ABSTRACT
Labial salivary gland biopsy (LSGB) is one of the specific diagnostic criteria for primary Sjögren's syndrome (pSS). In traditional LSGB, there is no lower lip fixation device, the field of view is unclear due to intraoperative bleeding, and the incision is large, which is unfavourable for healing. The use of auxiliary devices to improve the shortcomings of traditional LSGB technique would be meaningful. Therefore, this case-control study aimed to assess the value of modified LSGB using chalazion forceps as compared with traditional LSGB. After obtaining written informed consent from all participating parents and patients, we randomly assigned 217 eligible participants to undergo LSGB using chalazion forceps (n = 125) or traditional LSGB (n = 92). The outcome variables were surgical time, incision length, intraoperative bleeding, pain score at 24 h after surgery, incision healing status at 7 days after surgery, gland collection, and pathological results. The final diagnostic results of the two surgical methods were compared, and the match rates between the pathological results and the final clinical diagnoses were compared between the two groups. The data were analysed using parametric and nonparametric tests. Compared with the traditional group, the modified group had a smaller incision, shorter operative time, less blood loss, lower 24 h pain score, and better Grade A incision healing at 7 days after surgery (p < 0.01). There was no statistically significant difference between the patients in the two surgical-method groups in terms of the positive biopsy results and the final diagnosis based on expert opinions (p > 0.05). By multivariable regression analysis, only a focus score (FS) of ≥ 1 (p < 0.01), dry eye disease (p < 0.05) and anti-nuclear antibodies (ANA) titre ≥ 1:320 (p < 0.05) were correlated with the diagnosis of pSS. The positive biopsy results of patients in the different surgical-method groups had a biopsy accuracy of > 80.0% for the diagnosis of pSS. The positive biopsy results in the different surgical-method groups were consistent with the expert opinions and the 2016 ACR-EULAR primary SS classification criteria. The modified LSGB using an auxiliary chalazion forceps offers a good safety with a small incision, shorter operative time, less bleeding, reduced pain and a low incidence of postoperative complications.The match rate of LSGB pathological results of the proposed surgical procedure with the final diagnosis of pSS is high.
Subject(s)
Surgical Instruments , Humans , Female , Biopsy/methods , Biopsy/instrumentation , Adult , Prospective Studies , Middle Aged , Male , Case-Control Studies , Salivary Glands/pathology , Salivary Glands/surgery , Young Adult , Operative Time , AgedABSTRACT
Fine-needle aspiration represents a valid tool for the diagnosis/management of salivary gland lesions. The past years assessed the lack of uniform diagnostic reports for salivary cytopathology leading to interpretative issues. In 2015, an international group of cytopathologists developed an evidence-based tiered classification system for reporting salivary gland fine-needle aspiration (FNA) specimens, the "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC). The present landscape of salivary cytology is represented by the growing adoption of the MSRSGC and the assessment of its diagnostic role. The future landscape is characterized by the increasing role of ancillary techniques for diagnostic and prognostic purposes.
Subject(s)
Salivary Gland Neoplasms , Salivary Glands , Humans , Biopsy, Fine-Needle/methods , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/diagnosis , Salivary Glands/pathology , PrognosisABSTRACT
Sjögren's Syndrome (SS) is an autoimmune disorder characterized by dysfunction of exocrine glands. Primarily affected are the salivary glands, which exhibit the most frequent pathological changes. The pathogenesis involves susceptibility genes, non-genetic factors such as infections, immune cells-including T and B cells, macrophage, dendritic cells, and salivary gland epithelial cells. Inflammatory mediators such as autoantibodies, cytokines, and chemokines also play a critical role. Key signaling pathways activated include IFN, TLR, BAFF/BAFF-R, PI3K/Akt/mTOR, among others. Comprehensive understanding of these mechanisms is crucial for developing targeted therapeutic interventions. Thus, this study explores the cellular and molecular mechanisms underlying SS-related salivary gland damage, aiming to propose novel targeted therapeutic approaches.
Subject(s)
Salivary Glands , Signal Transduction , Sjogren's Syndrome , Sjogren's Syndrome/immunology , Sjogren's Syndrome/pathology , Sjogren's Syndrome/metabolism , Sjogren's Syndrome/genetics , Sjogren's Syndrome/etiology , Humans , Salivary Glands/pathology , Salivary Glands/metabolism , Salivary Glands/immunology , Animals , Cytokines/metabolismABSTRACT
Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4+ T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4+ T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.
