Materiały źródłowe

• #1 Pathogenesis of salivary gland neoplasms: The concepts of histogenesis and morphogenesis – Journal of Global Oral Health

  https://jglobaloralhealth.org/pathogenesis-of-salivary-gland-neoplasms-the-concepts-of-histogenesis-and-morphogenesis/

  Many features overlap between different salivary gland neoplasms (SGNs) and as a result, classifying them distinctly has always been challenging. The differences in pathogenesis give rise to variations in the histopathological morphology of the SGNs. […] The present review aims to elaborate on the classification of SGNs based on the concepts of histogenesis and morphogenesis. […] The type of cell in which neoplastic transformation has occurred governs the events that follow the initiation of the multistage process which results in neoplasia. Our review elucidates the pathogenesis of the salivary gland tumor to understand the resulting histopathology, tumor morphology, and cellular differentiation of the tumor which reflects the parent cell. […] The differences in pathogenesis give rise to variations in the histopathological morphology of the SGNs.

• #2 An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8345412/

  Diagnosing salivary gland neoplasms (SGN) remain a challenge, given their underlying biological nature and overlapping features. […] This review delves into the molecular etiopathogenesis of SGN, highlighting advanced diagnostic protocols that may facilitate the identification and therapy of a variety of SGN. […] The diverse histomorphological appearance of SGN is attributed to their heterogenic and complex cellular behavior. […] Advances in molecular pathology have uncovered genetic patterns and biomarkers that may potentially contribute to innovating diagnostic approaches in identifying various salivary gland pathologies. […] In this paper, we delve into the molecular pathways of salivary gland tumorigenesis, highlighting recent diagnostic protocols that may facilitate the identification and management of SGN.

• #3 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  Salivary gland tumors are a rare group of complex, heterogeneous histologies located in the parotid gland, submandibular gland, sublingual gland, and minor salivary glands of the upper aerodigestive tract. […] The exact etiology of salivary gland cancer is unknown. Still, various mechanisms have been proposed, including radiation, viruses (EBV and HIV), immunosuppression, ultraviolet light exposure, occupational exposures in rubber or nickel industries, prior diagnosis of medulloblastoma, prior diagnosis of basal cell carcinoma, androgen receptor expression, and genetics. […] In studies involving Japanese survivors of the atomic bomb and patients who received radiation treatment during childhood for benign conditions, radiation exposure was identified as a significant risk factor for the development of salivary malignancies.

• #4 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  Over the years there has been some progress in clarifying specific causes of salivary gland cancer. The best known risk factor is that of radiation exposure as evident in the increased risk in atomic bomb survivors and in patients receiving therapeutic radiation. […] A dose response effect for low dose irradiation has been shown with a mean latency period of tumor development of 11 years for malignant tumors and 21.5 years for benign tumors. […] Of potential viral etiologies, only EBV infection is implicated in the pathogenesis of salivary lymphoepithelioma-like carcinomas that are more commonly encountered in Eskimo and Chinese rather than Western populations. […] Cytogenetic analyses of benign tumors show common abnormalities like trisomy 8 or translocations, often reciprocal, that involve activation of oncogenes HMGIC located on chromosome 12q13 and PLAG1 found on chromosome 8q12.

• #5 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  Salivary gland tumors are a rare group of complex, heterogeneous histologies located in the parotid gland, submandibular gland, sublingual gland, and minor salivary glands of the upper aerodigestive tract. […] The exact etiology of salivary gland cancer is unknown. Still, various mechanisms have been proposed, including radiation, viruses (EBV and HIV), immunosuppression, ultraviolet light exposure, occupational exposures in rubber or nickel industries, prior diagnosis of medulloblastoma, prior diagnosis of basal cell carcinoma, androgen receptor expression, and genetics. […] In studies involving Japanese survivors of the atomic bomb and patients who received radiation treatment during childhood for benign conditions, radiation exposure was identified as a significant risk factor for the development of salivary malignancies.

• #6 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  Over the years there has been some progress in clarifying specific causes of salivary gland cancer. The best known risk factor is that of radiation exposure as evident in the increased risk in atomic bomb survivors and in patients receiving therapeutic radiation. […] A dose response effect for low dose irradiation has been shown with a mean latency period of tumor development of 11 years for malignant tumors and 21.5 years for benign tumors. […] Of potential viral etiologies, only EBV infection is implicated in the pathogenesis of salivary lymphoepithelioma-like carcinomas that are more commonly encountered in Eskimo and Chinese rather than Western populations. […] Cytogenetic analyses of benign tumors show common abnormalities like trisomy 8 or translocations, often reciprocal, that involve activation of oncogenes HMGIC located on chromosome 12q13 and PLAG1 found on chromosome 8q12.

• #7 Pathogenesis of salivary gland neoplasms: The concepts of histogenesis and morphogenesis – Journal of Global Oral Health

  https://jglobaloralhealth.org/pathogenesis-of-salivary-gland-neoplasms-the-concepts-of-histogenesis-and-morphogenesis/

  The etiological factors of human SGNs remain obscure except for radiation and certain viruses. EpsteinBarr virus DNA sequences have been detected in malignant lymphoepithelial lesions and Warthins tumor. […] As more clarity is achieved regarding the pathogenesis of these tumors, corresponding modifications are being made in the standard classification system. […] The histogenic concept of salivary gland tumors has usually relied on histologic observations of the fetal salivary gland and the cellular differentiation involved in particular segments of the duct system. […] The presence or absence of luminal and abluminal cells, myoepithelial cells, and extracellular matrix (ECM) consisting of proteoglycans, laminin, and elastin, form the basis of the morphogenic concept of SGN pathogenesis. […] The advent of IHC has confirmed much of the assumptions on which the histogenic and morphogenic concepts of SGN pathogenesis were based.

• #8 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  Over the years there has been some progress in clarifying specific causes of salivary gland cancer. The best known risk factor is that of radiation exposure as evident in the increased risk in atomic bomb survivors and in patients receiving therapeutic radiation. […] A dose response effect for low dose irradiation has been shown with a mean latency period of tumor development of 11 years for malignant tumors and 21.5 years for benign tumors. […] Of potential viral etiologies, only EBV infection is implicated in the pathogenesis of salivary lymphoepithelioma-like carcinomas that are more commonly encountered in Eskimo and Chinese rather than Western populations. […] Cytogenetic analyses of benign tumors show common abnormalities like trisomy 8 or translocations, often reciprocal, that involve activation of oncogenes HMGIC located on chromosome 12q13 and PLAG1 found on chromosome 8q12.

• #9 New Systemic Therapies in Salivary Gland Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-23175-9_20

  Salivary gland cancer (SGC) encompasses a group of rare malignancies with distinct molecular, histologic, and clinical characteristics. […] Although the causes remain largely unknown, several factors have been associated with the development of malignant salivary gland tumors, including radiation exposure, history of prior malignancy, viral infections (i.e., Epstein Barr virus [EBV], human immunodeficiency virus [HIV]), industrial chemicals (rubber manufacturing), and nickel compounds. […] Recent advances in molecular characterization of SGCs have uncovered subtype-specific genomic alterations with potential clinical significance. […] These approaches have provided deeper understanding of the molecular pathogenesis and are presently included in the definition of several entities, aiding in proper diagnosis.

• #10 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  Salivary gland tumors are a rare group of complex, heterogeneous histologies located in the parotid gland, submandibular gland, sublingual gland, and minor salivary glands of the upper aerodigestive tract. […] The exact etiology of salivary gland cancer is unknown. Still, various mechanisms have been proposed, including radiation, viruses (EBV and HIV), immunosuppression, ultraviolet light exposure, occupational exposures in rubber or nickel industries, prior diagnosis of medulloblastoma, prior diagnosis of basal cell carcinoma, androgen receptor expression, and genetics. […] In studies involving Japanese survivors of the atomic bomb and patients who received radiation treatment during childhood for benign conditions, radiation exposure was identified as a significant risk factor for the development of salivary malignancies.

• #11 New Systemic Therapies in Salivary Gland Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-23175-9_20

  Salivary gland cancer (SGC) encompasses a group of rare malignancies with distinct molecular, histologic, and clinical characteristics. […] Although the causes remain largely unknown, several factors have been associated with the development of malignant salivary gland tumors, including radiation exposure, history of prior malignancy, viral infections (i.e., Epstein Barr virus [EBV], human immunodeficiency virus [HIV]), industrial chemicals (rubber manufacturing), and nickel compounds. […] Recent advances in molecular characterization of SGCs have uncovered subtype-specific genomic alterations with potential clinical significance. […] These approaches have provided deeper understanding of the molecular pathogenesis and are presently included in the definition of several entities, aiding in proper diagnosis.

• #12 Head and Neck: Salivary gland tumors: Warthins tumors

  https://atlasgeneticsoncology.org/solid-tumor/5424/head-and-neck-salivary-gland-tumors-warthins-tumors

  In the WHO classification of salivary gland tumors, certain diseases of the salivary glands are considered tumor-like lesions. Warthins tumor may therefore also be classified in the group of tumor-like lesions, since both the epithelial and lymphoid tumor components are polyclonal in origin. […] Several studies showed that a significant number of patients suffering from Warthins tumor are smokers, in contrast to patients with other salivary gland tumors. […] Warthins tumor consists of oncocytic cells containing numerous mitochondria frequently showing structural abnormalities and reduced metabolic function. […] The role of hormones in the etiology of this disease has also been discussed. […] Few Studies have shown clonal genetic abnormalities at the cytogenetic level. However, other later studies showed a polyclonal pattern in Warthins tumor. […] Deletions of mitochondrial DNA is significantly higher in oncocytic tumor cells than parotid epithelia cells.

• #13 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  Over the years there has been some progress in clarifying specific causes of salivary gland cancer. The best known risk factor is that of radiation exposure as evident in the increased risk in atomic bomb survivors and in patients receiving therapeutic radiation. […] A dose response effect for low dose irradiation has been shown with a mean latency period of tumor development of 11 years for malignant tumors and 21.5 years for benign tumors. […] Of potential viral etiologies, only EBV infection is implicated in the pathogenesis of salivary lymphoepithelioma-like carcinomas that are more commonly encountered in Eskimo and Chinese rather than Western populations. […] Cytogenetic analyses of benign tumors show common abnormalities like trisomy 8 or translocations, often reciprocal, that involve activation of oncogenes HMGIC located on chromosome 12q13 and PLAG1 found on chromosome 8q12.

