The transcription factor BMI1 increases hypoxic signaling in oral cavity epithelia.

The tongue epithelium is maintained by a proliferative basal layer. This layer contains long-lived stem cells (SCs), which produce progeny cells that move up to the surface as they differentiate. B-lymphoma Mo-MLV insertion region 1 (BMI1), a protein in mammalian Polycomb Repressive Complex 1 (PRC1) and a biomarker of oral squamous cell carcinoma, is expressed in almost all basal epithelial SCs of the tongue, and single, Bmi1-labelled SCs give rise to cells in all epithelial layers. We previously developed a transgenic mouse model (KrTB) containing a doxycycline- (dox) controlled, Tet-responsive element system to selectively overexpress Bmi1 in the tongue basal epithelial SCs. Here, we used this model to assess BMI1 actions in tongue epithelia. Genome-wide transcriptomics revealed increased levels of transcripts involved in the cellular response to hypoxia in Bmi1-overexpressing (KrTB+DOX) oral epithelia even though these mice were not subjected to hypoxia conditions. Ectopic Bmi1 expression in tongue epithelia increased the levels of hypoxia inducible factor-1 alpha (HIF1α) and HIF1α targets linked to metabolic reprogramming during hypoxia. We used chromatin immunoprecipitation (ChIP) to demonstrate that Bmi1 associates with the promoters of HIF1A and HIF1A-activator RELA (p65) in tongue epithelia. We also detected increased SC proliferation and oxidative stress in Bmi1-overexpressing tongue epithelia. Finally, using a human oral keratinocyte line (OKF6-TERT1R), we showed that ectopic BMI1 overexpression decreases the oxygen consumption rate while increasing the extracellular acidification rate, indicative of elevated glycolysis. Thus, our data demonstrate that high BMI1 expression drives hypoxic signaling, including metabolic reprogramming, in normal oral cavity epithelia.

Which devices can be used to decompress odontogenic cystic lesions in the oral cavity? A systematic review.

Odontogenic cysts are bony lesions in the jaws that can reach large sizes. Decompression, a technique that helps in their surgical treatment, aims to reduce their size. We aimed to conduct a systematic review of the main types of device used for the decompression of odontogenic cysts and to analyse the indications, types, advantages, and disadvantages of the devices used. We searched PubMed, Science Direct, LILACS, EMBASE, and Web of Science until February 2023, with no time restriction. We considered studies with a minimum of 10 patients published only in English, those that reported cases and case series, randomised clinical trials of the decompression of odontogenic cysts, and the types of devices used during the decompression period. All reported odontogenic cysts had to have been confirmed by biopsy in their respective publications. We found 713 articles in the selected databases. After removing duplicates, 499 remained. After reading the titles and abstracts, we excluded 461 articles so 38 remained. Nine studies were selected for the review, totalling 244 patients. A total of 206 lesions were identified and confirmed by anatomopathological examination: 123 keratocysts, 40 dentigerous cysts, 34 radicular cysts, one cyst of epithelial origin but without specification, and eight unicystic ameloblastomas. Although we did not find out which device is best for the decompression of odontogenic cysts, our findings show that those that are most effective should be as comfortable as possible and should remain in place. They should have stability in the oral cavity and be easy for the patient to clean.

Unveiling the Immunomodulatory Potential of Phenolic Compounds in Food Allergies.

Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.

Multiple palisaded encapsulated neuromas presenting as cobblestoned plaques over palms and oral cavity.

Palisaded encapsulated neuroma (PEN) is a benign circumscribed nerve sheath tumor usually seen as a solitary painless papule on the face in middle-aged adults. We report a 22-year-old male with multiple adolescent-onset PENs distributed extensively, including the oral cavity and palms, contrary to the typical presentations. The lesions formed cobblestoned plaques and were confirmed through a skin biopsy, showing characteristic nodules of wavy spindle cells forming interlacing fascicles with interspersed clefts, and positive staining for specific markers, including markers for axons and perineurium. Notably, this case deviates from the usual presentation, shedding light on atypical manifestations of PEN in a young individual without any features suggestive of a neurocutaneous syndrome or multiple endocrine neoplasia syndrome.

Applications of artificial intelligence in the field of oral and maxillofacial pathology: a systematic review and meta-analysis.