Subject(s)
Carcinoma, Adenoid Cystic , Salivary Gland Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Adenoid Cystic/immunology , Carcinoma, Adenoid Cystic/metabolism , Carcinoma, Adenoid Cystic/genetics , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/immunology , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/mortality , Male , Female , Tumor Microenvironment/immunology , Middle Aged , Aged , Gene Expression Regulation, Neoplastic , Adult , Salivary Glands/pathology , Salivary Glands/metabolism , Salivary Glands/immunology , PrognosisABSTRACT
Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.
Subject(s)
Coinfection , Cytomegalovirus Infections , Cytomegalovirus , Salivary Gland Neoplasms , Salivary Glands , Humans , Coinfection/virology , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Male , Female , Salivary Gland Neoplasms/virology , Middle Aged , Adult , Aged , Salivary Glands/virology , Salivary Glands/pathology , Adenoma/virology , Aged, 80 and over , Carcinoma/virology , DNA, Viral/genetics , DNA, Viral/analysis , Young Adult , AdolescentABSTRACT
Introduction: Salivary gland dysfunction, often resulting from salivary gland obstruction-induced inflammation, is a prevalent condition. Corticosteroid, known for its anti-inflammatory and immunomodulatory properties, is commonly prescribed in clinics. This study investigates the therapeutic implications and potential side effects of dexamethasone on obstructive sialadenitis recovery using duct ligation mice and salivary gland organoid models. Methods: Functional and pathological changes were assessed after administering dexamethasone to the duct following deligation 2 weeks after maintaining ligation of the mouse submandibular duct. Additionally, lipopolysaccharide- and tumor necrosis factor-induced salivary gland organoid inflammation models were established to investigate the effects and underlying mechanisms of action of dexamethasone. Results: Dexamethasone administration facilitated SG function restoration, by increasing salivary gland weight and saliva volume while reducing saliva lag time. Histological evaluation revealed, reduced acinar cell atrophy and fibrosis with dexamethasone treatment. Additionally, dexamethasone suppressed pro-inflammatory cytokines IL-1ß and TNF expression. In a model of inflammation in salivary gland organoids induced by inflammatory substances, dexamethasone restored acinar markers such as AQP5 gene expression levels, while inhibiting pro-inflammatory cytokines TNF and IL6, as well as chemokines CCL2, CXCL5, and CXCL12 induction. Macrophages cultured in inflammatory substance-treated media from salivary gland organoid cultures exhibited pro-inflammatory polarization. However, treatment with dexamethasone shifted them towards an anti-inflammatory phenotype by reducing M1 markers (Tnf, Il6, Il1b, and Cd86) and elevating M2 markers (Ym1, Il10, Cd163, and Klf4). However, high-dose or prolonged dexamethasone treatment induced acino-ductal metaplasia and had side effects in both in vivo and in vitro models. Conclusions: Our findings suggest the effectiveness of corticosteroids in treating obstructive sialadenitis-induced salivary gland dysfunction by regulating pro-inflammatory cytokines.
Subject(s)
Dexamethasone , Kruppel-Like Factor 4 , Sialadenitis , Animals , Dexamethasone/pharmacology , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Mice , Sialadenitis/drug therapy , Sialadenitis/pathology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Disease Models, Animal , Organoids/drug effects , Cytokines/metabolism , Mice, Inbred C57BL , Salivary Glands/drug effects , Salivary Glands/pathology , Salivary Glands/metabolism , Salivary Glands/immunology , Aquaporin 5/metabolism , Aquaporin 5/genetics , Male , Macrophages/drug effects , Macrophages/immunology , Acinar Cells/drug effects , Acinar Cells/metabolism , Acinar Cells/pathology , HumansABSTRACT
Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.
