Acquired oral syphilis: A multicenter study of 339 patients from South America.

OBJECTIVE: To report the clinicopathologic features of acquired oral syphilis cases in South American countries. MATERIALS AND METHODS: Clinical data were retrospectively collected from the records of 18 oral diagnostic services in Argentina, Brazil, Chile, Colombia, Venezuela, Uruguay, and Peru. Serologies of nontreponemal and treponemal tests were used for diagnosis. RESULTS: The series comprised 339 cases of acquired oral syphilis. Secondary syphilis ranked as the most common stage (86.7%). Lesions were more frequent among males (58.0%) and young adults with a mean age of 33.3 years. Individuals aged 20-29 years were most affected (35.3%). The most commonly involved sites were the tongue (31.6%), lip/labial commissure (25.1%), and hard/soft palate (20.4%). Clinically, acquired oral syphilis usually presented as mucous patches (28.4%), papules (25.7%), and ulcers (18.1%). Skin manifestations occurred in 67.7% of individuals, while lymphadenopathy and fever were observed in 61.3% and 11.6% of all subjects, respectively. Most patients were treated with the benzathine penicillin G antibiotic. CONCLUSION: This report validates the spread of acquired oral syphilis infection among young adults in South America. Our directives include accessible diagnostic tools for proper disease screening, surveillance, and counselling of affected individuals, especially in low- and middle-income countries.

Oral and oropharyngeal lymphomas: A multi-institutional collaborative study.

BACKGROUND: Lymphomas in the oral and oropharyngeal regions are relatively uncommon, and their diagnosis is challenging and complex due to the myriad histopathological subtypes. Herein, we report a large series of oral and oropharyngeal lymphomas and compare our data with the currently available literature. METHODS: All cases diagnosed as lymphomas affecting the oral and oropharyngeal regions were retrospectively retrieved from seven Brazilian institutions. Clinicodemographic data and histopathological features were evaluated and described, while a comprehensive literature review was undertaken in order to compare our findings. RESULTS: A total of 304 cases of oral and oropharyngeal lymphomas were obtained, mostly affecting individuals aged 60-69 years (n = 68) with a mean age at diagnosis of 54.2 ± 20.1 years. Males and females were equally affected. Mature B-cell neoplasms (87.2%) were the most common group, followed by mature T- and NK-cell neoplasms (11.2%) and precursor lymphoid neoplasms (1.6%). The most frequent subtypes in each group were diffuse large B-cell lymphomas, not otherwise specified (n = 99), extranodal NK/T-cell lymphomas, nasal type (n = 12), and B-lymphoblastic leukaemia/lymphomas, not otherwise specified (n = 4). The most commonly involved sites were the palate (26.3%), mandible (13%), and maxilla (10.5%). CONCLUSION: Diffuse large B-cell lymphoma, not otherwise specified, remains the most common subtype of lymphomas in the oral and oropharyngeal region. Older patients are the most affected, with no gender predilection and the palate and jaw are usually affected.

Metallothionein immunoexpression in selected benign epithelial odontogenic tumors.

BACKGROUND: Odontogenic tumors exhibited variable biologica behaviors. Metallothionein (MT) is correlated with the cellular homeostasis of essential metals, cellular differentiation, and proliferation. The core goals of this study are (i) to report and to compare MT expression among benign epithelial odontogenic tumors; (ii) to correlate MT with cellular proliferation index; and (iii) to evaluate the influence of the inflammatory infiltrate on MT expression. MATERIALS AND METHODS: Ten cases of solid ameloblastomas (SABs), 4 squamous odontogenic tumors (SOTs), 5 adenomatoid odontogenic tumors (AOTs), and 3 calcifying epithelial odontogenic tumors (CEOTs) were subjected to immunohistochemical to anti-MT, anti-Ki-67, and anti-PCNA. Statistical analysis was performed using BioEstat(®) 4.0. RESULTS: Metallothionein staining was found to be the highest in the SABs (93.1%), followed by SOTs (52.9%), AOTs (38.4%), and CEOTs (0%). MT staining exhibited statistically significant differences between the SABs and the SOTs (P = 0.0047) and the AOTs (P = 0.0022). A weak-to-strong positive correlation between IMT and IK or IP was observed in SABs and SOTs, whereas a strong negative correlation was observed in AOTs. No differences in IMT, IK, and IP were observed between inflammation groups A and B. CONCLUSIONS: The increased MT expression observed in the SABs might be correlated with clinical behavior (local invasiveness and high rate of recurrence). In the SABs and SOTs, MT plays a role in the stimulation of cellular proliferation. In contrast, MT can inhibit cellular proliferation in the AOT. The IMT, IK, and IP are not affected by inflammation.

Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact.

The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

Effect of photobiomodulation on inflammatory cytokines produced by HaCaT keratinocytes.

Objective: to evaluate the effects of the red and near-infrared wavelength lasers in isolated and simultaneous way on the modulation of inflammatory cytokines produced by human keratinocytes (HaCaT) challenged by cytokines of human monocytes stimulated by lipopolysaccharide from Escherichia coli. Design: HaCaT cells was previously exposed to the laser with wavelengths red (660 nm), near-infrared (808 nm). Then, HaCat cells were stimulated with the supernatant of lipopolysaccharide-challenged peripheral blood cells. The cytokines expressed by HaCat cells were measured using multiplex CBA assay. Results: HaCaT cells increased the production of inflammatory cytokines when stimulated with infrared laser compared to the control group (IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL -12p70, IL -17A, IL-23, IL-33), the red laser group (IFN-γ and IL-23) and the group of two lasers used simultaneously (IFN-α2, IFN-γ, IL-6 and IL-8, IL-17A, IL-18 and IL-23) (p < 0.05). The red laser also stimulated an increase in the expression of IFN-α2 by HaCaT cells in relation to the control group (p < 0.05). Conclusion: Infrared laser, with an energy density of 5 J/cm2, appear to be able to modulate inflammatory cytokines produced by HaCaT cells challenged by human monocyte cytokines.

Evaluation of GLUT-1 in the granular cell tumour and congenital granular cell epulis.

BACKGROUND: The glucose transporter type 1 (GLUT-1) protein is a useful marker for perineurial cells. Because of the possible neuroectodermal histogenesis of the granular cell tumour and congenital granular cell epulis, the aim of this study was to assess the immunoexpression of GLUT-1 protein in granular cell tumour and congenital granular cell epulis to aid in clarifying their histogenesis. METHODS: The protocol of this study was approved by the Committee of Bioethics in Research at Universidade Federal Minas Gerais. Six cases of granular cell tumour and three cases of congenital granular cell epulis were submitted to immunohistochemistry for GLUT-1 and S-100 using the streptavidin-biotin standard protocol. RESULTS: Five cases of granular cell tumour were located on the tongue and one case on the upper lip. All cases of congenital granular cell epulis were observed in the alveolar ridge of newborns. All lesions evaluated proved to be immunonegative for GLUT-1. S-100 was found to be positive in all granular cell tumours and negative in congenital granular cell epulis. CONCLUSIONS: Neither granular cell tumour nor congenital granular cell epulis is directly related to perineurial cells.

Lymphatic Vascular Density, the Expression of Podoplanin and Tumor Budding in Oral Squamous Cell Carcinoma.

