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

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          Abstract

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          Diagnosing salivary gland neoplasms (SGN) remain a challenge, given their underlying biological nature and overlapping features. Evolving techniques in molecular pathology have uncovered genetic mutations resulting in these tumors. This review delves into the molecular etiopatho-genesis of SGN, highlighting advanced diagnostic protocols that may facilitate the identification and therapy of a variety of SGN.

          Abstract

          Salivary gland neoplasms (SGN) remain a diagnostic dilemma due to their heterogenic complex behavior. Their diverse histomorphological appearance is attributed to the underlying cellular mechanisms and differentiation into various histopathological subtypes with overlapping fea-tures. Diagnostic tools such as fine needle aspiration biopsy, computerized tomography, magnetic resonance imaging, and positron emission tomography help evaluate the structure and assess the staging of SGN. Advances in molecular pathology have uncovered genetic patterns and oncogenes by immunohistochemistry, fluorescent in situ hybridization, and next–generation sequencing, that may potentially contribute to innovating diagnostic approaches in identifying various SGN. Surgical resection is the principal treatment for most SGN. Other modalities such as radiotherapy, chemotherapy, targeted therapy (agents like tyrosine kinase inhibitors, monoclonal antibodies, and proteasome inhibitors), and potential hormone therapy may be applied, depending on the clinical behaviors, histopathologic grading, tumor stage and location, and the extent of tissue invasion. This review delves into the molecular pathways of salivary gland tumorigenesis, highlighting recent diagnostic protocols that may facilitate the identification and management of SGN.

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          Most cited references106

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          Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland.

          The salivary gland section in the 4th edition of the World Health Organization classification of head and neck tumors features the description and inclusion of several entities, the most significant of which is represented by (mammary analogue) secretory carcinoma. This entity was extracted mainly from acinic cell carcinoma based on recapitulation of breast secretory carcinoma and a shared ETV6-NTRK3 gene fusion. Also new is the subsection of "Other epithelial lesions," for which key entities include sclerosing polycystic adenosis and intercalated duct hyperplasia. Many entities have been compressed into their broader categories given clinical and morphologic similarities, or transitioned to a different grouping as was the case with low-grade cribriform cystadenocarcinoma reclassified as intraductal carcinoma (with the applied qualifier of low-grade). Specific grade has been removed from the names of the salivary gland entities such as polymorphous adenocarcinoma, providing pathologists flexibility in assigning grade and allowing for recognition of a broader spectrum within an entity. Cribriform adenocarcinoma of (minor) salivary gland origin continues to be divisive in terms of whether it should be recognized as a distinct category. This chapter also features new key concepts such as high-grade transformation. The new paradigm of translocations and gene fusions being common in salivary gland tumors is featured heavily in this chapter.
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            An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma

            Translocation events are frequent in cancer and may create chimeric fusions or ‘regulatory rearrangements’ that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole-genome sequencing data and chromatin maps reveal distinct chromosomal rearrangements that juxtapose super-enhancers to the MYB locus. Chromosome conformation capture confirms that the translocated enhancers interact with the MYB promoter. Remarkably, MYB protein binds to the translocated enhancers, creating a positive feedback loop that sustains its expression. MYB also binds enhancers that drive different regulatory programs in alternate cell lineages in ACC, cooperating with TP63 in myoepithelial cells and a Notch program in luminal epithelial cells. Bromodomain inhibitors slow tumor growth in ACC primagraft models in vivo. Thus, our study identifies super-enhancer translocations that drive MYB expression and provides insight into downstream MYB functions in the alternate ACC lineages.
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              Treatment of late sequelae after radiotherapy for head and neck cancer

              Radiotherapy (RT) is used to treat approximately 80% of patients with cancer of the head and neck. Despite enormous advances in RT planning and delivery, a significant number of patients will experience radiation-associated toxicities, especially those treated with concurrent systemic agents. Many effective management options are available for acute RT-associated toxicities, but treatment options are much more limited and of variable benefit among patients who develop late sequelae after RT. The adverse impact of developing late tissue damage in irradiated patients may range from bothersome symptoms that negatively affect their quality of life to severe life-threatening complications. In the region of the head and neck, among the most problematic late effects are impaired function of the salivary glands and swallowing apparatus. Other tissues and structures in the region may be at risk, depending mainly on the location of the irradiated tumor relative to the mandible and hearing apparatus. Here, we review the available evidence on the use of different therapeutic strategies to alleviate common late sequelae of RT in head and neck cancer patients, with a focus on the critical assessment of the treatment options for xerostomia, dysphagia, mandibular osteoradionecrosis, trismus, and hearing loss.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                03 August 2021
                August 2021
                : 13
                : 15
                : 3910
                Affiliations
                [1 ]McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC H3A 0C7, Canada; janaki.iyer@ 123456mail.mcgill.ca (J.I.); arvind.hariharan@ 123456mail.mcgill.ca (A.H.); cmnuyen.chrhm18@ 123456ump.edu.vn (U.M.N.C.); crystal.mai@ 123456mail.utoronto.ca (C.T.T.M.); athw13@ 123456student.ubc.ca (A.W.); parisa.khayambashi@ 123456mail.mcgill.ca (P.K.); lydia.safi@ 123456mail.mcgill.ca (L.S.)
                [2 ]Department of Orthodontics, Faculty of Dentistry, Ho Chi Minh University of Medicine and Pharmacy, Ho Chi Minh City 700000, Vietnam
                [3 ]CHU Sainte Justine Hospital, Montreal, QC H3T 1C5, Canada; bich.hong.nguyen@ 123456umontreal.ca
                Author notes
                [* ]Correspondence: simon.tran@ 123456mcgill.ca
                Author information
                https://orcid.org/0000-0003-2033-7391
                https://orcid.org/0000-0001-5594-359X
                Article
                cancers-13-03910
                10.3390/cancers13153910
                8345412
                34359811
                9c72718b-62e1-444a-8ef8-b28be4680a8f
                © 2021 by the authors.

                Submitted for possible open access publication under the terms and conditions of the Creative Com-mons Attribution (CC BY-NC-ND 4.0) license ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 04 June 2021
                : 29 July 2021
                Categories
                Review

                salivary glands,salivary gland neoplasms,epithelial tumors,head and neck cancer,molecular pathology,diagnostic advances

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