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Nix, P., A. Nicolaides, and A. P. Coatesworth. "Thyroid cancer review 2: management of differentiated thyroid cancers." International Journal of Clinical Practice 59, no. 12 (November 18, 2005): 1459–63. http://dx.doi.org/10.1111/j.1368-5031.2005.00672.x.
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Krause, Kerstin, Stefan Karger, Oliver Gimm, Sien-Yi Sheu, Henning Dralle, Andrea Tannapfel, Kurt Werner Schmid, Corinne Dupuy, and Dagmar Fuhrer. "Characterisation of DEHAL1 expression in thyroid pathologies." European Journal of Endocrinology 156, no. 3 (March 2007): 295–301. http://dx.doi.org/10.1530/eje-06-0596.
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Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide in the human thyroid. The aim of the present study was (I) to investigate whether DEHAL1 expression is different in differentially functioning thyroid pathologies and (II) to evaluate DEHAL1 as a possible marker of thyroid cell differentiation. Design and methods: Real-time PCR for DEHAL1 and its isoform DEHAL1B was performed in a series of 105 thyroid specimens, including toxic thyroid nodules (TTN), Graves’ disease (GD) thyroids, benign cold thyroid nodules (CTN), normal thyroid tissues and thyroid cancers (follicular thyroid carcinomas (FTC), papillary thyroid carcinomas (PTC), partially differentiated thyroid cancers (PDTC) and anaplastic thyroid carcinomas (ATC)). In addition, DEHAL1 protein expression was studied by immunohistochemistry in 163 benign and malignant thyroid pathologies and normal thyroids. Results: (I) The highest DEHAL1 mRNA levels were found in GD thyroids, while downregulation of DEHAL1 and DEHAL1B mRNA occurred in PTC and ATC (P<0.001 and <0.05 respectively); (II) DEHAL1 protein was overexpressed in TTNs and GD thyroids with predominant apical staining in all samples; (III) a weaker and patchy staining pattern was found in CTNs and normal thyroids; (IV) in differentiated thyroid cancers (FTC and PTC), a diffuse cytoplasmic DEHAL1 expression was found; and (V) in PDTC and ATC, DEHAL1 expression was faint or absent. Conclusion: Upregulation of DEHAL1 protein expression and sublocalisation of DEHAL1 at the apical cell pole in TTNs and GD thyroids is consistent with increased thyroid hormone turnover during thyrotoxicosis. Diffuse cytoplasmatic localisation or downregulation of DEHAL1 expression in thyroid cancers suggests alteration or loss of DEHAL1 function during thyroid cell dedifferentiation.
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Iftikhar, Haissan, Mubasher Ikram, Adnan Muhammad, and Karim Nathani. "Unusual Presentation of Differentiated Thyroid Cancer Metastasis." International Archives of Otorhinolaryngology 22, no. 02 (July 14, 2017): 167–70. http://dx.doi.org/10.1055/s-0037-1604038.
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Introduction The rates of thyroid cancers are on a rise, especially well-differentiated thyroid cancers. This could be partly due to newer diagnostic modalities, like high-resolution ultrasound, that can pick up smaller lesions. Differentiated thyroid cancers with distant metastases are not common, and even rarer is the initial presentation with complaints not related to the neck. Objectives The objective of this series was to study and report the unusual cases of patients with differentiated thyroid cancer with distant metastasis. There is a lack of data in the literature on these cases, and due to the rarity of such metastases, no definite treatment protocol has been defined. Methods A retrospective chart review of 1,200 cases of thyroid surgeries was performed. A total of 10 cases of well-differentiated thyroid cancer on the final histopathology exam that had initially presented with usual complaints to departments other than the Otolaryngology Department were identified. Results A total of 6 patients had papillary carcinoma, whereas 4 patients had follicular carcinoma on final the histopathology exam. Two patients presented with iliac crest lesions, 2 with vertebral lesions one each with parapharyngeal mass, supraclavicular mass, labia majora swelling and bleeding, lung, rib and neck of femur lesion. Conclusion There are still no specific guidelines on how to address these patients with differentiated thyroid cancer with distant metastasis (except for the cases of bone and lung lesions) and on which treatment should be offered in case of recurrence. More studies on the subject are required.
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Busaidy, Naifa Lamki, and Maria E. Cabanillas. "Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease." Journal of Thyroid Research 2012 (2012): 1–12. http://dx.doi.org/10.1155/2012/618985.
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Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on the management and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine.
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Hartl, Dana M., Joanne Guerlain, Ingrid Breuskin, Julien Hadoux, Eric Baudin, Abir Al Ghuzlan, Marie Terroir-Cassou-Mounat, Livia Lamartina, and Sophie Leboulleux. "Thyroid Lobectomy for Low to Intermediate Risk Differentiated Thyroid Cancer." Cancers 12, no. 11 (November 6, 2020): 3282. http://dx.doi.org/10.3390/cancers12113282.
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Many recent publications and guidelines have promoted a “more is less” approach in terms of treatment for low to intermediate risk differentiated thyroid cancer (DTC), which comprise the vast majority of thyroid cancers: less extensive surgery, less radioactive iodine, less or no thyroid hormone suppression, and less frequent or stringent follow-up. Following this approach, thyroid lobectomy has been proposed as a means of decreasing short- and long-term postoperative morbidity while maintaining an excellent prognosis for tumors meeting specific macroscopic and microscopic criteria. This article will examine the pros and cons of thyroid lobectomy for low to intermediate risk cancers and discuss, in detail, criteria for patient selection and oncological outcomes.
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Colevas, A. Dimitrios, and Manisha H. Shah. "Evaluation of Patients with Disseminated or Locoregionally Advanced Thyroid Cancer: A Primer for Medical Oncologists." American Society of Clinical Oncology Educational Book, no. 32 (June 2012): 384–88. http://dx.doi.org/10.14694/edbook_am.2012.32.30.
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Overview: Historically, patients with thyroid cancers are managed by endocrinologists, surgeons and radiation oncologists. Due to recent progress in this field with advances in treatment of thyroid cancer, medical oncologists are now commonly involved in care of patients with advanced thyroid cancers. In this manuscript, we describe general principles in management of patients with various types of thyroid cancers including differentiated, medullary and anaplastic thyroid cancers.
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Suteau, Valentine, Mathilde Munier, Claire Briet, and Patrice Rodien. "Sex Bias in Differentiated Thyroid Cancer." International Journal of Molecular Sciences 22, no. 23 (November 30, 2021): 12992. http://dx.doi.org/10.3390/ijms222312992.
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Differentiated thyroid cancers are more frequent in women than in men. These different frequencies may depend on differences in patient’s behavior and in thyroid investigations. However, an impact on sexual hormones is likely, although this has been insufficiently elucidated. Estrogens may increase the production of mutagenic molecules in the thyroid cell and favor the proliferation and invasion of tumoral cells by regulating both the thyrocyte enzymatic machinery and the inflammatory process associated with tumor growth. On the other hand, the worse prognosis of thyroid cancer associated with the male gender is poorly explained.
