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BMC Oral Health Nov 2023Minor salivary glands can be found in the ventral and anterior part of the tongue; these glands can rarely develop mucoceles that, due to their rarity and their unusual...
BACKGROUND
Minor salivary glands can be found in the ventral and anterior part of the tongue; these glands can rarely develop mucoceles that, due to their rarity and their unusual clinical appearance, may present an interesting differential diagnosis. Mucoceles appear as an exophytic, sometimes pedunculated, lesion, which is a feature that is due to the absence of a capsule; thus, the glands are right beneath the mucosa and over the muscle tissue. The aim of this article is to retrospectively present and discuss the anatomy, pathology, clinical features and therapy of several cases of Blandin-Nunh mucoceles collected from two different institutions.
METHODS
A retrospective case review was carried out in two university institutions, retrieving all cases of tongue mucoceles from 1999 to today. Two oral pathologists reviewed all the slides, confirming the diagnosis. Demographic data of the patient, anatomic location and clinical appearance were retrieved from clinical charts, together with the type of surgical procedure and possible relapses.
RESULTS
A total of 240 cases of tongue mucoceles were gathered from the archives: the mean age was 22 years (DS = 14,7; Range 2-83), 126 were females (52,5%, mean age 22,7 years, DS = 16,5; Range 2-83), and 114 were males (47,5%, mean age 20,9 years, DS = 12,4; Range 3-73); in all cases, a history of trauma was reported. The ventral surface was the most frequent location (224 cases - 93,3%), and in the great majority (235 cases - 97,9%), pathology revealed mucous spillage with a wall formed by fibrous connective and granulation tissue with no epithelium lining the cavity. Superficial mucocele and sclerosing sialoadenitis were the more frequent pathological variants (21 cases - 8,8%). All lesions were treated with excision and enucleation of the servicing gland. The healing was uneventful in all cases, but there were four recurrences and two cases of sensory paraesthesia of the border of the tongue, all in males, except one case of paraesthesia in a female.
CONCLUSIONS
Tongue mucoceles must be differentiated from many benign and malignant lesions. For this reason, surgical removal of the lesion and of the associated gland with a pathological exam is mandatory. In fact, the anatomical location of the glands and the possible pathological variants must be considered to reach a correct diagnosis and diminish possible relapses.
TRIAL REGISTRATION
CE-Muc_Ton_3/2023.
Topics: Male; Humans; Female; Young Adult; Adult; Salivary Gland Diseases; Mucocele; Retrospective Studies; Paresthesia; Neoplasm Recurrence, Local; Tongue; Recurrence
PubMed: 37964264
DOI: 10.1186/s12903-023-03485-y -
Disease Models & Mechanisms Jan 2024Organoid culture systems are very powerful models that recapitulate in vivo organ development and disease pathogenesis, offering great promise in basic research, drug...
Organoid culture systems are very powerful models that recapitulate in vivo organ development and disease pathogenesis, offering great promise in basic research, drug screening and precision medicine. However, the application of organoids derived from patients with cancer to immunotherapeutic research is a relatively untapped area. Esophageal cancer is one of the most lethal malignancies worldwide, including two major pathological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. ESCC shares many biological and genomic features with oral squamous cell cancers. Herein, we provide a versatile protocol for the establishment and maintenance of oral and esophageal organoid cultures derived from both murine and human samples. We describe culture conditions for organoids derived from normal tongue, esophagus and gastroesophageal junction, esophageal cancer and Barrett's esophagus. In addition, we establish an ex vivo model by co-culturing patient tumor-derived organoids and autologous CD8+ T lymphocytes to assess CD8+ T cell-mediated tumor killing. Our protocol can also be modified for organoid establishment from other squamous epithelia and carcinomas. The co-culture model can serve as a template for studies of other tumor-immune cell interactions and the efficacy of immune checkpoint blockade therapy.
Topics: Humans; Animals; Mice; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Adenocarcinoma; Organoids
PubMed: 38258518
DOI: 10.1242/dmm.050319 -
Journal For Immunotherapy of Cancer Sep 2023Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises....
BACKGROUND
Oral squamous cell carcinoma (OSCC) is a devastating disease most often associated with tobacco consumption that induces a field of mutations from which a tumor arises. Identification of ways to prevent the emergence of cancer in high-risk patients is an ultimate goal for combatting all types of cancer, including OSCC.
