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Cureus Jul 2023Pleomorphic adenomas (PA) are the most common benign salivary gland tumors. They arise from the major salivary glands, as well as the minor salivary glands. They may... (Review)
Review
Pleomorphic adenomas (PA) are the most common benign salivary gland tumors. They arise from the major salivary glands, as well as the minor salivary glands. They may arise rarely from the palate, oral cavity, neck, and nasal cavity also. Yet, the fourth, fifth, and sixth decades of life are the most common for them to manifest. Forty percent of them occur in males and 60% in females. It is a benign mixed tumor, which has three components: an epithelial component, a myoepithelial cell component, and a mesenchymal component. A fibrous capsule separates these cells from the surrounding tissues. It generally presents as a slowly progressing painless swelling, which is well-delineated, nonsymptomatic, and not involving the facial nerve. Salivary gland tumors can be accurately diagnosed before surgery using fine-needle aspiration (FNA), ultrasonography (USG), and computed tomography (CT) scan. Calponin, cluster of differentiation 9 (CD9), glial fibrillary acidic protein (GFAP), Mcl-2, metastasis suppressor gene (NM23), p63, S-100, smooth muscle actin (SMA), and SRY-box transcription factor 10 (SOX10) exhibit the majority of the positive reactions in pleomorphic adenomas. The diagnostic marker pleomorphic adenoma gene 1 (PLAG1) is frequently employed since it is specific for pleomorphic adenoma. Although benign, these epithelial tumors have a propensity to recur and undergo malignant transformation if incompletely excised, leading to increased morbidity in these patients. A review of the consensus guidelines and literature was conducted, and the online literature on the subject from 2002 was included. This article is not a complete review of all the available literature; rather, it is a comprehensive review of the topic.
PubMed: 37614271
DOI: 10.7759/cureus.42311 -
Histopathology Nov 2023The discovery of tumour type-specific gene fusion oncogenes in benign and malignant salivary gland and sinonasal (SGSN) tumours has significantly increased our knowledge...
AIMS
The discovery of tumour type-specific gene fusion oncogenes in benign and malignant salivary gland and sinonasal (SGSN) tumours has significantly increased our knowledge about their molecular pathology and classification.
METHODS AND RESULTS
We developed a new targeted multiplexed next-generation sequencing (NGS)-based method that utilizes ligation dependent reverse-transcriptase polymerase chain reaction (LD-RT-PCR) to detect oncogenic fusion transcripts involving 116 genes, leading to 96 gene fusions known to be recurrently rearranged in these tumours. In all, 180 SGSN tumours (formalin-fixed, paraffin-embedded samples, 141 specimens and 39 core needle biopsies) from the REFCORpath (French network for rare head and neck cancers) with previously identified fusion genes by fluorescent in situ hybridisation (FISH), RT-PCR, or molecular immunohistochemistry were selected to test its specificity and sensitivity and validate its diagnostic use. Tested tumours encompassed 14 major tumours types, including secretory carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary gland intraductal carcinoma, clear cell carcinoma, pleomorphic adenoma, adamantinoma-like Ewing Sarcoma, EWSR1::COLCA2 sinonasal sarcoma, DEK::AFF2 sinonasal carcinoma, and biphenotypic sinonasal sarcoma. In-frame fusion transcripts were detected in 97.8% of cases (176/180). Gene fusion assay results correlated with conventional techniques (immunohistochemistry [IHC], FISH, and RT-PCR) in 176/180 tumours (97.8%).
CONCLUSION
This targeted multiplexed NGS-based LD-RT-PCR method is a robust, highly sensitive method for the detection of recurrent gene fusions from routine clinical SGSN tumours. It can be easily customized to cover new fusions. These results are promising for implementing an integrated NGS system to rapidly detect genetic aberrations, facilitating accurate, genomics-based diagnoses, and accelerate time to precision therapies in SGSN tumours.
