Non-invasive imaging for predicting labial salivary gland biopsy outcomes in patients with suspected primary Sjögren syndrome.

To identify the value of salivary gland ultrasound (SGUS) combined with magnetic resonance imaging (MRI) and magnetic resonance sialography (MRS) in predicting the results of labial salivary gland biopsy (LSGB) in patients with suspected primary Sjögren syndrome (pSS), and construct a nomogram model to predict LSGB results. A total of 181 patients who were admitted with suspected pSS from December 2018 to April 2023 were examined and divided into a training set (n = 120) and a validation set (n = 61). Baseline data of the two groups were examined, and the value of SGUS, MRI, and MRS in predicting LSGB was analyzed. Multivariate logistic analysis was used to screen for risk factors, and nomogram prediction models were constructed using these results. In the training set, the SGUS, MRI, and MRS scores of patients in the LSGB + group were higher than those in the LSGB - group (all P < 0.001). The positive prediction value (PPV) was 91% for an SGUS score of 3, and 82% for MRI and MRS scores of 2 or more. We developed a nomogram prediction model based on SGUS, MRI, and MRS data, and it had a concordance index (C-index) of 0.94. The Hosmer-Lemeshow test (χ2 = 3.17, P = 0.92) also indicated the nomogram prediction model had good accuracy and calibration for prediction of LSGB results. A nomogram model based on SGUS, MRI, and MRS results can help rheumatologists decide whether LSGB should be performed in patients with suspected pSS.

B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren's Disease: A Pilot Monocentric Exploratory Study.

Primary Sjögren's disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin's lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren's disease remains elusive. Thus, the purpose of this study was (i) to explore miR-155, B-cell activating factor (BAFF)-receptor (BAFF-R), and Interleukin 6 receptor (IL-6R) expression in the labial salivary glands (LSG) of patients with primary Sjögren's disease, aiming to identify potential B-cell activation biomarkers related to NHL development. Twenty-four patients with primary Sjögren's disease, and with available tissue blocks from a LSG biopsy performed at diagnosis, were enrolled. Among them, five patients developed B-cell NHL during follow-up (7.3 ± 3.1 years). A comparison group of 20 individuals with sicca disease was included. Clinical and laboratory parameters were recorded and the LSG biopsies were evaluated to assess local inflammation in terms of miR-155/BAFF-R and IL-6R expression. Stratifying the primary Sjögren's disease cohort according to lymphomagenesis, miR-155 was upregulated in primary Sjögren's disease patients who experienced NHL, more so than those who did not experience NHL. Moreover, miR-155 expression correlated with the focus score (FS), as well as BAFF-R and IL-6R expression, which were increased in primary Sjögren's disease patients and in turn related to neoplastic evolution. In conclusion, epigenetic modulation may play a crucial role in the aberrant activation of B-cells in primary Sjögren's disease, profoundly impacting the risk of NHL development.

B cell receptor repertoire analysis in primary Sjogren's syndrome salivary glands identifies repertoire features associated with clinical activity.

BACKGROUND: Primary Sjogren's syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells. METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq. RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity. CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.

Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.

Introduction: This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS). Methods: The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted. Results: A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers. Discussion: Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci.

Involvement of expanded cytotoxic and proinflammatory CD28null T cells in primary Sjögren's syndrome.

