Journal of Oral Pathology & Medicine最新文献

Background

This study presents a case series and scoping review of oral melanoacanthoma to examine its clinical, histopathological, and immunohistochemical characteristics.

Methods

Nine cases of oral melanoacanthoma were included in the case series. Clinical data were collected from biopsy charts. Hematoxylin–eosin and immunohistochemistry for TRP2, CD3, and CD20 were done. For the scoping review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched.

Results

Case series: The mean age was 46.8 years (female-to-male ratio 2:1). Lesion's mean size was 11.0 mm (±9.3). Lesions were mainly macular (77.8%) with brown or black coloration (88.9%) and often affected multiple sites (44.4%). The evolution time ranged from 15 days to 96 months. Lesions commonly showed epithelial acanthosis (66.7%), spongiosis (55.6%), exocytosis (77.8%), melanin incontinence (88.9%), and inflammatory infiltrate in the lamina propria (77.8%), from which all showed lymphocytes. TRP2-positive melanocytes were identified in the basal and spinous layer of all cases, and in the superficial layer of three cases. CD3-positive cells predominate over the CD20-positive. Scoping review: 85 cases of oral melanoacanthoma were retrieved from 55 studies. Patients were primarily female (female-to-male ratio 2.2:1), black-skinned (64.1%), with a mean age of 36.13 (± 17.24). Lesions were flat (81.9%), often brown (62.4%). Buccal mucosa was the preferred site (32.9%), followed by multiple sites (28.2%).

Conclusion

Oral melanoacanthoma mainly affects women across a wide age range, with lesions commonly appearing as brown/black macules, particularly on the buccal mucosa. TRP2-positive melanocytes and T-lymphocytes were consistently found and could participate in oral melanoacanthoma pathogenesis.

Background

Oral mucositis (OM) is a severe and common adverse effect of cancer treatment. The oral microbiome appears to play a role on the onset and severity of OM. Therefore, this systematic review aims to characterize the oral dysbiosis associated with OM.

Methods

The PRISMA checklist was followed and PubMed, Web of Science, and Scopus were screened for clinical studies characterizing the oral microbiome alterations in patients with OM.

Results

From a total of 2500 articles retrieved, we included nine articles in this systematic review. Certain types of bacteria, as Fusobacterium, were recognized as predictors of the onset of OM. In addition, it was reported that patients with severe OM presented a reduction in alpha-diversity, an increase in beta-diversity. The abundance of some taxa significantly changed with OM severity, with Bacillota phylum and genera Leptotrichia, Actinomyces, and Prevotella decreasing and Treponema increasing with disease progression. Additionally, during cancer treatment, changes in the oral microbiome have been observed in OM patients, with an increase in Candida and nosocomial pathogens, including Staphylococcus species.

Conclusion

Our review indicates that cancer treatment can significantly alter the oral microbiome, with more pronounced changes observed in patients with severe OM in all relevant oral phyla, but more pronounced in Bacillota phylum.

Background

Oral leukoplakia (OL) is an unfavorable oral disease often resistant to therapy. To this end, cold physical plasma technology was explored as a novel therapeutic agent in an experimental setup.

Methods

Biopsies with a diameter of 3 mm were obtained from non-diseased and OL tissues. Subsequently, cold atmospheric pressure plasma (CAP) exposure was performed ex vivo in the laboratory. After 20 h of incubation, biopsies were cryo-conserved, and tissue sections were quantified for lymphocyte infiltrates, discriminating between naïve and memory cytotoxic and T-helper cells. In addition, the secretion pattern related to inflammation was investigated in the tissue culture supernatants by quantifying 10 chemokines and cytokines.

Results

In CAP-treated OL tissue, significantly decreased overall lymphocyte numbers were observed. In addition, reduced levels were observed when discriminating for the T-cell subpopulations but did not reach statistical significance. Moreover, CAP treatment significantly reduced levels of C-X-C motif chemokine 10 (CXCL10) and granulocyte-macrophage colony-stimulating factor in the OL biopsies' supernatants. In idiopathically inflamed tissues, ex vivo CAP exposure reduced T-cells and CXCL10 as well but also led to markedly increased interleukin-1β secretion.

Conclusion

Our findings suggest CAP to have immuno-modulatory properties, which could be of therapeutic significance in the therapy of OL. Future studies should investigate the efficacy of CAP therapy in vivo in a larger cohort.

