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

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cancers Review An Overview on the Histogenesis and Morphogenesis of Salivary Gland Neoplasms and Evolving Diagnostic Approaches Janaki Iyer 1 , Arvind Hariharan 1, Uyen Minh Nha Cao 1,2, Crystal To Tam Mai 1, Athena Wang 1, Parisa Khayambashi 1, Bich Hong Nguyen 3, Lydia Safi 1 and Simon D. Tran 1,* 1 McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, 3640 University Street, Montreal, QC H3A 0C7, Canada; [email protected] (J.I.); [email protected] (A.H.); [email protected] (U.M.N.C.); [email protected] (C.T.T.M.); [email protected] (A.W.); [email protected] (P.K.); lydia.safi@mail.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; [email protected] * Correspondence: [email protected] Simple Summary: 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 molecu- lar etiopatho-genesis of SGN, highlighting advanced diagnostic protocols that may facilitate the Citation: Iyer, J.; Hariharan, A.; Cao, identification and therapy of a variety of SGN. U.M.N.; Mai, C.T.T.; Wang, A.; Khayambashi, P.; Nguyen, B.H.; Safi, Abstract: Salivary gland neoplasms (SGN) remain a diagnostic dilemma due to their heterogenic L.; Tran, S.D. An Overview on the complex behavior. Their diverse histomorphological appearance is attributed to the underlying Histogenesis and Morphogenesis of cellular mechanisms and differentiation into various histopathological subtypes with overlapping Salivary Gland Neoplasms and fea-tures. Diagnostic tools such as fine needle aspiration biopsy, computerized tomography, magnetic Evolving Diagnostic Approaches. Cancers 2021, 13, 3910. https:// resonance imaging, and positron emission tomography help evaluate the structure and assess the doi.org/10.3390/cancers13153910 staging of SGN. Advances in molecular pathology have uncovered genetic patterns and oncogenes by immunohistochemistry, fluorescent in situ hybridization, and next–generation sequencing, that Academic Editors: Paola Ferrari and may potentially contribute to innovating diagnostic approaches in identifying various SGN. Surgical Andrea Nicolini resection is the principal treatment for most SGN. Other modalities such as radiotherapy, chemother- apy, targeted therapy (agents like tyrosine kinase inhibitors, monoclonal antibodies, and proteasome Received: 4 June 2021 inhibitors), and potential hormone therapy may be applied, depending on the clinical behaviors, Accepted: 29 July 2021 histopathologic grading, tumor stage and location, and the extent of tissue invasion. This review Published: 3 August 2021 delves into the molecular pathways of salivary gland tumorigenesis, highlighting recent diagnostic protocols that may facilitate the identification and management of SGN. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in Keywords: salivary glands; salivary gland neoplasms; epithelial tumors; head and neck cancer; published maps and institutional affil- molecular pathology; diagnostic advances iations. 1. Introduction Copyright: © 2021 by the au- thors. Submitted for possible Salivary glands are tubulo-acinar exocrine organs that embryonically initiate in the open access publication under sixth–eighth week of intrauterine life. The parotid gland is believed to arise from the the terms and conditions of the Cre- oral ectoderm, while the submandibular and sublingual glands are from the embryonic ative Com-mons Attribution (CC endoderm [1,2]. Their development is attributed to the physiologic process of ‘branching BY-NC-ND 4.0) license (https:// morphogenesis’, described as the rearrangement of a single epithelial bud to generate creativecommons.org/licenses/by-nc- multiple acinar and ductal units, through continuous multi-directional branching [3]. nd/ 4.0/). ‘Epithelial–mesenchymal interaction’, described as a secondary induction of the epithelium Cancers 2021, 13, 3910. https://doi.org/10.3390/cancers13153910 https://www.mdpi.com/journal/cancers Cancers 2021, 13, x 2 of 20 Cancers 2021, 13, 3910 2 of 20 ‘Epithelial–mesenchymal interaction’, described as a secondary induction of the epithe- liumby its by underlying its underlying mesenchyme, mesenchyme, is also is also essential essential for the for normalthe normal development development of salivary of sal- ivaryglands glands [4]. This [4]. cascade This cascade of events of ultimatelyevents ultimately forms multiple forms multiple secretory secretory units, each units, consisting each consistingof a terminal of a acinar terminal (serous/mucous) acinar (serous/mucous) cell, myoepithelial cell, myoepithelial cell, intercalated cell, intercalated duct, striated duct, striatedduct, and duct, excretory and excretory duct, as duct, elaborated as elaborated in Figure in1 [Figure1,2]. 