunohistochemically in a retrospective metastatic and non-metastatic OSCC samples. We analyzed the association between these markers with clinical-pathological data and survival rates. Hyperacetylation of H3K9ac was associated with cervical lymph node metastasis and local relapse. High expression levels of H3K9m3 were related to age and symptomatology. Furthermore, it was also found a statistically significant association between high HP1γ-expressing tumors and tumor size. However, no markers were associated with reduced overall survival rate. Our results suggest that covalent histone modifications contribute to OSCC behavior, and H3K9ac may play a critical role in OSCC-derived cervical lymph node metastasis.

Simple bone cyst: description of 60 cases seen at a Brazilian School of Dentistry and review of international literature

BACKGROUND: The aim of this study was to describe the relative frequency and the main demographic and clinic-radiographic features related to patients diagnosed with Simple bone cyst (SBC) in an Oral Diagnosis Service in Southeast Brazil and present a review and discussion of international literature on this topic. MATERIAL AND METHODS: SBC cases from our service encompassing the period between 1978 and 2017 were selected. In addition, a literature search was performed in the Pubmed/MEDLINE online electronic database published between 1951 and 2019. RESULTS: A total of 2,459 cystic lesions were documented in our service, thus 60 patients were diagnosed with the SBC representing 2.4% of all jaw cystic. Most of cases were asymptomatic. Multiple SBC lesions were seen in two patients (3.4%) and association with cemento-osseous dysplasia was seen in one female patient (1.7%). A total of 793 cases were enrolled in this literature review. CONCLUSIONS: The SBC is an asymptomatic lesion often discovered in routine image exams in young patients. The unilocular, well defined margin with scalloped appearance is characteristic and helps the definition of diagnosis. This review suggests a different epidemiologic trend concerning to the sex and it confirms the posterior region of mandible as the more frequent location. The conservative treatment with limited exploration and curettage remains as the gold-standard treatment

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Upregulation of tropomyosin alpha-4 chain in patients' saliva with oral squamous cell carcinoma as demonstrated by Phage display.

Patients with oral squamous cell carcinoma (OSCC) present significant alterations in their saliva proteome. We have used the shotgun Phage Display (PD) technology to identify candidate proteins that were upregulated in saliva of OSCC by selecting ligands to salivary proteins from a single-chain variable fragment (scFv) PD combinatorial library. After two selection cycles, the highly reactive clone scFv-D09 was able to distinguish saliva of OSCC patients from healthy subjects by enzyme-linked immunosorbent assay (ELISA) with sensitivity and specificity of 96.67%. Additionally, the scFv-D09 clone presented a positive immunostaining for invasive malignant epithelial cells in the connective tissue, keratin pearls in the OSCC, and ducts of salivary glands. We have further identified the target protein as the tropomyosin alpha-4 chain (TPM4) by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry, and its binding to the scFV-D09 was demonstrated by bioinformatics. Briefly, we have identified TPM4 as upregulated salivary protein in patients with OSCC, which plays a central role in stabilizing cytoskeleton actin filaments, probably linked with tumor tissue remodeling. Long-term longitudinal studies are needed to validate TPM4 as a potential marker of a malignant process.

The importance of inducible nitric oxide synthase and nitrotyrosine as prognostic markers for oral squamous cell carcinoma.

BACKGROUND: The prognosis of human cancer depends on the deregulations of many molecular patterns. In recent years, a great interest in the intracellular signaling mechanisms related to nitric oxide (NO)-induced carcinogenesis has appeared, as one of the most preeminent prognostic markers for many types of neoplasms. In this study, we identify the levels of iNOS and nitrotyrosine in the sample of normal oral mucosa (NOM), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). METHODS: Quantitative polymerase chain reactions (qPCRs) were utilized to detect the NOS2 levels in fresh-frozen tissue samples of NOM (n = 6), OL (n = 20), and OSCC (n = 15). Moreover, the immunohistochemical method was used to examine the levels of iNOS and nitrotyrosine in 85 cases of OSCC (39 cases without metastases and 46 with metastases), 42 cases of OL, and 16 cases of NOM. RESULTS: There are rising tendencies in the iNOS mRNA and protein levels during human oral carcinogenesis. Similar findings were obtained in the nitrotyrosine staining. Furthermore, iNOS and nitrotyrosine immunostaining are associated with several clinical-pathological features of OSCC (site, presence of metastasis, staging, recidivism, and survival). CONCLUSIONS: The NO-signaling pathway plays a vital role in the development and progression of human oral dysplastic and neoplastic diseases. Nitrotyrosine was a significant marker for the discrimination of OSCC prognosis and survival.

Multiple calcifying epithelial odontogenic tumor: case report and review of the literature.

