Oral manifestations of amyloidosis and the diagnostic applicability of oral tissue biopsy.

BACKGROUND: Amyloidosis exhibits a variable spectrum of systemic signs and oral manifestations that can be difficult to diagnose. This study aimed to characterize the clinical, demographic, and microscopic features of amyloidosis in the oral cavity. METHODS: This collaborative study involved three Brazilian oral pathology centers and described cases with a confirmed diagnosis of amyloidosis on available oral tissue biopsies. Clinical data were obtained from medical records. H&E, Congo-red, and immunohistochemically stained slides were analyzed. RESULTS: Twenty-six oral biopsies from 23 individuals (65.2% males; mean age: 59.6 years) were included. Oral involvement was the first sign of the disease in 67.0% of cases. Two patients had no clinical manifestation in the oral mucosa, although the histological analysis confirmed amyloid deposition. Amyloid deposits were distributed in perivascular (88.0%), periacinar and periductal (80.0%), perineurial (80.0%), endoneurial (33.3%), perimuscular (88.2%), intramuscular (94.1%), and subepithelial (35.3%) sites as well as around fat cells (100.0%). Mild/moderate inflammation was found in 65.4% of cases and 23.1% had giant cells. CONCLUSIONS: Amyloid deposits were consistently found in oral tissues, exhibiting distinct deposition patterns. Oral biopsy is less invasive than internal organ biopsy and enables the reliable identification of amyloid deposits even in the absence of oral manifestations. These findings corroborate the relevance of oral biopsy for the diagnosis of amyloidosis.

Palatal Stent Following Tumor Ablative Surgery.

Mucoepidermoid carcinoma is one of the most prevalent malignant tumors of the salivary glands. Resection of this tumor can result in postsurgical morbidity, affecting the patient's quality of life and normal oral functioning. This study aimed to present a successful case of postsurgical rehabilitation following mucoepidermoid carcinoma resection in the palate. Following tumor ablative surgery, the 32-year-old patient experienced impairments in both speech and feeding due to the surgical wound. A protective stent that covered the entire extent of the palate and teeth was made. This esthetic device was fabricated in a single session and provided sealing and protection of the surgical site, ensuring comfort, functionality, and, consequently, a higher quality of life during the postoperative period. The simplicity and low cost of the custom palatal stent make it applicable for use in a diverse range of postsurgical oncology patients, providing protection for surgical wounds and reducing postoperative morbidity.

Rhabdomyosarcoma of the oral cavity in children aged 0-2 years: A scoping review.

BACKGROUND: The aim of this study was to collect, synthesize, and analyze the clinic-demographic data of rhabdomyosarcoma affecting the oral cavity of young children. METHODS: The clinical question was "What are the clinical characteristics of oral rhabdomyosarcoma in children aged zero to two years?" Two independent reviewers selected the studies, extracted data, and assessed the methodological quality through the Joanna Briggs Institute Checklist. Descriptive statistics were performed in SPSS. (protocol: osf.io/b9hvy). RESULTS: Thirty case reports with 41 patients were included (22 males; mean age at diagnosis: 15 months). All studies had some methodological limitations, mainly due to the lack of clarity for a final judgment. More than 70% of the cases affected the tongue or lips. Tumors had a fast growth (mean 2.5 months), usually with red coloration, and variable shape and consistency. Embryonal (63.41%) and alveolar (29.27%) were the most common histological subtypes. Treatment was quite variable but usually included surgery. Most patients (53.66%) were alive without disease at follow-up. CONCLUSION: Oral rhabdomyosarcoma is rare in children aged 0-2 years without a marked gender predilection. The tumor presents as a fast and infiltrative growth leading to local and/or systemic symptoms, and a favorable prognosis for most patients.

Clinical and demographic features of minor salivary gland tumors: A collaborative study of 480 cases.

OBJECTIVE: To describe the frequency, clinical, and demographic features of minor salivary gland tumors and possible associated factors. MATERIALS AND METHODS: A cross-sectional study was conducted. Clinical and demographic data were collected from biopsy records of two oral pathology services. Chi-square test, Fisher's exact test, and descriptive statistical analysis were performed. RESULTS: A total of 480 (0.89%) minor salivary gland tumors were retrieved, 272 (56.7%) benign and 147 (30.7%) malignant. Sixty-one (12.6%) had no subtype specification. Most patients were women (307/64.0%), in sixth decade of life (80/16.7%), with a mean age of 45.32 years. Palate was the most common site (336/70.1%). Pleomorphic adenoma (PA; 245/51.1%), mucoepidermoid carcinoma (MEC; 70/14.6%), and adenoid cystic carcinoma (ACC; 43/8.9%) were the most frequent tumors. Symptomatic case, recurrence, and tobacco use were associated with malignancy (p < 0.05). PA and MEC were more frequent in palate (p < 0.05). No association between the three most frequent histological types and gender or age group was observed (p > 0.05). CONCLUSIONS: This represents one of the largest exclusive series of minor salivary gland tumors in Brazil and worldwide. PA, MEC, and ACC were the most frequent tumors. Clinical and demographic data are similar from Brazilian studies or from other countries.

