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      Low-invasive somatic oncogenes and lymph node metastasis in pediatric papillary thyroid cancer: implications for prophylactic central neck dissection

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          Abstract

          Objective

          The American Thyroid Association (ATA) Pediatric Guidelines recommend selective, prophylactic central neck dissection (pCND) for patients with papillary thyroid carcinoma (PTC) based on tumor focality, tumor size, and the surgeon’s experience. With the expansion of pre-surgical somatic oncogene testing and continued controversy over the benefits of pCND, oncogenic alteration data may provide an opportunity to stratify pCND. This study compared lymph node (LN) involvement in pediatric patients with PTC between tumors with low- and high-invasive-associated alterations to explore the potential utility of preoperative oncogenic alterations in the stratification of pCND.

          Methods

          This is retrospective cohort study of pediatric patients who underwent somatic oncogene testing post thyroidectomy for PTC between July 2003 and July 2022.

          Results

          Of 192 eligible PTC patients with postoperative somatic oncogene data, 19 tumors harbored somatic alterations associated with low-invasive disease (19/192, 10%), and 128 tumors harbored a BRAF V600E alteration (45/192, 23%) or an oncogenic fusion (83/192, 43%). Tumors with low-invasive alterations were less likely to present malignant preoperative cytology (2/18, 11%) than those with high-invasive alterations (97/124, 78%; P < 0.001). Twelve patients with low-invasive alterations had LNs dissected from the central neck (12/19, 63%) compared to 127 patients (127/128, 99%) with high-invasive alterations. LN metastasis was identified in two patients with low-invasive alterations (2/19, 11%) compared to 107 patients with high-invasive alterations (107/128, 84%; P < 0.001).

          Conclusion

          Pediatric patients with low-invasive somatic oncogenic alterations are at low risk for metastasis to central neck LNs. Our findings suggest that preoperative knowledge of somatic oncogene alterations provides objective data to stratify pediatric patients who may not benefit from pCND.

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          Most cited references42

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          Welcome to the Tidyverse

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            R: A Language and Environment for Statistical Computing

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              Integrated genomic characterization of papillary thyroid carcinoma.

              (2014)
              Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.

                Author and article information

                Journal
                Eur Thyroid J
                Eur Thyroid J
                ETJ
                European Thyroid Journal
                Bioscientifica Ltd (Bristol )
                2235-0640
                2235-0802
                02 August 2024
                10 July 2024
                01 August 2024
                : 13
                : 4
                : e230265
                Affiliations
                [1 ]Division of Endocrinology and Diabetes , The Thyroid Center, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
                [2 ]Department of Pathology and Laboratory Medicine , Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA
                [3 ]Department of Surgery , Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
                [4 ]Division of Oncology , Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
                [5 ]Division of Pediatric Otolaryngology , Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
                [6 ]Department of Otorhinolaryngology: Head and Neck Surgery , University of Pennsylvania, Philadelphia, Pennsylvania, USA
                Author notes
                Correspondence should be addressed to A J Bauer: bauera@ 123456chop.edu

                *(J A Baran and M Bojarsky contributed equally to this work)

                Author information
                http://orcid.org/0000-0003-0629-0160
                http://orcid.org/0000-0003-0863-7500
                http://orcid.org/0000-0002-3952-881X
                Article
                ETJ-23-0265
                10.1530/ETJ-23-0265
                11301529
                38984999
                2b91a3d1-0ca2-40bb-923a-78bdd0c882d1
                © the author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 13 December 2023
                : 09 July 2024
                Categories
                Research
                ETJ-pediatric-thyroid-diseases, Pediatric thyroid diseases
                Custom metadata
                ETJ-pediatric-thyroid-diseases

                pediatrics,somatic oncogenes,thyroid cancer
                pediatrics, somatic oncogenes, thyroid cancer

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