Subject(s)
Head and Neck Neoplasms , Mitochondria , Salivary Glands , Xerostomia , Xerostomia/etiology , Xerostomia/prevention & control , Humans , Mitochondria/drug effects , Mitochondria/radiation effects , Head and Neck Neoplasms/radiotherapy , Salivary Glands/radiation effects , Salivary Glands/drug effects , Salivary Glands/pathology , Radiation Injuries/prevention & control , Radiation Injuries/etiology , Animals , Radiotherapy/adverse effects , Radiotherapy/methods , Quality of LifeABSTRACT
Since 2019, Coronavirus Disease 2019(COVID-19) has affected millions of people worldwide. Except for acute respiratory distress syndrome, dysgeusis is also a common symptom of COVID-19 that burdens patients for weeks or permanently. However, the mechanisms underlying taste dysfunctions remain unclear. Here, we performed complete autopsies of five patients who died of COVID-19. Integrated tongue samples, including numerous taste buds, salivary glands, vessels, and nerves were collected to map the pathology, distribution, cell tropism, and receptor distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the tongue. Our results revealed that all patients had moderate lymphocyte infiltration around the salivary glands and in the lamina propria adjacent to the mucosa, and pyknosis in the epithelia of taste buds and salivary glands. This may be because the serous acini, salivary gland ducts, and taste buds are the primary sites of SARS-CoV-2 infection. Multicolor immunofluorescence showed that SARS-CoV-2 readily infects Keratin (KRT)7+ taste receptor cells in taste buds, secretory cells in serous acini, and inner epithelial cells in the ducts. The major receptors, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), were both abundantly expressed in these cells. Viral antigens and receptor were both rarely detected in vessels and nerves. This indicates that SARS-CoV-2 infection triggers pathological injury in the tongue, and that dysgeusis may be directly related to viral infection and cellular damage.
Subject(s)
Angiotensin-Converting Enzyme 2 , Autopsy , COVID-19 , SARS-CoV-2 , Serine Endopeptidases , Tongue , Viral Tropism , Humans , COVID-19/pathology , COVID-19/virology , SARS-CoV-2/pathogenicity , Tongue/virology , Tongue/pathology , Male , Angiotensin-Converting Enzyme 2/metabolism , Female , Middle Aged , Serine Endopeptidases/metabolism , Salivary Glands/virology , Salivary Glands/pathology , Aged , Taste Buds/virology , Taste Buds/pathology , Receptors, Virus/metabolismABSTRACT
Sjögren syndrome (SS) is an autoimmune disease characterized by chronic inflammatory infiltrates in the salivary and lacrimal glands. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T-cells, predominantly found in mucosal tissues with crucial role in epithelial homeostasis. Thus, MAIT cells may be implicated in mucosal alterations of SS patients. Activation markers, inflammatory and cytotoxic cytokines were examined in 23 SS patients and compared to 23 healthy controls (HC). Tissular MAIT cells in salivary gland (SG) biopsies were also analyzed. Circulating MAIT cells were decreased in SS patients with a higher expression of CD69 and a higher CD4/CD8 ratio of MAIT cells. MAIT cells showed a higher production of IFNγ, TNFα and GzB in SS compare to HC. Tissular MAIT cells were present within inflamed SG of SS patients, while they were absent in SG of HC. Overall, circulating MAIT cells are decreased in the peripheral blood of SS albeit producing higher amounts of IFNγ, TNFα, and GzB. Tissular MAIT cells are detected in salivary glands from SS with a proinflammatory tissular cytokine environment. MAIT cells with abnormal phenotype, functions and tissular homeostasis may contribute to epithelial damage in SS.
Subject(s)
Mucosal-Associated Invariant T Cells , Salivary Glands , Sjogren's Syndrome , Humans , Sjogren's Syndrome/immunology , Sjogren's Syndrome/pathology , Mucosal-Associated Invariant T Cells/immunology , Mucosal-Associated Invariant T Cells/metabolism , Female , Middle Aged , Male , Salivary Glands/pathology , Salivary Glands/immunology , Salivary Glands/metabolism , Adult , Cytokines/metabolism , Aged , Case-Control StudiesABSTRACT
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease primarily affecting exocrine glands such as the salivary glands, leading to impaired secretion and sicca symptoms. As the mainstay of salivation, salivary gland epithelial cells (SGECs) have an important role in the pathology of pSS. Emerging evidence suggests that the interplay between immunological factors and SGECs may not be the initial trigger or the sole mechanism responsible for xerostomia in pSS, challenging conventional perceptions. To deepen our understanding, current research regarding SGECs in pSS was reviewed. Among the extensive aberrations in cellular architecture and function, this review highlighted certain alterations of SGECs that were identified to occur independently of or in absence of lymphocytic infiltration. In particular, some of these alterations may serve as upstream factors of immuno-inflammatory responses. These findings underscore the significance of introspecting the pathogenesis of pSS and developing interventions targeting SGECs in the early stages of the disease.