Background

Oral squamous cell carcinoma is an increasingly prevalent cancer type characterized by high incidence and mortality rates. Its early detection is challenging, primarily because of the absence of early molecular markers. Cuproptosis is a novel regulatory mechanism of cell death with implications in various cancers. In this study, we aimed to study cuproptosis-related genes in oral squamous cell carcinoma to identify their prognostic value.

Methods

By analyzing genomic, bulk RNA-seq, and single-cell RNA-seq data, we investigated 13 cuproptosis-related genes in The Cancer Genome Atlas-Oral Squamous Cell Carcinoma dataset and Gene Expression Omnibus repository (GSE172577).

Results

ATP7A, ATP7B, and DLST were the most frequently mutated genes, with nine of our studied genes associated with overall survival. Single-cell analysis was conducted to identify cuproptosis-related tumor cells in oral squamous cell carcinoma, which revealed two distinct patterns based on the expression of cuproptosis-related genes. These patterns exhibit differences in genetic alterations and tumor immune microenvironment. Finally, we developed a cuproptosis index using a random forest algorithm based on cuproptosis pattern-related genes in which higher levels were linked to poorer prognosis.

Conclusion

Our findings provide valuable insights into the mechanisms underlying oral squamous cell carcinoma-associated cuproptosis.

Background

Compelling evidence implicates diabetes-associated hyperglycemia as a promoter of tumor progression in oral potentially malignant disorders (OPMD). Yet, information on hyperglycemia-induced cell signaling networks in oral oncology remains limited. Our group recently reported that glucose-rich conditions significantly enhance oral dysplastic keratinocyte viability and migration through epidermal growth factor receptor (EGFR) activation, a pathway strongly linked to oral carcinogenesis. Here, we investigated the basal metabolic phenotype in these cells and whether specific glucose-responsive EGFR ligands mediate these responses.

Methods

Cell energy phenotype and lactate concentration were evaluated via commercially available assays. EGFR ligands in response to normal (5 mM) or high (20 mM) glucose were analyzed by quantitative real-time PCR, ELISA, and western blotting. Cell viability and migration assays were performed in the presence of pharmacological inhibitors or RNA interference.

Results

When compared to normal keratinocytes, basal glycolysis in oral dysplastic keratinocytes was significantly elevated. In highly glycolytic cells, high glucose-activated EGFR increasing viability and migration. Notably, we identified amphiregulin (AREG) as the predominant glucose-induced EGFR ligand. Indeed, enhanced cell migration in response to high glucose was blunted by EGFR inhibitor cetuximab and AREG siRNA. Conversely, AREG treatment under normal glucose conditions significantly increased cell viability, migration, lactate levels, and expression of glycolytic marker pyruvate kinase M2.

Conclusion

These novel findings point to AREG as a potential high glucose-induced EGFR activating ligand in highly glycolytic oral dysplastic keratinocytes. Future studies are warranted to gain more insight into the role of AREG in hyperglycemia-associated OPMD tumor progression.

Background

Oral squamous cell carcinoma is characterized by high rates of morbidity and mortality. Evidence obtained for different types of cancer shows that tumor initiation, progression, and therapeutic resistance are regulated by heat shock factor 1. This research aimed to analyze the effects of heat shock factor 1 on the biological behavior of oral squamous cell carcinoma.

Methods

Clinicopathological and immunoexpression study of heat shock factor 1 in 70 cases of oral tongue SCC and functional assays by gene silencing of this factor in an oral tongue SCC cell line.

Results

Heat shock factor 1 was overexpressed in oral tongue SCC specimens compared to normal oral mucosa (p < 0.0001) and in the SCC15 line compared to immortalized keratinocytes (p < 0.005). No significant associations were observed between overexpression of heat shock factor 1 and clinicopathological parameters or survival rates of the oral tongue SCC cases in the present sample. In vitro experiments showed that heat shock factor 1 silencing inhibited cell proliferation (p < 0.005) and cell cycle progression, with the accumulation of cells in the G0/G1 phase (p < 0.01). In addition, heat shock factor 1 silencing reduced cell invasion capacity (p < 0.05) and epithelial-mesenchymal transition, characterized by a decrease in vimentin expression (p < 0.05) and an increase in E-cadherin expression (p < 0.001).

Conclusion

Heat shock factor 1 may exert several functions that help maintain cell stability under the stressful conditions of the tumor microenvironment. Thus, strategies targeting the regulation of this protein may in the future be a useful therapeutic tool to control the progression of oral squamous cell carcinoma.

