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      Developing Classifications of Laryngeal Dysplasia: The Historical Basis

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          Abstract

          During the last 60 years numerous significant attempts have been made to achieve a widely acceptable terminology and histological grading for laryngeal squamous intraepithelial lesions. While dysplasia was included in the pathology of the uterine cervix already in 1953, the term dysplasia was accepted in laryngeal pathology first after the Toronto Centennial Conference on Laryngeal Cancer in 1974. In 1963 Kleinsasser proposed a three-tier classification, and in 1971 Kambic and Lenart proposed a four-tier classification. Since then, four editions of the World Health Organisation (WHO) classification have been proposed (1978, 1991, 2005 and 2017). Several terms such as squamous intraepithelial neoplasia (SIN) and laryngeal intraepithelial neoplasia (LIN) are now being abandoned and replaced by squamous intraepithelial lesions (SIL). The essential change between the 2005 and 2017 WHO classifications is the attempt to induce a simplification from a four- to a two-tier system. The current WHO classification (2017) thus recommends the use of a two-tier system with reasonably clear histopathological criteria for the two groups: low-grade and high-grade dysplasia. Problems with interobserver variability apart, subjectivities and uncertainties remain, but to a lesser degree. Ongoing and additional molecular studies may help to clarify underlying events that will increase our understanding and possibly can facilitate our attempts to obtain an even better classification. The classification needs to be easier for the general pathologist to perform and easier for the clinician to interpret. These two objectives are equally important to provide each patient the best personalised treatment available for squamous intraepithelial lesions.

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          Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement.

          At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the United Kingdom issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers. In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine use. Although most oral pathologists possibly recognize and accept the criteria for grading epithelial dysplasia, firstly based on architectural features and then of cytology, there is great variability in their interpretation of the presence, degree and significance of the individual criteria. Several studies have shown great interexaminer and intraexaminer variability in the assessment of the presence or absence and the grade of oral epithelial dysplasia. The Working Group considered the two class classification (no/questionable/ mild - low risk; moderate or severe - implying high risk) and was of the view that reducing the number of choices from 3 to 2 may increase the likelihood of agreement between pathologists. The utility of this need to be tested in future studies. The variables that are likely to affect oral epithelial dysplasia scoring were discussed and are outlined here; these need to be researched in longitudinal studies to explore the biological significance of a low-risk or high-risk dysplasia.
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            Detection of transcriptionally active high-risk HPV in patients with head and neck squamous cell carcinoma as visualized by a novel E6/E7 mRNA in situ hybridization method.

            Evidence for transcriptional activation of the viral oncoproteins E6 and E7 is regarded as the gold standard for the presence of clinically relevant human papillomavirus (HPV), but detection of E6/E7 mRNA requires RNA extraction and polymerase chain reaction amplification-a challenging technique that is restricted to the research laboratory. The development of RNA in situ hybridization (ISH) probes complementary to E6/E7 mRNA permits direct visualization of viral transcripts in routinely processed tissues and has opened the door for accurate HPV detection in the clinical care setting. Tissue microarrays containing 282 head and neck squamous cell carcinomas from various anatomic subsites were tested for the presence of HPV using p16 immunohistochemistry, HPV DNA ISH, and an RNA ISH assay (RNAscope) targeting high-risk HPV E6/E7 mRNA transcripts. The E6/E7 mRNA assay was also used to test an additional 25 oropharyngeal carcinomas in which the HPV status as recorded in the surgical pathology reports was equivocal due to conflicting detection results (ie, p16 positive, DNA ISH negative). By the E6/E7 mRNA method, HPV was detected in 49 of 282 (17%) HNSCCs including 43 of 77 (56%) carcinomas from the oropharynx, 2 of 3 (67%) metastatic HNSCCs of an unknown primary site, 2 of 7 (29%) carcinomas from the sinonasal tract, and 2 of 195 (1%) carcinomas from other head and neck sites. p16 expression was strongly associated with the presence of HPV E6/E7 mRNA: 46 of 49 HPV-positive tumors exhibited p16 expression, whereas only 22 of 233 HPV-negative tumors were p16 positive (94% vs. 9%, P<0.0001). There was also a high rate of concordance (99%) between the E6/E7 mRNA method and HPV DNA ISH. For the selected group of discordant HNSCCs (p16/HPV DNA), the presence of E6/E7 transcripts was detected in 21 of 25 (84%) cases. The E6/E7 mRNA method confirmed the presence of transcriptionally active HPV-related HNSCC that has a strong predilection for the oropharynx and is strongly associated with high levels of p16 expression. Testing for HPV E6/E7 transcripts by RNA ISH is ideal because it confirms the presence of integrated and transcriptionally active virus, permits visualization of viral transcripts in tissues, and is technically feasible for routine testing in the clinical laboratory.
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              The risk and interval to malignancy of patients with laryngeal dysplasia; a systematic review of case series and meta-analysis.

              Laryngeal dysplasia is a pre-malignant condition with wide variability in rates of malignant transformation reported in the literature. The management and follow-up strategies of these lesions vary widely.
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                Author and article information

                Contributors
                henrikhellquist@gmail.com
                Journal
                Adv Ther
                Adv Ther
                Advances in Therapy
                Springer Healthcare (Cheshire )
                0741-238X
                1865-8652
                23 April 2020
                23 April 2020
                2020
                : 37
                : 6
                : 2667-2677
                Affiliations
                [1 ]Epigenetics and Human Disease Laboratory, Faro, Portugal
                [2 ]Department of Biomedical Sciences and Medicine, Faro, Portugal
                [3 ]Centre of Biomedical Research (CBMR) and Algarve Biomedical Center (ABC), Faro, Portugal
                [4 ]International Head and Neck Scientific Group, Padua, Italy
                [5 ]GRID grid.7737.4, ISNI 0000 0004 0410 2071, Department of Otorhinolaryngology Head and Neck Surgery, , University of Helsinki and Helsinki University Hospital, ; Helsinki, Finland
                [6 ]GRID grid.417224.6, ISNI 0000 0004 0445 0789, Department of Pathology, Southern California Permanente Medical Group, , Woodland Hills Medical Center, ; Woodland Hills, CA USA
                [7 ]GRID grid.267313.2, ISNI 0000 0000 9482 7121, Department of Pathology, , University of Texas Southwestern Medical Center, ; Dallas, TX USA
                [8 ]Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
                [9 ]GRID grid.468198.a, ISNI 0000 0000 9891 5233, Department of Pathology, , Moffitt Cancer Centre, ; Tampa, FL USA
                [10 ]GRID grid.40263.33, ISNI 0000 0004 1936 9094, Department of Pathology, , Alpert Medical School at Brown University, ; Providence, RI USA
                [11 ]GRID grid.4494.d, ISNI 0000 0000 9558 4598, Department of Pathology and Medical Biology, , University Medical Center Groningen, ; Groningen, The Netherlands
                [12 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Pathology, , Radboud University Nijmegen Medical Center, ; Nijmegen, The Netherlands
                [13 ]GRID grid.5390.f, ISNI 0000 0001 2113 062X, University of Udine School of Medicine, ; Udine, Italy
                Article
                1348
                10.1007/s12325-020-01348-4
                7467449
                32329013
                be85ce17-d827-468b-baf4-fa3b9fa20977
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 19 March 2020
                Categories
                Review
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                © Springer Healthcare Ltd., part of Springer Nature 2020

                laryngeal dysplasia,laryngeal precancerous lesions,laryngeal precursor lesions,who classification

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