OBJECTIVE: The absence of CD28 is a feature of antigen-experienced, highly differentiated and aged T cells. The pathogenicity of CD28null T cells remains elusive in primary Sjögren's syndrome (pSS). Therefore, this study was performed to explore the characteristics of CD28null T cells in both peripheral blood and minor salivary glands (MSGs) of pSS patients. METHODS: pSS patients and paired healthy controls (HCs) were enrolled. The phenotype of peripheral CD28null T cells was analyzed using flow cytometry. In vitro functional assays were performed to evaluate the cytotoxic and proinflammatory effects of peripheral CD28null T cells. In addition, polychromatic immunofluorescence staining was performed to investigate infiltrating CD28null T cells in MSGs. RESULTS: A significant expansion of peripheral CD28null T cells was observed in pSS patients compared with HCs (p < 0.001), which were primarily CD8+CD28null T cells. The proportion of peripheral CD8+CD28null T cells moderately correlated with the erythrocyte sedimentation rate (r = 0.57, p < 0.01) and IgG levels (r = 0.44, p < 0.01). Peripheral CD28null T cells had stronger capacities to secrete granzyme B and perforin, but comparable capacities to secrete IFN-γ and TNF-α than their CD28+ counterparts. An abundant amount of cytotoxic and pro-inflammatory CD28null T cells was also found in MSGs. Moreover, a high expression of the chemokine receptor CXCR3 was found on peripheral and tissue-resident CD28null T cells, with its ligands CXCL9/10 abundantly present in MSGs. CONCLUSION: Increasing CD28null T cells with strong cytotoxicity and proinflammatory effects were observed in both peripheral blood and MSGs from pSS patients. The precise mechanism of action and migration still needs further investigation.

Dysgenetic Polycystic Disease of the Salivary Glands: A Case Report of This Rare Entity Occurring for the First Time in the Minor Salivary Glands of the Tongue, and a Review of the Literature.

Dysgenetic polycystic disease, also known just as polycystic disease, is a very rare developmental abnormality affecting the salivary gland duct system. This entity has been reported in only 21 patients previously, although a careful review suggests only 16 patients have histological evidence of the disease. In previously reported cases, this lesion most commonly presents as either an incidental finding or as a swelling affecting the parotid glands bilaterally, or rarely the submandibular glands bilaterally. This case report details the first time dysgenetic polycystic disease is found affecting the minor salivary glands of the tongue in a 55-year-old male. Histochemical and immunohistochemical stains are presented and include positivity for AE1/AE3 and p63, and negativity for progesterone receptor, androgen receptor, mammaglobin, S100 and BRAF V600E. PAS-D and Congo Red highlight special microamyloid spheroliths structures intraluminally.

Microanatomical, histochemical and morphometric features of the major and selected minor salivary glands in laboratory Wistar rat.

The major and minor salivary glands are responsible for saliva production, a fluid drained in the oral cavity that will be involved in several functions at this level. The present study aimed to compare the microanatomy of the major (parotid, mandibular, sublingual) and minor salivary glands (von Ebner's and Weber's) of the Wistar rat, from a histological, histochemical and morphometrically point of view. Predominantly serous glands (parotid, mandibular and von Ebner's) showed differences in the secretion composition on both PAS and alcian blue reactions. The same observations were identified also for the mostly mucous salivary glands (sublingual and Weber). In terms of surface dimensions, the measurements suggested that the mucous acini have a greater surface compared with the serous ones, and, at the same time, a better-represented polymorphism. In conclusion, the major and minor salivary glands in Wistar rats, a commonly used species in experimental procedures, showed similarities with other species including humans, but some structural traits are breed-specific, this finding is very important for an extensive understanding of the morphophysiology of the salivary glands.

Increased Diagnostic Accuracy of the Labial Gland Biopsy in Primary Sjögren Syndrome When Multiple Histopathological Features Are Included.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of the labial salivary gland biopsy based on multiple histopathological features in patients with suspected primary Sjögren syndrome (pSS). METHODS: Patients from a diagnostic sicca cohort with clinically suspected pSS who underwent a labial gland biopsy were included. Patients were categorized as having pSS or non-Sjögren syndrome sicca (non-SS sicca) based on vignettes scored by an expert panel. Labial gland biopsies were analyzed for the presence of four histopathological features: focus score (FS) ≥1, prelymphoepithelial and lymphoepithelial lesions, immunoglobulin G plasma cell shift, and germinal centers. Sensitivity and specificity of histologic features were calculated, and the optimal cutoff value for the number of histopathological features needed to diagnose pSS was determined with receiver operating curve analysis. RESULTS: A total of 38 patients were categorized as having pSS and 65 as having non-SS sicca. In labial gland biopsies of patients with pSS, the prevalence of FS ≥1 was 82%, followed by 68% for pre-lymphoepithelial and lymphoepithelial lesions, 63% for plasma cell shift, and 24% for germinal centers. Although FS ≥1 showed the highest sensitivity for patients with pSS (82%), specificity was higher for the other three features (98%-100%). The presence of two or more (of four) histopathological features had almost comparable sensitivity to FS alone, but specificity increased with 12% to 100%. For fulfillment of American College of Rheumatology/EULAR criteria, specificity increased from 84% to 95% when an abnormal biopsy was defined by the presence of two or more histopathological features instead of FS ≥1 only. CONCLUSION: The diagnostic accuracy of the labial gland biopsy increases when other histopathological features besides FS are taken into account, by reducing the number of false-positive biopsies.