Calcifying epithelial odontogenic tumor (CEOT) is a rare benign neoplasm, and few cases of multiple lesions have been published. This article reports the case of a 26-year-old male patient with bilateral gingival lesions near the maxillary canines and a hard tumor on the left side of the mandible. All lesions presented mixed radiographic appearance (radiolucent and radiopaque). Incisional biopsies revealed typical histopathologic findings of CEOT. The gingival lesions were removed by curettage, and the mandibular tumor was surgically resected. No recurrence was detected after 6 years of treatment. Five well-documented cases of multiple CEOT were retrieved from the PubMed database. These patients were slightly older than those with solitary tumors, and none of them presented syndromic features. Three cases had only multiple central tumors, and the other 2 had multiple peripheral lesions, so the present patient is the first to manifest with both central and peripheral tumors.

Um raro diagnóstico de osteoma periférico em palato duro: relato de caso / A rare diagnosis of peripheral osteoma in the hard palate: case report

Objetivo: relatar uma biópsia excisional de um osteoma periférico no palato duro direito de uma paciente jovem, do sexo feminino e não sindrômica. Relato de caso: paciente do sexo feminino, 32 anos de idade, melanoderma e normossitêmico, buscou atendimento no ambulatório de diagnóstico estomatológico da Faculdade de Odontologia da Universidade Federal de Uberlândia com queixa quanto ao surgimento de lesão na região de palato. Após avaliação clínica e imaginológica, foi decidido realizar biópsia excisional sob anestesia local da lesão. Foram levantadas três hipóteses de diagnóstico: osteoma periférico, exostose ou osteossarcoma. O material coletado foi enviado para análise histopatológica, que confirmou a hipótese de osteoma periférico. Considerações finais: os osteomas periféricos na região de palato duro são raríssimos. Essa lesão geralmente é assintomática ­ exceto quando há impacto traumático durante a mastigação ­, de crescimento lento, podendo se desenvolver em osso cortical ou medular. O tratamento de escolha é a remoção cirúrgica e o índice de recorrência é raro. O caso enfatiza a condição rara, pois foram encontrados apenas seis casos semelhantes relacionados na literatura. (AU)

Objective: To report an excisional biopsy of a peripheral osteoma in the right hard palate in a non-syndromic young female patient. Case Report: A 32-year-old female patient, black, and normosystemic sought assistance in the stomatological diagnosis outpatient clinic of the School of Dentistry of the Federal University of Uberlândia, Brazil, complaining about the appearance of a lesion in the palate region. After clinical and imaging assessment, it was decided to perform an excisional biopsy under local anesthesia of the lesion. Three diagnostic hypotheses were raised - peripheral osteoma, exostosis, or osteosarcoma. The material collected was sent for histopathological analysis, which confirmed the hypothesis of peripheral osteoma. Final considerations: Peripheral osteomas in the hard palate region are very rare. This lesion is usually asymptomatic, except when there is a slow-growing chewing impact during mastication, which may develop in cortical or spinal bone. Surgical removal is the treatment of choice and the rate of recurrence is rare. The case emphasizes the rare condition, considering only six similar cases were found in the literature. (AU)

Reduced CD8+ T cells infiltration can be associated to a malignant transformation in potentially malignant oral epithelial lesions.

OBJECTIVE: The aim of this study was to evaluate the immunohistochemical expressions of PD1, CD4+, and CD8+ in premalignant lesions (OPML) that were transformed into oral squamous cell carcinoma OSCC (OPML-OSCC), in OSCC and also in premalignant lesions that were not transformed into OSCC (OPML-NOSSC). MATERIALS AND METHODS: Retrospective analyses were performed in order to verify the demographic characteristics of the patients. CD4, CD8, and PD1 IMH studies were carried out on OPML and OSCC samples from 11 patients with OPML-OSCC and OPML, together with samples from 14 patients with OPML-NOSCC. The differences between OPML-OSCC and OPML-NOSCC were analyzed. RESULTS: Non-homogenous leukoplakia, together with the related oral subsite, and the lack of an exposure to tobacco, were all associated with malignant transformations. There were no statistical differences in the PD1 expression and the CD4+ cells in OPML-OSCC and OPML-NOSCC. A significant increment in the CD8+ cells was noted in the OPML that evolved into carcinomas when compared with OPML-NOSCC (p = 0.05), whereas there were higher CD8+ cells levels in the carcinomas when compared with the OPML that evolved into carcinomas (p = 0.027). CONCLUSIONS: CD8+ cells infiltrate more in OPML-NOSCC than in OPML-OSCC. Carcinoma is more infiltrated by CD8+ cells than its associated OPML. CLINICAL RELEVANCE: Understanding immunological factors associated with malignant transformation of oral premalignant lesions can open a new way to treat this disease.

Odontogenic carcinosarcoma: morphologic and immunohistochemical description of a case.

