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      Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What Is New in the 2017 WHO Blue Book for Tumors and Tumor-Like Lesions of the Neck and Lymph Nodes

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          Abstract

          The World Health Organization (WHO) 2017 Classification of Head and Neck Tumors (“Blue Book”) will now include a new chapter on tumors and tumor-like lesions of the neck and lymph nodes, which was not included in the previous edition. Tumors and tumor-like lesions, including a variety of cysts and metastases, can arise in any component in the neck, including soft tissue, lymph nodes, and developmental remnants. The pathology and clinical features of metastatic carcinoma of unknown primary in the head and neck has changed dramatically in the last several years. Many of these tumors which were previously diagnosed as unknown primary are now identified as oropharyngeal and nasopharyngeal carcinomas related to human papillomavirus (HPV), less commonly to Epstein-Barr virus (EBV) and occasionally even to Merkel cell polyomavirus. Many unusual features can arise in these metastases, such as undifferentiated morphology, extensive cystic change with central degeneration, gland formation, and even ciliated cells. Rarely, carcinoma in the neck can arise in association with a heterotopic tissue, primarily thyroid or salivary gland tissue. Tumor-like lesions include branchial cleft cysts, thyroglossal duct cyst, dermoid and teratoid cyst, and ranula. Pathologists should be familiar with the diagnostic features and clinicopathologic corrections of these neck lesions in order to correctly diagnosis them and to provide for proper clinical management. This article will briefly describe the pathologic and clinical features of these entities as they are covered in the new 2017 Blue Book.

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          Most cited references 42

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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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            High-risk human papillomavirus E6/E7 mRNA detection by a novel in situ hybridization assay strongly correlates with p16 expression and patient outcomes in oropharyngeal squamous cell carcinoma.

            Human papillomavirus (HPV) is established as causative in oropharyngeal squamous cell carcinomas (OSCCs), being detected in 50% to 80% of tumors by DNA in situ hybridization (ISH) and/or polymerase chain reaction. However, these tests do not assess viral transcription. Many consider E6/E7 messenger ribonucleic acid (mRNA) the best indicator of HPV status, but it has not been detected in situ in OSCC. We constructed tissue microarrays (TMAs) from a cohort of OSCC for which p16 immunohistochemistry and HPV DNA ISH were previously performed on whole sections. We utilized a novel, chromogenic RNA ISH assay called RNAscope to detect E6/E7 mRNA of HPV-16 and other high-risk types on these TMAs. RNA ISH results were obtained for 196 of 211 TMA cases, of which 153 (78.1%) were positive. p16 immunohistochemistry and HPV DNA ISH were positive in 79.0% and 62.4% of cases, respectively. Concordance between RNA and p16, DNA and p16, and RNA and DNA were 96.4%, 78.7%, and 83.5%, respectively. Only 7 cases (3.6%) were discrepant between RNA ISH and p16. In univariate analysis, all 3 tests correlated with better overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) (all P<0.001). In multivariate analysis, OS correlated significantly with RNA (hazard ratio=0.39, P=0.001), DNA (0.53, P=0.03), and p16 (0.30, P<0.001), but DSS and DFS correlated significantly only with p16 (DSS: 0.36, P=0.006; DFS: 0.42, P=0.016). RNA ISH is more sensitive than DNA ISH in detecting HPV in OSCC, and it correlates strongly with p16. Although both tests were comparable, p16 more strongly stratified patient outcomes.
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              Management of well-differentiated thyroid carcinoma presenting within a thyroglossal duct cyst.

              Well-differentiated thyroid carcinoma (WDTC) is diagnosed in approximately 1.5% of thyroglossal duct cysts (TGDC). No clear consensus exists regarding further management after adequate excision of the cyst, especially the role of total thyroidectomy and postoperative radioactive iodine therapy. The current review was undertaken in an attempt to clarify these issues.
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                Author and article information

                Contributors
                katabin@mskcc.org
                Journal
                Head Neck Pathol
                Head Neck Pathol
                Head and Neck Pathology
                Springer US (New York )
                1936-055X
                1936-0568
                28 February 2017
                March 2017
                : 11
                : 1
                : 48-54
                Affiliations
                [1 ] ISNI 0000 0001 2171 9952, GRID grid.51462.34, Department of Pathology, , Memorial Sloan Kettering Cancer Center, ; 1275 York Avenue, New York, NY 10065 USA
                [2 ] ISNI 0000 0004 1936 9916, GRID grid.412807.8, Department of Pathology, Microbiology, and Immunology, , Vanderbilt University Medical Center, ; Nashville, TN USA
                [3 ] ISNI 0000 0004 1936 9916, GRID grid.412807.8, Department of Otolaryngology, , Vanderbilt University Medical Center, ; Nashville, TN USA
                Article
                PMC5340737 PMC5340737 5340737 796
                10.1007/s12105-017-0796-z
                5340737
                28247228
                © Springer Science+Business Media New York 2017
                Categories
                Original Paper
                Custom metadata
                © Springer Science+Business Media New York 2017

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