Glandular odontogenic cysts: A collaborative investigation of 22 cases and proteins related to invasiveness.

BACKGROUND: A glandular odontogenic cyst (GOC) has an intriguing, aggressive behaviour whose mechanisms have not yet been clarified. OBJECTIVE: To conduct a collaborative cross-sectional study on the clinical, demographic, microscopic and immunohistochemical characteristics of GOCs, emphasizing the histopathological characteristics and expression of proteins related to invasiveness. METHODS: Twenty-two cases of GOC from three oral and maxillofacial pathology services in Brazil were selected from 1988 to 2018. Clinical and demographic data were collected. Histopathological features were evaluated in detail. Sixteen cases of GOC were also submitted to immunohistochemistry to detect MT1-MMP, TKS4, TKS5 and cortactin, the key regulators of invadopodia formation. RESULTS: Glandular odontogenic cysts were primarily seen in men over 40 years of age, in the posterior mandible and the anterior maxilla as a unilocular, radiolucent lesion. All cases presented hobnail cells, clear cells and variable thickness of the lining epithelium, 3 of the 10 key histopathological parameters to be evaluated in GOCs. Immunohistochemistry revealed a greater expression of the studied proteins in the GOCs than in the controls (p < 0.0001). CONCLUSION: Overexpression of proteins that regulate cell invasiveness was identified, and the present study's findings suggest that invadopodia activity is a possible mechanism used by GOCs to promote local invasion, which could partly explain its intriguing biological behaviour.

Clinicopathological and immunohistochemical features of the oral lymphoepithelial cyst: A multicenter study.

BACKGROUND: Analyze the clinical, demographic, histopathological, and immunohistochemical features of oral lymphoepithelial cyst (OLEC). METHODS: Samples were retrospectively retrieved from five oral pathology services. Clinical and demographic data were collected from patient charts. Histopathological and immunohistochemical (CD3 and CD20) features were evaluated. Data analysis involved descriptive statistics and bivariate analyses (P ≤ .05). RESULTS: Seventy-seven cases were found among a total of 146 150 specimens (0.05%). OLEC was predominantly diagnosed in females (70.1%). Mean patient age was 46.51 years. The lesions arose mainly on the lateral border of the tongue (40.3%), measured up to 1 cm (61.0%), and were asymptomatic (64.9%). Twenty-four lesions (31.2%) were white. Forty-one cases (53.2%) presented lymphocytic inflammatory infiltrate with no specific arrangement. The cystic lining was composed of a non-keratinized stratified epithelium (59.7%) presenting hyperplasia (39.0%). Connection with the surface, epithelium was found in 23 cases (29.9%) and 31 (40.3%) cases had two or more cystic cavities. The lumen content was predominantly desquamated cells (48.1%). Subgemmal neurogenous plaque was found in 11/42 (26.2%) cases involving the tongue. CD20+ cells predominated in 36/63 cases (57.2%), and lymphocytic inflammatory infiltrate was not always continuous around the cystic cavity (52.4%). CONCLUSION: Lymphoepithelial cyst is an uncommon lesion of the oral cavity. The present study offers the largest sample of OLEC for which clinical, demographic, histopathological, and immunohistochemical features were evaluated. The clinical and demographic findings were similar to those described in previous reports, but the microscopic analyses revealed interesting aspects of the cystic epithelium and the lymphocytic inflammatory infiltrate in OLEC.

Tumor depth of invasion and prognosis of early-stage oral squamous cell carcinoma: A meta-analysis.

OBJECTIVES: To assess the prognosis for early-stage oral squamous cell carcinoma according to tumor depth of invasion (DOI). METHODS: This study was logged in the PROSPERO database under protocol # CRD42017059976. The search was conducted in six electronic databases up to May 2019. Fixed-effects meta-analysis was performed for the calculation of the odds ratio (OR) and respective 95% CI. Primary outcomes were lymph node metastasis, recurrence, and survival. Heterogeneity was calculated by the I2 test. The certainty of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Twenty-seven studies were included (19 in the meta-analysis) with 2,404 patients with a mean of 60 years of age. High tumor DOI is associated with a greater chance of presenting lymph node metastasis, regardless of the cutoff point for DOI (13 meta-analysis; OR 1.69-53.08), recurrence (five meta-analysis; OR 1.22-3.83), and lower chance of survival (1 meta-analysis; OR 0.49). The certainty of evidence varied from very low to low. CONCLUSIONS: Tumor DOI is a good prognosticator for early-stage OSCC. The findings of the current meta-analysis highlight the clinical relevance of DOI and corroborate its incorporation for staging OSCC.