METHODS
Our study employs a mouse model of tongue carcinogenesis induced by tobacco carcinogen mimetic, 4-nitroquinoline 1-oxide (4NQO), to establish tongue dysplasia and OSCC. We use conventional histology, immunohistochemistry, multispectral imaging, mass cytometry, novel cell lines, pharmaceutical inhibition of PI3Kγ, T-cell suppression assays and mouse transplant models in our functional experimentation.
RESULTS
In our study, we identify Ly6G+ granulocytes as the most abundant immune cell type in a model of tongue carcinogenesis induced by tobacco carcinogen mimetic 4NQO. Targeting Ly6G+ granulocytes with a pharmacologic inhibitor of PI3Kγ, an isoform of PI3K exclusively expressed by myeloid cells, resulted in reduced tongue dysplasia severity, and reduced rates of OSCC. Importantly, we performed functional assays with the Ly6G+ granulocytes induced in cell line models of 4NQO carcinogenesis to demonstrate that these granulocytes have increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) activity against T-cell proliferation and these PMN-MDSCs play a functional role in promoting tumor formation by inhibiting tumor regression in a PI3Kγ-dependent manner.
CONCLUSIONS
Overall, our data suggest that recruitment of PMN-MDSCs to sites of dysplasia is critical to immune suppression of CD8 T cells, thereby permitting malignancy, and PI3Kγ inhibitors are one mechanism to reduce PMN-MDSC recruitment, immunosuppression and tumorigenesis in OSCC.
Topics: Humans; Animals; Mice; Phosphatidylinositol 3-Kinase; Myeloid-Derived Suppressor Cells; Carcinoma, Squamous Cell; Mouth Neoplasms; Carcinogenesis; Carcinogens; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Phosphatidylinositols
PubMed: 37734878
DOI: 10.1136/jitc-2023-007110 -
BMC Cancer Aug 20233D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause...
BACKGROUND
3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices.
METHODS
We used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties.
RESULTS
OTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared with Myogel and h-LG. The highest number of unique adhesion-related proteins was present in h-LG.
CONCLUSIONS
We demonstrated that human pre-metastatic neck lymph node-derived matrix is suitable for studying metastatic OTSCC cells. As a whole-protein extract, h-LG provides new opportunities for in vitro carcinoma cell culture experiments.
Topics: Humans; Animals; Swine; Carcinoma, Squamous Cell; Proteomics; Tongue Neoplasms; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Lymph Nodes; Tumor Microenvironment
PubMed: 37580662
DOI: 10.1186/s12885-023-11275-6 -
BMC Cancer Nov 2023The recurrence site that influences post-recurrence survival (PRS) in patients with non-small cell lung cancer (NSCLC) undergoing surgery and the preoperative predictors...
BACKGROUND
The recurrence site that influences post-recurrence survival (PRS) in patients with non-small cell lung cancer (NSCLC) undergoing surgery and the preoperative predictors of recurrence remain unclear.
METHODS
Cohorts 1 and 2 had 4520 (who underwent complete resection for p-stage 0-IIIA NSCLC) and 727 (who experienced recurrence after surgery) patients, respectively. The initial sites of recurrence were the lungs (309 cases), thoracic lymph nodes (225 cases), pleura (112 cases), bone (110 cases), central nervous system (86 cases), adrenal gland (25 cases), abdomen (60 cases), cervical and axillary lymph nodes (38 cases), chest wall (13 cases), skin (5 cases), and eye and tongue (3 cases). For cohort 2 analysis, the initial recurrence site that resulted in poor PRS was analyzed by multivariable analysis using a Cox proportional hazard model. For cohort 1 analysis, the preoperative predictors of recurrence patterns with poor PRS were analyzed by multivariable analysis using a logistic regression model.