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Min, Seonyoung, and Hyunseok Kang. "What's New in Molecular Targeted Therapies for Thyroid Cancer?" Korean Society for Head and Neck Oncology 37, no. 2 (November 30, 2021): 1–9. http://dx.doi.org/10.21593/kjhno/2021.37.2.1.
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Thyroid cancer refers to various cancers arising from thyroid gland. Differentiated thyroid cancers (DTCs) include papillary, follicular, and Hurthle cell carcinomas and represent cancers retain normal thyroid functions such as iodine uptake. Radioactive iodine (RAI) is generally used for upfront treatment of metastatic DTCs, but RAI refractory DTCs remain to be clinical challenges. Sorafenib and lenvatinib were approved for the treatment of RAI refractory DTCs and more recently, genomics-based targeted therapies have been developed for NTRK and RET gene fusion-positive DTCs. Poorly differentiated and anaplastic thyroid cancers (ATCs) are extremely challenging diseases with aggressive courses. BRAF/MEK inhibition has been proven to be highly effective in BRAF V600E mutation-positive ATCs and immune checkpoint inhibitors have shown promising activities. Medullary thyroid cancers, which arise from parafollicular cells of thyroid, represent a unique subset of thyroid cancer and mainly driven by RET mutation. In addition to vandetanib and cabozantinib, highly specific RET inhibitors such as selpercatinib and pralsetinib have demonstrated impressive activity and are in clinical use.
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Park, Jong-Lyul, Seon-Kyu Kim, Sora Jeon, Chan-Kwon Jung, and Yong-Sung Kim. "MicroRNA Profile for Diagnostic and Prognostic Biomarkers in Thyroid Cancer." Cancers 13, no. 4 (February 5, 2021): 632. http://dx.doi.org/10.3390/cancers13040632.
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The challenge in managing thyroid nodules is to accurately diagnose the minority of those with malignancy. We aimed to identify diagnostic and prognostic miRNA markers for thyroid nodules. In a discovery cohort, we identified 20 candidate miRNAs to differentiate between noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and papillary thyroid carcinomas (PTC) by using the high-throughput small RNA sequencing method. We then selected three miRNAs (miR-136, miR-21, and miR-127) that were differentially expressed between the PTC follicular variant and other variants in The Cancer Genome Atlas data. High expression of three miRNAs differentiated thyroid cancer from nonmalignant tumors, with an area under curve (AUC) of 0.76–0.81 in an independent cohort. In patients with differentiated thyroid cancer, the high-level expression of the three miRNAs was an independent indicator for both distant metastases and recurrent or persistent disease. In patients with PTC, a high expression of miRNAs was associated with an aggressive histologic variant, extrathyroidal extension, distant metastasis, or recurrent or persistent disease. Three miRNAs may be used as diagnostic markers for differentiating thyroid cancers from benign tumors and tumors with extremely low malignant potential (NIFTP), as well as prognostic markers for predicting the risk of recurrent/persistent disease for differentiated thyroid cancer.
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Rao, Smitha S., and Sabaretnam Mayilvaganan. "Immuno-oncology of differentiated thyroid cancer." International Journal of Molecular & Immuno Oncology 6 (May 29, 2021): 72–75. http://dx.doi.org/10.25259/ijmio_36_2020.
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Thyroid cancer has become an epidemic due to easy availability of ultrasound of the neck, and in some countries, routine health checkup ultrasound of neck is routinely done and mandatory. Thyroid cancer detected incidentally and less than 1 cm may warrant only observation, whereas some cancers such as anaplastic thyroid cancer requires urgent intervention. Advances in the field of oncology have been revolutionized by the extensive study of tumor microenvironment (TME). The introduction of immune check point inhibitors resulted in a major shift in the understanding of differentiated thyroid cancer. Inflammation related to thyroid cancer involves various molecular patterns of cytokines and chemokines. They form the major targets for novel immunotherapies. Addition of discovery of newer tumor markers has significantly contributed to cancer management. Tumor immune escape is an important mechanism of oncogenesis. Innate immunity forms the major defense of the body to tumor cells. Polymorphonuclear leucocytes, macrophages, and lymphocytes form the defense that target tumor cells. The aim of this review is to comprehensively discuss the dynamic immune system, various oncogenic pathways and novel tumor antigens like cancer testis sperm associated antigen (SPAG9).
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Song, Eyun, Dong Eun Song, Jonghwa Ahn, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Min Ji Jeon, and Won Gu Kim. "Genetic profile of advanced thyroid cancers in relation to distant metastasis." Endocrine-Related Cancer 27, no. 5 (May 2020): 285–93. http://dx.doi.org/10.1530/erc-19-0452.
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Major clinical challenges exist with differentiated thyroid cancers with distant metastases or rare but aggressive types, such as poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas. The precise characterization of the mutational profile in these advanced thyroid cancers is crucial. Samples were collected from primary tumors and distant metastases of 64 patients with distant metastases from differentiated thyroid cancer, poorly differentiated thyroid carcinoma, or anaplastic thyroid carcinoma. Targeted next-generation sequencing was performed with 50 known thyroid-cancer-related genes. Of the 82 tissues, 63 were from primary tumors and 19 from distant metastases. The most prevalent mutation observed from the primary tumors was TERT promoter mutation (56%), followed by BRAF (41%) and RAS (24%) mutations. TP3 was altered by 11%. Mutations in histone methyltransferases, SWI/SNF subunit–related genes, and PI3K/AKT/mTOR pathway-related genes were present in 42%, 12%, and 22%, respectively. When the mutational status was analyzed in 15 matched pairs of thyroid tumors and their matched distant metastases and one pair of distant metastases with two distinct sites, the concordance was high. A similar frequency of mutations in TERT promoter (58%) and BRAF (42%) as well as histone methyltransferases (37%), SWI/SNF subunits (10%), and PI3K/AKT/mTOR pathway (26%) were noted. The same main, early and late mutations were practically always present in individual primary tumor–metastasis pairs. Enrichment of TERT promoter, BRAF, and RAS mutations were detected in highly advanced thyroid cancers with distant metastasis. The genetic profiles of primary thyroid tumors and their corresponding distant metastases showed a high concordance.
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Satapathy, Swayamjeet, and Chandrasekhar Bal. "Chapter 11: Pediatric Differentiated Thyroid Cancers." Journal of Head & Neck Physicians and Surgeons 12, Suppl 1 (January 2024): S58—S64. http://dx.doi.org/10.4103/jhnps.jhnps_13_24.