Sialendoscopy Findings Associated with Positive Minor Salivary Gland Biopsy.

OBJECTIVES: To determine the sialendoscopy findings associated with positive findings on minor salivary gland biopsy. STUDY DESIGN: Single-center retrospective study. METHODS: Patients ≥18 years old who underwent sialendoscopy from 2016 to 2022 and were evaluated for SS via labial minor salivary gland biopsy. Biopsy positive and negative patients were compared on the primary outcome measure of sialendoscopy findings. Data were abstracted from the sialendoscopy operative notes and included involved gland, location of ductal pathology, and the presence of scarring, stenosis, mucus plugs, webs, and dilations. Additional characteristics included demographics, presenting symptoms, caffeine or tobacco, use of drying medications, and need for additional treatments. RESULTS: The final cohorts included 22 biopsy positive and 21 biopsy negative patients with a total of 42 glands in the biopsy positive and 37 glands in the biopsy negative groups. Biopsy positive patients were found to require dilation at the hilum and distal duct at significantly higher rates than biopsy negative patients (p < 0.0001). However, there was no statistical difference in scarring, stenosis severity, mucus, webs, or dilations between each group. CONCLUSION: The outcomes of this study suggest that there are no distinct sialendoscopy findings associated with biopsy positive patients. The presence of significant distal stenosis on sialendoscopy may be associated with positive minor salivary biopsy. Other endoscopic parameters are likely more consistent with non-specific chronic sialadenitis. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1183-1189, 2024.

BubR1 and cyclin B1 immunoexpression in pleomorphic adenoma and polymorphous adenocarcinoma of minor salivary glands.

The immunoexpression of BubR1 and cyclin B1 in pleomorphic adenoma (PA) and polymorphic adenocarcinoma (PAC) in minor salivary glands is poorly studied. Thus, a retrospective and observational study was performed to provide a better understanding of the role and immunopositivity patterns of these proteins in these lesions. Sixteen cases of PA and 16 cases of PAC were selected. Parenchyma cells were submitted to quantitative immunohistochemical analysis through the labeling index. Cytoplasmic immunoexpression of BubR1 was observed in neoplastic cells from all analyzed PA and PAC cases. All PA cases and 93.7% of PAC exhibited nuclear immunoexpression of BubR1. Higher cytoplasmic and nuclear immunoexpression of BubR1 was observed in PAC (p = 0.001 and p = 0.122, respectively). Cytoplasmic immunoexpression of cyclin B1 was observed in all cases of PA and PAC, with a higher labeling index in the latter (p < 0.001). There was a significant positive correlation between nuclear and cytoplasmic BubR1 immunoexpressions (p < 0.001) in PA and a significant negative correlation between BubR1 and cyclin B1 cytoplasmic immunoexpressions (p = 0.014) in PAC. The higher cytoplasmic and nuclear immunoexpression of BubR1 in PACs suggests the continuous maintenance of neoplastic cells in the cell cycle and migration. Higher immunoexpression of cyclin B1 supports this lesion's enhanced proliferative and migration ability.

Human Minor Salivary Glands: A Readily Available Source of Salivary Stem/Progenitor Cells for Regenerative Applications.