• #14 An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8345412/

  Former concepts of pathogenesis of SGN were focused on the histologic cell of origin. […] The adult salivary glands consist of reserve cells that are believed to replicate pathologically to form SGN. […] The four commonly hypothesized histogenetic theories […] are as follows: Basal reserve cell or progenitor cell theory, Pluripotent unicellular reserve cell theory, Semi-pluripotent bicellular reserve cell theory, Multicellular theory. […] A pathologist typically considers the differentiation process and arrangement of tumor cells as crucial when classifying the neoplasm. […] The bicellular differentiation in the development of salivary glands can be revisited in the pathogenesis of SGN, along the ducto-acinar complex. […] Dardick deemed cellular morphology and cellular differentiation, derived from differential gene expression of a stem cell, in conjunction with tumor ECM production, to be better predictors of SGN, when compared to a specific proposed cell of origin. […] The recent advances in molecular pathology have aided deeper understanding of the etiopathogenesis of SGN.

• #15 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Salivary gland neoplasms are rare in children. Most tumors (65%) are benign, with hemangiomas being the most common, followed by pleomorphic adenomas. In children, 35% of salivary gland neoplasms are malignant. Mucoepidermoid carcinoma is the most common salivary gland malignancy in children. […] The etiology of salivary gland neoplasms is not fully understood. Two theories predominate: the bicellular stem cell theory and the multicellular theory. […] This theory holds that tumors arise from 1 of 2 undifferentiated stem cells: the excretory duct reserve cell or the intercalated duct reserve cell. Excretory stem cells give rise to squamous cell and mucoepidermoid carcinomas, while intercalated stem cells give rise to pleomorphic adenomas, oncocytomas, adenoid cystic carcinomas, adenocarcinomas, and acinic cell carcinomas.

• #16 An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8345412/

  Former concepts of pathogenesis of SGN were focused on the histologic cell of origin. […] The adult salivary glands consist of reserve cells that are believed to replicate pathologically to form SGN. […] The four commonly hypothesized histogenetic theories […] are as follows: Basal reserve cell or progenitor cell theory, Pluripotent unicellular reserve cell theory, Semi-pluripotent bicellular reserve cell theory, Multicellular theory. […] A pathologist typically considers the differentiation process and arrangement of tumor cells as crucial when classifying the neoplasm. […] The bicellular differentiation in the development of salivary glands can be revisited in the pathogenesis of SGN, along the ducto-acinar complex. […] Dardick deemed cellular morphology and cellular differentiation, derived from differential gene expression of a stem cell, in conjunction with tumor ECM production, to be better predictors of SGN, when compared to a specific proposed cell of origin. […] The recent advances in molecular pathology have aided deeper understanding of the etiopathogenesis of SGN.

• #17 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Salivary gland neoplasms are rare in children. Most tumors (65%) are benign, with hemangiomas being the most common, followed by pleomorphic adenomas. In children, 35% of salivary gland neoplasms are malignant. Mucoepidermoid carcinoma is the most common salivary gland malignancy in children. […] The etiology of salivary gland neoplasms is not fully understood. Two theories predominate: the bicellular stem cell theory and the multicellular theory. […] This theory holds that tumors arise from 1 of 2 undifferentiated stem cells: the excretory duct reserve cell or the intercalated duct reserve cell. Excretory stem cells give rise to squamous cell and mucoepidermoid carcinomas, while intercalated stem cells give rise to pleomorphic adenomas, oncocytomas, adenoid cystic carcinomas, adenocarcinomas, and acinic cell carcinomas.

• #18 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Salivary gland neoplasms are rare in children. Most tumors (65%) are benign, with hemangiomas being the most common, followed by pleomorphic adenomas. In children, 35% of salivary gland neoplasms are malignant. Mucoepidermoid carcinoma is the most common salivary gland malignancy in children. […] The etiology of salivary gland neoplasms is not fully understood. Two theories predominate: the bicellular stem cell theory and the multicellular theory. […] This theory holds that tumors arise from 1 of 2 undifferentiated stem cells: the excretory duct reserve cell or the intercalated duct reserve cell. Excretory stem cells give rise to squamous cell and mucoepidermoid carcinomas, while intercalated stem cells give rise to pleomorphic adenomas, oncocytomas, adenoid cystic carcinomas, adenocarcinomas, and acinic cell carcinomas.

• #19 An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8345412/

  Former concepts of pathogenesis of SGN were focused on the histologic cell of origin. […] The adult salivary glands consist of reserve cells that are believed to replicate pathologically to form SGN. […] The four commonly hypothesized histogenetic theories […] are as follows: Basal reserve cell or progenitor cell theory, Pluripotent unicellular reserve cell theory, Semi-pluripotent bicellular reserve cell theory, Multicellular theory. […] A pathologist typically considers the differentiation process and arrangement of tumor cells as crucial when classifying the neoplasm. […] The bicellular differentiation in the development of salivary glands can be revisited in the pathogenesis of SGN, along the ducto-acinar complex. […] Dardick deemed cellular morphology and cellular differentiation, derived from differential gene expression of a stem cell, in conjunction with tumor ECM production, to be better predictors of SGN, when compared to a specific proposed cell of origin. […] The recent advances in molecular pathology have aided deeper understanding of the etiopathogenesis of SGN.

• #20 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. […] Recent evidence suggests that the bicellular stem cell theory is the more probable etiology of salivary gland neoplasms. This theory more logically explains neoplasms that contain multiple discrete cell types, such as pleomorphic adenomas and Warthin tumors. […] As with most cancers, the exact molecular mechanism by which tumorigenesis occurs in salivary gland neoplasms is incompletely understood. Multiple pathways and oncogenes have been implicated, including oncogenes that are known to be associated with a wide variety of human cancers. These include p53, Bcl-2, PI3K/Akt, MDM2, and ras.

• #21 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. […] Recent evidence suggests that the bicellular stem cell theory is the more probable etiology of salivary gland neoplasms. This theory more logically explains neoplasms that contain multiple discrete cell types, such as pleomorphic adenomas and Warthin tumors. […] As with most cancers, the exact molecular mechanism by which tumorigenesis occurs in salivary gland neoplasms is incompletely understood. Multiple pathways and oncogenes have been implicated, including oncogenes that are known to be associated with a wide variety of human cancers. These include p53, Bcl-2, PI3K/Akt, MDM2, and ras.

• #22 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. […] Recent evidence suggests that the bicellular stem cell theory is the more probable etiology of salivary gland neoplasms. This theory more logically explains neoplasms that contain multiple discrete cell types, such as pleomorphic adenomas and Warthin tumors. […] As with most cancers, the exact molecular mechanism by which tumorigenesis occurs in salivary gland neoplasms is incompletely understood. Multiple pathways and oncogenes have been implicated, including oncogenes that are known to be associated with a wide variety of human cancers. These include p53, Bcl-2, PI3K/Akt, MDM2, and ras.

• #23 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. […] Recent evidence suggests that the bicellular stem cell theory is the more probable etiology of salivary gland neoplasms. This theory more logically explains neoplasms that contain multiple discrete cell types, such as pleomorphic adenomas and Warthin tumors. […] As with most cancers, the exact molecular mechanism by which tumorigenesis occurs in salivary gland neoplasms is incompletely understood. Multiple pathways and oncogenes have been implicated, including oncogenes that are known to be associated with a wide variety of human cancers. These include p53, Bcl-2, PI3K/Akt, MDM2, and ras.

• #24 Pathogenesis of salivary gland neoplasms: The concepts of histogenesis and morphogenesis – Journal of Global Oral Health

  https://jglobaloralhealth.org/pathogenesis-of-salivary-gland-neoplasms-the-concepts-of-histogenesis-and-morphogenesis/

  The etiological factors of human SGNs remain obscure except for radiation and certain viruses. EpsteinBarr virus DNA sequences have been detected in malignant lymphoepithelial lesions and Warthins tumor. […] As more clarity is achieved regarding the pathogenesis of these tumors, corresponding modifications are being made in the standard classification system. […] The histogenic concept of salivary gland tumors has usually relied on histologic observations of the fetal salivary gland and the cellular differentiation involved in particular segments of the duct system. […] The presence or absence of luminal and abluminal cells, myoepithelial cells, and extracellular matrix (ECM) consisting of proteoglycans, laminin, and elastin, form the basis of the morphogenic concept of SGN pathogenesis. […] The advent of IHC has confirmed much of the assumptions on which the histogenic and morphogenic concepts of SGN pathogenesis were based.

• #25 An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8345412/

  Former concepts of pathogenesis of SGN were focused on the histologic cell of origin. […] The adult salivary glands consist of reserve cells that are believed to replicate pathologically to form SGN. […] The four commonly hypothesized histogenetic theories […] are as follows: Basal reserve cell or progenitor cell theory, Pluripotent unicellular reserve cell theory, Semi-pluripotent bicellular reserve cell theory, Multicellular theory. […] A pathologist typically considers the differentiation process and arrangement of tumor cells as crucial when classifying the neoplasm. […] The bicellular differentiation in the development of salivary glands can be revisited in the pathogenesis of SGN, along the ducto-acinar complex. […] Dardick deemed cellular morphology and cellular differentiation, derived from differential gene expression of a stem cell, in conjunction with tumor ECM production, to be better predictors of SGN, when compared to a specific proposed cell of origin. […] The recent advances in molecular pathology have aided deeper understanding of the etiopathogenesis of SGN.