BACKGROUND: Since AI algorithms can analyze patient data, medical records, and imaging results to suggest treatment plans and predict outcomes, they have the potential to support pathologists and clinicians in the diagnosis and treatment of oral and maxillofacial pathologies, just like every other area of life in which it is being used. The goal of the current study was to examine all of the trends being investigated in the area of oral and maxillofacial pathology where AI has been possibly involved in helping practitioners. METHODS: We started by defining the important terms in our investigation's subject matter. Following that, relevant databases like PubMed, Scopus, and Web of Science were searched using keywords and synonyms for each concept, such as "machine learning," "diagnosis," "treatment planning," "image analysis," "predictive modelling," and "patient monitoring." For more papers and sources, Google Scholar was also used. RESULTS: The majority of the 9 studies that were chosen were on how AI can be utilized to diagnose malignant tumors of the oral cavity. AI was especially helpful in creating prediction models that aided pathologists and clinicians in foreseeing the development of oral and maxillofacial pathology in specific patients. Additionally, predictive models accurately identified patients who have a high risk of developing oral cancer as well as the likelihood of the disease returning after treatment. CONCLUSIONS: In the field of oral and maxillofacial pathology, AI has the potential to enhance diagnostic precision, personalize care, and ultimately improve patient outcomes. The development and application of AI in healthcare, however, necessitates careful consideration of ethical, legal, and regulatory challenges. Additionally, because AI is still a relatively new technology, caution must be taken when applying it to this industry.

Sarcoid within the oral cavity of a horse.

Equine sarcoids are common skin tumors that are thought to be caused by cross-species infection by bovine papillomaviruses (BPV). A 16-year-old horse developed a 1cm diameter mandibular gingival mass opposite the right second premolar tooth (406) and a 2cm diameter mass close to the commissure of the lips on the same side of the mouth. The right cheek was diffusely thickened. Histology of the smaller mass revealed a proliferation of mesenchymal cells covered by hyperplastic epithelium that formed thick rete pegs. BPV2 DNA was amplified from the mass. Although the mass had been incompletely excised, there was no recurrence after 5 months. The histological features and detection of BPV2 DNA is consistent with a diagnosis of equine sarcoid. Sarcoids have not previously been reported in the oral cavity of horses. It is hypothesized that trauma to the mouth may have been important for sarcoid development. Additionally, different BPV types may have variable ability to infect the gingiva. While rare, sarcoids are a differential for an oral mass in a horse.

Characterization, mechanism and in vivo validation of Helicobacter pylori antagonism by probiotics screened from infants' feces and oral cavity.

Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis, intestinal metaplasia, and gastric carcinoma. Antibiotics, the conventional regimen for eliminating H. pylori, cause severe bacterial resistance, gut dysbiosis and hepatic insufficiency. Here, fifty lactic acid bacteria (LAB) were initially screened out of 266 strains obtained from infants' feces and oral cavity. The antagonistic properties of these 50 strains against H. pylori were investigated. Based on eight metrics combined with principal component analysis, three LAB with probiotic function and excellent anti-H. pylori capacity were affirmed. Combining dynamics test, metabolite assays, adhesion assays, co-cultivation experiments, and SEM and TEM observations, LAB were found to antagonize H. pylori by causing coccoid conversion and intercellular adhesion. Furthermore, it was found that LAB antagonized H. pylori by four pathways, i.e., production of anti-H. pylori substances, inhibition of H. pylori colonization, enhancement of the gastric mucosal barrier, and anti-inflammatory effect. In addition, animal model experiments verified that the final screened superior strain L. salivarius NCUH062003 had anti-H. pylori activity in vivo. LAB also reduced IL-8 secretion, ultimately alleviating the inflammatory response of gastric mucosa. Whole genome sequencing (WGS) data showed that the NCUH062003 genome contained the secondary metabolite biosynthesis gene cluster T3PKS. Furthermore, NCUH062003 had a strong energy metabolism and substance transport capacity, and produced a small molecule heat stable peptide (SHSP, 4.1-6.5 kDa). Meanwhile, LAB proved to be safe through antibiotic susceptibility testing and CARD database comparisons.

Extracavitary Primary Effusion Lymphoma Affecting the Oral Cavity: A Rare Case Report.