Resident stem/progenitor cells within the secretory salivary glands offer a potential therapeutic resource for use in the regeneration of salivary glands needed to restore saliva production in patients with chronic xerostomia, or dry mouth. Methods were developed previously to isolate human stem/progenitor cells (hS/PCs) from major salivary glands (parotid/submandibular). Abundant minor salivary glands located in readily accessible locations in the oral cavity and lip could provide an additional valuable therapeutic resource. An advantage of this cell resource is that these minor glands about the size of grape seeds can be harvested from healthy donors using minimally invasive surgical procedures. The disadvantage of using minor glands is that they contain many fewer cells than do major glands, and thus harvested cells need to be expanded in the lab to create a therapeutic resource. While earlier work has described isolation of proliferative cell populations from minor salivary glands that could be used in regenerative medicine, most of these expanded cells possess properties of mesenchymal cells rather than the epithelial population that secretes salivary products.Here, we describe in detail our recently established methods to isolate and expand hS/PCs isolated from human labial minor salivary glands. Expanded hS/PC populations are epithelial assessed by their expression of epithelial progenitor markers K5 and K14. Like expandable cell populations previously isolated from the major salivary glands, these cells also express nuclear p63, consistent with their ability to be expanded after explant culture. When hS/PCs with these properties are encapsulated into a customized 3D biomimetic hyaluronic acid-based hydrogel, they will assemble into microstructures that retain some progenitor markers while also beginning to differentiate. The increased expression of secreted mucin MUC-7 was used to demonstrate differentiation and secretory potential in assembled hS/PC microstructures. Compared to hS/PCs from major glands, those from minor salivary glands tend to be more heterogeneous in early passage; thus, use of K5/K14/p63 as an early quality assessment tool is highly recommended. Additionally, hS/PCs from minor glands are sensitive to stress and if mishandled will demonstrate a stress response that leads to their transitioning to a flat, squamous cell-like appearance that is of limited utility in regenerative medicine applications. We conclude that properly handled hS/PCs from minor salivary glands represent a powerful new source of therapeutic cells for applications including treating patients with chronic xerostomia.

Incidência, epidemiologia e fatores prognósticos dos tumores de glândulas salivares menores da cavidade oral e orofaringe / Incidence, epidemiology and prognostic factors of tumors of minor salivary glands of the oral cavity and oropharynx

Introdução: Os carcinomas de glândulas salivares menores são tumores de comportamento muito heterógeno, englobam diversos tipos histológicos cujo tratamento deve ser diferenciado. Estudos demonstram a incidência e sítios principais destes carcinomas porem a definição dos fatores de pior prognostico para o planejamento terapêutico deve ser estabelecido. Métodos: Estudo retrospectivo de 451 pacientes com diagnostico histopatológico de tumor de glândulas salivares menores de cavidade oral e orofaringe no período de 1995-2015. Realizada coleta de dados histopatológicos, clínicos, tratamento e qualidade de vida. Resultados: Dos pacientes estudados, 408 (90%) apresentaram tumores malignos, 153 (40%) sexo masculino e 226 (60%) sexo feminino, faixa etária mediana de 53 anos. Sitios mais comuns foram o palato ósseo seguido por base de língua e mucosa jugal. Os três principais tipos histológicos se mantiveram como Adenocarcinoma (32%), Carcinoma mucoepidermoide (30%) e Carcinoma Adenoide Cistico (30%). Em torno de 6,8% dos casos foram diagnosticados com acometimento linfonodal e 7,1% com metástases a distância sendo o pulmão o principal sítio. A sobrevida global em 5 anos foi maior no Carcinoma mucoepidermoide (55,2%) e a menor no Carcinoma Adenoide Cistico (42,27%), deve ser considerado que a grande maioria dos diagnósticos (58%) foram realizados em estagio avançado T3 e T4. A sobrevida livre de doença nos pacientes tratados cirurgicamente associados a RT adjuvante ou não foi muito superior ao tratamento com quimioterapia e radioterapia associadas. A taxa de recidiva foi de 14%, Carcinoma adenoide cístico teve a maior taxa de recidiva local. Conclusão: Através deste estudo pudemos oberservar que os fatores que contribuem para pior desfecho prognóstico do tratamento dos tumores de glândulas salivares são o tipo histológico Carcinoma Adenóide Cístico, tumores avançados T3 e T4, presença de mestástase linfonodal e à distância, além do tratamento não cirúrgico