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ABSTRACT The document discusses pediatric differentiated thyroid cancer (DTC), focusing on papillary thyroid carcinoma (PTC), which is increasingly prevalent globally, including in India. Despite a more aggressive initial presentation in children, the long-term prognosis is generally positive. Key differences between pediatric and adult DTC are highlighted, such as a higher risk of malignancy in children with thyroid nodules and common RET/PTC gene rearrangements. There is a debate on the age cutoff for defining pediatric DTC, but the document suggests that 18 years is considered appropriate in the Indian context. Diagnostic methods, including ultrasonography-guided fine needle aspirate (FNA) and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), are emphasized. The importance of genomic analysis for indeterminate cytology is also proposed. Treatment approaches involve total thyroidectomy due to higher multifocality in children, with consideration of potential complications. Post-operative risk stratification, utilizing the TNM staging system, is seen as crucial and correlates with disease-free survival. Post-operative staging includes TSH-stimulated thyroglobulin (Tg) and anti-thyroglobulin antibody (ATg) levels, along with a diagnostic whole-body 131I scan to assess surgical completeness. Radioactive iodine therapy (RAI) is recommended for iodine-avid persistent/metastatic disease, with an empirical activity of 30 mCi for remnant ablation and adjustments based on age or weight. Regular follow-ups include monitoring TSH-suppressed Tg, Anti-Tg levels, and neck ultrasound. Dynamic risk stratification at 2 years refines risk based on treatment responses. Genetic considerations reveal prevalent RET fusion oncogene and less common BRAF mutations, which are associated with RAI refractoriness. In summary, the document provides a comprehensive understanding of pediatric DTC, emphasizing the need for tailored guidelines in the Indian context. It covers various aspects of diagnosis, surgery, and post-operative care, with a focus on age-appropriate management and ongoing research in this specialized field.
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Salehian, Behrouz, Zhong Liu, and Fouad Kandeel. "Genetic Alterations in Differentiated Thyroid Cancers." Endocrine, Metabolic & Immune Disorders - Drug Targets 9, no. 3 (September 1, 2009): 257–68. http://dx.doi.org/10.2174/187153009789044338.
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FIRAT, Sevde Nur, Işılay TAŞKALDIRAN, Şerife KUŞKONMAZ, and Cavit ÇULHA. "AST/ALT (De Ritis) Ratio in Early Stage Differentiated Thyroid Cancer." Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 8, no. 2 (May 31, 2022): 125–28. http://dx.doi.org/10.30934/kusbed.1009993.
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Objective: Differentiated thyroid cancers are the most common endocrine cancers and their frequency is increasing with the increase in imaging possibilities. In various malignancies; Even in the absence of liver metastases, it was determined that AST value increased compared to ALT due to increased metabolism, tissue damage and rapid tumor turnover. This rate is known as the De Ritis rate, and in our study, we planned to evaluate whether there is a relationship between histopathological subtype, multifocality, disease stage and risk group and AST/ALT (De Ritis) ratio in early stage thyroid cancers. Method: A total of 154 patients diagnosed with differentiated thyroid cancer in our clinic between 2016 and 2019 were included in the study. The AST/ALT ratios of the patients in the preoperative period were recorded. Tumor staging of each patient was performed according to the American Joint Cancer Committee (AJCC) 8 by evaluating the postoperative pathology reports. The correlation between the patients' preoperative De Ritis rates and postoperative staging was evaluated. Results: In our study, the mean De Ritis value of the patients was found to be 1.18. The rate of patients with De Ritis rate ≥1.5 was 15.9%. There was no statistically significant difference between preoperative De Ritis rate and histopathological subtype, vascular invasion, capsule invasion, tumor diameter, lymph node involvement and tumor stage. Conclusion: In our study it was found that preoperative De Ritis ratio was not associated with disease stage and risk status in early stage differentiated thyroid cancers. Additional studies are needed for its importance in advanced differentiated thyroid cancers.
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Boudina, Maria, Eleana Zisimopoulou, Persefoni Xirou, and Alexandra Chrisoulidou. "Aggressive Types of Malignant Thyroid Neoplasms." Journal of Clinical Medicine 13, no. 20 (October 14, 2024): 6119. http://dx.doi.org/10.3390/jcm13206119.
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Differentiated thyroid cancer (DTC) includes many subtypes, which demonstrate favorable to aggressive behavior. During the past decades, efforts have been made to describe aggressive thyroid cancers. Within DTC, aggressive variants constitute rare entities with unique histopathological features and compromised survival, as local and distant metastatic disease is frequent. In recent years, the distinct category of poorly differentiated thyroid cancer was introduced in 2004 and the type of differentiated high-grade thyroid carcinoma was recently added in the 2022 WHO classification of thyroid neoplasms. Finally, anaplastic thyroid cancer exhibits a rapid, resistant to therapy, progression and confers the shortest survival. In this review, we will present the characteristics of these thyroid cancer types and also discuss the treatment, management, and follow-up of these difficult cases. Emphasis was given to recent bibliography of the last decade.
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Moon, Jung-Eun, So Won Oh, Ho-Cheol Kang, Bon Seok Koo, Keunyoung Kim, Sun Wook Kim, Won Woong Kim, et al. "Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part V. Pediatric Differentiated Thyroid Cancer 2024." International Journal of Thyroidology 17, no. 1 (May 30, 2024): 193–207. http://dx.doi.org/10.11106/ijt.2024.17.1.193.
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Rusinek, Dagmara, Sylwia Szpak-Ulczok, and Barbara Jarzab. "Gene expression profile of human thyroid cancer in relation to its mutational status." Journal of Molecular Endocrinology 47, no. 3 (July 28, 2011): R91—R103. http://dx.doi.org/10.1530/jme-11-0023.
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This review describes the gene expression profile changes associated with the presence of different mutations that contribute to thyroid cell carcinogenesis. The results are discussed in the context of thyroid cancer biology and of the implications for disease prognosis, while the diagnostic aspect has been omitted. For papillary thyroid cancer (PTC), the most characteristic gene expression profile is associated with the presence ofBRAFmutation. BRAF-associated PTC differ profoundly from RET/PTC or RAS-associated cancers. Simultaneously, they retain many characteristic gene expression features common for all PTCs, induced by the alternative mutations activating MAPK pathway. Although the difference between papillary and follicular thyroid cancer (FTC) is significant at the gene expression profile level, surprisingly, the RAS-related signature of FTC is not well specified.PAX8/peroxisome proliferator-activated receptor γ (PPARγ) rearrangements, which occur in FTC as an alternative to theRASmutation, are associated with specific changes in gene expression. Furthermore, the difference between well-differentiated thyroid cancers and poorly differentiated and anaplastic thyroid cancers is mainly a reflection of tumor degree of differentiation and may not be attributed to the presence of characteristic mutations.
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Ahmadieh, Hala, and Sami T. Azar. "Controversies in the Management and Followup of Differentiated Thyroid Cancer: Beyond the Guidelines." Journal of Thyroid Research 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/512401.