1 [1,2]. Figure 1. 1. SchematicSchematic representation representation of ofthe the histology histology of salivary of salivary glands. glands. Reprinted Reprinted from from[5,6] wi [5,th6] permission. with permission. Ducto-acinar Ducto- architectureacinar architecture of salivary of salivary glands glandsis divided is divided by capsular by capsular conne connectivective tissue tissue septa septainto lobules. into lobules. Each Eachlobule lobule consists consists of nu- of merous serous/mucous/mixed (also known as serous demilune around mucous acini) secretory acini that are enveloped numerous serous/mucous/mixed (also known as serous demilune around mucous acini) secretory acini that are enveloped by myoepithelial cells. The secretory acini unite to form intercalated ducts (lined by simple squamous to low cuboidal by myoepithelial cells. The secretory acini unite to form intercalated ducts (lined by simple squamous to low cuboidal epithelium and wrapped by myoepithelial cells). Saliva is secreted by acinar cells and drains into the striated ducts that areepithelium lined by and simple wrapped or pseudostratified by myoepithelial columnar cells). Salivaepithelial is secreted cells. This by ductal acinar cellslining and transfor drainsms into into the stratified striated squamous ducts that epitheliumare lined by supported simple or by pseudostratified basal cells. Ultimately, columnar the epithelial striated cells. ducts This drain ductal into liningthe excretory transforms ducts into (also stratified known squamous as inter- lobularepithelium ducts) supported with tall by columnar basal cells. epithelial Ultimately, cells. the Figure striated adapted ducts drain from into Tran the et excretory al., 2019 ducts and Proctor (also known and asShaalan, interlobular 2018 [5,6].ducts) with tall columnar epithelial cells. Figure adapted from Tran et al., 2019 and Proctor and Shaalan, 2018 [5,6]. TheThe architecture architecture of of salivary salivary glands glands is two-tiered, consisting of luminal (acinar and ductal)ductal) and and abluminal abluminal (myoepithelial (myoepithelial and and basal) basal) cells [1,2]. [1,2]. These These cells cells enter enter the cell cycle rapidly,rapidly, thus acting as potentialpotential targetstargets forfor neoplasticneoplastic transformation.transformation. The estimated globalglobal incidence incidence of of salivary salivary gland gland neoplasm neoplasmss (SGN) (SGN) ranges ranges from from 0.4 0.4 to to 13.5 13.5 cases per 100,000100,000 annually, annually, and and constitutes constitutes approximately approximately 3 to 3 6% to 6% of head of head and andneck neck tumors tumors [7]. The [7]. diverseThe diverse histomorphological histomorphological appearance appearance of SGN of SGNis attributed is attributed to their to theirheterogenic heterogenic and complexand complex cellular cellular behavior. behavior. Differentiation Differentiation into various into various histopathological histopathological subtypes subtypes with overlappingwith overlapping features features both bothwithin within tumors tumors and in and different in different regions regions of the of same the same tumor, tumor, re- sultsresults in insignificant significant diagnostic diagnostic challenge challenge [1,2,8]. [1,2,8]. Advances Advances in in molecular molecular pathology pathology have uncovereduncovered genetic genetic patterns patterns and and biomarkers biomarkers that that may may potentially potentially contribute contribute to to innovating innovating diagnosticdiagnostic approaches approaches in in identifying identifying various various salivary salivary gland gland pathologies pathologies [9]. [9]. In In this this paper, paper, wewe delve into thethe molecularmolecular pathways pathways of of salivary salivary gland gland tumorigenesis, tumorigenesis, highlighting highlighting recent re- centdiagnostic diagnostic protocols protocols that that may may facilitate facilitate the identification the identification and managementand management of SGN. of SGN. 1.1. Pathogenesis of Salivary Gland Neoplasms (SGN) 1.1.1. Histogenic Concepts 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 Cancers 2021, 13, x 3 of 20 1.1. Pathogenesis of Salivary Gland Neoplasms (SGN) 1.1.1. Histogenic
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  • Understanding Paraxial Mesoderm Development and Sclerotome Specification for Skeletal Repair Shoichiro Tani 1,2, Ung-Il Chung2,3, Shinsuke Ohba4 and Hironori Hojo2,3