Primary effusion lymphoma (PEL) is an aggressive neoplasm often diagnosed in immunosuppressed patients demonstrating peritoneal, pleural, or pericardial effusions. This high-grade lymphoma is strongly associated with human herpesvirus 8 (HHV8) infection and most of the lesions also show the presence of Epstein-Barr virus in tumor cells, which lacks CD20 expression and reveals a plasmablastic morphology and phenotype. The extracavitary or solid variant of PEL is even rarer and usually affects the lymph nodes and is currently considered a clinical manifestation of the classic PEL. In the oral cavity, extracavitary PEL is extremely rare and only a few patients have been previously reported, with no detailed clinicopathological description. The recognition of oral extracavitary PEL is even more important given the occurrence of plasmablastic lymphoma in the oral mucosa, which shares many clinical, microscopic, and phenotypic features with PEL, therefore, demanding from pathologists the search for HHV8, especially in immunosuppressed patients, and an appropriate clinical evaluation. In this report, we aim to describe a very rare extracavitary PEL affecting the palate of a 36-year-old patient and to review the literature regarding the extracavitary presentation of this aggressive lymphoma. This report demonstrates the importance of searching for HHV8 infection in oral lymphomas with plasmablastic features.

A rare case of an extra-oral plasmablastic lymphoma presenting through a scrotal abscess in a 42-year-old man.

Plasmablastic lymphoma (PBL) is a rare lymphoid neoplasm frequently presenting in the oral cavity. It is an aggressive type of non-Hodgkin's lymphoma that shares pathological features with plasma cell myeloma. In addition to human immunodeficiency virus (HIV), it is also associated with Epstein-Bar virus (EBV) and immunosuppression in HIV-negative patients, for example, post transplantation. Extra-oral PBL is rare and only a few case reports involving the testis have been described. Here we describe the first reported case of PBL presenting with a scrotal abscess (not involving the testes) in a patient newly diagnosed with HIV. This case highlights the rare presentation of a rare disease, the difficulties in establishing a diagnosis and the importance of a timely multidisciplinary approach to its management.

The Larynx is Protected from Secondary and Vertical Papillomavirus Infection in Immunocompetent Mice.

OBJECTIVE: Mouse papillomavirus MmuPV1 causes both primary and secondary infections of the larynx in immunocompromised mice. Understanding lateral and vertical transmission of papillomavirus to the larynx would benefit patients with recurrent respiratory papillomatosis (RRP). To test the hypothesis that the larynx is uniquely vulnerable to papillomavirus infection, and to further develop a mouse model of RRP, we assessed whether immunocompetent mice were vulnerable to secondary or vertical laryngeal infection with MmuPV1. METHODS: Larynges were collected from 405 immunocompetent adult mice that were infected with MmuPV1 in the oropharynx, oral cavity, or anus, and 31 mouse pups born to immunocompetent females infected in the cervicovaginal tract. Larynges were analyzed via polymerase chain reaction (PCR) of lavage fluid or whole tissues for viral DNA, histopathology, and/or in situ hybridization for MmuPV1 transcripts. RESULTS: Despite some positive laryngeal lavage PCR screens, all laryngeal tissue PCR and histopathology results were negative for MmuPV1 DNA, transcripts, and disease. There was no evidence for lateral spread of MmuPV1 to the larynges of immunocompetent mice that were infected in the oral cavity, oropharynx, or anus. Pups born to infected mothers were negative for laryngeal MmuPV1 infection from birth through weaning age. CONCLUSION: Secondary and vertical laryngeal MmuPV1 infections were not found in immunocompetent mice. Further work is necessary to explore immunologic control of laryngeal papillomavirus infection in a mouse model and to improve preclinical models of RRP. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2322-2330, 2024.

Prognostic utility of preoperative platelet-to-albumin ratio in surgically treated oral cavity cancer patients.

BACKGROUND: This study aimed to explore the prognostic utility of the preoperative platelet-to-albumin ratio (PAR) among patients with oral cavity squamous cell carcinoma (OSCC). METHODS: We retrospectively reviewed of 355 patients with surgically-treated OSCC between 2008 and 2017. The optimal PAR cutoff for patient stratification was determined through X-tile analysis. Prognostic variables for disease-free survival (DFS) and overall survival (OS) were identified using Cox proportional hazards models. We developed a PAR-based nomogram to predict personalized OS. RESULTS: We determined the optimal PAR cutoff to be 7.45. A PAR of ≥7.45 was an independent negative prognostic factor for DFS and OS (hazard ratio = 1.748 and 2.386; p = 0.005 and p < 0.001, respectively). The developed nomogram demonstrates the practical utility of PAR and accurately predicts personalized OS. CONCLUSIONS: The preoperative PAR is a promising and cost-effective prognostic biomarker for patients with surgically-treated OSCC; the PAR-based nanogram accurately predicts OS for such patients.

Oral Trichogranuloma in an Asian 12-Year-Old Female With Trichotillomania.