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Thyroid cancer is among the most common endocrine malignancies. Genetic and environmental factors play an important role in the pathogenesis of differentiated thyroid cancer. Both have good prognosis but with frequent recurrences. Cancer staging is an essential prognostic part of cancer management. There are multiple controversies in the management and followup of differentiated thyroid cancer. Debate still exists with regard to the optimal surgical approach but trends toward a more conservative approach, such as lobectomy, are being more favored, especially in papillary thyroid cancer, of tumor sizes less than 4 cm, in the absence of other high-risk suggestive features. Survival of patients with well-differentiated thyroid cancer was adversely affected by lymph node metastases. Prophylactic central LN dissection did improve accuracy in staging and decrease postop TG level, but it had no effect on small-sized tumors. Conservative approach was more applied with regard to the need and dose of radioiodine given postoperatively. There have been several advancements in the management of radioiodine resistant advanced differentiated thyroid cancers. Appropriate followup is required based on risk stratification of patients postoperatively. Many studies are still ongoing in order to reach the optimal management and followup of differentiated thyroid cancer.
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Mills, Jonathan, and William Dalleywater. "Thyroid cancer." InnovAiT: Education and inspiration for general practice 11, no. 4 (March 1, 2018): 212–17. http://dx.doi.org/10.1177/1755738017752742.
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Thyroid neoplasms represent the most-common endocrine tumour and constitute an extremely varied spectrum of disease. At the most severe end, they may have a very poor prognosis. Malignant thyroid tumours constitute around 1% of cancers and cancer-specific deaths in the UK, with just under 3000 new diagnoses each year and around 350 deaths annually in the UK alone. Although the incidence has doubled over the last 20 years, the mortality rate among men has not changed, although survival rates have improved in women. Thyroid cancer originates from follicular or parafollicular thyroid cells that can give rise to cancer that is well-differentiated to poorly differentiated. Most tumours retain endocrine differentiation, however, and may cause problematic symptoms from aberrant hormone levels.
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Hilhorst, Riet, Adrienne van den Berg, Piet Boender, Tom van Wezel, Tim Kievits, Rik de Wijn, Rob Ruijtenbeek, Willem E. Corver, and Hans Morreau. "Differentiating Benign from Malignant Thyroid Tumors by Kinase Activity Profiling and Dabrafenib BRAF V600E Targeting." Cancers 15, no. 18 (September 8, 2023): 4477. http://dx.doi.org/10.3390/cancers15184477.
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Differentiated non-medullary thyroid cancer (NMTC) can be effectively treated by surgery followed by radioactive iodide therapy. However, a small subset of patients shows recurrence due to a loss of iodide transport, a phenotype frequently associated with BRAF V600E mutations. In theory, this should enable the use of existing targeted therapies specifically designed for BRAF V600E mutations. However, in practice, generic or specific drugs aimed at molecular targets identified by next generation sequencing (NGS) are not always beneficial. Detailed kinase profiling may provide additional information to help improve therapy success rates. In this study, we therefore investigated whether serine/threonine kinase (STK) activity profiling can accurately classify benign thyroid lesions and NMTC. We also determined whether dabrafenib (BRAF V600E-specific inhibitor), as well as sorafenib and regorafenib (RAF inhibitors), can differentiate BRAF V600E from non-BRAF V600E thyroid tumors. Using 21 benign and 34 malignant frozen thyroid tumor samples, we analyzed serine/threonine kinase activity using PamChip®peptide microarrays. An STK kinase activity classifier successfully differentiated malignant (26/34; 76%) from benign tumors (16/21; 76%). Of the kinases analyzed, PKC (theta) and PKD1 in particular, showed differential activity in benign and malignant tumors, while oncocytic neoplasia or Graves’ disease contributed to erroneous classifications. Ex vivo BRAF V600E-specific dabrafenib kinase inhibition identified 6/92 analyzed peptides, capable of differentiating BRAF V600E-mutant from non-BRAF V600E papillary thyroid cancers (PTCs), an effect not seen with the generic inhibitors sorafenib and regorafenib. In conclusion, STK activity profiling differentiates benign from malignant thyroid tumors and generates unbiased hypotheses regarding differentially active kinases. This approach can serve as a model to select novel kinase inhibitors based on tissue analysis of recurrent thyroid and other cancers.
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Singh, Amandeep, Jeehoon Ham, Joseph William Po, Navin Niles, Tara Roberts, and Cheok Soon Lee. "The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy." Cells 10, no. 5 (May 1, 2021): 1082. http://dx.doi.org/10.3390/cells10051082.
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Thyroid cancer is the most prevalent endocrine malignancy that comprises mostly indolent differentiated cancers (DTCs) and less frequently aggressive poorly differentiated (PDTC) or anaplastic cancers (ATCs) with high mortality. Utilisation of next-generation sequencing (NGS) and advanced sequencing data analysis can aid in understanding the multi-step progression model in the development of thyroid cancers and their metastatic potential at a molecular level, promoting a targeted approach to further research and development of targeted treatment options including immunotherapy, especially for the aggressive variants. Tumour initiation and progression in thyroid cancer occurs through constitutional activation of the mitogen-activated protein kinase (MAPK) pathway through mutations in BRAF, RAS, mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and/or receptor tyrosine kinase fusions/translocations, and other genetic aberrations acquired in a stepwise manner. This review provides a summary of the recent genetic aberrations implicated in the development and progression of thyroid cancer and implications for immunotherapy.
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Puttergill, B., S. Khan, I. Christakis, R. Dumbill, A. Mclaren, G. Sadler, and R. Mihai. "Thyroid lobectomy for low-risk thyroid cancers." Annals of The Royal College of Surgeons of England 104, no. 2 (February 2022): 113–16. http://dx.doi.org/10.1308/rcsann.2021.0058.
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Background The 2016 American Thyroid Association (ATA) guidelines proposed thyroid lobectomy for low-risk differentiated thyroid cancer (DTC); however, this approach is yet to be widely adopted. The aim of the study was to review our practice over three years following the publication of these guidelines identifying patients who underwent lobectomy-only for low-risk DTC in two regional units in the same multidisciplinary team (MDT). Method A retrospective review of patients who were operated between January 2016 and December 2018 was carried out. Results In total, 288 patients undergoing thyroid surgery were included. The preoperative distribution of cytology was: Thy 1 or 2 in 46, THY3a in 57, THY3f in 154, THY4 in 18 and THY5 in 13 patients. Median size of nodules was 26mm (range 1–70mm). DTC was diagnosed in 95 patients (33%). Overall, 39% (n = 37) of patients underwent completion thyroidectomy according to ATA recommendations on size or adverse histological features. The only variable associated with likelihood of completion was tumour size (p < 0.05, OR 1.14). Ten patients were discharged following surgery with no further follow-up as they had T1a/b well-differentiated DTC with no high-risk histological features. Conclusion Lobectomy-only appears to be the current surgical practice in two-thirds of patients presenting to our regional units with differentiated thyroid carcinoma. In the context of the current drive to reduce the extent of treatment for low-risk thyroid cancer, there is a need for a more homogeneous approach to these patients and for protocols for long-term follow-up after lobectomy-only.