• #26 An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8345412/

  Former concepts of pathogenesis of SGN were focused on the histologic cell of origin. […] The adult salivary glands consist of reserve cells that are believed to replicate pathologically to form SGN. […] The four commonly hypothesized histogenetic theories […] are as follows: Basal reserve cell or progenitor cell theory, Pluripotent unicellular reserve cell theory, Semi-pluripotent bicellular reserve cell theory, Multicellular theory. […] A pathologist typically considers the differentiation process and arrangement of tumor cells as crucial when classifying the neoplasm. […] The bicellular differentiation in the development of salivary glands can be revisited in the pathogenesis of SGN, along the ducto-acinar complex. […] Dardick deemed cellular morphology and cellular differentiation, derived from differential gene expression of a stem cell, in conjunction with tumor ECM production, to be better predictors of SGN, when compared to a specific proposed cell of origin. […] The recent advances in molecular pathology have aided deeper understanding of the etiopathogenesis of SGN.

• #27 Pathogenesis of salivary gland neoplasms: The concepts of histogenesis and morphogenesis – Journal of Global Oral Health

  https://jglobaloralhealth.org/pathogenesis-of-salivary-gland-neoplasms-the-concepts-of-histogenesis-and-morphogenesis/

  The etiological factors of human SGNs remain obscure except for radiation and certain viruses. EpsteinBarr virus DNA sequences have been detected in malignant lymphoepithelial lesions and Warthins tumor. […] As more clarity is achieved regarding the pathogenesis of these tumors, corresponding modifications are being made in the standard classification system. […] The histogenic concept of salivary gland tumors has usually relied on histologic observations of the fetal salivary gland and the cellular differentiation involved in particular segments of the duct system. […] The presence or absence of luminal and abluminal cells, myoepithelial cells, and extracellular matrix (ECM) consisting of proteoglycans, laminin, and elastin, form the basis of the morphogenic concept of SGN pathogenesis. […] The advent of IHC has confirmed much of the assumptions on which the histogenic and morphogenic concepts of SGN pathogenesis were based.

• #28 Immunohistochemical Analysis of Salivary Gland Tumors: Application for Surgical Pathology Practice

  https://www.jstage.jst.go.jp/article/ahc/45/5/45_12019/_article

  Salivary gland tumors are relatively uncommon and there exists a considerable diagnostic difficulty owing to their diverse histological features in individual lesions and the presence of a number of types and variants, in addition to overlapping histological patterns similar to those observed in different tumor entities. […] Although hematoxylin-eosin staining is still the gold standard method used for the diagnosis, immunohistochemistry (IHC) can enhance the accuracy and be a helpful tool when in cases to investigate the subjects that cannot be assessed by histological examination, such as the cell nature and differentiation status, cell proliferation, and tumor protein expression. […] IHC plays a limited, even though important, role in the diagnosis of salivary gland tumors, but is often useful to support the histological assessment. However, unfortunately few tumor type-specific markers are still currently available. For these reasons, IHC should be considered a method that can be used to assist the final diagnosis, and its results themselves do not directly indicate a definitive diagnosis.

• #29 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. […] Recent evidence suggests that the bicellular stem cell theory is the more probable etiology of salivary gland neoplasms. This theory more logically explains neoplasms that contain multiple discrete cell types, such as pleomorphic adenomas and Warthin tumors. […] As with most cancers, the exact molecular mechanism by which tumorigenesis occurs in salivary gland neoplasms is incompletely understood. Multiple pathways and oncogenes have been implicated, including oncogenes that are known to be associated with a wide variety of human cancers. These include p53, Bcl-2, PI3K/Akt, MDM2, and ras.

• #30 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. […] Recent evidence suggests that the bicellular stem cell theory is the more probable etiology of salivary gland neoplasms. This theory more logically explains neoplasms that contain multiple discrete cell types, such as pleomorphic adenomas and Warthin tumors. […] As with most cancers, the exact molecular mechanism by which tumorigenesis occurs in salivary gland neoplasms is incompletely understood. Multiple pathways and oncogenes have been implicated, including oncogenes that are known to be associated with a wide variety of human cancers. These include p53, Bcl-2, PI3K/Akt, MDM2, and ras.

• #31 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #32 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #33 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #34 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #35 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #36 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #37 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  In the multicellular theory, each tumor type is associated with a specific differentiated cell of origin within the salivary gland unit. Squamous cell carcinomas arise from excretory duct cells, pleomorphic adenomas arise from the intercalated duct cells, oncocytomas arise from the striated duct cells, and acinic cell carcinomas arise from acinar cells. […] Recent evidence suggests that the bicellular stem cell theory is the more probable etiology of salivary gland neoplasms. This theory more logically explains neoplasms that contain multiple discrete cell types, such as pleomorphic adenomas and Warthin tumors. […] As with most cancers, the exact molecular mechanism by which tumorigenesis occurs in salivary gland neoplasms is incompletely understood. Multiple pathways and oncogenes have been implicated, including oncogenes that are known to be associated with a wide variety of human cancers. These include p53, Bcl-2, PI3K/Akt, MDM2, and ras.

• #38 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Seventy percent of pleomorphic adenomas have associated chromosomal rearrangements. The most common is a rearrangement of 8q12, occurring in 39% of pleomorphic adenomas. The target gene at this locus is PLAG1, which encodes a zinc finger transcription factor. The other target gene is HMGA2, which encodes a nonhistone chromosomal high mobility group protein that is involved in structural regulation of the chromosome and transcription. […] In mucoepidermoid carcinoma, the t(11;19)(q21;p13) chromosomal translocation has been identified in up to 70% of cases. This translocation creates a MECT1-MAML2 fusion protein that disrupts the Notch signaling pathway. This fusion protein is expressed by all cell types of mucoepidermoid when the translocation is present. Interestingly, fusion-positive tumors appear to be much less aggressive than fusion-negative tumors. Fusion-positive patients have significantly longer median survival and lower rates of local recurrence and distant metastasis.

• #39 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Seventy percent of pleomorphic adenomas have associated chromosomal rearrangements. The most common is a rearrangement of 8q12, occurring in 39% of pleomorphic adenomas. The target gene at this locus is PLAG1, which encodes a zinc finger transcription factor. The other target gene is HMGA2, which encodes a nonhistone chromosomal high mobility group protein that is involved in structural regulation of the chromosome and transcription. This gene is located at 12q13-15. Because these rearrangements are unique to pleomorphic adenomas amongst salivary gland neoplasms, interrogation of these rearrangements by RT-PCR or FISH may aid in diagnosis. […] In mucoepidermoid carcinoma, the t(11;19)(q21;p13) chromosomal translocation has been identified in up to 70% of cases. This translocation creates a MECT1-MAML2 fusion protein that disrupts the Notch signaling pathway. This fusion protein is expressed by all cell types of mucoepidermoid when the translocation is present. Interestingly, fusion-positive tumors appear to be much less aggressive than fusion-negative tumors. Fusion-positive patients have significantly longer median survival and lower rates of local recurrence and distant metastasis.

• #40 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Seventy percent of pleomorphic adenomas have associated chromosomal rearrangements. The most common is a rearrangement of 8q12, occurring in 39% of pleomorphic adenomas. The target gene at this locus is PLAG1, which encodes a zinc finger transcription factor. The other target gene is HMGA2, which encodes a nonhistone chromosomal high mobility group protein that is involved in structural regulation of the chromosome and transcription. […] In mucoepidermoid carcinoma, the t(11;19)(q21;p13) chromosomal translocation has been identified in up to 70% of cases. This translocation creates a MECT1-MAML2 fusion protein that disrupts the Notch signaling pathway. This fusion protein is expressed by all cell types of mucoepidermoid when the translocation is present. Interestingly, fusion-positive tumors appear to be much less aggressive than fusion-negative tumors. Fusion-positive patients have significantly longer median survival and lower rates of local recurrence and distant metastasis.

• #41 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Seventy percent of pleomorphic adenomas have associated chromosomal rearrangements. The most common is a rearrangement of 8q12, occurring in 39% of pleomorphic adenomas. The target gene at this locus is PLAG1, which encodes a zinc finger transcription factor. The other target gene is HMGA2, which encodes a nonhistone chromosomal high mobility group protein that is involved in structural regulation of the chromosome and transcription. This gene is located at 12q13-15. Because these rearrangements are unique to pleomorphic adenomas amongst salivary gland neoplasms, interrogation of these rearrangements by RT-PCR or FISH may aid in diagnosis. […] In mucoepidermoid carcinoma, the t(11;19)(q21;p13) chromosomal translocation has been identified in up to 70% of cases. This translocation creates a MECT1-MAML2 fusion protein that disrupts the Notch signaling pathway. This fusion protein is expressed by all cell types of mucoepidermoid when the translocation is present. Interestingly, fusion-positive tumors appear to be much less aggressive than fusion-negative tumors. Fusion-positive patients have significantly longer median survival and lower rates of local recurrence and distant metastasis.

• #42 Head and Neck: Salivary gland tumors: an overview

  https://atlasgeneticsoncology.org/solid-tumor/5328/head-and-neck-salivary-gland-tumors-an-overview

  PLAG1 may play a role in PA pathogenesis by inducing growth factor production, hence cell proliferation. It was demonstrated by Western blot and immunohistochemical analyses that PLAG1 expression was up-regulated in epithelial and myoepithelial cells, as well as in the mesenchymal component of PA. […] The prognosis of pleomorphic adenoma is excellent if completely removed. Recurrence rates at 5 year- and 10 year-follow-up are 3.4% and 6.8%, respectively. […] The prognosis of carcinoma ex PA depends on its extension. Prognosis is excellent when the malignant component is confined to the PA nodule whereas it may be dismal when carcinoma extends beyond the capsule and infiltrates into adjacent soft tissues. Capsular penetration of more than 1.5 mm and a high-grade carcinomatous component are associated with poor prognosis. Survival rates at 5, 10, 15, and 20 years range from 25-65%, 18-50%, 10-35%, and 0-38%, respectively.