BACKGROUND: Notwithstanding recent advances in oral squamous cell carcinoma (OSCC) management, its mortality rate is still high. It is imperative to investigate new parameters that are complementary to clinical staging for OSCC to provide better prognostic insight. The presence of isolated neoplastic cells or small clusters of up to four cells at the tumor's invasive front, called tumor budding, is a morphological marker of OSCC with prognostic value. Increased lymphatic vascular density (LVD) and a high expression of podoplanin in neoplastic cells have also been associated with worse prognosis in OSCC. To investigate these markers in OSCC, we evaluated differences in LVD and the expression of podoplanin in neoplastic cells between tumors with high-intensity tumor budding versus low-intensity or no tumor budding. In the samples of high-intensity budding, differences in those parameters between the​​ budding area and the area outside the budding were also evaluated. Furthermore, the study assessed differences in LVD and in the expression of podoplanin in neoplastic cells concerning OSCC clinicopathological characteristics. METHODS: To those ends, we subjected 150 samples of OSCC to immunohistochemistry to evaluate the intensity of tumor budding (via multi-cytokeratin immunostaining). Moreover, the 150 samples of OSCC and 15 specimens of normal oral mucosa (used as a control) were employed to assess LVD and the expression of podoplanin (in neoplastic cells of OSCC and in the lining epithelium of normal oral mucosa), both via podoplanin immunostaining. Data were processed into descriptive and analytical statistics. RESULTS: No differences were observed neither in the LVD nor in the expression of podoplanin in neoplastic cells concerning sex, age, tobacco smoking, tumor location and tumor size. The LVD was greater in OSCC and in tumors with high-intensity budding than in normal mucosa but did not differ between normal mucosa and tumors with low-intensity or no tumor budding. The data analyses also revealed that LVD was greater in tumors with high-intensity tumor budding than in tumors with low-intensity or no budding and showed no difference in LVD between the budding area and the area outside the budding. When compared to the lining epithelium of the normal mucosa, the expression of podoplanin was greater in neoplastic cells of OSCC, tumors with high-intensity budding and tumors with low-intensity or no tumor budding. The expression of podoplanin in neoplastic cells was also greater in tumors with high-intensity budding and, within those tumors, greater in the budding area than in the area outside de budding. CONCLUSION: Those findings support the hypothesis that tumor budding is a biological phenomenon associated with the progression and biological behavior of OSCC.

Exploring the association between a standardized extract of pequi peels (Caryocar brasiliense Cambess) and blue light as a photodynamic therapy for treating superficial wounds.

Natural products derived from plants can be used as photosensitizers for antimicrobial photodynamic therapy (aPDT) combining key therapeutic strategies for tissue repair while controlling microorganisms' growth. We investigated a standardized extract of pequi peels (Caryocar brasiliense Cambess) as a brownish natural photosensitizer for aPDT using blue light. Three concentrations of the pequi extract (PE; 10, 30, or 90 µg/mL) were tested solely or associated with blue laser (445 nm, 100 mW, 138 J/cm2 , 6 J, 60 s). In vitro, we quantified reactive oxygen species (ROS), assessed skin keratinocytes (HaCat) viability and migration, and aPDT antimicrobial activity on Streptococcus or Staphylococcus strains. In vivo, we assessed wound closure for the most active concentration disclosed by the in vitro assay (30 µg/mL). Upon aPDT treatments, ROS were significantly increased in cell monolayers regardless of PE concentration. PE at low doses stimulates epithelial cells. Although PE stimulated cellular migration, aPDT was moderately cytotoxic to skin keratinocytes, particularly at the highest concentration. The antimicrobial activity was observed for PE at the lowest concentration (10 µg/mL) and mostly at PE 10 µg/mL and 30 µg/mL when used as aPDT photosensitizers. aPDT with PE 30 µg/mL presents antimicrobial activity without compromising the initial phases of skin repair.

Assessment of screening programs as a strategy for early detection of oral cancer: a systematic review.

The present study is a systematic review of the evaluation of screening programs as a strategy for early detection of oral cancer. The aim of this study was to assess whether screening through visual inspection is able to identify injuries in early stages, to increase survival, and to decrease the incidence and mortality of oral cancer. Studies using visual inspection to screen for oral cancer and potentially malignant lesions in apparently healthy individuals over 18 years without previous diagnosis of the disease were included. The MEDLINE/PubMed, Cochrane databases Library, EMBASE, and LILACS, including manual search and gray literature, were searched through January 2021 with no language or date restrictions. The risk of bias and the methodological quality were evaluated according to the appropriate tool for each study design. The analysis of the results was narrative. Seventeen studies were reviewed that included cohort, accuracy, and randomized clinical trial studies. The tracking type performed was opportunistic and organized in a variety of environments. The age of participants ranged between 18 and 60 years old and, in some programs, only people with risk habits for oral cancer were included. The screeners were healthcare professionals, physicians, and dentists. Two studies reported data on the incidence rate of severe cases and mortality and showed a reduction when patients were at risk for the disease and participated in the program more than once. A limitation of this review was the great variability observed in the estimates of the screening effectiveness among the studies, which made comparisons difficult. If a screening program is continuous and able to ensure the inclusion of high-risk individuals, it can contribute to improvement in survival rates with a change of stage and can have a significant impact on incidence and mortality due to the disease. Registration in the Open Science Framebook (OSF) with the osf.io/zg8nr link.