Topics: Humans; Reverse Transcriptase Polymerase Chain Reaction; Salivary Glands; Sarcoma, Ewing; Adenocarcinoma; Salivary Gland Neoplasms; Sarcoma; High-Throughput Nucleotide Sequencing; Oncogene Proteins, Fusion; Neoplasm Proteins
PubMed: 37350081
DOI: 10.1111/his.14971 -
Acta Oto-laryngologica 2023Lymphomas constitute 2% of all salivary gland tumors and are the second most common group of malignancies in the head and neck region. (Review)
Review
BACKGROUND
Lymphomas constitute 2% of all salivary gland tumors and are the second most common group of malignancies in the head and neck region.
OBJECTIVES
In this systematic review, the demographics and characteristics of salivary gland lymphomas are presented.
METHODS
All types of studies that involve data of salivary gland lymphomas between 1990 and 2020 were identified and screened.
RESULTS
A total of 169 articles with 1640 patients were identified. The median age of the patients was 59 years with a range between 10 and 87 years. The anatomic locations of salivary gland lymphomas were distributed with 88% in the parotid glands, 9% in the submandibular glands, 1% in the minor salivary glands, and 0.3% in the sublingual glands. The overall survival at 12 months is high and in line with the outcome of indolent lymphomas in general. The predominant indolent subtypes were extranodal marginal zone lymphomas and follicular lymphomas, whereas the more aggressive subtypes were mainly diffuse large B-cell lymphomas, mantle cell lymphomas, and T-cell lymphomas.
CONCLUSION
In conclusion, lymphomas occur in all salivary glands and mainly in elderly female patients. Sjögren's syndrome is frequently associated. Depending on the anatomical location, the lymphoma subtypes vary in aggressiveness, stage, and prognosis.
Topics: Adult; Humans; Female; Aged; Child; Adolescent; Young Adult; Middle Aged; Aged, 80 and over; Salivary Glands; Lymphoma, B-Cell, Marginal Zone; Sjogren's Syndrome; Salivary Gland Neoplasms; Parotid Gland
PubMed: 37572309
DOI: 10.1080/00016489.2023.2226689 -
Head & Neck Jul 2023Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs,...
BACKGROUND
Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data.
METHODS
A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features.
RESULTS
The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003).
CONCLUSIONS
Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.
Topics: Humans; Retrospective Studies; Neoplasm Recurrence, Local; Salivary Gland Neoplasms; Salivary Glands, Minor
PubMed: 37084179
DOI: 10.1002/hed.27376 -
Head & Neck Sep 2023In this systematic review, we aimed to evaluate the clinicopathological profile of sclerosing polycystic adenoma (SPA). PubMed, Scopus, EMBASE, Lilacs, Web of Science,... (Review)
Review
In this systematic review, we aimed to evaluate the clinicopathological profile of sclerosing polycystic adenoma (SPA). PubMed, Scopus, EMBASE, Lilacs, Web of Science, and gray literature were searched to access cases of SPA in salivary glands. One hundred and thirty cases of SPA were found across 61 selected articles. SPA affected mainly the parotid gland of adults with a mean age of 44.6 years old, with a slight preference for females. The lesion was usually presented as a painless firm mass with a long period of evolution. Histologically, they are well-delimitated lesions composed of acinar and ductal elements with a variety of cytomorphologic features surrounded by a densely collagenized stroma. PI3K was the most common gene mutation related to SPA. SPA is a benign condition that mainly affects the parotid gland of female patients and it is usually treated by surgical resection with a good prognosis.