• #43 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  Recent evidence shows that PLAG1 is a nuclear protein that activates transcription of human insulin growth factor II (IGF-II) by binding to the promotor 3 site. Deregulation of this IGF-II target gene, inactive in adult salivary glands, is a recent molecular clue in salivary gland tumorigenesis. […] Genetic abnormalities common to the malignancies include trisomy 8 but also loss of genetic material like Y chromosome and deletion 6q2123.3 and 6q27. […] It is hypothesized that these chromosomal abnormalities reflect inactivation of more than one tumor suppressor gene. […] With the advent of gene and protein expression profiling, future molecular and genetic insights are bound to influence current understanding of salivary gland tumorigenesis and its classification. […] The concept of dedifferentiation in salivary tumor pathology is essentially the identification of the clonal evolution of a poorly differentiated or high grade element arising within a low-grade carcinoma.

• #44 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Seventy percent of pleomorphic adenomas have associated chromosomal rearrangements. The most common is a rearrangement of 8q12, occurring in 39% of pleomorphic adenomas. The target gene at this locus is PLAG1, which encodes a zinc finger transcription factor. The other target gene is HMGA2, which encodes a nonhistone chromosomal high mobility group protein that is involved in structural regulation of the chromosome and transcription. […] In mucoepidermoid carcinoma, the t(11;19)(q21;p13) chromosomal translocation has been identified in up to 70% of cases. This translocation creates a MECT1-MAML2 fusion protein that disrupts the Notch signaling pathway. This fusion protein is expressed by all cell types of mucoepidermoid when the translocation is present. Interestingly, fusion-positive tumors appear to be much less aggressive than fusion-negative tumors. Fusion-positive patients have significantly longer median survival and lower rates of local recurrence and distant metastasis.

• #45 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Seventy percent of pleomorphic adenomas have associated chromosomal rearrangements. The most common is a rearrangement of 8q12, occurring in 39% of pleomorphic adenomas. The target gene at this locus is PLAG1, which encodes a zinc finger transcription factor. The other target gene is HMGA2, which encodes a nonhistone chromosomal high mobility group protein that is involved in structural regulation of the chromosome and transcription. This gene is located at 12q13-15. Because these rearrangements are unique to pleomorphic adenomas amongst salivary gland neoplasms, interrogation of these rearrangements by RT-PCR or FISH may aid in diagnosis. […] In mucoepidermoid carcinoma, the t(11;19)(q21;p13) chromosomal translocation has been identified in up to 70% of cases. This translocation creates a MECT1-MAML2 fusion protein that disrupts the Notch signaling pathway. This fusion protein is expressed by all cell types of mucoepidermoid when the translocation is present. Interestingly, fusion-positive tumors appear to be much less aggressive than fusion-negative tumors. Fusion-positive patients have significantly longer median survival and lower rates of local recurrence and distant metastasis.

• #46 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  MEC appears to be the most common salivary gland malignancy associated with radiation exposure. […] Over 50% of AdCC tumors contain the t(6;9)(q22-23;p23-24) translocation, which fuses the MYB protooncogene on chromosome 6q to the NFIB gene on chromosome 9p, resulting in an overexpression of MYB-NFIB fusion oncogene and worse prognosis. […] ACC develops from tumorigenesis of cells responsible for acinar development, namely the reserve cells of the intercalated ducts and terminal tubules. […] The presence of biological receptors in salivary gland malignancies has recently come under investigation. Tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) are present in up to 71% of all salivary gland cancers. […] Epigenetic mutations involving DNA promoter methylation of tumor suppressor genes can lead to transcriptional inactivation and increase both the risk of salivary duct carcinoma and the transformation of pleomorphic adenoma into carcinoma ex pleomorphic adenoma. […] The development of lymphoma from Sjogren syndrome is theorized to be due to prolonged B-cell activity and survival.

• #47 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  MEC appears to be the most common salivary gland malignancy associated with radiation exposure. […] Over 50% of AdCC tumors contain the t(6;9)(q22-23;p23-24) translocation, which fuses the MYB protooncogene on chromosome 6q to the NFIB gene on chromosome 9p, resulting in an overexpression of MYB-NFIB fusion oncogene and worse prognosis. […] ACC develops from tumorigenesis of cells responsible for acinar development, namely the reserve cells of the intercalated ducts and terminal tubules. […] The presence of biological receptors in salivary gland malignancies has recently come under investigation. Tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) are present in up to 71% of all salivary gland cancers. […] Epigenetic mutations involving DNA promoter methylation of tumor suppressor genes can lead to transcriptional inactivation and increase both the risk of salivary duct carcinoma and the transformation of pleomorphic adenoma into carcinoma ex pleomorphic adenoma. […] The development of lymphoma from Sjogren syndrome is theorized to be due to prolonged B-cell activity and survival.

• #48 Head and Neck: Salivary gland tumors: an overview

  https://atlasgeneticsoncology.org/solid-tumor/5328/head-and-neck-salivary-gland-tumors-an-overview

  The target gene in 12q13-15 rearrangements is HMGA2 (high motility group 2, also known as HMGIC). It maps to 12q14.3 and encodes a small non-histone, chromatin-associated protein that can modulate transcription by altering the chromatin architecture. The highest expression levels of HMGA2 gene are detected in fetal tissues whereas gene expression is undetectable in normal adult tissues. The translocations involving 12q13-15 generate gene fusions in which the 5 part of HMGA2 (encoding the three DNA-binding domains) are linked to various fusion partner genes. […] Deregulation of expression of MYB and its target genes may be a key oncogenic event in the pathogenesis of adenoid cystic carcinoma.

• #49 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  Salivary duct carcinomas may overexpress Her-2 and androgen receptor, with promising clinical outcomes after exposure to targeted therapies approved for other indications. […] Secretory carcinoma, previously known as mammary analogue secretory carcinoma, is distinguished by an ETV6-NTRK3 fusion that can both help differentiate it from its morphologically similar acinar cell carcinoma and also make it susceptible to Trk inhibitors. […] The aim of this article is to review the main molecular and immunohistochemical characteristics of the most common histological subtypes of SGC, in addition to reviewing current data on biomarker-driven targeted therapy and genomic findings that may be potentially actionable in the future. […] Myb, a nuclear transcription factor, is overexpressed in 60–80% of ACCs, usually correlated with a genetic translocation of the MYB gene to the transcription factor gene NFIB, resulting in the MYB-NFIB fusion, an important oncogene.

• #50 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  Salivary duct carcinomas may overexpress Her-2 and androgen receptor, with promising clinical outcomes after exposure to targeted therapies approved for other indications. […] Secretory carcinoma, previously known as mammary analogue secretory carcinoma, is distinguished by an ETV6-NTRK3 fusion that can both help differentiate it from its morphologically similar acinar cell carcinoma and also make it susceptible to Trk inhibitors. […] The aim of this article is to review the main molecular and immunohistochemical characteristics of the most common histological subtypes of SGC, in addition to reviewing current data on biomarker-driven targeted therapy and genomic findings that may be potentially actionable in the future. […] Myb, a nuclear transcription factor, is overexpressed in 60–80% of ACCs, usually correlated with a genetic translocation of the MYB gene to the transcription factor gene NFIB, resulting in the MYB-NFIB fusion, an important oncogene.

• #51 Characterization of novel genetic alterations in salivary gland secretory carcinoma | Modern Pathology

  https://www.nature.com/articles/s41379-019-0427-1

  Secretory carcinoma is a salivary gland tumor with a characteristic chromosomal translocation that results in an ETV6-NTRK3 fusion gene. […] Apart from the ETV6 gene translocation, little is known about genomic alterations in secretory carcinoma. […] The comprehensive targeted deep sequencing analyses of the secretory carcinoma cases were performed using cancer-related gene panels. These analyses revealed novel recurrent somatic mutations, especially in the PRSS1 gene. […] The PRSS1 gene encodes a cationic trypsinogen, which is a member of the trypsin family of serine proteases. […] The identification of a recurrent A16V mutation in the PRSS1 gene in secretory carcinoma is of clinical interest and warrants further in-depth studies as well in other subtypes of salivary gland tumors.

• #52 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #53 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #54 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #55 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #56 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #57 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #58 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  This fusion has been postulated as the main driver of tumor proliferation in ACC. […] Notch are transmembrane proteins that bind to neighboring cells and activate a biochemical cascade that gives rise to the process of cell differentiation, in addition to acting in the process of lateral regulation, proliferation, and angiogenesis of cells through the MAPK pathways. […] Mutations in the NOTCH gene family, particularly NOTCH1, are present in around 20% of ACC patients and are potential oncogenic drivers. […] Mechanisms of acquired resistance to larotrectinib have been described with an on-target mutation in the drug-binding site. […] The presence of a chromosomal translocation, t(12, 15), between the ETV6 gene on chromosome 12 with NTRK3 on chromosome 15, generates the fusion product ETV6–NTRK3. […] The literature demonstrates that 5-year disease-free survival in patients with ACC is only 30–40%. […] Molecular diagnostics are able to aid in diagnosis and guide discovery for subtype-specific targeted therapy.

• #59 New Systemic Therapies in Salivary Gland Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-23175-9_20

  MYB overexpression as well as the presence of activating NOTCH1 mutations have also been shown to confer a poor prognosis for patients with ACC. […] Activating NOTCH1 mutations have been shown to possess carcinogenic potential, driving 50% of T-cell acute lymphoblastic leukemias (T-ALLs). […] They have also been found in 11-29% of patients with ACC. […] Such patients are more likely to have solid pattern on histology, advanced disease at diagnosis, non-lung metastases, including in liver, bone, or other atypical sites, and ultimately shorter relapse-free survival (RFS) and OS. […] Recent advances in the molecular characterization of these tumors have unveiled multiple, oftentimes targetable, subtype-specific alterations. […] Thus, adequate pathological diagnosis by an expert salivary gland pathologist to determine the exact subtype of SGC is key in choosing the right systemic therapy.