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Iñiguez-Ariza, Nicole M., Sina Jasim, Mabel M. Ryder, Ashish V. Chintakuntlawar, John C. Morris, Crystal R. Hilger, Michael E. Menefee, et al. "Foundation One Genomic Interrogation of Thyroid Cancers in Patients With Metastatic Disease Requiring Systemic Therapy." Journal of Clinical Endocrinology & Metabolism 105, no. 7 (May 18, 2020): e2346-e2357. http://dx.doi.org/10.1210/clinem/dgaa246.
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Abstract Context Clinical applications of genomic assessment of thyroid cancers are rapidly evolving. Objectives, Design, and Setting We studied tumor samples from patients with imminently threatening and rare thyroid cancers to identify genomic alterations that might correlate with outcomes and/or be productively therapeutically targetable. Patient Context Progressive and metastatic, and/or rare, thyroid cancers were studied, 2012 to 2016, at Mayo Clinic sites. Intervention The intervention was Foundation One tumor interrogation. Main Outcome Measures Main outcome measures included genomic alterations, patient characteristics, and overall survival. Results Samples from 55 patients were evaluated: 20 anaplastic thyroid cancers (ATCs) (36%), 25 radioactive iodine–refractory differentiated thyroid cancers (DTCs)/poorly differentiated thyroid cancers (PDTCs) (45%; 14 papillary thyroid cancer [PTCs], 6 PDTCs, 5 Hürthle cell cancers), 8 medullary thyroid cancers (MTCs) (15%), and 2 others (a spindle epithelial tumor with thymus-like differentiation, and a primary thyroid sarcoma). Overall, 72% of DTCs, 79% of ATCs, and 75% of MTCs were deemed to have potentially productively targetable alterations. The most commonly encountered mutation was of TERT promoter (56% of DTCs, 68% of ATCs)—but this is not presently targetable. Targetable BRAFV600E mutations were found in 40% of DTCs/PDTCs (83% of PTCs) and 32% of ATCs; of MTCs, 75% had targetable RET mutations, and 25% HRAS mutations. Of patient tumors with nonmutated BRAFV600E, 53% of DTC/PDTCs and 69% of ATCs had other potentially productively targetable mutations. Genomic alterations in our series of poor prognosis metastatic DTC/PDTCs also closely resembled those seen in ATC. Conclusions Whereas genomic interrogation of favorable prognosis thyroid cancer seems ill advised, potentially productively targetable mutations were demonstrated in the majority of tumors from patients with metastatic thyroid cancers requiring systemic therapy, suggesting a rationale for the selective application of this technology.
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Weng, Xun, YangYang, and Yujiao Cai. "Clinical Significance of Circulating Tumor Cells (CTCs) and Survivin on Predicting Prognosis in Thyroid Cancer Patients." Disease Markers 2022 (January 31, 2022): 1–8. http://dx.doi.org/10.1155/2022/5188006.
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Background. Clinical significance of circulating tumor cell (CTC) count, mesenchymal CTCs (MCTCs), and survivin in patients with thyroid cancer remains unclear. We evaluated the relationship between the expression of different CTC subtypes or survivin and the prognosis in patients with thyroid cancer. Patients and Methods. This study enrolled 164 patients with thyroid cancer who were diagnosed from January 2013 to September 2020 in our hospital. Among these patients, there were 73 cases with papillary thyroid cancer (PTC), 60 cases with follicular thyroid cancer (FTC), 12 medullary thyroid cancers (MTC), 10 poorly differentiated thyroid cancers (PDTC), 9 anaplastic thyroid cancers, and 10 control patients with nonmalignant thyroid nodules based on their histopathological characteristics. Only 5 milliliters (mL) of peripheral blood from the patients with thyroid cancer and control was used to detect the CTC cell number via CanPatrol capture technique before treatments. We also isolated mononuclear cells (MNC) from the peripheral blood and performed quantity reverse transcriptase polymerase chain reaction (qPCR) for survivin gene expression among these patients. Results. The overall positive rates of CTC at diagnosis were 56.1%. The relapse and metastasis rates in PTC and FTC patients with more than 6 CTCs and positive MCTCs were significantly higher than those in the patients with 6 or less than 6 CTCs and MCTCs. It was also found that these patients with >6 CTCs and MCTCs had shorter progression-free survival (PFS). Additionally, the survivin level of the patients with thyroid cancer was strongly relative to differentiation grades of thyroid cancers. Conclusions. The detection of more than six of total CTCs and positive MCTCs in the patients with differentiated thyroid cancer is an excellent biomarker for predicting the prognosis of patients. Survivin also is a good biomarker for thyroid cancer differentiation.
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Perveen, Rahima, Jasmin Ferdous, Sharmin Quddus, and Tapati Mandal. "Solitary Liver Metastasis from Follicular Variant Papillary Thyroid Carcinoma: A Case Report." Bangladesh Journal of Nuclear Medicine 22, no. 2 (February 1, 2021): 146–49. http://dx.doi.org/10.3329/bjnm.v22i2.51768.
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Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Sites of metastases from follicular thyroid cancer (FTC) are usually osseous, and those from papillary thyroid cancer (PTC) metastasize to regional nodal basins and the lungs. Visceral metastases are rare, but the involvement of multiple sites has been reported so far. Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare.We present the case of a patient with follicular variant of papillary thyroid carcinoma (FVPTC) unusually involving the liver.
Bangladesh J. Nuclear Med. 22(2): 146-149, Jul 2019
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Shin, Dong Yeob, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Young Shin Song, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, and Won Gu Kim. "Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 4. Systemic Therapy for Progressive Radioiodine-Refractory Differentiated Thyroid Cancer 2024." International Journal of Thyroidology 17, no. 1 (May 30, 2024): 168–81. http://dx.doi.org/10.11106/ijt.2024.17.1.168.
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Métayé, Thierry, Pierre Levillain, Jean-Louis Kraimps, and Rémy Perdrisot. "Immunohistochemical detection, regulation and antiproliferative function of G-protein-coupled receptor kinase 2 in thyroid carcinomas." Journal of Endocrinology 198, no. 1 (April 23, 2008): 101–10. http://dx.doi.org/10.1677/joe-07-0562.