Introduction: Minor salivary gland carcinomas are tumors with a very heterogeneous behavior, encompassing several histological types whose treatment must be differentiated. Studies demonstrate the incidence and main sites of these carcinomas, but the definition of the worst prognostic factors for therapeutic planning must be established. Methods: Retrospective study of 451 patients with histopathological diagnosis of minor salivary gland tumor of the oral cavity and oropharynx in the period 1995-2015. Histopathological, clinical, treatment and quality of life data were collected. Results: Of the patients studied, 408 (90%) had malignant alterations, 153 (40%) male and 226 (60%) female, median age of 53 years. Most common sites were the bony palate followed by the base of the tongue and buccal mucosa. The three main histological types remained as Adenocarcinoma (32%), Mucoepidermoid Carcinoma (30%) and Adenoid Cystic Carcinoma (30%). In about 6.8% of the cases, lymph nodes were affected and 7.1% had distant metastases, with the lung being the main site. Overall survival at 5 years was highest in Mucoepidermoid Carcinoma (55.2%) and lowest in Adenoid Cystic Carcinoma (42.27%), it must be considered that the vast majority of diagnoses (58%) were performed in advanced stage T3 and T4. Diseasefree survival in patients treated surgically associated with adjuvant or not RT was much superior to treatment with associated chemotherapy and radiotherapy. The recurrence rate was 14%, adenoid cystic carcinoma had the highest local recurrence rate. Conclusion: Through this study we were able to observe that the factors that contribute to a worse prognostic outcome of the treatment of salivary gland: Adenoid Cystic Carcinoma, advanced T3 and T4 tumors, presence of lymph node and distant metastasis, in addition to non-surgical treatment

Nuts and bolts of salivary gland pathology in primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic, systemic, inflammatory autoimmune disease characterised by lymphocyte proliferation and progressive damage to exocrine glands. Salivary gland histopathology based on salivary gland biopsy is relevant for the diagnosis of pSS and therefore broadly applied in clinical practice. Tissue can be obtained from labial salivary glands (LSG) biopsy or from major salivary glands (MSG) biopsy, namely the parotid; in this latter scenario, the procedure can be either an open surgical biopsy or a US guided core needle biopsy.In this review we will: i) present the histopathological findings that may be encountered by pathologists on biopsies from pSS patients; ii) discuss the advantages and disadvantages of the surgical and/or imaging guided procedures to obtain tissues from LSG or MSG; iii) describe the histopathological features of lymphoma of MSG in pSS patients.

Sjögren's syndrome: one year in review 2023.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterised by the T-cell-mediated hyperactivation of B-cells and cytokine production. The condition may evolve from an asymptomatic, indolent course, with glandular involvement, to extra-glandular systemic manifestations up to lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T- and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. Recently, increasing research focused on the investigation of mechanisms underlying the complex pathogenesis of the disease and highlighted the multi-factorial nature of SS consisting of concomitant involvement of environmental, genetic, neuroendocrine and immune factors. In particular, many aspects have been investigated regarding genetic and epigenetics, the role of specific B- and T-cell phenotypes and the investigation of disease-specific biomarkers as predictors of disease development, activity, and lymphomagenesis. Surely, a deeper understanding of these multiple mechanisms may facilitate earlier diagnosis, enable subphenotyping of patients and open novel therapeutic possibilities to address the unmet needs of the disease in the upcoming years.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.

Anticholinergic burden of medications is associated with dry mouth and reflected in minor labial gland secretion.