• #60 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  MEC appears to be the most common salivary gland malignancy associated with radiation exposure. […] Over 50% of AdCC tumors contain the t(6;9)(q22-23;p23-24) translocation, which fuses the MYB protooncogene on chromosome 6q to the NFIB gene on chromosome 9p, resulting in an overexpression of MYB-NFIB fusion oncogene and worse prognosis. […] ACC develops from tumorigenesis of cells responsible for acinar development, namely the reserve cells of the intercalated ducts and terminal tubules. […] The presence of biological receptors in salivary gland malignancies has recently come under investigation. Tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) are present in up to 71% of all salivary gland cancers. […] Epigenetic mutations involving DNA promoter methylation of tumor suppressor genes can lead to transcriptional inactivation and increase both the risk of salivary duct carcinoma and the transformation of pleomorphic adenoma into carcinoma ex pleomorphic adenoma. […] The development of lymphoma from Sjogren syndrome is theorized to be due to prolonged B-cell activity and survival.

• #61 An overview of the rare parotid gland cancer | Head & Neck Oncology | Full Text

  https://headandneckoncology.biomedcentral.com/articles/10.1186/1758-3284-3-40

  Cancer of the parotid gland is relatively rare, but carries poor prognosis owing to its prevailing distant metastases. […] we review some current discoveries of its tumorigenesis molecular mechanism. […] The mechanism behind the development of parotid gland cancer is not fully understood. One theory involves vacuolar protein sorting-associated protein 4B homolog (VPS4B). […] Given the essential role for VPS4B in MVB maturation, it is speculated that loss of VPS4 function might promote tumorigenesis through its effect of prolonging the duration of EGFR signaling. […] Although increased levels of EGFR expression are observed in a variety of cancers, including head and neck, ovary, cervix, bladder, esophagus, stomach, brain, breast, colon, and lung, and frequently confer an adverse prognosis, but many cancers exhibited EGFR over-expression in the absence of EGFR gene amplification. […] It is therefore postulated that the widespread phenomenon of EGFR over-expression in human cancers occurs, at least in part, as a consequence of common pathological events, other than genomic changes, associated with solid tumors.

• #62

  https://link.springer.com/article/10.1007/s12070-023-03906-y

  Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, followed by Warthins tumor (WT). […] Immune escape is a carcinogenesis mechanism of tumors to avoid the host immune system by producing PD-L1. […] Therefore, PD-L1 is one of the PA pathways to transform into CXPA through immune escape. […] WT expressed PD-L1 in the cytoplasm and lymphoid stroma but not on the cell membrane. It is interpreted as positive constitutive, which may have the function of increasing tumor cell growth, while overexpressed PD-L1 in lymphoid stroma is thought to be associated with a poor prognosis of the tumor and is suspected to transform into malignancy, such as B-cell Lymphoma.

• #63 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  MEC appears to be the most common salivary gland malignancy associated with radiation exposure. […] Over 50% of AdCC tumors contain the t(6;9)(q22-23;p23-24) translocation, which fuses the MYB protooncogene on chromosome 6q to the NFIB gene on chromosome 9p, resulting in an overexpression of MYB-NFIB fusion oncogene and worse prognosis. […] ACC develops from tumorigenesis of cells responsible for acinar development, namely the reserve cells of the intercalated ducts and terminal tubules. […] The presence of biological receptors in salivary gland malignancies has recently come under investigation. Tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) are present in up to 71% of all salivary gland cancers. […] Epigenetic mutations involving DNA promoter methylation of tumor suppressor genes can lead to transcriptional inactivation and increase both the risk of salivary duct carcinoma and the transformation of pleomorphic adenoma into carcinoma ex pleomorphic adenoma. […] The development of lymphoma from Sjogren syndrome is theorized to be due to prolonged B-cell activity and survival.

• #64 Role of Histone Deacetylases in the Pathogenesis of Salivary Gland Tumors and Therapeutic Targeting Options

  https://www.mdpi.com/1422-0067/24/12/10038

  The regulation of gene expression is complicated, and there are diverse mechanisms of epigenetic modifications that might interact, such as histone modifications, DNA methylation and miRNAs. […] Therefore, the screening of distinct SGTs is essential for their diagnosis and targeted management. […] Despite their heterogeneity, SGTs are often jointly included in clinical studies. […] Owing to their rareness, the genetic and epigenetic characteristics of SGTs are just emerging, and their hallmarks are not well elucidated, harnessing their therapeutic targeting. […] Thus, further insights on vulnerabilities and molecular landscape are necessary for these life-threatening and hard to treat tumors. […] In this review, we are interested in the role of histone modifications in SGTs and particularly on histone deacetylation mechanisms that might be effective on neoplasms with relevant epigenetic signatures.

• #65 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #66 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #67 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #68 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  CD117 or c-kit is a tyrosine kinase receptor that is found in adenoid cystic carcinoma, myoepithelial carcinoma, and lymphoepitheliomalike carcinoma. CD117 expression is able to reliably differentiate ACC from polymorphous low-grade adenocarcinoma, and small molecule inhibitors of this receptor are currently being studied as a potential therapeutic agent. […] Other salivary gland neoplasms have been associated with overexpressed beta-catenin through abnormal Wnt signaling. Adenoid cystic carcinoma with mutations in CTNNB1 (b-catenin gene), AXIN1 (axis inhibition protein 1), and APC (adenomatosis polyposis coli tumor suppressor) show tumorigenesis via this process. Promoter methylation is known to develop tumors by inactivating tumor suppressor genes. Mutations that cause hypermethylation and downregulation of 14-3-3, a target gene for p53 in the Gap2/mitosis (G2/M) cell cycle checkpoint, was found to be extensive in adenoid cystic carcinoma (ACC). The methylation of genes that control apoptosis and DNA repair were also found in ACC, especially in high-grade tumors.

• #69 Role of Histone Deacetylases in the Pathogenesis of Salivary Gland Tumors and Therapeutic Targeting Options

  https://www.mdpi.com/1422-0067/24/12/10038

  Salivary gland tumors (SGTs) comprise a rare and heterogenous category of benign/malignant neoplasms with progressively increasing knowledge of the molecular mechanisms underpinning their pathogenesis, poor prognosis, and therapeutic treatment efficacy. […] Emerging data are pointing toward an interplay of genetic and epigenetic factors contributing to their heterogeneity and diverse clinical phenotypes. […] Post-translational histone modifications such as histone acetylation/deacetylation have been shown to actively participate in the pathobiology of SGTs, further suggesting that histone deacetylating factors (HDACs), selective or pan-HDAC inhibitors (HDACis), might present effective treatment options for these neoplasms. […] Herein, we describe the molecular and epigenetic mechanisms underlying the pathology of the different types of SGTs, focusing on histone acetylation/deacetylation effects on gene expression as well as the progress of HDACis in SGT therapy and the current status of relevant clinical trials.

• #70 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #71 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #72 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #73 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #74 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #75 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #76 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #77 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #78 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #79 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Mutation in p53 have been found in both benign and malignant salivary gland neoplasms and some evidence suggests that the presence of p53 mutations correlates with a higher rate of tumor recurrence. RAS is a G protein involved in growth signal transduction, and derangements in ras signalling are implicated in a wide variety of solid tumors. H-Ras mutations have been shown in a significant proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid carcinomas. […] Studies that look at the neovascularization in salivary gland neoplasms have revealed factors that increase angiogenesis and are important in the progression of salivary gland neoplasms. Vascular endothelial growth factor (VEGF) is expressed by over half of salivary gland carcinomas tested and is correlated with clinical stage, recurrence, metastasis, and survival.

• #80 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #81 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #82 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #83 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Chromosomal loss has been found to be an important cause of mutations and tumorigenesis in salivary gland tumors. Allelic loss of chromosomal arm 19q has been reported to occur commonly in adenoid cystic carcinoma. Mucoepidermoid carcinomas also show the loss of chromosomal arms 2q, 5p, 12p, and 16q more than 50% of the time. […] Multiple other genes are being investigated in the tumorigenesis of salivary gland neoplasms. Hepatocyte growth factor (HGF), a protein that causes morphogenesis and dispersion of epithelial cells, has been found to increase adenoid cystic carcinoma scattering and perhaps invasiveness. Expression of proliferating cell nuclear antigen (PCNA) was found in the 2 most common malignant salivary tumors, mucoepidermoid carcinomas and adenoid cystic carcinomas, with higher expression in submandibular gland-derived malignancies. Overexpression of fibroblast growth factor 8b has been shown to lead to salivary gland tumors in transgenic mice.

• #84 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Newer research in salivary gland neoplasms is focusing on factors that increase tumor invasion and spread. Matrix metalloproteinase-1, tenascin-C, and beta-6 integrin have been found to be associated with benign tumor expansion and tissue invasion by malignant tumors. In adenoid cystic carcinoma, increased immunoreactivity for nerve growth factor and tyrosine kinase A has been correlated with perineural invasion.

• #85 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Newer research in salivary gland neoplasms is focusing on factors that increase tumor invasion and spread. Matrix metalloproteinase-1, tenascin-C, and beta-6 integrin have been found to be associated with benign tumor expansion and tissue invasion by malignant tumors. In adenoid cystic carcinoma, increased immunoreactivity for nerve growth factor and tyrosine kinase A has been correlated with perineural invasion.

• #86 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  Over the years there has been some progress in clarifying specific causes of salivary gland cancer. The best known risk factor is that of radiation exposure as evident in the increased risk in atomic bomb survivors and in patients receiving therapeutic radiation. […] A dose response effect for low dose irradiation has been shown with a mean latency period of tumor development of 11 years for malignant tumors and 21.5 years for benign tumors. […] Of potential viral etiologies, only EBV infection is implicated in the pathogenesis of salivary lymphoepithelioma-like carcinomas that are more commonly encountered in Eskimo and Chinese rather than Western populations. […] Cytogenetic analyses of benign tumors show common abnormalities like trisomy 8 or translocations, often reciprocal, that involve activation of oncogenes HMGIC located on chromosome 12q13 and PLAG1 found on chromosome 8q12.

• #87

  https://link.springer.com/article/10.1007/s12070-023-03906-y

  Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, followed by Warthins tumor (WT). […] Immune escape is a carcinogenesis mechanism of tumors to avoid the host immune system by producing PD-L1. […] Therefore, PD-L1 is one of the PA pathways to transform into CXPA through immune escape. […] WT expressed PD-L1 in the cytoplasm and lymphoid stroma but not on the cell membrane. It is interpreted as positive constitutive, which may have the function of increasing tumor cell growth, while overexpressed PD-L1 in lymphoid stroma is thought to be associated with a poor prognosis of the tumor and is suspected to transform into malignancy, such as B-cell Lymphoma.