Pilonidal sinus is an acquired chronic inflammatory condition associated with the penetration of hair fragments into the skin. In the pathogenesis of most of these cases, a traumatic event initiates the process allowing the introduction of the hairs into the skin. We report an unusual case of acquired pilonidal sinus as a consequence of the unconscious habit of chewing on the hairs in a 12-year-old girl. Although most commonly located in the gluteal cleft, it has been reported in several areas of the body (including face), but to the best of our knowledge, this is the first report in the oral cavity. Our case presented as a palatal and vestibular fistula in a patient who suffered from an undiagnosed peculiar form of hair pulling disorder that involved hair chewing but not trichophagia.

Clinical predictors of premature radiotherapy terminations in senior adults with oral cavity and laryngeal carcinoma.

INTRODUCTION: The underlying factors that contribute to early radiotherapy (RT) termination are understudied, especially in the era of hypofractionated treatment regimens. In this retrospective investigation, we examined the characteristics and causes of premature RT terminations in senior adults (>70 years old) with oral cavity (OC) and laryngeal carcinomas. METHODS: Hundred and eighty-eight patients treated with RT ± systemic therapy for OC and laryngeal cancer from 2017 to 2022 were identified. Premature termination was defined as completion of less than 95% of the prescribed RT. Logistic regression analysis was performed to examine factors predictive of premature termination, and survival was determined using the Kaplan-Meier method. RESULTS: Twenty patients (10.6%) experienced premature RT terminations. On regression analysis, ECOG score at initiation of RT was the only covariate studied to be independently associated with premature termination (OR 2.00, 95%CI: [1.21, 3.30], p = 0.007). Three-year overall survival (49.1% vs. 77.3%) was significantly reduced in the termination cohort (p < 0.0001). CONCLUSIONS: This analysis demonstrated over 1 in 10 patients had premature RT termination, which prognosticated inferior survival outcomes. Poor performance status may highlight patients at risk for premature termination and thus identify good candidates for hypofractionated protocols.

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.

Oral Pyogenic Granuloma: A Narrative Review.

Pyogenic granuloma (PG) is a benign vascular lesion found predominantly in the oral cavity. Characterized by rapid growth and propensity to bleed, PG presents diagnostic challenges due to its similarity and alarming proliferation. This narrative review synthesizes current knowledge on the epidemiology, etiopathogenesis, clinical manifestations, and management of oral PG, with emphasis on recent advances in diagnostic and therapeutic approaches. The epidemiology of the injury is meticulously analyzed, revealing a higher incidence in women and a wide range of ages of onset. It delves into the etiopathogenesis, highlighting the uncertainty surrounding the exact causal factors, although historical attributions suggest an infectious origin. It exhaustively analyzes the clinical and histopathological aspects of oral PG, offering information on its various presentations and the importance of an accurate diagnosis to guide effective treatment. It details treatment strategies, emphasizing the personalized approach based on individual patient characteristics. This comprehensive review consolidates current knowledge on oral PG, highlighting the need for further research to clarify its pathogenesis and optimize treatment protocols.

Relationship between transcriptional expression of pyruvate dehydrogenase and local control of disease in patients with oral cavity carcinomas / Relación entre la expresión transcripcional de piruvato deshidrogenasa y el control local de la enfermedad en pacientes con cáncer en la cavidad oral

Background The altered cellular metabolism is one of the hallmarks of the cancer cells, favoring the process of aerobic glycolysis, known as the Warburg effect. The pyruvate dehydrogenase (PDH) complex is one of the elements involved in this metabolic process. The present study aims to evaluate the relationship between the transcriptional expression of PDHB and the risk of local recurrence in patients with oral cavity carcinomas. Methods We determined the transcriptional expression of PDHB in biopsies from 41 patients with oral cavity carcinomas treated with surgery. The PDHB expression was categorized according to the local control of the disease with a recursive partitioning analysis. Results During the follow-up period 13 patients (31.7%) had a local recurrence of the tumor. Considering local disease control as the dependent variable, the recursive partitioning analysis classified the patients in two categories according to high (n=16, 39.0%) or low (n=25, 61.0%) PDHB expression. Five-year local recurrence-free survival for patients with high PDHB expression was 84.8% (95% CI: 65.2-100%), and for patients with low expression it was 54.3% (95% CI: 34.3–74.2 %) (P=0.034). The results of multivariate analysis showed that patients with a low PDHB expression had a 4.90 times higher risk of local recurrence of the tumor (95% CI: 1.02–22.68, P=0.042). Conclusion There is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence. (AU)