OBJECTIVE: Medications with anticholinergic potential inhibit saliva secretion. Polypharmacy potentiates anticholinergic burden, causing dry mouth symptoms and chronic deterioration of oral health. Patients of any age can be affected by anticholinergic medication-triggered hyposalivation (the objective measure of dry mouth); therefore, seeking predictions of hyposalivation to screen dry mouth is needed. DESIGN: In our prospective, cross-sectional clinical study, 55 middle-aged adult patients participated. We examined whether the anticholinergic burden calculated from anticholinergic medications (anticholinergic drug score; ADS) and blood serum anticholinergic activity (SAA; the gold standard measure of anticholinergic burden) is associated with hyposalivation. As no prior studies measured minor salivary glands regarding the quantifiable anticholinergic burden, we assessed hyposalivation by the minor saliva flow (MSF) and unstimulated whole saliva (UWS) secretion. RESULTS: Our data showed a negative linear relationship between SAA and UWS (p < 0.05); when SAA increases by one pmol/ml unit, the saliva flow decreases by 0.058 ml/min. MSF showed a linear correlation (p < 0.005) with UWS. In a multivariate logistic regression model (including age, gender, race, smoking status, xerostomia severity, ADS, and BMI), we identified SAA and age as predictors of hyposalivation (p < 0.05). CONCLUSIONS: We provide evidence for the significant relationship between measurable anticholinergic burden and saliva flow. The correlation between UWS and MSF suggests that both saliva flow rate measurement methods could reflect anticholinergics-induced changes in salivary health.

Treatment and outcomes of minor salivary gland cancers of the larynx and trachea: a systematic review.

Objectives: Malignant minor salivary glands carcinomas (MiSGC) of the larynx and trachea are rare tumours and published evidence is sparse. We conducted a systematic review to describe shareable treatment strategies and oncological outcomes of these neoplastic entities. Methods: Full text English manuscripts published from January 1st 2000 to December 14th 2022 were included. Data on demographics, treatments and outcomes were collected. A pooled analysis of 5-year overall survival (OS) was performed. Results: Seventeen articles and 365 patients met the inclusion criteria. The most common subsites involved were subglottic and distal trachea. Adenoid cystic carcinoma was, by far, the most frequent histotype. The first-choice treatment strategy was surgery (86.8%), while adjuvant treatments were delivered in 57.4% of patients. Only 12.9% were treated with definitive radiotherapy with/without chemotherapy. The mean follow-up was 68.3 months. One hundred nine (34.9%) deaths were recorded and 62.4% were cancer-related. Five-year OS ranged from 20% to 100% and, at pooled analysis, it was 83% (range, 78-87%). Conclusions: In case of MiSGC of the larynx and trachea, surgery remains the mainstay of treatment. Adjuvant treatments are frequently delivered. Survival estimates are good overall, but highly heterogeneous.

[Imaging findings of carcinoma ex pleomorphic adenoma in minor salivary glands].

PURPOSE: To summarize the CT and MR imaging features of carcinoma ex pleomorphic adenoma(Ca-ex-PA) in minor salivary gland, and analyze the correlation between various features and pathological classification. METHODS: Forty-three patients with Ca-ex-PA in minor salivary gland were collected. The CT and MRI findings were retrospectively analyzed and correlated with their pathological types. Fisher's exact test was used to analyze the correlation between various imaging features (tumor morphology, boundary, internal structure, bone invasion, cervical lymph node metastasis) and pathological types with SPSS 25.0 software package. RESULTS: Among the 43 patients with Ca-ex-PA, 83.7%(36/43) of the tumors were lobulated; 81.4%(35/43) showed cystic degeneration or necrosis, with heterogeneous enhancement. Coarse calcification or mixed calcification was found in 37.2%(16/43), 25.6%(11/43) had compressive absorption of adjacent bone. 75%(12/16) of type Ⅰ/Ⅱ tumors had regular morphology (round or oval), and 77.8%(21/27) of type Ⅲ tumors had irregular morphology, 93.8%(15/16) of type Ⅰ/Ⅱ tumors had well-defined margin and 66.7%(18/27) of type Ⅲ tumors had ill-defined margin. Osteolytic bone resorption occurred in 59.3%(16/27) of type Ⅲ tumors. The average maximum diameter of type Ⅰ/Ⅱ tumors was significantly shorter than that of type Ⅲ(P＜0.05). Fisher's exact test showed the characteristics of tumor morphology, boundary and osteolytic bone resorption were related to pathological grouping(P＜0.001). CONCLUSIONS: Most Ca-ex-PA in minor salivary glands is characterized by lobular and heterogeneous enhanced neoplasm on CT and MR imaging. A round or oval tumor with well-defined margin usually correlates with typeⅠ and Ⅱ, contrarily, an irregular mass with ill-defined margin and osteolytic bone destruction usually correlates with type Ⅲ. Combining the three characteristics of morphology, boundary and osteolysis is more helpful to distinguish type Ⅰ/Ⅱ and type Ⅲ tumors.