• #88 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  Recent evidence shows that PLAG1 is a nuclear protein that activates transcription of human insulin growth factor II (IGF-II) by binding to the promotor 3 site. Deregulation of this IGF-II target gene, inactive in adult salivary glands, is a recent molecular clue in salivary gland tumorigenesis. […] Genetic abnormalities common to the malignancies include trisomy 8 but also loss of genetic material like Y chromosome and deletion 6q2123.3 and 6q27. […] It is hypothesized that these chromosomal abnormalities reflect inactivation of more than one tumor suppressor gene. […] With the advent of gene and protein expression profiling, future molecular and genetic insights are bound to influence current understanding of salivary gland tumorigenesis and its classification. […] The concept of dedifferentiation in salivary tumor pathology is essentially the identification of the clonal evolution of a poorly differentiated or high grade element arising within a low-grade carcinoma.

• #89 Head and Neck: Salivary gland tumors: an overview

  https://atlasgeneticsoncology.org/solid-tumor/5328/head-and-neck-salivary-gland-tumors-an-overview

  PLAG1 may play a role in PA pathogenesis by inducing growth factor production, hence cell proliferation. It was demonstrated by Western blot and immunohistochemical analyses that PLAG1 expression was up-regulated in epithelial and myoepithelial cells, as well as in the mesenchymal component of PA. […] The prognosis of pleomorphic adenoma is excellent if completely removed. Recurrence rates at 5 year- and 10 year-follow-up are 3.4% and 6.8%, respectively. […] The prognosis of carcinoma ex PA depends on its extension. Prognosis is excellent when the malignant component is confined to the PA nodule whereas it may be dismal when carcinoma extends beyond the capsule and infiltrates into adjacent soft tissues. Capsular penetration of more than 1.5 mm and a high-grade carcinomatous component are associated with poor prognosis. Survival rates at 5, 10, 15, and 20 years range from 25-65%, 18-50%, 10-35%, and 0-38%, respectively.

• #90 Salivary Gland Tumors – Ear, Nose, and Throat Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/ear-nose-and-throat-disorders/tumors-of-the-head-and-neck/salivary-gland-tumors

  Most salivary gland tumors are benign and occur in the parotid glands. […] About 75 to 80% are benign, slow-growing, movable, painless, usually solitary nodules beneath normal skin or mucosa. […] Pleomorphic adenomas (mixed-type tumors) can undergo malignant transformation, but this transformation usually occurs only after the benign tumor has been present for 15 to 20 years. […] Once malignant degeneration of a pleomorphic adenoma occurs, it is known as carcinoma ex pleomorphic adenoma. […] Carcinomatous elements in the tumor metastasize, making carcinoma ex pleomorphic adenoma a highly aggressive tumor with very low cure rates regardless of treatment. […] Benign cylindromas (cutaneous adnexal tumors) can slowly undergo malignant transformation into adenoid cystic carcinomas, the most common malignant tumor of minor salivary glands (and of the trachea).

• #91 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  MEC appears to be the most common salivary gland malignancy associated with radiation exposure. […] Over 50% of AdCC tumors contain the t(6;9)(q22-23;p23-24) translocation, which fuses the MYB protooncogene on chromosome 6q to the NFIB gene on chromosome 9p, resulting in an overexpression of MYB-NFIB fusion oncogene and worse prognosis. […] ACC develops from tumorigenesis of cells responsible for acinar development, namely the reserve cells of the intercalated ducts and terminal tubules. […] The presence of biological receptors in salivary gland malignancies has recently come under investigation. Tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) are present in up to 71% of all salivary gland cancers. […] Epigenetic mutations involving DNA promoter methylation of tumor suppressor genes can lead to transcriptional inactivation and increase both the risk of salivary duct carcinoma and the transformation of pleomorphic adenoma into carcinoma ex pleomorphic adenoma. […] The development of lymphoma from Sjogren syndrome is theorized to be due to prolonged B-cell activity and survival.

• #92 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  Salivary duct carcinomas may overexpress Her-2 and androgen receptor, with promising clinical outcomes after exposure to targeted therapies approved for other indications. […] Secretory carcinoma, previously known as mammary analogue secretory carcinoma, is distinguished by an ETV6-NTRK3 fusion that can both help differentiate it from its morphologically similar acinar cell carcinoma and also make it susceptible to Trk inhibitors. […] The aim of this article is to review the main molecular and immunohistochemical characteristics of the most common histological subtypes of SGC, in addition to reviewing current data on biomarker-driven targeted therapy and genomic findings that may be potentially actionable in the future. […] Myb, a nuclear transcription factor, is overexpressed in 60–80% of ACCs, usually correlated with a genetic translocation of the MYB gene to the transcription factor gene NFIB, resulting in the MYB-NFIB fusion, an important oncogene.

• #93 New Systemic Therapies in Salivary Gland Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-23175-9_20

  MYB overexpression as well as the presence of activating NOTCH1 mutations have also been shown to confer a poor prognosis for patients with ACC. […] Activating NOTCH1 mutations have been shown to possess carcinogenic potential, driving 50% of T-cell acute lymphoblastic leukemias (T-ALLs). […] They have also been found in 11-29% of patients with ACC. […] Such patients are more likely to have solid pattern on histology, advanced disease at diagnosis, non-lung metastases, including in liver, bone, or other atypical sites, and ultimately shorter relapse-free survival (RFS) and OS. […] Recent advances in the molecular characterization of these tumors have unveiled multiple, oftentimes targetable, subtype-specific alterations. […] Thus, adequate pathological diagnosis by an expert salivary gland pathologist to determine the exact subtype of SGC is key in choosing the right systemic therapy.

• #94 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  This fusion has been postulated as the main driver of tumor proliferation in ACC. […] Notch are transmembrane proteins that bind to neighboring cells and activate a biochemical cascade that gives rise to the process of cell differentiation, in addition to acting in the process of lateral regulation, proliferation, and angiogenesis of cells through the MAPK pathways. […] Mutations in the NOTCH gene family, particularly NOTCH1, are present in around 20% of ACC patients and are potential oncogenic drivers. […] Mechanisms of acquired resistance to larotrectinib have been described with an on-target mutation in the drug-binding site. […] The presence of a chromosomal translocation, t(12, 15), between the ETV6 gene on chromosome 12 with NTRK3 on chromosome 15, generates the fusion product ETV6–NTRK3. […] The literature demonstrates that 5-year disease-free survival in patients with ACC is only 30–40%. […] Molecular diagnostics are able to aid in diagnosis and guide discovery for subtype-specific targeted therapy.

• #95 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  This fusion has been postulated as the main driver of tumor proliferation in ACC. […] Notch are transmembrane proteins that bind to neighboring cells and activate a biochemical cascade that gives rise to the process of cell differentiation, in addition to acting in the process of lateral regulation, proliferation, and angiogenesis of cells through the MAPK pathways. […] Mutations in the NOTCH gene family, particularly NOTCH1, are present in around 20% of ACC patients and are potential oncogenic drivers. […] Mechanisms of acquired resistance to larotrectinib have been described with an on-target mutation in the drug-binding site. […] The presence of a chromosomal translocation, t(12, 15), between the ETV6 gene on chromosome 12 with NTRK3 on chromosome 15, generates the fusion product ETV6–NTRK3. […] The literature demonstrates that 5-year disease-free survival in patients with ACC is only 30–40%. […] Molecular diagnostics are able to aid in diagnosis and guide discovery for subtype-specific targeted therapy.

• #96 Salivary Gland Tumors – Ear, Nose, and Throat Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/ear-nose-and-throat-disorders/tumors-of-the-head-and-neck/salivary-gland-tumors

  Mucoepidermoid carcinoma is the most common salivary gland cancer, typically occurring in people in their 20s to 50s. […] Intermediate and high-grade mucoepidermoid carcinomas may metastasize to the regional lymphatics. […] Treatment of mucoepidermoid carcinoma consists of wide excision and postoperative radiation for high-grade lesions. […] Metastases to the regional lymphatics must be addressed with surgical resection and postoperative radiation therapy. […] Treatment of adenoid cystic carcinoma is wide surgical excision, but local recurrence is common due to the propensity for perineural spread. […] Although the 5- and 10-year survival rates are favorable, cause-specific survival continues to decline up to 30 years after diagnosis due to a high rate of late distant metastasis, primarily to the lung. […] Primary treatment for carcinoma ex pleomorphic adenoma is parotidectomy with the goal of complete resection of all disease.

• #97 Malignant Salivary Gland Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK563022/

  MEC appears to be the most common salivary gland malignancy associated with radiation exposure. […] Over 50% of AdCC tumors contain the t(6;9)(q22-23;p23-24) translocation, which fuses the MYB protooncogene on chromosome 6q to the NFIB gene on chromosome 9p, resulting in an overexpression of MYB-NFIB fusion oncogene and worse prognosis. […] ACC develops from tumorigenesis of cells responsible for acinar development, namely the reserve cells of the intercalated ducts and terminal tubules. […] The presence of biological receptors in salivary gland malignancies has recently come under investigation. Tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) are present in up to 71% of all salivary gland cancers. […] Epigenetic mutations involving DNA promoter methylation of tumor suppressor genes can lead to transcriptional inactivation and increase both the risk of salivary duct carcinoma and the transformation of pleomorphic adenoma into carcinoma ex pleomorphic adenoma. […] The development of lymphoma from Sjogren syndrome is theorized to be due to prolonged B-cell activity and survival.