Malignant lesion of clear cells: A diagnostic challenge of an unusual presentation mimicking a benign lesion.

In the oral cavity, a broad spectrum of differential diagnostics includes lesions composed of clear cells. Under this umbrella, Clear Cell Odontogenic Carcinoma (CCOC) and Hyalinizing Clear Cell Carcinoma (HCCC) are rare malignancies that arise from different histological origins. However, the histology is similar; therefore, differentiation of CCOC and HCCC lesions is difficult and, in some cases, impossible to distinguish morphologically and immunohistochemically. Herein, we report an unusual presentation of a well-defined nodular lesion affecting the maxillary gingiva in a 19-year-old female, which presented clinically as a benign or reaction etiology lesion. Microscopic evaluation showed a tumor composed of cell sheets with clear cytoplasm, separated by septa of fibrous tissue and invading the connective tissue. Tumor cells were positive for p63 and AE1/AE3 and negative for PAX8, smooth muscle actin (AML) and estrogen receptor. The diagnosis was carcinoma with a clear cell pattern, and it was not possible to distinguish between HCCC and CCOC. In this study, clinicopathologic, histologic, and immunohistochemistry features of CCOC and HCCC were discussed due to the challenging histological diagnosis. Radical surgical treatment and rehabilitation of the patient through graft and dental implants were performed. The patient is under follow-up with no signs of recurrence.

Oral and oropharyngeal diffuse large B-cell lymphoma and high-grade B-cell lymphoma: A clinicopathologic and prognostic study of 69 cases.

OBJECTIVE: The objective of this study was to describe the clinicopathological, molecular, and prognostic features of oral/oropharyngeal diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma. STUDY DESIGN: All cases were retrieved from 7 Brazilian institutions. Immunohistochemical reactions were performed to confirm the diagnoses and to categorize the tumors. In situ hybridization was used to detect Epstein-Barr virus (EBV) and fluorescence in situ hybridization was used to identify gene rearrangements. RESULTS: Most cases involved the oral cavity (76.8%). Males and females, with a mean age of 60 years, were evenly affected. Tumors mostly presented as painful swellings. Forty cases represented germinal center B-cell type (58%). Five cases presented double-hit translocation and 3 harbored rearrangement for MYC/BCL2/BCL6. EBV was detected in 3 cases (4.3%). The 5-year overall survival was 44.4%. Female sex, presence of pain and ulcer, microscopic "starry sky pattern" and necrosis, co-expression of c-Myc/Bcl2, and translocation of MYC were associated with a lower survival in univariate analysis (P = .05, P = .01, P = .01, P = .03, P = .05, P = .006, P = .05, respectively). CONCLUSION: Patients affected by oral/oropharyngeal DLBCL have a low survival rate. High-grade B-cell lymphoma (17.7%) and EBV-positive DLBCL, not otherwise specified (4.3%) account for a small number of cases.

Tobacco use increase the number of aneuploid nuclei in the clinically healthy oral epithelium.

BACKGROUND: The most important risk factor linked to the development of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) is tobacco use. Tobacco contains carcinogens that influence the DNA repair, cell cycle control and may produce chromosomal aberrations. The loss or acquisition of one or more chromosomes is defined as aneuploidy. METHODS: Aneuploidy was determined by means of the DNA-content included in cells obtained by exfoliative cytology and Feulgen's staining. The cells were collected from the clinically healthy lateral margin of the tongue of non-smokers without oral lesions, smokers without oral lesions, smokers with OL, and smokers with OSCC, using the CytoBrush(®). Each group was composed of 20 individuals. A Carl Zeiss image analyzer system and the KS300 software were used. Statistical analysis was performed with BioEstat(®) software. RESULTS: The mean percentage of aneuploid nuclei was statistically higher in the smokers (79.65%), smokers with OL (68.4%), and smokers with OSCC (93.65%), as compared to non-smokers (39.3%) (P<0.05). A trend toward an increase in the aneuploidy of the smokers with OSCC group (P=0.02), as compared to the non-smoker group, could be observed. No significant difference could be observed as regards the mean percentage of aneuploid nuclei in relation to duration of tobacco use or the number of the cigarettes smoked. CONCLUSIONS: Tobacco use is responsible for an increased number of aneuploid nuclei in the oral epithelium.