OBJECTIVES: The goal of this study was to describe an extremely rare case of odontogenic carcinosarcoma and compare the findings with those of a literature review. STUDY DESIGN: The clinical and pathologic data of an odontogenic carcinosarcoma affecting the posterior maxilla of a 42-year-old male patient was described. The lesion was immunostained for cell-cycle, cytokeratin, and mesenchymal markers. A review of literature from 1960 to 2017 was conducted in a search for similar well-documented case reports. Descriptive statistics were calculated to compare clinical and pathologic variables. RESULTS: In the reported case, the percentage of Ki-67-positive epithelial and mesenchymal cells was estimated as 40% and 25%, respectively. Epithelial cells were focally positive for cytokeratin 7, -8, -14, and -18, and diffusely positive for cytokeratin 19, p53, and p16. Mesenchymal cells were strongly positive for desmin, HHF-35, and vimentin. Our review showed that odontogenic carcinosarcoma is diagnosed mostly in the advanced stage. All patients with relapsed tumors had died as a result of the disease. CONCLUSIONS: Very few cases have been reported in the literature supporting that most odontogenic carcinosarcoma develop in the posterior mandible in a wide age range, without gender and racial predilections. Only one case of odontogenic carcinosarcoma in the maxilla other than the one described here has been reported. Until today, the best treatment remains unknown.

Pathologic significance of AKT, mTOR, and GSK3ß proteins in oral squamous cell carcinoma-affected patients.

Phosphatidylinositol-3-kinases are kinases that lead to AKT phosphorylation and thus mTOR and GSK3ß activation. These proteins are linked to tumorigenesis, but their roles in driving cervical lymph node (CLN) metastasis of oral squamous cell carcinoma (OSCC) cells are unknown. This study aimed to investigate the role of AKT, mTOR, and GSK3ß proteins in the occurrence of CLN metastasis in OSCC patients. Ninety and 18 paraffin-embedded OSCC and oral mucosa samples were included, respectively. We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1Thr308, pAKTSer473, GSK3ß, pGSK3ßSer9, and pmTORSer2448 was analyzed by immunohistochemistry. The mean expression of GSK3ß, pGSK3ßSer9, total AKT, and pmTOR2448 was always higher in the OSCC tissues than that in the controls. A positive correlation was also found among these proteins. Total AKT, pmTORSer2448, and pGSK3ßSer9 expression was significantly higher in the PNM and PM groups than that in the control group. However, only GSK3ß expression was significantly higher in the PM group compared with the PNM group. High expression levels of GSK3ß and pGSK3ßSer9 were significantly associated with CLN metastasis, but only GSK3ß remained an independent predictor of CLN metastasis. pGSK3ßSer9 and CLN metastasis were associated with a poor prognosis, but only the latter remained an independent prognostic parameter. Kaplan-Meier survival curves showed that pGSK3ßSer9 and CLN metastasis were significantly related to reduced survival rates. These results suggest that AKT and mTOR proteins are involved in OSCC biology and that GSK3ß itself may drive CLN metastatic spread of OSCC cells.

Differential metallothionein expression in oral lichen planus and amalgam-associated oral lichenoid lesions

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease mediated by T cells, which manifests as reticular (white) or erosive (red) lesions, that are eventually painful. Oral lichenoid lesion (OLL) are distinguished from OLP by the presence of precipitating factors. The aim of this study was to evaluate whether the presence of metallothionein, which is involved in anti-apoptotic pathways and the anti-oxidative response, could serve as a differential diagnostic for OLP and OLL. MATERIAL AND METHODS: We evaluated the expression of metallothionein in 40 cases of OLP and 20 cases of OLL using immunohistochemistry. Results and CONCLUSIONS: White OLP has higher concentrations of metallothionein than red OLP in basal and parabasal layers. Moreover, metallothionein was more frequently observed in the cytoplasm and nuclei of basal cells in OLP patients compared to the same regions of OLL cases. Metallothionein levels are related to OLP severity and may contribute to a differential diagnosis between OLP and OLL

Variation of Energy in Photobiomodulation for the Control of Radiotherapy-Induced Oral Mucositis: A Clinical Study in Head and Neck Cancer Patients.

Oral mucositis (OM) is a frequent and severe adverse effect of therapy against head and neck cancer. Photobiomodulation with the low-power laser is known to be effective against OM, but the diversity of protocols and the possibility of stimulating residual tumor cells are still obstacles. The present study aimed to compare two doses of laser energy delivered to the oral mucosa of patients under oncologic treatment for head and neck cancer, looking for differences in the control of mucositis, as well as in the frequency of tumoral recurrences. Fifty-eight patients undergoing radiotherapy were randomized into two groups, distinguished according to the energy delivered by laser irradiation, namely, 0.25 J and 1.0 J. The groups were compared according to frequency, severity, or duration of OM, as well as the frequency of tumoral recurrences. OM was significantly less frequent in patients receiving 1.0 J of energy, but the groups did not differ regarding severity or duration of OM. Tumoral recurrence also did not vary significantly between the groups. Photobiomodulation with a higher dose of energy (1.0 J versus 0.25 J) is associated with better control of radiotherapy-induced OM and does not significantly increase the risk of neoplastic recurrence.