Topics: Adult; Humans; Female; Parotid Gland; Adenoma; Sclerosis
PubMed: 37403748
DOI: 10.1002/hed.27435 -
Japanese Journal of Clinical Oncology Mar 2024Salivary gland-type tumors of the lung are thought to originate from the submucosal exocrine glands of the large airways. Due to their rare occurrence, reports of their... (Review)
Review
Salivary gland-type tumors of the lung are thought to originate from the submucosal exocrine glands of the large airways. Due to their rare occurrence, reports of their study are limited to small-scale or case reports. Therefore, daily clinical practices often require a search for previous reports. In the last 20 years, several genetic rearrangements have been identified, such as MYB::NF1B rearrangements in adenoid cystic carcinoma, CRTC1::MAML2 rearrangements in mucoepidermoid carcinoma, EWSR1::ATF1 rearrangements in hyalinizing clear cell carcinoma and rearrangements of the EWSR1 locus or FUS (TLS) locus in myoepithelioma and myoepithelial carcinoma. These molecular alterations have been useful in diagnosing these tumors, although they have not yet been linked to molecularly targeted therapies. The morphologic, immunophenotypic, and molecular characteristics of these tumors are similar to those of their counterparts of extrapulmonary origin, so clinical and radiologic differential diagnosis is required to distinguish between primary and metastatic disease of other primary sites. However, these molecular alterations can be useful in differentiating them from other primary lung cancer histologic types. The management of these tumors requires broad knowledge of the latest diagnostics, surgery, radiotherapy, bronchoscopic interventions, chemotherapy, immunotherapy as well as therapeutic agents in development, including molecularly targeted agents. This review provides a comprehensive overview of the current diagnosis and treatment of pulmonary salivary gland tumors, with a focus on adenoid cystic carcinoma and mucoepidermoid carcinoma, which are the two most common subtypes.
Topics: Humans; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Salivary Gland Neoplasms; Carcinoma; Myoepithelioma; Salivary Glands; Lung Neoplasms
PubMed: 38018262
DOI: 10.1093/jjco/hyad160 -
Current Topics in Developmental Biology 2024The salivary gland undergoes branching morphogenesis to elaborate into a tree-like structure with numerous saliva-secreting acinar units, all joined by a hierarchical... (Review)
Review
The salivary gland undergoes branching morphogenesis to elaborate into a tree-like structure with numerous saliva-secreting acinar units, all joined by a hierarchical ductal system. The expansive epithelial surface generated by branching morphogenesis serves as the structural basis for the efficient production and delivery of saliva. Here, we elucidate the process of salivary gland morphogenesis, emphasizing the role of mechanics. Structurally, the developing salivary gland is characterized by a stratified epithelium tightly encased by the basement membrane, which is in turn surrounded by a mesenchyme consisting of a dense network of interstitial matrix and mesenchymal cells. Diverse cell types and extracellular matrices bestow this developing organ with organized, yet spatially varied mechanical properties. For instance, the surface epithelial sheet of the bud is highly fluidic due to its high cell motility and weak cell-cell adhesion, rendering it highly pliable. In contrast, the inner core of the bud is more rigid, characterized by reduced cell motility and strong cell-cell adhesion, which likely provide structural support for the tissue. The interactions between the surface epithelial sheet and the inner core give rise to budding morphogenesis. Furthermore, the basement membrane and the mesenchyme offer mechanical constraints that could play a pivotal role in determining the higher-order architecture of a fully mature salivary gland.
Topics: Salivary Glands; Animals; Morphogenesis; Humans; Basement Membrane; Cell Movement; Biomechanical Phenomena; Mesoderm; Cell Adhesion
PubMed: 38937029
DOI: 10.1016/bs.ctdb.2024.05.002 -
American Family Physician Jun 2024The major salivary glands are the paired parotid, submandibular, and sublingual glands. Salivary gland disorders can affect the glandular tissue or its excretory system.... (Review)
Review
The major salivary glands are the paired parotid, submandibular, and sublingual glands. Salivary gland disorders can affect the glandular tissue or its excretory system. The parotid glands are the largest and produce aqueous serous secretions that are less immunogenic. They are more susceptible to infections and neoplasms. The submandibular glands produce mucinous secretions that are high in calcium and phosphate salts through a long submandibular duct that flows against gravity. The submandibular glands are responsible for more than 80% of salivary stones. Sialadenitis can be acute or chronic and caused by bacterial, viral, and obstructive etiologies; the most common bacteria is Staphylococcus aureus. The most common viral etiologies in children are mumps (globally) and juvenile recurrent parotitis (in vaccinated populations). Sialadenosis is a chronic asymptomatic enlargement of the salivary glands due to systemic disease. Sialolithiasis causes up to 50% of salivary gland disorders. It is associated with salivary stasis and inflammation caused by dehydration, malnutrition, medications, or chronic illness. Obstruction is also caused by trauma, stenosis, and mucoceles. Neoplasms are rare and typically benign, but they warrant referral and imaging with ultrasonography, computed tomography, or magnetic resonance sialography. Most disorders are managed with conservative measures by treating the underlying etiology, optimizing predisposing factors, controlling pain, and increasing salivary flow with sialagogues, hydration, massage, warm compresses, oral hygiene, and medication adjustment. Sialendoscopy is a gland-sparing technique that can treat obstructive and nonobstructive disorders. (Am Fam Physician. 2024;109(6):550-559.