Thrombocytopenia-Absent Radius (TAR): Case report of dental implant and surgical treatment.

Thrombocytopenia-absent radius (TAR) syndrome is a congenital malformation in which affected individuals present reductions in the number of platelets, hypoplasia, or absence of radial bone unilaterally or bilaterally. Hematologic, skeletal, cardiac (particularly tetralogy of Fallot and septal-atrial defects), and gastrointestinal anomalies are most commonly associated with TAR syndrome. Skeletal changes result in a higher risk of dental and craniofacial trauma in patients with the syndrome. Thus, it is important for the dentist to be aware of the characteristics of TAR syndrome and its clinical management for better care of these patients. The objective of this study is to describe a case report of a 26-year-old patient with TAR syndrome with a history of trauma and root fracture of tooth 11 and alveolar bone ridge. During anamnesis, root fractures requiring the extraction of the 11 tooth, alveolar bone ridge fracture in the adjacent region, and dental trauma were observed. A hematological evaluation and blood and radiological examinations were performed. Osseointegrated implant was performed using the guided surgery and flapless technique, as well as prosthetic rehabilitation in the affected region. This report discusses the importance of careful planning, such as the use of incisions and conservative surgery, techniques for alveolar ridge preservation, gingival manipulation, and prosthesis confection. The patient was attended by a hematologist throughout the treatment. Key words:TAR syndrome, absent radii and thrombocytopenia, dental implants, oral surgery.

Two rare cases of oral metastasis arising from lung adenocarcinoma and esophageal carcinoma.

Metastasis to the oral cavity are rare, representing only 1% of all oral malignancies, and originate from various sites such as the breast, prostate, lung and kidney. Clinically, they can simulate reactive and inflammatory lesions common in the oral cavity, and the clinical and microscopic diagnosis of these metastasis is a challenge. In this article, we report two new cases of esophageal and lung metastasis to oral tissues, highlighting their clinical characteristics and the process of diagnostic elucidation. We emphasize the importance for clinicians to consider the possibility of metastatic lesions in the oral cavity in patients previously diagnosed with malignant lesions in distant tissues and organs. Key words:Diagnosis, esophageal squamous cell carcinoma, adenocarcinoma of lung, oral cavity, metastasis.

Effect of porous tantalum on the biological response of human peripheral mononuclear cells exposed to Porphyromonas gingivalis.

AIM: To evaluate biological behavior of human peripheral mononuclear cells (PBMC) in contact with porous tantalum (PT) and Porphyromonas gingivalis (Pg). METHODS: Pg was incubated for 8 hours. The groups formed were: PBMC (control), PBMC + PT, PBMC + Pg and PBMC + PT + Pg. Cell viability was evaluated using MTT assay. The morphology and adhesion of PBMC to PT was evaluated using scanning electron microscopy. Expression of interleukin (IL)-10, transforming growth factor (TGF)-ß, matrix metallopeptidase (MMP)-9 and receptor activator of nuclear factor-κΒ ligand (RANKL) was determined by enzyme-linked immunosorbent assay. RESULTS: MTT assay revealed that PT did not interfere in the mitochondrial activity of PBMC (P > .05). Scanning electron microscopy showed the adherence of PBMC to PT. IL-10 levels in PBMC + PT were similar to PBMC and lower than PBMC + Pg. TGF-ß levels in PBMC + PT were higher than PBMC and PBMC + Pg. MMP-9 levels in PBMC + PT were similar to PBMC and lower than PBMC + Pg and PBMC + PT + Pg. RANKL levels in PBMC + PT were lower than in PBMC. CONCLUSION: PT did not affect PBMC viability, allowed cell adhesion, reduced expression of RANKL and enhanced TGF-ß in comparison with the control group.