RESULTS
In cohort 2 analysis, recurrence in the central nervous system (hazard ratio [HR], 1.70; p < 0.001), bone (HR, 1.75; p < 0.001), abdomen (HR, 2.39; p < 0.001), and pleura (HR, 1.69; p < 0.001) were independent poor prognostic recurrent sites for PRS and they were high-risk sites (HRS). Intrathoracic lymph nodes, cervical and axillary lymph nodes, lungs, chest wall, adrenal gland, eye and tongue, and skin were low-risk sites (LRS) that did not affect PRS. Patients with multiple LRS without HRS recurrence had a worse prognosis than those with a single LRS without HRS recurrence (5-year PRS 20.2% vs. 37.7%, p < 0.001) and were comparable to those with HRS recurrence (p = 1.000). In cohort 1 analysis, preoperative predictors for HRS and multiple LRS recurrences were positron emission tomography (PET) maximum standardized uptake value (maxSUV) ≥ 3.2 (HR, 5.09; p < 0.001), clinical nodal metastasis (HR, 2.00; p < 0.001), tumor size ≥ 2.4 cm (HR, 1.96; p < 0.001) and carcinoembryonic antigen (CEA) ≥ 5 ng/ml (HR, 1.41; p = 0.004). The cumulative incidence rates of HRS and multiple LRS recurrences within 5 years were 55.9%, 40.9%, 26.3%, 11.1%, and 3.5% (p < 0.001) in patients with 4, 3, 2, 1 and 0 of the above risks, respectively.
CONCLUSIONS
HRS and multiple LRS were vital recurrences associated with poor PRS. Preoperative PET maxSUV, clinical nodal metastasis, tumor size, and CEA level predicted the incidence of vital recurrence.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Carcinoembryonic Antigen; Neoplasm Staging; Tomography, X-Ray Computed
PubMed: 37926846
DOI: 10.1186/s12885-023-11582-y -
Lasers in Medical Science Sep 2023The choice between radiotherapy (RT) and CO laser surgery (CO-LS) for early glottic cancer remains controversial. We systematically examined electronic databases in... (Meta-Analysis)
Meta-Analysis Review
The choice between radiotherapy (RT) and CO laser surgery (CO-LS) for early glottic cancer remains controversial. We systematically examined electronic databases in order to identify prospective trials comparing patients who had undergone CO-LS or RT to treat early glottic cancer. Eleven studies involving 1053 patients were included. In the selected literature, the parameter setting of CO laser equipment can be summarized as wavelength 10.6 µm, superpulsed mode, continuous setting, power tailored on target structures (1-3 W for subtle resections and 4-15 W for cutting a larger tumor), and approximately 2080-3900 W/cm of laser energy. Using RevMan 5.3, we estimated pooled odds ratios (ORs) for dichotomous variables and pooled mean differences (MDs) for continuous variables, along with associated 95% confidence intervals (CIs). The heterogeneity in the treatment variables was measured using Higgins' inconsistency test and expressed as I values. The continuous variables were then depicted as histograms developed using PlotDigitizer 2.6.8. Compared to patients treated with CO-LS, those treated with RT had better jitter (MD 1.27%, 95% CI 1.21 ~ 1.32, P < 0.001), and high scores on the "Grade (MD 6.54, 95% CI 5.31 ~ 7.76, P < 0.001), Breathiness (MD 9.08, 95% CI 4.02 ~ 14.13, P < 0.001), Asthenia (MD 2.13, 95% CI 0.29 ~ 3.98, P = 0.02), and Strain (MD 3.32, 95% CI 0.57 ~ 6.07, P = 0.02)" scale. Patients treated with CO-LS had worse local control rates (OR 3.14, 95% CI 1.52 ~ 6.48, P = 0.002) while lower incidence of second primary tumor (OR 0.30, 95% CI 0.15 ~ 0.61, P < 0.001). It is hoped that retrospective analysis can provide suggestions for early glottis patients to choose personalized treatment.
Topics: Humans; Carbon Dioxide; Treatment Outcome; Retrospective Studies; Microsurgery; Laryngeal Neoplasms; Prospective Studies; Laser Therapy; Glottis; Tongue Neoplasms
PubMed: 37758965
DOI: 10.1007/s10103-023-03890-3 -
Frontiers in Immunology 2024The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well....
INTRODUCTION
The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined.
METHODS
We assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively.
RESULTS
MUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells , in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice.
CONCLUSION
The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.
Topics: Humans; Animals; Mice; Carcinoma, Squamous Cell; Tongue Neoplasms; Killer Cells, Natural; Cell Line; Tongue; Mucin-1
PubMed: 38390321
DOI: 10.3389/fimmu.2024.1337557 -
The Laryngoscope Aug 2023Oral cancers in the US-affiliated Pacific Islands are poorly described despite disproportionately higher incidences in certain jurisdictions. This study attempts to...
OBJECTIVE/HYPOTHESIS
Oral cancers in the US-affiliated Pacific Islands are poorly described despite disproportionately higher incidences in certain jurisdictions. This study attempts to better characterize the incidence, staging, and management of oral cancers in this region.