Antecedentes La alteración del metabolismo celular es una de las características distintivas de las células cancerígenas, y favorece el proceso de la glucólisis aeróbica, conocido como efecto de Warburg. El complejo de piruvato deshidrogenasa (PDH) es uno de los elementos implicados en este proceso metabólico. El objetivo del presente estudio es evaluar la relación entre la expresión transcripcional de PDHB y el riesgo de recidiva local en los pacientes con cáncer en la cavidad oral. Métodos Determinamos la expresión transcripcional de PDHB en biopsias de 41 pacientes con cáncer en la cavidad oral tratados con cirugía. Se categorizó la expresión de PDHB de acuerdo con el control local de la enfermedad, con un análisis de partición recursiva. Resultados Durante el periodo de seguimiento, trece pacientes (31,7%) tuvieron una recidiva local del tumor. Considerando el control de la enfermedad local como variable dependiente, el análisis de partición recursiva clasificó a los pacientes en dos categorías, de acuerdo con la expresión de PDHB alta (n=16, 39%) o baja (n=25, 61%). La tasa de supervivencia libre de enfermedad a cinco años con expresión alta de PDHB fue del 84,8% (95% IC: 65,2–100%), siendo del 54,3% (95% IC: 34,3–74,2%) (P=0,034) para los pacientes con expresión baja. Los resultados del análisis multivariante reflejaron que los pacientes con expresión baja de PDHB tuvieron un riesgo 4,90 veces mayor de recidiva local del tumor (95% IC: 1,02–22,68, P=0,042). Conclusión Existe una relación entre las características metabólicas del tumor y su agresividad. Conforme a nuestros resultados, los pacientes con cáncer en la cavidad oral y bajos niveles transcripcionales de PDHB tienen un riesgo significativamente mayor de recidiva local del tumor. (AU)

Oral vitiligo: a predominant spread from oral mucosa.

Depigmented lesions of the oral cavity have been rarely reported. Vitiligo has been defined as an acquired, slowly progressive loss of cutaneous pigment which occurs as irregular, sharply defined patches which may or may not be surrounded by macroscopic hyperpigmentation. Though vitiligo is a common condition affecting the skin having global a prevalence of 0.5%-2% the same affecting the oral mucosal tissue is a rare scenario. Literature review yields only a dearth of cases of oral vitiligo until now. Here we report a case of oral vitiligo involving the entire oral mucosal tissues with anaemic stomatitis. This case is unique as it had entire oral mucosal involvement and the skin involvement being minimal.

Common soft tissue and hard tissue lesions in children and young people (Part 2).

Children and young people can present with a wide variety of symptomatic orofacial pathologies, which can often cause concern. As one presentation may masquerade in multiple pathologies, we start this chapter with a reminder of the surgical sieve used to form a differential diagnosis. An accurate history and examination are essential following which, multiple special investigations may be required. The role of the primary care clinician is recognising soft and hard tissue pathology, considering a differential diagnosis, arranging special investigations, and either initiating care for more straightforward conditions or referring for specialist input. This chapter covers common soft and hard tissue pathology, but is not an exhaustive list.This chapter aims to provide the reader with a practical guide to aid the diagnosis of orofacial pathology in the paediatric age group.

Factors associated with quality of life among patients with a newly diagnosed oral cavity and oropharyngeal cancer.

PURPOSE: The objectives of this report were 1) to examine the quality of life (QOL) of patients with a newly diagnosed oral cavity or oropharyngeal (OCOP) cancer; and 2) to examine factors contributing to QOL before cancer treatment. METHODS: The sample included 115 participants with a new diagnosis of OCOP cancer. Participants completed the demographic form, oral cancer disease and treatment form, Hospital Anxiety and Depression Scale (HADS), Brief Health Literacy Screen (BHLS), and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Pearson correlations and linear regressions were used for data analysis. RESULTS: Participants had a median global health related QOL score of 66.7 (interquartile range, IQR = 50.0, 83.4) with median scores for the subdomains being generally high (all >80 of possible 100). Anxiety and depression were significantly inversely correlated with all areas of EORTC QOL (r = - 0.48 to -0.78, all p < .001). Multivariable associations were strongest with the physical functioning domain (R = 0.56, p < .001), with younger age, higher income, Stage I/II cancer (compared to Stage III/IV) significant contributors to the multiple correlation (beta > ± 0.20, p < .05). CONCLUSIONS: Health care providers should be attentive to OCOP cancer patients with older age, lower household income, advanced cancer stage, and presence of anxious and/or depressive symptoms for indicators of poor QOL. CLINICIANS SHOULD CONSIDER THE BENEFIT OF: initiating supportive interventions before cancer treatment among OCOP cancer patients with poor QOL.