The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas Receptor axis as a key player in alveolar bone remodeling.

The renin-angiotensin system (RAS), aside its classical hormonal properties, has been implicated in the pathogenesis of inflammatory disorders. The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas Receptor (ACE2/Ang-(1-7)/MasR) axis owns anti-inflammatory properties and was recently associated with bone remodeling in osteoporosis. Thus, the aim of this study was to characterize the presence and effects of the ACE2/Ang-(1-7)/MasR axis in osteoblasts and osteoclasts in vitro and in vivo. ACE2 and MasR were detected by qPCR and western blotting in primary osteoblast and osteoclast cell cultures. Cells were incubated with different concentrations of Ang-(1-7), diminazene aceturate (DIZE - an ACE2 activator), A-779 (MasR antagonist) and/or LPS in order to evaluate osteoblast alkaline phosphatase and mineralized matrix, osteoclast differentiation and cytokine expression, and mRNA levels of osteoblasts and osteoclasts markers. An experimental model of alveolar bone resorption triggered by dysbiosis in rats was used to evaluate bone remodeling in vivo. Rats were treated with Ang-(1-7), DIZE and/or A-779 and periodontal samples were collected for immunohistochemistry, morphometric analysis, osteoblast and osteoclast count and cytokine evaluation. Human gingival samples from healthy and periodontitis patients were also evaluated for detection of ACE2 and MasR expression. Osteoblasts and osteoclasts expressed ACE2 and MasR in vitro and in vivo. LPS stimulation or alveolar bone loss induction reduced ACE2 expression. Treatment of bone cells with Ang-(1-7) or DIZE stimulated osteoblast ALP, matrix synthesis, upregulated osterix, osteocalcin and collagen type 1 transcription, reduced IL-6 expression, and decreased osteoclast differentiation, RANK and IL-1ß mRNA transcripts, and IL-6 and IL-1ß levels, in a MasR-dependent manner. In vivo, Ang-(1-7) and DIZE decreased alveolar bone loss through improvement of osteoblast/osteoclast ratio. A-779 reversed such phenotype. ACE2/Ang-(1-7)/MasR axis activation reduced IL-6 expression, but not IL-1ß. ACE2 and MasR were also detected in human gingival samples, with higher expression in the healthy than in the inflamed tissues. These findings show that the ACE2/Ang-(1-7)/MasR is an active player in alveolar bone remodeling.

Immunolocalization of Cancer Stem Cells Marker ALDH1 and its Association with Tumor Budding in Oral Squamous Cell Carcinoma.

Tumor budding is a prognostic marker for oral squamous cell carcinoma (OSCC) characterized by the presence of isolated or small clusters of neoplastic cells at the tumor invasive front. Aldehyde dehydrogenase-1 (ALDH1) is associated with tumorigenesis, linked to treatment resistance and shown to identify cancer stem cells (CSC)-like cells. This study aimed to evaluate the expression of ALDH1 and its association with tumor budding in OSCC. Immunohistochemistry was employed in 163 OSCC samples to identify pancytokeratin (AE1/AE3) and ALDH1. While pancytokeratin (AE1/AE3) identified squamous tumor buds, the CSC-like cells were identified using ALDH1. A Chi square test was used to evaluate association between ALDH1 expression and tumor budding, while McNemar's test was used to identify differences in ALDH1 expression between the budding area and the area outside the budding. A positive expression of ALDH1 was observed in 47.24% of the samples and in 70% of anatomic locations affected. No association was observed between ALDH1 expression and tumor budding (p > 0.05). In tumors with high-intensity tumor budding, ALDH1 expression was higher in the budding area than in the area outside the budding (p < 0.05). The finding that tumor bud cells in OSCC show phenotypic characteristics of CSC-like cells reinforces the relevance of tumor budding in determining the biological behavior of this malignant neoplasm. Moreover, the presence of CSC-like cells in nearly half of evaluated samples of OSCC and in most of the affected anatomic locations is in accordance with the CSC model of oral carcinogenesis.