Subject(s)
Epithelial Cells , Salivary Glands , Sjogren's Syndrome , Sjogren's Syndrome/pathology , Sjogren's Syndrome/immunology , Humans , Epithelial Cells/pathology , Salivary Glands/pathologyABSTRACT
To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-κB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-κB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-κB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-κB signaling by targeting IκBα, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.
Subject(s)
Apoptosis , Epithelial Cells , MicroRNAs , Mitochondria , NF-kappa B , Salivary Glands , Signal Transduction , Sjogren's Syndrome , MicroRNAs/genetics , MicroRNAs/metabolism , Humans , Mitochondria/metabolism , NF-kappa B/metabolism , Salivary Glands/metabolism , Salivary Glands/pathology , Animals , Epithelial Cells/metabolism , Epithelial Cells/pathology , Mice , Sjogren's Syndrome/metabolism , Sjogren's Syndrome/genetics , Sjogren's Syndrome/pathology , Female , Cell Line , Male , Middle AgedABSTRACT
Elevated oxidative stress can play a pivotal role in autoimmune diseases by exacerbating inflammatory responses and tissue damage. In Sjögren's disease (SjD), the contribution of oxidative stress in the disease pathogenesis remains unclear. To address this question, we created mice with a tamoxifen-inducible conditional knockout (KO) of a critical antioxidant enzyme, superoxide dismutase 2 (Sod2), in the salivary glands (i-sg-Sod2 KO mice). Following tamoxifen treatment, Sod2 deletion occurred primarily in the ductal epithelium, and the salivary glands showed a significant downregulation of Sod2 expression. At twelve weeks post-treatment, salivary glands from the i-sg-Sod2 KO mice exhibited increased 3-Nitrotyrosine staining. Bulk RNA-seq revealed alterations in gene expression pathways related to ribosome biogenesis, mitochondrial function, and oxidative phosphorylation. Significant changes were noted in genes characteristic of salivary gland ionocytes. The i-sg-Sod2 KO mice developed reversible glandular hypofunction. However, this functional loss was not accompanied by glandular lymphocytic foci or circulating anti-nuclear antibodies. These data demonstrate that although localized oxidative stress in salivary gland ductal cells was insufficient for SjD development, it induced glandular dysfunction. The i-sg-Sod2 KO mouse resembles patients classified as non-Sjögren's sicca and will be a valuable model for deciphering oxidative-stress-mediated glandular dysfunction and recovery mechanisms.
Subject(s)
Epithelial Cells , Mice, Knockout , Mitochondria , Oxidative Stress , Salivary Glands , Sjogren's Syndrome , Superoxide Dismutase , Animals , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Salivary Glands/pathology , Salivary Glands/metabolism , Sjogren's Syndrome/metabolism , Sjogren's Syndrome/pathology , Sjogren's Syndrome/genetics , Mice , Epithelial Cells/metabolism , Epithelial Cells/pathology , Mitochondria/metabolism , Disease Models, AnimalABSTRACT
Interstitial lung disease is a common complication of anti-synthetase syndrome (ASS), and lymphocytic infiltration is often observed in the lesion. We have recently reported that disease-specific autoantibodies are produced by infiltrating lymphocytes in some autoimmune diseases. Here, we investigate the antigen specificity of B cells in the lung lesions of ASS patients. A total of 177 antibodies were produced from antibody-secreting cells in bronchoalveolar fluid (BALF) of three each of serum anti-Jo-1 and serum anti-EJ antibody-positive patients. Twelve to 30% and 50 to 62% of these antibodies were disease-specific autoantibodies, respectively. These autoantibodies recognized conformational epitopes of the whole self-antigen and had affinity maturations, indicating that self-antigens themselves are the target of humoral immunity. In addition, 100 antibodies were produced from two salivary gland tissues, obtained by chance, of ASS patients. Salivary glands are not generally recognized as lesions of ASS, but unexpectedly, ASS-related autoantibody production was also observed similar to that of BALF. Immunostaining confirmed the presence of ASS-related autoantibody-producing cells in salivary glands. Our results suggest that disease-specific autoantibody production at lesion sites is a common pathogenesis of autoimmune diseases, and that tissue-specific production of autoantibodies can provide insights regarding the distribution of organ manifestations in autoimmune diseases.