STUDY DESIGN
Retrospective Epidemiological Study.
METHODS
A retrospective review was conducted across the US-affiliated Pacific Islands between 2007 and 2019. Patient data were obtained for individuals with primary head and neck cancers from the Pacific Regional Central Cancer Registry database. All cohorts were age-adjusted to the 2000 US Standard Population. Further analysis was performed on oral cavity cancers due to their clear predominance within the sample.
RESULTS
A total of 585 patients with primary head and neck cancers were included. The average age was 54.5 ± 12.9 years, and most patients were male (76.8%). Oral cancer subsite analysis revealed the proportional incidence of buccal mucosa was higher in 5 of 9 jurisdictions when compared with the United States (p < 0.001). Tongue and lip cancers were not found to have significantly higher incidence proportions. Patients in the Pacific Islander group were less likely to be detected at earlier stages for cancers of the cheek and other mouth (p < 0.001), tongue (p < 0.001), and lips (p < 0.001) compared with the United States.
CONCLUSIONS
Many Pacific Island populations are burdened with higher incidences of oral cancer with later staging. Further investigation is recommended to evaluate oral cancer-related outcomes and mortality in this region.
LEVEL OF EVIDENCE
3 Laryngoscope, 133:1899-1905, 2023.
Topics: Humans; Male; United States; Adult; Middle Aged; Aged; Female; Pacific Islands; Lip Neoplasms; Retrospective Studies; Mouth Neoplasms; Lip
PubMed: 36165583
DOI: 10.1002/lary.30419 -
Oral Oncology Aug 2023Understanding the tumor immune microenvironment is becoming increasingly necessary for risk prediction and treatment selection. In particular, oral cancer has various...
Personal immune profiles: Diversity and prognostic value for oral tongue squamous cell carcinoma evaluated by comprehensive immune parameter analyses with multiplex immunofluorescence.
OBJECTIVES
Understanding the tumor immune microenvironment is becoming increasingly necessary for risk prediction and treatment selection. In particular, oral cancer has various immunosuppressive characteristics in the tumor microenvironment. Therefore, we comprehensively assessed the immune profiles of oral tongue squamous cell carcinoma (OTSCC).
MATERIALS AND METHODS
Multiplex immunofluorescence and tissue imaging analyses were performed to evaluate immune profiles at the invasive tumor front of 60 OTSCC surgical specimens. We analyzed 58 immune parameters including the density and proportion (%) of total leukocytes (Leu) and T cells, six subsets of T and myeloid cells, and the expression of programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1).
RESULTS
The density, proportion, and location of CD45 Leu, three T cell subsets (CD8, Foxp3CD4 conventional, and Foxp3CD4 regulatory T cells), CD163CD68 M1 and CD163CD68 M2 macrophages, and neutrophils were highly variable at the individual level. The density and proportion of M2 macrophages were significantly lower in the T1 stage group. Risk prediction analyses for recurrence and/or metastasis (R/M) showed that R/M (+) T1 cases had significantly higher M2 density and percentages.
CONCLUSIONS
The immune profiles of OTSCC patients are diverse and cannot be predicted from clinicopathological information alone. The M2 macrophage abundance is a potential candidate biomarker for R/M in the early stage of OTSCC. Personal immune profiling may provide beneficial information for risk prediction and treatment selection.
Topics: Humans; Prognosis; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Programmed Cell Death 1 Receptor; Tongue Neoplasms; Head and Neck Neoplasms; Fluorescent Antibody Technique; Forkhead Transcription Factors; Tumor Microenvironment; B7-H1 Antigen; Lymphocytes, Tumor-Infiltrating
PubMed: 37329869
DOI: 10.1016/j.oraloncology.2023.106458 -
Journal of Pharmacy & Bioallied Sciences Feb 2024Traumatic or irritation fibroma is the healed end product of the inflammatory hyperplastic lesion, which can occur at any age from almost any softtissue site, tongue,...
Traumatic or irritation fibroma is the healed end product of the inflammatory hyperplastic lesion, which can occur at any age from almost any softtissue site, tongue, gingiva, and buccal mucosa being the most common. It is usually characterized by a slow, painless growth accumulated over a period of months or years.
PubMed: 38595470
DOI: 10.4103/jpbs.jpbs_650_23