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TSH, via its G-protein-coupled receptor, activates cell growth of both benign and malignant thyroid tumors. G-protein-coupled receptors (GR) kinase 2 (GRK2) has been reported to regulate the TSH receptor but its role in cancer is unknown. To determine a possible function for GRK2 in the growth process of thyroid cancers, we analysed its expression in normal and tumoral thyroid tissues and studied thyroid cancer cell line proliferation after GRK2 overexpression. Thirty one thyroid tissues, including 16 non-medullary thyroid cancers and 15 adjacent normal tissues, were analysed by immunohistochemistry. Five paired tissues were also studied by western blotting for the GRK2 enzymatic activity. Immunohistochemical staining showed an increase in GRK2 in thyroid cancers including papillary, follicular, and anaplastic types, compared with their adjacent normal tissues. Immunoblot analysis and GRK2 enzymatic activity measurement confirmed immunohistochemical study. TSH and TSH in association with insulin or IGF-I stimulated GRK2 protein accumulation in normal human thyroid cells in primary culture. The TSH effect on the GRK2 expression was mimicked by forskolin. After GRK2 overexpression in two poorly differentiated thyroid cell lines, all the clones showed a significant reduction in cell proliferation, ranging from 28 to 65% inhibition compared with vector alone after 96-h culture. In conclusion, thyroid mitogenic factor-stimulated GRK2 accumulation may explain, in part, high GRK2 levels in differentiated carcinoma, because TSH, insulin, or IGF-I is known to be involved in the thyroid cancer progression. Surprisingly, instead of stimulating, GRK2 reduced cell proliferation revealing a new role for this kinase in the growth of thyroid cancers.
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Boucai, Laura, Mark Zafereo, and Maria E. Cabanillas. "Thyroid Cancer." JAMA 331, no. 5 (February 6, 2024): 425. http://dx.doi.org/10.1001/jama.2023.26348.
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ImportanceApproximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer.ObservationsPapillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma.ConclusionsApproximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival in patients at high risk of recurrence. Antiangiogenic multikinase inhibitors and targeted therapies to genetic mutations that give rise to thyroid cancer are increasingly used in the treatment of metastatic disease.
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Woyach, Jennifer A., and Manisha H. Shah. "New therapeutic advances in the management of progressive thyroid cancer." Endocrine-Related Cancer 16, no. 3 (September 2009): 715–31. http://dx.doi.org/10.1677/erc-08-0335.
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The spectrum of thyroid cancers ranges from one of the most indolent to one of the most aggressive solid tumors identified. Conventional therapies for thyroid cancers are based on the histologic type of thyroid cancers such as papillary or follicular thyroid cancer (differentiated thyroid cancer (DTC)), medullary thyroid cancer (MTC), or anaplastic thyroid cancer (ATC). While surgery is one of the key treatments for all such types of thyroid cancers, additional therapies vary. Effective targeted therapy for DTC is a decades-old practice with systemic therapies of thyroid stimulating hormone suppression and radioactive iodine therapy. However, for the iodine-refractory DTC, MTC, and ATC there is no effective systemic standard of care treatment. Recent advances in understanding pathogenesis of DTC and development of molecular targeted therapy have dramatically transformed the field of clinical research in thyroid cancer. Over the last five years, incredible progress has been made and phases I–III clinical trials have been conducted in various types of thyroid cancers with some remarkable results that has made an impact on lives of patients with thyroid cancer. Such history-making events have boosted enthusiasm and interest among researchers, clinicians, patients, and sponsors and we anticipate ongoing efforts to develop more effective and safe therapies for thyroid cancer.
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Tung, William S., Douglas W. Shevlin, Detlef Bartsch, Jeffrey A. Norton, Samuel A. Wells, and Paul J. Goodfellow. "InfrequentCDKN2 mutation in human differentiated thyroid cancers." Molecular Carcinogenesis 15, no. 1 (January 1996): 5–10. http://dx.doi.org/10.1002/(sici)1098-2744(199601)15:1<5::aid-mc2>3.0.co;2-k.
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Santiago Carrion, Ada Marie, and Yanerys Agosto-Vargas. "Concurrent Papillary and Follicular Thyroid Cancer Presenting as Shoulder Pain." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A888. http://dx.doi.org/10.1210/jendso/bvab048.1812.
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Abstract Differentiated thyroid cancer arises from thyroid follicular epithelial cells. It accounts for more than 90% of thyroid cancers. In areas of sufficient iodine nutrition, about 85% of differentiated thyroid cancers are papillary, 10% are follicular and 3% are Hurthle cell carcinomas. The coexistence of different types of thyroid cancer in a single patient is a rare condition. This is the case of a 56 year-old man with medical history of arterial hypertension who presented to clinics with right shoulder pain. Imaging of the right shoulder showed a osteolytic lesion involving the right humerus with associated cortical disruption consistent with pathological fracture secondary to metastatic disease. Bone biopsy showed papillary thyroid carcinoma. Subsequently, ultrasound-guided fine needle aspiration biopsy to a right lobe nodule was performed, which confirmed the presence of papillary thyroid carcinoma. There was also evidence of cervical lymph node involvement. Patient proceeded to total thyroidectomy with neck dissection, and surgical pathology revealed the presence of 2.5 cm right lobe papillary carcinoma and 1.5 cm left lobe follicular carcinoma. Postoperatively, he was found with persistent elevated thyroid-stimulating hormone (TSH) and elevated quantitative thyroglobulin with elevated thyroglobulin antibodies. Patient received therapeutic radioiodine (I-131) for ablation of thyroid cancer. Whole body iodine scan demonstrated residual functioning thyroid tissue within post-thyroidectomy bed, with or without residual carcinoma, and large expansile uptake lesion involving the right humeral head and neck. Therefore, patient will receive a second dose of radioactive iodine. He has been started on thyroid hormone replacement with a goal of TSH <0.1 uIU/mL for high risk American Thyroid Association (ATA) stratification, and has remained clinically euthyroid. Thyroid carcinoma is the most common endocrine malignancy and one of the most rapidly increasing cancers in the United States. This increase in incidence is largely due to incidental detection on diagnostic imaging. Here we present an uncommon case of two distinct thyroid malignancies occurring simultaneously in a patient presenting with a pathological fracture. Synchronous occurrence of two types of differentiated thyroid cancer is a rare event, and has only been reported in case series. Bone metastasis from differentiated thyroid cancer can occur in 2-13% of patients. Despite the therapy for papillary thyroid carcinoma and follicular thyroid carcinoma remain the same, proper identification will lead to prompt therapy and increased survival. Physicians should be aware of this variety.
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Montero-Conde, Cristina, Luis J. Leandro-Garcia, Xu Chen, Gisele Oler, Sergio Ruiz-Llorente, Mabel Ryder, Iñigo Landa, et al. "Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene." Proceedings of the National Academy of Sciences 114, no. 25 (June 5, 2017): E4951—E4960. http://dx.doi.org/10.1073/pnas.1702723114.
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Oncogenic RAS mutations are present in 15–30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with HrasG12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-HrasG12V mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7, a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene.
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Vaidya, Abhishek, and Madan Kapre. "Chapter 4: Surgery for Locally Advanced Thyroid Cancers." Journal of Head & Neck Physicians and Surgeons 12, Suppl 1 (January 2024): S16—S21. http://dx.doi.org/10.4103/jhnps.jhnps_6_24.