Subject(s)
Autoantibodies , Lung , Myositis , Salivary Glands , Humans , Salivary Glands/immunology , Salivary Glands/pathology , Autoantibodies/immunology , Myositis/immunology , Female , Male , Lung/immunology , Lung/pathology , Middle Aged , Bronchoalveolar Lavage Fluid/immunology , Adult , B-Lymphocytes/immunology , Lung Diseases, Interstitial/immunology , Autoantigens/immunology , Antibodies, Antinuclear/immunology , AgedABSTRACT
BACKGROUND: Paclitaxel is a highly effective chemotherapeutic agent used to treat breast, ovarian, and other cancers. At the same time, paclitaxel causes peripheral neuropathy as a side effect in 45%-70% of patients. AIM: The aim of the study was to investigate the effect of paclitaxel-induced peripheral neuropathy on the development of pathological changes in the salivary glands of animals and to explore the possibility of correction of the identified changes with vitamin B/ATP complex. MATERIALS AND METHODS: To simulate toxic neuropathy, animals were injected i/p with paclitaxel 2 mg/kg for 4 days. In order to correct the identified changes, rats were injected i/m with vitamin B/ATP complex (1 mg/ kg) for 9 days. In the homogenate of the submandibular salivary glands, α-amylase activity, total proteolytic activity, total antitryptic activity, the content of medium mass molecules, thiobarbituric acid reactive substances (TBARS), oxidatively modified proteins, and catalase activity were determined. RESULTS: A significant increase in the content of oxidatively modified proteins, medium mass molecules, and the content of TBARS and significant decrease in the activity of catalase and amylase were determined in the salivary glands of animals with toxic neuropathy compared to these parameters in intact animals. Administration of vitamin B/ATP complex for 9 days against the background of paclitaxel-induced neuropathy led to normalization of antitryptic activity and amylase activity, a significant decrease in the content of oxidatively modified proteins, medium mass molecules, and TBARS along with a significant increase in catalase activity in the salivary glands of animals compared to the untreated rats with neuropathy. CONCLUSION: Paclitaxel-induced neuropathy caused the development of pathological changes in the salivary glands of rats, which was evidenced by a carbonyl- oxidative stress and impaired protein synthetic function. The correction with vitamin B/ATP complex restored the protein-synthetic function and the proteinase-inhibitor balance, suppressed the oxidative stress and normalized free radical processes in the salivary glands of rats.
Subject(s)
Paclitaxel , Peripheral Nervous System Diseases , Salivary Glands , Animals , Paclitaxel/adverse effects , Paclitaxel/pharmacology , Salivary Glands/drug effects , Salivary Glands/pathology , Salivary Glands/metabolism , Rats , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/pathology , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/pharmacology , Rats, Wistar , Oxidative Stress/drug effects , Adenosine Triphosphate/metabolism , Vitamin B Complex/pharmacology , Vitamin B Complex/therapeutic use , Male , Thiobarbituric Acid Reactive Substances/metabolism , Catalase/metabolismABSTRACT
Salivary gland tumors (SGT) display morphological diversity and pose diagnostic challenges. Preoperative fine needle aspiration cytology (FNAC) is a minimally invasive and efficient diagnostic test. However, due to the limited sample size, the final diagnosis may not be established based on FNAC alone. Although cytomorphology and architecture are usually preserved on FNAC, morphologic changes specific to FNAC can complicate the diagnosis. The Milan System for Reporting Salivary Gland Cytopathology categorizes complex FNAC interpretations. Because the cytological diagnosis is closely linked to the histological diagnosis, a multidimensional approach considering the possibility of several differential diagnoses is necessary. From the standpoint of treatment, distinguishing high-grade malignancy from low-grade malignancy is more important than distinguishing malignancy from benign tumors.
