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      Subcentimetric papillary thyroid carcinoma with extensive lymph node and brain metastasis: case report and review of literature

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          Abstract

          Summary

          We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case.

          Learning points
          • Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival.

          • PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome.

          • Brain metastasis although rare indicate aggressive phenotypic features.

          • Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.

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          Most cited references36

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          2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

          Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer.
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            Is Open Access

            Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

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              TERT promoter mutations in thyroid cancer.

              The 2013 discovery of Telomerase reverse transcriptase (TERT) promoter mutations chr5, 1,295,228 C>T (C228T) and 1,295,250 C>T (C250T) in thyroid cancer represents an important event in the thyroid cancer field and much progress has occurred since then. This article provides a comprehensive review of this exciting new thyroid cancer field. The oncogenic role of TERT promoter mutations involves their creation of consensus binding sites for E-twenty-six transcriptional factors. TERT C228T is far more common than TERT C250T and their collective prevalence is, on average, 0, 11.3, 17.1, 43.2 and 40.1% in benign thyroid tumors, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer, respectively, displaying an association with aggressive types of thyroid cancer. TERT promoter mutations are associated with aggressive thyroid tumor characteristics, tumor recurrence and patient mortality as well as BRAF V600E mutation. Coexisting BRAF V600E and TERT promoter mutations have a robust synergistic impact on the aggressiveness of PTC, including a sharply increased tumor recurrence and patient mortality, while either mutation alone has a modest impact. Thus, TERT with promoter mutations represents a prominent new oncogene in thyroid cancer and the mutations are promising new diagnostic and prognostic genetic markers for thyroid cancer, which, in combination with BRAF V600E mutation or other genetic markers (e.g. RAS mutations), are proving to be clinically useful for the management of thyroid cancer. Future studies will specifically define such clinical utilities, elucidate the biological mechanisms and explore the potential as therapeutic targets of TERT promoter mutations in thyroid cancer.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                18 December 2023
                01 October 2023
                : 2023
                : 4
                : 23-0025
                Affiliations
                [1 ]Centro Hospitalar Vila Nova de Gaia/Espinho , Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal
                [2 ]i3S - Instituto de Investigação e Inovação em Saúde , Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
                [3 ]IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto , Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
                [4 ]Faculdade de Medicina da Universidade do Porto , Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
                [5 ]Centro Hospitalar Universitário São João , Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
                [6 ]Instituto de Ciências Biomédicas de Abel Salazar , Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
                Author notes
                Correspondence should be addressed to A Amado; Email: carla.pires@ 123456chvng.min-saude.pt
                Author information
                http://orcid.org/0000-0003-3305-8201
                Article
                EDM230025
                10.1530/EDM-23-0025
                10762550
                38108305
                6809a6ae-9bf7-4f13-8385-8e0cc9ee81e5
                © the author(s)

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

                History
                : 22 February 2023
                : 27 October 2023
                Funding
                Funded by: BD, doi http://dx.doi.org/10.13039/100017412;
                Categories
                Geriatric
                Male
                White
                Portugal
                Thyroid
                Thyroid
                Genetics and Mutation
                Endocrine-Related Cancer
                Unique/Unexpected Symptoms or Presentations of a Disease
                Unique/Unexpected Symptoms or Presentations of a Disease

                geriatric,male,white,portugal,thyroid,genetics and mutation,endocrine-related cancer,unique/unexpected symptoms or presentations of a disease,december,2023

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