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.

Cell proliferation is associated with intensity of tumor budding in oral squamous cell carcinoma.

BACKGROUND: Tumor budding is a morphological marker of cancer invasion, defined as the presence of isolated or small clusters of neoplastic cells at the tumor invasive front. This study aimed to evaluate the association between intensity of tumor budding and cell proliferation in oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemistry was employed in 163 OSCC samples to detect the cell proliferation marker Ki-67 and multicytokeratin (to identify OSCC cells in tumor budding evaluation). The Mann-Whitney test was used to evaluate differences in the cell proliferation index between samples with high-intensity tumor budding and samples with low-intensity or no tumor budding. In samples with high-intensity tumor budding, the Wilcoxon test was used to evaluate differences in the cell proliferation index between the budding area and the area outside the budding. The chi-square test assessed the association between cell proliferation index and intensity of tumor budding. RESULTS: The cell proliferation index was higher in samples with high-intensity tumor budding than in samples with low-intensity or no tumor budding (P < .05). Tumors with high-intensity tumor budding showed a higher cell proliferation index in the budding area than in the area outside the budding (P < .05). Finally, samples showing high-intensity tumor budding were associated with high cell proliferation index (P < .05). CONCLUSION: Cell proliferation is positively associated with intensity of tumor budding in OSCC. Moreover, in tumors showing high-intensity tumor budding, the budding area is the location of higher cell proliferation. These findings reinforce the hypothesis that tumor budding is associated with the biological behavior of OSCC.

Immunoexpression of SOX-2 in oral leukoplakia.

OBJECTIVE: This study was conducted to correlate and compare the immunoexpression of sex-determining region Y-box 2 (SOX-2) in oral leukoplakia (OL) lesions with that in normal buccal mucosa (control). MATERIALS AND METHODS: In this observational study, OL with low-risk (n = 34) and high-risk (n = 33) dysplasia and control samples (n = 25) were subjected to immunohistochemical analysis for SOX-2. In the epithelium, SOX-2 positive and negative cells, as well as semiautomatic segmentation of the immunopositive nuclear area were counted. Statistical tests included chi-square, one-way analysis of variance, Tukey, and Games-Howell. The level of significance was 5%. RESULTS: Groups with OL lesions (low and high-risk) showed higher mean numbers of SOX-2 positive cells (63.47 ± 25.70 and 68.18 ± 21.17) compared to the control group (45.85 ± 27.38) (p = 0.00). Groups with OL lesions (low and high-risk) exhibited higher mean positive nuclear area (0.24 ± 0.47 and 1.09 ± 2.06) compared to the control group (0.00 ± 0.01) (p = 0.01). CONCLUSION: Oral leukoplakia lesions showed a higher expression of SOX-2, suggesting its contribution to the pathogenesis of OL.

Immunophenotype of neutrophils in oral squamous cell carcinoma patients.

BACKGROUND: The aim was to explore the immunophenotype of neutrophils and lymphocytes and the inflammatory mediators in patients with oral squamous cell carcinoma, comparing with controls; and to associate with clinicopathological data. METHODS: Blood was collected from 13 patients and 13 controls. The immunophenotype of neutrophils (CD66b, CD16, CD11a, arginase-1), T lymphocytes (CD4, CD8) and the intracellular cytokine production (IL-10, TNF, IFN-γ) was evaluated by flow cytometry. Plasma concentration of sVCAM-1, sTNF-RI, sTNF-RII, and IL-1ß was measured by ELISA. MPO, Lipocalin-2/NGAL, sICAM-1, and p-selectin were quantified by Luminex assay. The excised tumors were submitted to immunohistochemistry for neutrophils (CD66b) and lymphocytes (CD3, CD4, CD8). Association with clinical data was explored. P values <.05 were considered significant. RESULTS: Patients presented higher percentage of neutrophils and lower lymphocytes, resulting a higher neutrophil/lymphocyte ratio than controls. They also presented higher percentage of neutrophils expressing CD66b+ , CD66b+ Arginase-1+ , CD66b+ IL10+ , CD66b+ TNF+ , CD66b+ Arginase-1+ IL-10+ , and lower CD66b+ CD16+ CD11a+ and CD66b+ Arginase-1+ TNF+ . CD66b+ neutrophils were detected in all tumors, with a CD66b+ /CD3+ ratio of 0.40. Patients showed higher concentration of plasmatic sVCAM-1 and lower Lipocalin-2/NGAL. Patients with good outcome presented lower percentage of neutrophils, higher percentage of lymphocytes, and lower NLR than patients who died. CONCLUSION: The amount and immunophenotype of neutrophils and lymphocytes differ between patients and healthy individuals, with a pro-tumorigenic profile of neutrophils. As these cells also get within tumor microenvironment, they possibly exert systemic and local functions in cancer pathogenesis. The association of neutrophil count with outcome corroborates recent studies and this merits further investigation for applicability as a prognosticator.