Subject(s)
Salivary Gland Neoplasms , Humans , Biopsy, Fine-Needle , Cytodiagnosis/methods , Diagnosis, Differential , Salivary Gland Neoplasms/pathology , Salivary Gland Neoplasms/diagnosis , Salivary Glands/pathologyABSTRACT
Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix (ECM) destruction within the salivary and lacrimal glands, followed by immune cell infiltration. In this review, we have assessed the current understanding of epithelial-mesenchymal transition (EMT)-associated changes within the salivary epithelium potentially involved in salivary dysfunction and SjD pathogenesis. We performed a PubMed literature review pertaining to the determination of pathogenic events that lead to EMT-related epithelial dysfunction and signaling in SjD. Molecular patterns of epithelial dysfunction in SjD salivary glands share commonalities with EMT mediating wound healing. Pathological changes altering salivary gland integrity and function may precede direct immune involvement while perpetuating MMP9-mediated ECM destruction, inflammatory mediator expression, and eventual immune cell infiltration. Dysregulation of EMT-associated factors is present in the salivary epithelium of SjD and may be significant in initiating and perpetuating the disease. In this review, we further highlight the gap regarding mechanisms that drive epithelial dysfunction in salivary glands in the early or subclinical pre-lymphocytic infiltration stages of SjD.
Subject(s)
Epithelial-Mesenchymal Transition , Salivary Glands , Sjogren's Syndrome , Humans , Sjogren's Syndrome/pathology , Sjogren's Syndrome/metabolism , Salivary Glands/pathology , Salivary Glands/metabolism , Animals , Epithelium/pathology , Epithelium/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Signal Transduction , Extracellular Matrix/metabolismABSTRACT
AIMS: The Milan system for reporting salivary gland cytopathology was developed by an international group of experts and first published in 2018 with the goal to standardise reporting of salivary gland aspirates. Seven categories with distinct risks of malignancy were proposed. Core needle biopsies (CNB) of salivary glands are also common, but reporting lacks standardisation. Here we explore the feasibility of a Milan-like reporting system on CNB of the parotid gland. METHODS AND RESULTS: Our laboratory information system was searched for parotid gland CNBs from 2010 to 2021. Reports were translated into a Milan-like reporting system. When available, CNB findings were correlated with cytology and resection specimens. In order to compare the performance of CNB with fine-needle aspirations (FNA), we established a second cohort of cases consisting of parotid FNA with surgical follow-up. The risk of neoplasia (RON) and risk of malignancy (ROM) was calculated for FNA and CNB Milan categories using cases with follow-up resection. We analysed 100 cases of parotid gland CNB. Of these cases, 32 underwent subsequent resection, while 52 had concurrent FNA. A total of 20 cases had concurrent FNA and underwent follow-up resection. In 63 (63%) cases, a specific diagnosis was provided on CNB, with 18 cases undergoing follow-up resection having an accuracy rate of 94%. CONCLUSIONS: This study confirms the feasible of using a Milan-like system in the setting of parotid gland CNB with differentiation in RON and ROM. CNB allows assessment of architectural features that may allow more specific diagnoses in some cases.
Subject(s)
Parotid Gland , Humans , Biopsy, Large-Core Needle , Parotid Gland/pathology , Female , Male , Middle Aged , Aged , Adult , Biopsy, Fine-Needle , Parotid Neoplasms/pathology , Parotid Neoplasms/diagnosis , Aged, 80 and over , Salivary Glands/pathology , Young Adult , Cytodiagnosis/methods , Adolescent , CytologyABSTRACT
BACKGROUND: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. RESULTS: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. CONCLUSIONS: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.
Subject(s)
Deglutition Disorders , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Xerostomia , Humans , Deglutition Disorders/etiology , Male , Xerostomia/etiology , Female , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/complications , Nasopharyngeal Carcinoma/pathology , Middle Aged , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Follow-Up Studies , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/complications , Adult , Aged , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Deglutition , Salivary Glands/radiation effects , Salivary Glands/pathology , Salivary Glands/diagnostic imaging , Radiotherapy Dosage , Prognosis , Young AdultABSTRACT
The differential diagnosis of salivary gland lesions with epithelial components and lymphoid stroma is often challenging. Salivary gland carcinoma with tumor-associated lymphoid proliferation, tumors composed of both epithelial and lymphoid components, lymphoid neoplasms in the salivary gland, and inflammatory lesions are all included in this category. It encompasses inflammatory lesions and neoplastic lesions. With the exception of Warthin tumors, these lesions are rare, making them more difficult to diagnose. Carcinoma showing thymus-like elements has recently been reported in the salivary gland. Similar to thymic carcinoma, tumor cells are positive for CD5 and are accompanied by T lymphocytes.