Topics: Humans; Salivary Gland Diseases; Sialadenitis
PubMed: 38905553
DOI: No ID Found -
Nature Communications Oct 2023Exocrine acinar cells in salivary glands (SG) are critical for oral health and loss of functional acinar cells is a major clinical challenge. Fibroblast growth factor...
Exocrine acinar cells in salivary glands (SG) are critical for oral health and loss of functional acinar cells is a major clinical challenge. Fibroblast growth factor receptors (FGFR) are essential for early development of multiple organs, including SG. However, the role of FGFR signaling in specific populations later in development and during acinar differentiation are unknown. Here, we use scRNAseq and conditional deletion of murine FGFRs in vivo to identify essential roles for FGFRs in craniofacial, early SG development and progenitor function during duct homeostasis. Importantly, we also discover that FGFR2 via MAPK signaling is critical for seromucous acinar differentiation and secretory gene expression, while FGFR1 is dispensable. We show that FGF7, expressed by myoepithelial cells (MEC), activates the FGFR2-dependent seromucous transcriptional program. Here, we propose a model where MEC-derived FGF7 drives seromucous acinar differentiation, providing a rationale for targeting FGFR2 signaling in regenerative therapies to restore acinar function.
Topics: Animals; Mice; Cell Differentiation; Homeostasis; Orosomucoid; Salivary Glands; Signal Transduction
PubMed: 37838739
DOI: 10.1038/s41467-023-42243-0 -
Journal of Leukocyte Biology Jan 2024Sjögren's syndrome is a systemic autoimmune disease characterized by dysfunction of the affected exocrine glands. Lymphocytic infiltration within the inflamed glands... (Review)
Review
Sjögren's syndrome is a systemic autoimmune disease characterized by dysfunction of the affected exocrine glands. Lymphocytic infiltration within the inflamed glands and aberrant B-cell hyperactivation are the two salient pathologic features in Sjögren's syndrome. Increasing evidence indicates that salivary gland epithelial cells act as a key regulator in the pathogenesis of Sjögren's syndrome, as revealed by the dysregulated innate immune signaling pathways in salivary gland epithelium and increased expression of various proinflammatory molecules as well as their interaction with immune cells. In addition, salivary gland epithelial cells can regulate adaptive immune responses as nonprofessional antigen-presenting cells and promote the activation and differentiation of infiltrated immune cells. Moreover, the local inflammatory milieu can modulate the survival of salivary gland epithelial cells, leading to enhanced apoptosis and pyroptosis with the release of intracellular autoantigens, which further contributes to SG autoimmune inflammation and tissue destruction in Sjögren's syndrome. Herein, we reviewed recent advances in elucidating the role of salivary gland epithelial cells in the pathogenesis of Sjögren's syndrome, which may provide rationales for potential therapeutic targeting of salivary gland epithelial cells to alleviate salivary gland dysfunction alongside treatments with immunosuppressive reagents in Sjögren's syndrome.
Topics: Humans; Sjogren's Syndrome; Salivary Glands; Epithelial Cells; Epithelium; Inflammation
PubMed: 37134025
DOI: 10.1093/jleuko/qiad049