Reproducibility, repeatability, and level of difficulty of two methods for tumor budding evaluation in oral squamous cell carcinoma.

BACKGROUND: This study aimed to analyze the reproducibility, repeatability, and level of difficulty of two methods for tumor budding evaluation in oral squamous cell carcinoma (OSCC): staining by hematoxylin and eosin (HE) and immunostaining for multicytokeratin. METHODS: The evaluation of tumor budding was performed by three examiners in 103 samples of OSCC, using the two methods. A Likert-type scale was used to measure the difficulty in the assessment. The interexaminer agreement (reproducibility) was estimated using Fleiss's kappa and the intra-examiner agreement (repeatability) was estimated using Cohen's kappa. The agreement between the two methods was evaluated using Cohen's Kappa. The Friedman test was used to compare the three examiners' perceived levels of difficulty of assessment. The Wilcoxon test was used to compare the level of difficulty of the evaluation between the two methods. RESULTS: Reproducibility by the immunostaining method for multicytokeratin was substantial, being higher than the only fair agreement by the HE. Repeatability by the HE ranged from moderate to substantial among examiners, regardless of the examiner's experience. Repeatability by the immunostaining method for multicytokeratin did not vary among examiners, showing almost perfect agreement. The agreement between the two methods ranged from fair to moderate among examiners, being lower in the less experienced examiner. All the examiners presented greater difficulty in the evaluation by the HE. CONCLUSION: In view of the unsatisfactory agreement between the two methods of tumor budding evaluation in OSCC, it is recommended that this evaluation should be performed by the immunostaining method for multicytokeratin, considering its higher reproducibility, greater replicability, and lower difficulty compared to the HE.

Metallothionein immunoexpression in non-syndromic and syndromic keratocystic odontogenic tumour.

BACKGROUND: To compare the metallothionein (MT) immunoexpression in non-syndromic and syndromic keratocystic odontogenic tumour (KOT), to correlate MT with cellular proliferation, and to evaluate the influence of inflammation in MT. STUDY DESIGN: Fourteen cases of KOT were submitted to immunohistochemistry for MT and Ki-67 analysis. The lesions were grouped according to their grade of inflammation, and statistical analysis was performed. RESULTS: MT was higher in non-syndromic KOT than in syndromic KOT (p<0.05). No statistical difference in Ki-67 could be identified; however, an inverse correlation was observed between MT and Ki-67 in both lesions. When analysing inflammation, non-syndromic KOT showed no differences in either MT or Ki-67. CONCLUSIONS: The MT immunophenotype of syndromic KOT was different from non-syndromic KOT. MT might not be involved in the proliferation control of both KOT. MT and Ki-67 immunoexpressions proved to be unaffected by inflammation in non-syndromic KOT.

Laminin-5 gamma 2 chain expression is associated with intensity of tumor budding and density of stromal myofibroblasts in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide. Laminin-5 gamma 2 chain (laminin-5 γ2) is a protein associated to a migratory phenotype in epithelial neoplastic cells. Stromal myofibroblasts also play a significant role in tumor invasion, due to its ability to modify the extracellular matrix. Tumor budding is a morphologic marker of tumor invasion. The aim of this study was to evaluate the expression of laminin-5 γ2 in OSCC and its association with intensity of tumor budding and density of stromal myofibroblasts. METHODS: Paraffin-embedded archival samples of 57 OSCC patients were evaluated. Immunohistochemistry was employed to detect laminin-5 γ2, alpha smooth muscle actin (marker of stromal myofibroblasts), and multicytokeratin (to identify OSCC cells in tumor budding evaluation). Laminin-5 γ2 expression and its association with intensity of tumor budding and density of stromal myofibroblasts were analyzed. Association among intensity of tumor budding and density of stromal myofibroblasts was also evaluated. RESULTS: Higher laminin-5 γ2 expression was associated with high-intensity tumor budding (P < 0.05) and with higher density of stromal myofibroblasts (P < 0.05). Moreover, high-intensity tumor budding was associated with higher density of stromal myofibroblasts (P < 0.05). CONCLUSIONS: In OSCC, higher laminin-5 γ2 expression is associated with high-intensity tumor budding and with higher density of stromal myofibroblasts, suggesting that this expression is related to the establishment of an invasive phenotype of neoplastic cells and a permissive environment for tumor invasion in this neoplasia.