Analysis of Hepatitis D Virus in Minor Salivary Gland of Sjögren's Disease.

Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren's disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation.

Maintenance of adult stem cells from human minor salivary glands via the Wnt signaling pathway.

BACKGROUND: Xerostomia is a salivary gland dysfunction that negatively impacts the life quality of patients; however, there is no effective treatment for xerostomia. Bioengineered organs, generated using stem cells obtained from newborn salivary glands and ligated injury models, are a new organ transplantation strategy that could be feasible for xerostomia treatment. Reconstruction of salivary gland organoids by seed cells obtained from human minor salivary glands will offer theoretical fundaments and technology support for clinical application and organ regeneration research. Herein, we aimed to propose a new method for culturing and enriching adult human minor salivary gland stem cells in vitro in a three-dimensional (3D) environment via Wnt signaling activation. METHODS: Obtained and characterized human minor salivary gland stem cells (hMSGSCs) with self-organization ability were 3D-cultured to generate organoids. We examined hMSGSCs proliferation and colony formation using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. Telomerase reverse transcriptase staining, flow cytometry, immunofluorescence assay, RNA isolation, RT-PCR, and qPCR were performed to assess hMSGSCs structure and the function of reconstructive organoids in vitro. RESULTS: hMSGSCs showed typical epithelial-like characteristics, such as positive for CD49f and cell KRT expression. hMSGSCs served as adult stem cells in salivary glands and could differentiate into acinar and duct cells. Upon the addition of Noggin, CHIR99021, and Wnt3A to the 3D culture system, hMSGSCs showed higher LGR5 expression and decreased AMY1B and MUC5B expression. Therefore, the Wnt and bone morphogenetic protein (BMP) pathways are important in regulating hMSGSCs self-organization and differentiation. CONCLUSIONS: We showed that the stem cell properties of hMSGSCs in a 3D culture system can be maintained by activating the Wnt signaling pathway and inhibiting the BMP signaling pathway. Our findings contribute new insights on salivary gland organoid generation in vitro.

Feline minor salivary gland adenocarcinoma: retrospective case series and literature review.

CASE SERIES SUMMARY: Salivary gland adenocarcinoma, of major or minor salivary gland origin, is an uncommon tumor in cats. This article describes the clinical features, morbidity and survival rates of four cats with salivary gland adenocarcinoma arising from minor salivary gland tissue. Medical records from a private multicenter dentistry and oral surgery practice were reviewed for the period between 2007 and 2021. Four cats were included in this retrospective case series study, with oral masses on either the right or left caudal mandibular labial buccal mucosa. The inclusion criteria included a diagnosis of salivary gland adenocarcinoma in an anatomical location with lack of involvement of a major salivary gland, complete medical history and a follow-up of at least 6 months. The age range of the cats was 9-15 years; three of the cats were castrated males and one was a spayed female. Curative intent surgery was performed in three cats, whereas palliative surgery (debulking) owing to extensive soft tissue invasion was performed in one cat. Survival times were in the range of 210-1730 (mean 787) days. All four cats were euthanized owing to local recurrence and decreased quality of life, regardless of treatment modality. RELEVANCE AND NOVEL INFORMATION: There are limited documented studies reporting the prevalence of salivary gland neoplasia affecting minor disseminated glands in the oral cavity of feline patients. Salivary gland adenocarcinoma should be a differential in cats presenting with caudal labial masses. Surgical resection has been the recommended treatment for salivary gland neoplasia of major salivary gland origin. According to this current case series, we propose that early aggressive surgical treatment with wide surgical margins should be performed for cats with salivary gland adenocarcinoma of minor salivary gland origin. Surgery increased the quality and duration of life; however, each patient was euthanized owing to local recurrence and morbidity.