    Understanding Paraxial Mesoderm Development and Sclerotome Specification for Skeletal Repair Shoichiro Tani 1,2, Ung-Il Chung2,3, Shinsuke Ohba4 and Hironori Hojo2,3

    Tani et al. Experimental & Molecular Medicine (2020) 52:1166–1177 https://doi.org/10.1038/s12276-020-0482-1 Experimental & Molecular Medicine REVIEW ARTICLE Open Access Understanding paraxial mesoderm development and sclerotome specification for skeletal repair Shoichiro Tani 1,2, Ung-il Chung2,3, Shinsuke Ohba4 and Hironori Hojo2,3 Abstract Pluripotent stem cells (PSCs) are attractive regenerative therapy tools for skeletal tissues. However, a deep understanding of skeletal development is required in order to model this development with PSCs, and for the application of PSCs in clinical settings. Skeletal tissues originate from three types of cell populations: the paraxial mesoderm, lateral plate mesoderm, and neural crest. The paraxial mesoderm gives rise to the sclerotome mainly through somitogenesis. In this process, key developmental processes, including initiation of the segmentation clock, formation of the determination front, and the mesenchymal–epithelial transition, are sequentially coordinated. The sclerotome further forms vertebral columns and contributes to various other tissues, such as tendons, vessels (including the dorsal aorta), and even meninges. To understand the molecular mechanisms underlying these developmental processes, extensive studies have been conducted. These studies have demonstrated that a gradient of activities involving multiple signaling pathways specify the embryonic axis and induce cell-type-specific master transcription factors in a spatiotemporal manner. Moreover, applying the knowledge of mesoderm development, researchers have attempted to recapitulate the in vivo development processes in in vitro settings, using mouse and human PSCs. In this review, we summarize the state-of-the-art understanding of mesoderm development and in vitro modeling of mesoderm development using PSCs. We also discuss future perspectives on the use of PSCs to generate skeletal tissues for basic research and clinical applications.
  • Floral Ontogeny and Histogenesis in Leguminosae. Kittie Sue Derstine Louisiana State University and Agricultural & Mechanical College

    Floral Ontogeny and Histogenesis in Leguminosae. Kittie Sue Derstine Louisiana State University and Agricultural & Mechanical College

    Louisiana State University LSU Digital Commons LSU Historical Dissertations and Theses Graduate School 1988 Floral Ontogeny and Histogenesis in Leguminosae. Kittie Sue Derstine Louisiana State University and Agricultural & Mechanical College Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_disstheses Recommended Citation Derstine, Kittie Sue, "Floral Ontogeny and Histogenesis in Leguminosae." (1988). LSU Historical Dissertations and Theses. 4493. https://digitalcommons.lsu.edu/gradschool_disstheses/4493 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Historical Dissertations and Theses by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. INFORMATION TO USERS The most advanced technology has been used to photo­ graph and reproduce this manuscript from the microfilm master. UMI films the original text directly from the copy submitted. Thus, some dissertation copies are in typewriter face, while others may be from a computer printer. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyrighted material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are re­ produced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each oversize page is available as one exposure on a standard 35 mm slide or as a 17" x 23" black and white photographic print for an additional charge. Photographs included in the original manuscript have been reproduced xerographically in this copy.