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.

Profile of usage of a reference diagnostic service on oral pathology: a 10-year evaluation.

BACKGROUND: Despite the professional and academic relevance of the Brazilian oral pathology diagnostic laboratories, no information about their usage profile is available in the English literature. The objective of the present study is to report data about the histopathological and immunohistochemical exams performed in a Brazilian regional reference laboratory of oral pathology, as well as its main users. METHODS: Information about all histopathological exams performed between 2002 and 2012 was retrieved from the files of the Oral and Maxillofacial Pathology Service of the School of Dentistry of Universidade Federal de Minas Gerais. Data collected included: 1) requestor of exam; 2) diagnosis classification; and 3) immunohistochemical tests. Descriptive statistical analyses were done. RESULTS: 13,522 histopathological exams were performed, mean 1,229/year. The Public Health System of the city of Belo Horizonte was the main requestor of exams (77.13%), followed by private professionals (19.26%), and other cities (2.03%). Most lesions were considered benign (12,599/ 93.17%), with 854 malignant lesions (6.32%). 469 immunohistochemical tests were performed; 324 (69.08%) were from benign diagnosis, and 145 (30.92%) from malignant diagnosis. The most used antibodies were against S100, vimentin, smooth muscle actin, actin muscle specific HHF-35, and pan-cytokeratin AE1/AE3. CONCLUSIONS: Public Health System is the major user of the diagnostic service on oral pathology in our institution. Most diagnoses were of benign lesions, although many malignant lesions were detected. Immunohistochemistry was particularly important in solving challenging cases.

Clinical and demographic overlaps among immunologically mediated oral diseases: a challenge for clinicians.

This study sought to assess and compare retrospective demographic and clinical data of oral lesions of lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid from the records of the Department of Oral Pathology and Surgery, School of Dentistry, Universidade Federal de Minas Gerais, Brazil, covering a period of 55 years. Out of 25,435 specimens, these immunologically-mediated diseases accounted for 301 (1.18%) cases, of which 250 (0.98%) were lichen planus, 27 (0.11%) were pemphigus vulgaris, and 24 (0.09%) were mucous membrane pemphigoid. Lichen planus presented mainly as white asymptomatic plaques on buccal mucosa. Pemphigus vulgaris was usually characterized by multiple symptomatic erithematous ulcers on the buccal mucosa. Painful ulcers and/or blisters on the gingiva were the most common presentation for mucous membrane pemphigoid. Desquamative gingivitis was noted for all 3 diseases, but mainly for mucous membrane pemphigoid. Overall, lesions were more frequent in white women >50 years. Oral manifestations of immunologically-mediated diseases are relatively rare, and the correct diagnosis can be a challenge for dentists as the lesions often share similar clinical and demographic features.

Subgemmal neurogenous plaque: a series of six cases and a literature overview.

The study aims to describe six subgemmal neurogenous plaque (SNP) cases and compile the previously available data on SNP. Searches on PubMed, Web of Science, Embase, Scopus, and a two-step study selection were performed to compile data from case reports/series of SNP published in English literature. Our six patients (range 29-63 years) had SNP in the posterior lateral border of the tongue. Four of them were associated with lymphoepithelial cysts. A total of 15 studies, comprising 116 patients, were included in this overview. There was a slight predilection for female patients (56.0%) in the 5th (22.4%) and the 7th (23.9%) decades. The lateral border of the tongue (66.4%) was the most common anatomical location. The major manifestation was nodule/papule. Histologically, the presence of taste buds (n = 40/ 34.5%), superficial neural plexus (n = 32/ 27.6%), deep nerve fascicles (n = 32/ 27.6%), ganglion cells (n = 41/ 35.3%), and lymphoid tissue (n = 22/ 19.0%) was mainly reported. Surgical removal was the primary approach, with a low recurrence rate. Although largely unknown, SNP is a regular and likely frequent structure located in the tongue. The findings emphasize the importance of describing clinicopathological patterns of SNP as a differential diagnosis of neural lesions that affect the tongue.