Background

The present network meta-analysis aims to answer the question “what is the best topical intervention for the treatment of recurrent aphthous stomatitis that can provide an acceptable pain relief and promote wound healing?”

Methods

From inception to October 2022, PubMed, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure were searched to identify all potentially eligible randomized controlled trials. The primary outcomes were pain scores and/or healing time, while the secondary outcomes were the associated side effects. The Bayesian network meta-analysis accompanied by a random effect model and 95% credible intervals were calculated.

Results

Forty-three randomized controlled trials with a total of 3067 participants, comparing 20 different topical medications, were included. Concerning pain reduction, the network meta-analysis failed to show any statistically significant differences when different topical treatments were compared together or even with a placebo at different time intervals. Except for doxycycline, which showed a statistically significant difference in terms of accelerating healing time, other topical interventions showed no statistically significant differences when compared with placebo or with each other.

Conclusion

Background

Mucoepidermoid carcinoma is a rare salivary gland malignant tumour. This study aimed to investigate inflammatory and immune signatures of mucoepidermoid carcinoma by identifying potential proteo-transcriptomic biomarkers towards the development of precision immuno-oncology treatment strategies.

Methods

A total of 30 biopsies obtained from patients diagnosed with mucoepidermoid carcinoma between 2013 and 2022 were analysed after H&E staining for scoring of histological inflammatory stroma subtypes and inflammatory hotspots with QuPath. Multiplex immunofluorescence staining and NanoString nCounter PanCancer IO 360™ panel were used to assess stroma and tumour inflammation signatures in high grade mucoepidermoid carcinoma cases in the tumour microenvironment via proteomics and transcriptomics, respectively.

Results

Inflammatory cells within the histological inflammatory stroma inflammatory (HIS-INF/hot) tumour neighbourhoods were greater compared to the histological inflammatory stroma-immune desert (HIS-ID/cold) (p = 0.001). A similar trend was observed between treatment non-responders and responders in stroma neighbourhoods (p = 0.0625) and in stroma-to-interface inflammatory hotspots (p = 0.0081), indicating an augmented inflammatory response in hot tumours and non-responders. Furthermore, there were striking differences in the expression of pan-immune leukocyte marker CD45 between responders and non responders particularly in the tumour neighbourhoods (p = 0.0341), but such were not robust for PD-1 and macrophage fractions. Additionally, transcriptomic analysis revealed key differences in leukocyte activation profiles between responders and non-responders.

Conclusion

This preliminary report unveils the importance of assessing immune leukocyte cellular fractions and pathways for future prognostic biomarker discoveries in mucoepidermoid carcinoma as per the involvement of CD45-driven inflammatory and immune mediators in high grade mucoepidermoid carcinoma in non-responders to treatment. These findings will potentially contribute to the development of novel personalised immunotherapies.

Objective

Oral leukoplakia is the most common oral potentially malignant disorder. Malignant transformation of oral leukoplakia occurs at an annual rate of 1%–7%. WHO-defined classic epithelial dysplasia is an important predictor of malignant transformation of oral leukoplakia, but we have previously shown in a proof of concept study that prediction improves by incorporation of an architectural pattern of dysplasia, also coined as differentiated dysplasia. We aimed to analyze this finding in a larger cohort of patients.

Method

For this retrospective study 176 oral leukoplakia patients were included. Biopsies for all patients were assessed for the presence of dysplasia and analyzed for cytokeratin 13 and 17 expression. Moreover, the inter-observer agreement for the diagnosis of differentiated dysplasia was determined.

Results

In total, 33 of 176 patients developed oral squamous cell carcinoma during follow-up. Presence of classic epithelial dysplasia increased cancer risk two-fold (HR = 2.18, p = 0.026). Lesions without classic epithelial dysplasia could be further risk-stratified by the presence of differentiated dysplasia (HR = 7.36, p < 0.001). Combined classic epithelial and differentiated dysplasia imparted a seven-fold increased risk of malignant transformation (7.34, p = 0.001). Inter-observer agreement for the diagnosis of dysplasia, including differentiated dysplasia, was moderate (κ = 0.56, p < 0.001).

Discussion

This study emphasizes the importance of the recognition of the architectural pattern of differentiated dysplasia as a separate entity for risk prediction of malignant transformation of oral leukoplakia. Presence of any pattern of dysplasia results in accurate prediction of malignant transformation risk of oral leukoplakia.