• #98 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Seventy percent of pleomorphic adenomas have associated chromosomal rearrangements. The most common is a rearrangement of 8q12, occurring in 39% of pleomorphic adenomas. The target gene at this locus is PLAG1, which encodes a zinc finger transcription factor. The other target gene is HMGA2, which encodes a nonhistone chromosomal high mobility group protein that is involved in structural regulation of the chromosome and transcription. […] In mucoepidermoid carcinoma, the t(11;19)(q21;p13) chromosomal translocation has been identified in up to 70% of cases. This translocation creates a MECT1-MAML2 fusion protein that disrupts the Notch signaling pathway. This fusion protein is expressed by all cell types of mucoepidermoid when the translocation is present. Interestingly, fusion-positive tumors appear to be much less aggressive than fusion-negative tumors. Fusion-positive patients have significantly longer median survival and lower rates of local recurrence and distant metastasis.

• #99 Salivary Gland Tumors – Ear, Nose, and Throat Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/ear-nose-and-throat-disorders/tumors-of-the-head-and-neck/salivary-gland-tumors

  Mucoepidermoid carcinoma is the most common salivary gland cancer, typically occurring in people in their 20s to 50s. […] Intermediate and high-grade mucoepidermoid carcinomas may metastasize to the regional lymphatics. […] Treatment of mucoepidermoid carcinoma consists of wide excision and postoperative radiation for high-grade lesions. […] Metastases to the regional lymphatics must be addressed with surgical resection and postoperative radiation therapy. […] Treatment of adenoid cystic carcinoma is wide surgical excision, but local recurrence is common due to the propensity for perineural spread. […] Although the 5- and 10-year survival rates are favorable, cause-specific survival continues to decline up to 30 years after diagnosis due to a high rate of late distant metastasis, primarily to the lung. […] Primary treatment for carcinoma ex pleomorphic adenoma is parotidectomy with the goal of complete resection of all disease.

• #100 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  Salivary duct carcinomas may overexpress Her-2 and androgen receptor, with promising clinical outcomes after exposure to targeted therapies approved for other indications. […] Secretory carcinoma, previously known as mammary analogue secretory carcinoma, is distinguished by an ETV6-NTRK3 fusion that can both help differentiate it from its morphologically similar acinar cell carcinoma and also make it susceptible to Trk inhibitors. […] The aim of this article is to review the main molecular and immunohistochemical characteristics of the most common histological subtypes of SGC, in addition to reviewing current data on biomarker-driven targeted therapy and genomic findings that may be potentially actionable in the future. […] Myb, a nuclear transcription factor, is overexpressed in 60–80% of ACCs, usually correlated with a genetic translocation of the MYB gene to the transcription factor gene NFIB, resulting in the MYB-NFIB fusion, an important oncogene.

• #101 Characterization of novel genetic alterations in salivary gland secretory carcinoma | Modern Pathology

  https://www.nature.com/articles/s41379-019-0427-1

  Secretory carcinoma is a salivary gland tumor with a characteristic chromosomal translocation that results in an ETV6-NTRK3 fusion gene. […] Apart from the ETV6 gene translocation, little is known about genomic alterations in secretory carcinoma. […] The comprehensive targeted deep sequencing analyses of the secretory carcinoma cases were performed using cancer-related gene panels. These analyses revealed novel recurrent somatic mutations, especially in the PRSS1 gene. […] The PRSS1 gene encodes a cationic trypsinogen, which is a member of the trypsin family of serine proteases. […] The identification of a recurrent A16V mutation in the PRSS1 gene in secretory carcinoma is of clinical interest and warrants further in-depth studies as well in other subtypes of salivary gland tumors.

• #102 Characterization of novel genetic alterations in salivary gland secretory carcinoma | Modern Pathology

  https://www.nature.com/articles/s41379-019-0427-1

  Given that zymogen granules contain many digestive enzymes, such as trypsin, mutant PRSS1 may be involved in the tumorigenesis of this zymogen granule-poor cancer. […] The mutation frequency of PRSS1 was 56% (5/9) in the aggressive group and 27% (3/11) in the indolent group. […] These gene alterations may help to classify the high risk group among patients diagnosed with secretory carcinoma.

• #103 An Unusual Hybrid Salivary Gland Tumor: Molecular Analysis Informs the Potential Pathogenesis of This Rare Neoplasm. – Document – Gale Academic OneFile

  https://go.gale.com/ps/i.do?id=GALE%7CA617388207&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=20906781&p=AONE&sw=w

  The presence of two or more tumor entities growing in adjacent locations within the salivary gland is very rare, and pathologic studies on such lesions are limited, particularly those with molecular information. […] Hybrid salivary gland tumors are rare, and their pathogenesis is controversial. The combination of mucoepidermoid carcinoma and basal cell adenoma has not been previously described. While malignant transformation of adenoma to carcinoma seems plausible, gene sequencing was more suggestive of their independent derivation.

• #104 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  These morphologic observations are significant and portend clinical aggressiveness but molecular mechanisms of dedifferentiation in salivary gland neoplasia are yet to be clarified. […] In the future there may be some role for the pathologic assessment of myoepithelial differentiation in salivary gland tumor types, as there appears to be a modifying effect of this cell type on biologic behavior. […] These factors may relate to the lobulated, pushing, hypovascular invasive character and prolonged survivals despite distant metastasis attributed to tumors like epithelial-myoepithelial carcinoma and myoepithelial carcinoma.

• #105 Salivary gland tumor pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Salivary_gland_tumor_pathophysiology

  The pathophysiology of salivary gland tumors depends on the histological subtype. […] The parotid gland is the most frequent site of salivary gland tumors which accounts for approximately 80 to 85 percent of these tumors. […] About 75 percent of parotid lesions are benign and approximately 25 percent are malignant. […] In comparison to tumors arising in the parotid, 70 to 90 percent of sublingual gland tumors, 50 to 75 percent of minor salivary gland tumors, and 40 to 45 percent of submandibular gland tumors are malignant. […] Approximately 85% of salivary gland tumors occur in the parotid glands, followed by the minor salivary glands and submandibular, and approximately 1% occur in the sublingual glands. […] Overall approximately 80% of all parotid masses are benign.

• #106 Pathogenesis of salivary gland neoplasms: The concepts of histogenesis and morphogenesis – Journal of Global Oral Health

  https://jglobaloralhealth.org/pathogenesis-of-salivary-gland-neoplasms-the-concepts-of-histogenesis-and-morphogenesis/

  Many features overlap between different salivary gland neoplasms (SGNs) and as a result, classifying them distinctly has always been challenging. The differences in pathogenesis give rise to variations in the histopathological morphology of the SGNs. […] The present review aims to elaborate on the classification of SGNs based on the concepts of histogenesis and morphogenesis. […] The type of cell in which neoplastic transformation has occurred governs the events that follow the initiation of the multistage process which results in neoplasia. Our review elucidates the pathogenesis of the salivary gland tumor to understand the resulting histopathology, tumor morphology, and cellular differentiation of the tumor which reflects the parent cell. […] The differences in pathogenesis give rise to variations in the histopathological morphology of the SGNs.

• #107 Benign and Malignant Salivary Gland Tumors – Clinical and Demographic Characteristics | Anticancer Research

  https://ar.iiarjournals.org/content/36/8/4151

  Aim: To examine the demographic, ethnic, and clinical characteristics of salivary benign and malignant tumors for better etiological understanding. […] The purpose of the current study was to examine various demographic, ethnic, and systemic characteristics of patients diagnosed with benign and malignant salivary gland tumors in order to better understand their possible etiological roles. […] The synchronous diagnosis possibly points to a systemic etiological factor and the fact that it is found with benign, rather than malignant tumors raises very interesting questions relating to the neoplastic pathogenesis of these diseases regarding the salivary parenchyma. […] Thus it seems that the more mucous-like (as opposed to serous-like) the gland is, the more it will favor malignant rather than benign transformation.

• #108 Salivary Gland Neoplasia: A Review for the Practicing Pathologist | Modern Pathology

  https://www.nature.com/articles/3880525

  These morphologic observations are significant and portend clinical aggressiveness but molecular mechanisms of dedifferentiation in salivary gland neoplasia are yet to be clarified. […] In the future there may be some role for the pathologic assessment of myoepithelial differentiation in salivary gland tumor types, as there appears to be a modifying effect of this cell type on biologic behavior. […] These factors may relate to the lobulated, pushing, hypovascular invasive character and prolonged survivals despite distant metastasis attributed to tumors like epithelial-myoepithelial carcinoma and myoepithelial carcinoma.

• #109 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/852373-overview

  Salivary gland neoplasms are rare in children. Most tumors (65%) are benign, with hemangiomas being the most common, followed by pleomorphic adenomas. In children, 35% of salivary gland neoplasms are malignant. Mucoepidermoid carcinoma is the most common salivary gland malignancy in children. […] The etiology of salivary gland neoplasms is not fully understood. Two theories predominate: the bicellular stem cell theory and the multicellular theory. […] This theory holds that tumors arise from 1 of 2 undifferentiated stem cells: the excretory duct reserve cell or the intercalated duct reserve cell. Excretory stem cells give rise to squamous cell and mucoepidermoid carcinomas, while intercalated stem cells give rise to pleomorphic adenomas, oncocytomas, adenoid cystic carcinomas, adenocarcinomas, and acinic cell carcinomas.

• #110 Salivary Gland Neoplasms: Practice Essentials, Epidemiology, Etiology

  https://emedicine.medscape.com/article/194522-overview

  Salivary gland neoplasms are rare in children. Most tumors (65%) are benign, with hemangiomas being the most common, followed by pleomorphic adenomas. In children, 35% of salivary gland neoplasms are malignant. Mucoepidermoid carcinoma is the most common salivary gland malignancy in children. […] The etiology of salivary gland neoplasms is not fully understood. Two theories predominate: the bicellular stem cell theory and the multicellular theory. […] This theory holds that tumors arise from 1 of 2 undifferentiated stem cells: the excretory duct reserve cell or the intercalated duct reserve cell. Excretory stem cells give rise to squamous cell and mucoepidermoid carcinomas, while intercalated stem cells give rise to pleomorphic adenomas, oncocytomas, adenoid cystic carcinomas, adenocarcinomas, and acinic cell carcinomas.