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ABSTRACT A small proportion of Differentiated Thyroid Cancers (DTCs) may present with gross tumor extension outside the thyroid, these constitute the locally advanced thyroid cancers. They often carry worse prognosis in terms of local recurrence and disease free survival. The surgical management of these locally advanced thyroid cancers may be challenging. This narrative review provides an overview of the management strategy of such thyroid cancers.
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Cho, Yoon Young, Cho Rok Lee, Ho-Cheol Kang, Bon Seok Koo, Hyungju Kwon, Sun Wook Kim, Won Woong Kim, et al. "Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 2. Surgical Management of Thyroid Cancer 2024." International Journal of Thyroidology 17, no. 1 (May 30, 2024): 30–52. http://dx.doi.org/10.11106/ijt.2024.17.1.30.
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Nikitski, Alyaksandr V., Marina N. Nikiforova, Linwah Yip, Esra Karslioglu-French, Sally E. Carty, and Yuri E. Nikiforov. "Can TP53-mutant follicular adenoma be a precursor of anaplastic thyroid carcinoma?" Endocrine-Related Cancer 28, no. 9 (September 1, 2021): 621–30. http://dx.doi.org/10.1530/erc-21-0095.
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Mutations of the TP53 tumor suppressor gene are highly prevalent in thyroid anaplastic carcinomas (AC) but are also reported in some well-differentiated cancers and even in benign adenomas. The natural history of TP53-mutant adenomas and whether they may represent a precursor for well-differentiated cancer or AC is largely unknown. Similarly, the frequency of TP53 mutations in thyroid nodules found on routine molecular analysis of fine-needle aspiration (FNA) samples is not established. A database on 44,510 FNA samples from thyroid nodules with predominantly indeterminate cytology tested using ThyroSeq v3 was reviewed to identify TP53-mutant cases and analyze their genetic profile and available clinicopathological findings. Among 260 (0.6%) selected thyroid nodules, 36 had an isolated TP53 mutation and 224 carried a combination of TP53 with other genetic alterations. No significant difference was observed between these groups with respect to patient age, gender, nodule size, and spectrum of TP53 mutations. Histopathologically, 86% of the resected nodules with isolated TP53 mutations were benign (mostly adenomas), whereas 82% of nodules carrying TP53 mutations co-occurring with other alterations were cancers (P = 0.001), including de-differentiated AC. TP53-mutant benign tumors and well-differentiated cancers often had scattered single neoplastic cells with bizarre nuclei resembling those comprising AC. Our study demonstrates that a small but distinct proportion of thyroid nodules carry a TP53 mutation, either as a single genetic event or in combination with other alterations. While the latter is mostly cancers prone to dedifferentiation, there is at least a theoretical possibility that TP53-mutated adenomas may represent a precursor for such cancers, including AC.
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Mishra, Ayush, Vijay Singh, Yogita Khandelwal, Aswath Manikantan Smitha, David Jaya Prakash Kavali, and Sukanta Barai. "Incidentally Detected Metachronous Malignancy in Patients of Papillary Carcinoma of Thyroid Posthigh-Dose Radioiodine Therapy." Indian Journal of Nuclear Medicine 38, no. 3 (2023): 264–69. http://dx.doi.org/10.4103/ijnm.ijnm_188_22.
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Thyroid cancer is one of the most common endocrine cancers. The most common histological subtypes are papillary and follicular variants; these are “differentiated thyroid cancers” and are associated with an excellent prognosis. The exact mechanism of thyroid cancer is not known. Several genetic alterations and environmental factors are found to be associated with this cancer. Patients with differentiated thyroid cancer are treated with postoperative radioactive iodine (RAI) therapy to ablate residual thyroid tissue and metastatic micro-foci. It is thought that after RAI, there is an increased risk of secondary malignancies such as lung, renal, and stomach cancer and lymphomas. However, the risk of secondary malignancy is not clear. They may be associated with genetic syndromes, environmental factors, and radiation exposure. The secondary malignancy may be detected incidentally during follow-up or present with signs and symptoms of that malignancy. There is no direct association between second malignancy and radiation exposure in I-131 therapies. We present a case series of five patients treated with high doses of I-131 for the remnant. The patients developed metachronous malignancies later in life.
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Wiseman, S. M., H. Masoudi, P. Niblock, D. Turbin, A. Rajput, J. Hay, D. Filipenko, A. Melck, B. Gilks, and D. Huntsman. "Derangement of p53 and MDM2 is involved in transformation of differentiated into anaplastic thyroid cancer." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 5556. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.5556.
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5556 Background: Anaplastic thyroid cancer arises as a consequence of tumor progression, or transformation, from pre-existing differentiated thyroid cancer. Mutation of the p53 tumor-suppressor gene represents a common event in thyroid tumor progression. MDM2 encodes a protein that complexes with p53, downregulates its function, and leads to its degradation via a ubiquitin-proteasome pathway. The objective of this study was to evaluate the change in p53 and MDM2 expression in the transformation of differentiated to anaplastic thyroid carcinoma. Methods: Of 94 cases of anaplastic thyroid cancer diagnosed and treated in British Columbia Canada over a 20 year period (1984–2004) 32 cases (34%) had adequate tissue available for evaluation and 12 of these cases had associated foci of differentiated thyroid carcinoma. A tissue microarray was constructed from these 12 anaplastic thyroid tumors and their associated differentiated foci. Immunohistochemistry was utilized to evaluate expression of p53 and MDM2 by these tumors. Results: There was decreased expression of p53 and MDM2 by the anaplastic tumors when compared to the differentiated thyroid tumors from which they evolved. The expression of p53 and MDM2 was 17% and 8%, respectively, by the differentiated thyroid carcinoma, and 83% and 25%, respectively, by the anaplastic tumors. Evaluating the anaplastic cancers and the differentiated foci from which they evolved, p53 overexpression developed in 8 (67%) of tumors and MDM2 overexpression developed in 3 (25%) of tumors. All the anaplastic tumors that developed MDM2 overexpression also concurrently developed p53 overexpression. Conclusions: This report is the first to demonstrate derangement of p53, and its regulator, MDM2, is involved in the transformation of a subset of differentiated into anaplastic thyroid tumors. Isolated MDM2 overexpression does not appear to play an important role in anaplastic transformation of thyroid cancer. No significant financial relationships to disclose.
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Ni, Ying, Spencer Seballos, Shireen Ganapathi, Danielle Gurin, Benjamin Fletcher, Joanne Ngeow, Rebecca Nagy, et al. "Germline and somatic SDHx alterations in apparently sporadic differentiated thyroid cancer." Endocrine-Related Cancer 22, no. 2 (January 5, 2015): 121–30. http://dx.doi.org/10.1530/erc-14-0537.