• #111 Diseases of the salivary glands in infants and adolescents | Head & Face Medicine | Full Text

  https://head-face-med.biomedcentral.com/articles/10.1186/1746-160X-6-1

  Diseases of the salivary glands are rare in infants and children (with the exception of diseases such as parotitis epidemica and cytomegaly) and the therapeutic regimen differs from that in adults. […] The etiology and pathogenesis of these entities in young patients, however, are still not yet sufficiently understood, so that therapeutic strategies based on extensive clinical experience cannot be defined, particularly in view of the small number of patients in the relevant age groups. […] Neoplastic changes are very rare in children and adolescents, compared to salivary gland inflammations. […] Their annual incidence in all juvenile age groups is 1 to 2 tumor cases in 100,000 persons. […] According to Eneroth salivary gland tumors make up 0.3% of all human tumors, and less than 10% of all juvenile head and neck tumors are located in the salivary glands.

• #112 Diseases of the salivary glands in infants and adolescents | Head & Face Medicine | Full Text

  https://head-face-med.biomedcentral.com/articles/10.1186/1746-160X-6-1

  Only 1% of all head and neck tumors originate in the salivary glands, regardless of patient age. […] Not only makes this low incidence the establishment of a generally applicable therapeutic regime difficult; this task is not made easier by the circumstance that not more than 5% of all salivary gland tumors are found in the age group of up to 16 years. […] As a consequence therapies very often lean on experience gained in the last decades from long-term studies for the treatment of adult patients. […] Due to the fact that tumors of the salivary glands in childhood and adolescence are a rare disease, it is in our opinion not very easy to make a comparison with a similar adult population. […] Since malignant salivary gland tumors are relatively more frequent in young person’s than in adults, a safe diagnosis has to be made quickly and without delay.

• #113 Diseases of the salivary glands in infants and adolescents | Head & Face Medicine | Full Text

  https://head-face-med.biomedcentral.com/articles/10.1186/1746-160X-6-1

  This is even more important as according to Ussmller et al. about one half of all juvenile salivary gland tumors may be malignant tumors. […] Although malignant salivary gland tumors are uncommon in children and adolescents, clinical diagnosis has to be made very carefully, since compared with adults the proportion of malignancies among all neoplasms is relatively high. […] Many publications agree that mucoepidermoid carcinoma is the most abundant malignant salivary gland tumor in young patients. […] Our surgical concept and our favorable long-term results show that total or radical parotidectomy, sometimes including extended resection of neighbouring structures, is the best therapy for malignant parotid tumors in children, with relatively few complications throughout the follow-up period.

• #114 Role of Histone Deacetylases in the Pathogenesis of Salivary Gland Tumors and Therapeutic Targeting Options

  https://www.mdpi.com/1422-0067/24/12/10038

  Salivary gland tumors (SGTs) comprise a rare and heterogenous category of benign/malignant neoplasms with progressively increasing knowledge of the molecular mechanisms underpinning their pathogenesis, poor prognosis, and therapeutic treatment efficacy. […] Emerging data are pointing toward an interplay of genetic and epigenetic factors contributing to their heterogeneity and diverse clinical phenotypes. […] Post-translational histone modifications such as histone acetylation/deacetylation have been shown to actively participate in the pathobiology of SGTs, further suggesting that histone deacetylating factors (HDACs), selective or pan-HDAC inhibitors (HDACis), might present effective treatment options for these neoplasms. […] Herein, we describe the molecular and epigenetic mechanisms underlying the pathology of the different types of SGTs, focusing on histone acetylation/deacetylation effects on gene expression as well as the progress of HDACis in SGT therapy and the current status of relevant clinical trials.

• #115 Molecular Pathology of Salivary Gland Neoplasms: Diagnostic, Prog…: Ingenta Connect

  https://www.ingentaconnect.com/content/wk/adapa/2021/00000028/00000002/art00003

  Salivary gland neoplasms are an uncommon and widely heterogeneous group of tumors. In recent years, there has been considerable progress in efforts to reveal the molecular landscape of these tumors, although it is still limited and appears to be only the tip of the iceberg. Genomic aberrations, especially specific chromosomal rearrangements including CRTC1-MAML2 and CRTC3-MAML2 in mucoepidermoid carcinoma, MYB-NFIB and MYBL1-NFIB fusions in adenoid cystic carcinoma, PLAG1 and HMGA2 alterations in pleomorphic adenoma and carcinoma ex pleomorphic adenoma, ETV6-NTRK3 and ETV6-RET in secretory carcinoma, EWSR1-ATF1 and EWSR1-CREM in clear cell carcinoma, provide new insights into the molecular pathogenesis of various salivary gland neoplasms and help to better classify them. […] These genetic aberrations primarily serve as diagnostic tools in salivary gland tumor diagnosis; however, some also have promise as prognostic or predictive biomarkers. This review summarizes the latest developments in molecular pathology of salivary gland tumors with a focus on distinctive molecular characteristics.

• #116 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  Salivary gland carcinomas (SGC) account for less than 5% of head and neck malignant neoplasms, further subcategorized in over 20 histological subtypes. […] More recently, next-generation sequencing provided significant input on the molecular characterization of each SGC subtype, not only improving diagnostic differentiation between morphologically similar tumor types, but also identifying novel driver pathways that determine tumor biology and may be amenable to targeted therapy. […] Amongst the most common histological subtype is adenoid cystic carcinoma, which often harbors a chromosome translocation resulting in a MYB-NFIB oncogene, with various degrees of Myb expression. […] In a smaller subset, NOTCH1 mutations occur, conferring a more aggressive disease and potential sensitivity to Notch inhibitors.

• #117 Parotid tumors – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/parotid-tumor/symptoms-causes/syc-20578986

  Parotid tumors happen when cells in the parotid glands develop changes in their DNA. […] A cell’s DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In tumor cells, the DNA changes give different instructions. The changes tell the tumor cells to grow and multiply quickly. Tumor cells can keep living when healthy cells would die. This causes too many cells. […] Sometimes the changes in the DNA turn the cells into cancer cells. Cancer cells can invade and destroy healthy body tissue. In time, cancer cells can break away and spread to other parts of the body. When cancer spreads, it’s called metastatic cancer.

• #118 New Systemic Therapies in Salivary Gland Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-031-23175-9_20

  MYB overexpression as well as the presence of activating NOTCH1 mutations have also been shown to confer a poor prognosis for patients with ACC. […] Activating NOTCH1 mutations have been shown to possess carcinogenic potential, driving 50% of T-cell acute lymphoblastic leukemias (T-ALLs). […] They have also been found in 11-29% of patients with ACC. […] Such patients are more likely to have solid pattern on histology, advanced disease at diagnosis, non-lung metastases, including in liver, bone, or other atypical sites, and ultimately shorter relapse-free survival (RFS) and OS. […] Recent advances in the molecular characterization of these tumors have unveiled multiple, oftentimes targetable, subtype-specific alterations. […] Thus, adequate pathological diagnosis by an expert salivary gland pathologist to determine the exact subtype of SGC is key in choosing the right systemic therapy.

• #119 Salivary Gland Cancer | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/salivary-gland

  Salivary gland cancer is a rare type of head and neck cancer. It begins when the cells that make up the salivary glands grow out of control and form lesions or tumors. […] Most tumors begin in the parotid glands. They are the largest of the salivary glands, located just in front of the ears. Parotid gland tumors are often benign. Tumors also form in the other salivary glands, such as the submandibular gland, the sublingual gland, and the minor salivary glands. Tumors in these locations are more likely to be cancer. […] Other aspects of salivary gland cancer care include radiation therapy and drug therapies. MSKs radiation team has special training in caring for people with salivary gland tumors. […] We offer clinical trials using tumor-sequencing technology to find new treatment approaches to many types of salivary gland cancer. We are exploring drug therapies, ranging from hormone therapy to immunotherapy.

• #120 Frontiers | Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.580141/full

  This fusion has been postulated as the main driver of tumor proliferation in ACC. […] Notch are transmembrane proteins that bind to neighboring cells and activate a biochemical cascade that gives rise to the process of cell differentiation, in addition to acting in the process of lateral regulation, proliferation, and angiogenesis of cells through the MAPK pathways. […] Mutations in the NOTCH gene family, particularly NOTCH1, are present in around 20% of ACC patients and are potential oncogenic drivers. […] Mechanisms of acquired resistance to larotrectinib have been described with an on-target mutation in the drug-binding site. […] The presence of a chromosomal translocation, t(12, 15), between the ETV6 gene on chromosome 12 with NTRK3 on chromosome 15, generates the fusion product ETV6–NTRK3. […] The literature demonstrates that 5-year disease-free survival in patients with ACC is only 30–40%. […] Molecular diagnostics are able to aid in diagnosis and guide discovery for subtype-specific targeted therapy.

• #121 Head and Neck: Salivary gland tumors: an overview

  https://atlasgeneticsoncology.org/solid-tumor/5328/head-and-neck-salivary-gland-tumors-an-overview

  The etiology of SGTs is so far unknown. Putative risk factors include cigarette smoking, genetic predisposition, viral infections, rubber manufacturing, plumbing, some types of woodworking, as well as asbestos mining, exposure to nickel compounds, and cellular phone use. The only well-established risk factor is ionizing radiation. Atomic bomb survivors and cancer patients treated by radiation present with a substantially higher risk of developing SGTs. However, there is a strong association between Warthin tumor (WT) and cigarette smoking, with WT occurring 8 times more often in smokers than in non-smokers. Irritants in tobacco smoke may cause metaplasia in the parotid gland. The association with tobacco use may explain the higher incidence of WT in males. […] A growing number of both benign and malignant SGTs are characterized by recurrent genetic alterations, particularly chromosome translocations. Specific chromosomal rearrangements are commonly found in malignant hematopoietic proliferations as well as in sarcomas, but less than 1% of all epithelial cancers are characterized by such distinct, recurrent genomic anomalies. Those anomalies may serve as diagnostic, prognostic and/or predictive markers in SGTs and their identification may complement the morphologic evaluation. Chromosome translocations in SGTs result in pathogenetically relevant fusion oncogenes. Those genes encode novel fusion proteins as well as ectopically expressed normal or truncated proteins that may play a role in tumor initiation and/or progression.

Zobacz więcej