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Along with breast and endometrial cancers, thyroid cancer is a major component cancer in Cowden syndrome (CS). Germline variants in SDHB/C/D (SDHx) genes account for subsets of CS/CS-like cases, conferring a higher risk of breast and thyroid cancers over those with only germline PTEN mutations. To investigate whether SDHx alterations at both germline and somatic levels occur in apparently sporadic breast cancer and differentiated thyroid cancer (DTC), we analyzed SDHx genes in the following four groups: i) 48 individuals with sporadic invasive breast adenocarcinoma for germline mutation; ii) 48 (expanded to 241) DTC for germline mutation; iii) 37 pairs DTC tumor-normal tissues for germline and somatic mutation and mRNA expression levels; and iv) data from 476 patients in the Cancer Genome Atlas thyroid carcinoma dataset for validation. No germline SDHx variant was found in a pilot series of 48 breast cancer cases. As germline SDHx variants were found in our pilot of 48 thyroid cancer cases, we expanded to three series of DTC comprising a total 754 cases, and found 48 (6%) with germline SDHx variants (P<0.001 compared with 0/350 controls). In 513 tumors, we found 27 (5%) with large somatic duplications within chromosome 1 encompassing SDHC. Both papillary and follicular thyroid tumors showed consistent loss of SDHC/D gene expression (P<0.001), which is associated with earlier disease onset and higher pathological-TNM stage. Therefore, we conclude that both germline and somatic SDHx mutations/variants occur in sporadic DTC but are very rare in sporadic breast cancer, and overall loss of SDHx gene expression is a signature of DTC.
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Mazzaferri, Ernest L. "Thyroid Cancer - Changing Patterns of Diagnosis and Treatment." US Endocrinology 00, no. 01 (2005): 62. http://dx.doi.org/10.17925/use.2005.00.01.62.
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Thyroid cancer is the most common endocrine malignancy. It comprises several distinct tumor types; including papillary thyroid cancer (PTC); follicular thyroid cancer (FTC); and Hürthle cell thyroid cancer (HTC), which are tumors of the thyroid follicular cell derived from the embryonic foregut. They ordinarily concentrate iodine and sometimes synthesize and secrete thyroid hormone, and for this reason are collectively referred to as differentiated thyroid cancer (DTC). The three tumor types represent 80%, 11%, and 3% of all thyroid cancers, respectively, and have 10-year mortality rates of approximately 7%, 15%, and 25%, respectively.1
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Lee, Eun Kyung. "Systemic therapy for differentiated thyroid cancer with distant metastasis." Journal of the Korean Medical Association 67, no. 7 (July 10, 2024): 484–91. http://dx.doi.org/10.5124/jkma.2024.67.7.484.
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Background: Thyroid cancer is a slow-growing tumor with excellent oncological outcomes. However, few patients with unexpectedly severe outcomes are usually ignored.Current Concepts: Radioactive iodine therapy is the mainstay treatment for differentiated thyroid cancer with distant metastasis. The refractoriness to radioactive iodine therapy has been overcome by the emergence of targeted agents. First, multikinase inhibitors (sorafenib and lenvatinib) targeting the growth factor pathway were developed and approved as anticancer agents for patients with advanced differentiated thyroid cancer, regardless of their genetic features. With progress in sequencing techniques, the genetic backgrounds of tumors have unveiled new targets, including rearrangements during transformation and tropomyosin receptor kinase. Special attention should be paid to the national health insurance coverage of systemic therapeutics and genetic studies.Discussion and Conclusion: New drugs were introduced to treat previously untreatable advanced thyroid cancers. However, the cost of these drugs has increased with new developments, and only first-line drugs for thyroid cancer are still covered by insurance. These medical advances will remain an illusion for clinics and patients if improvements in healthcare policies do not accompany them.
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Liu, Shirley Yuk Wah, and Enders Kwok Wai Ng. "Robotic versus Open Thyroidectomy for Differentiated Thyroid Cancer: An Evidence-Based Review." International Journal of Endocrinology 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/4309087.
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While open thyroidectomy (OT) is advocated as the gold standard treatment for differentiated thyroid cancer, the contemporary use of robotic thyroidectomy (RT) is often controversial. Although RT combines the unique benefits of the surgical robot and remote access thyroidectomy, its applicability on cancer patients is challenged by the questionable oncological benefits and safety. This review aims to analyze the current literature evidence in comparing RT to OT on thyroid cancers for their perioperative and oncological outcomes. To date, no randomized controlled trial is available in comparing RT to OT. All published studies are nonrandomized or retrospective comparisons. Current data suggests that RT compares less favorably than OT for longer operative time, higher cost, and possibly inferior oncological control with lower number of central lymph nodes retrieved. In terms of morbidity, quality of life outcomes, and short-term recurrence rates, RT and OT are comparable. While conventional OT continues to be appropriate for most thyroid cancers, RT should better be continued by expert surgeons on selected patients who have low-risk thyroid cancers and have high expectations on cosmetic outcomes. Future research should embark on prospective randomized studies for unbiased comparisons. Long-term follow-up studies are also needed to evaluate outcomes on recurrence and survival.
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Giovanella, Luca, Desiree’ Deandreis, Alexis Vrachimis, Alfredo Campenni, and Petra Petranovic Ovcaricek. "Molecular Imaging and Theragnostics of Thyroid Cancers." Cancers 14, no. 5 (March 1, 2022): 1272. http://dx.doi.org/10.3390/cancers14051272.
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Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with varying radioisotopes of iodine (i.e., 131I, 123I, 124I) is an indispensable component of dynamic and theragnostic risk stratification of differentiated carcinoma (DTC) while [18F]F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) helps in addressing disease aggressiveness, detects distant metastases, and risk-stratifies patients with radioiodine-refractory DTC, poorly differentiated and anaplastic thyroid cancers. For medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells, [18F]F-dihydroxyphenylalanine (6-[18F]FDOPA) PET/CT and/or [18F]FDG PET/CT can be used dependent on serum markers levels and kinetics. In addition to radioiodine therapy for DTC, some theragnostic approaches are promising for metastatic MTC as well. Moreover, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC while new theragnostic approaches showed promising preliminary results for advanced and aggressive forms of follicular-cell derived thyroid cancers (i.e., peptide receptor radiotherapy). In order to help clinicians put the role of molecular imaging into perspective, the appropriate role and emerging opportunities for molecular imaging and theragnostics in thyroid cancer are discussed in our present review.
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Lin, Shu-Fu, Jen-Der Lin, Chuen Hsueh, Ting-Chao Chou, and Richard J. Wong. "Potent effects of roniciclib alone and with sorafenib against well-differentiated thyroid cancer." Endocrine-Related Cancer 25, no. 10 (October 2018): 853–64. http://dx.doi.org/10.1530/erc-18-0150.
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Activation of cyclin-dependent kinase activity is frequently observed in many human cancers; therefore, cyclin-dependent kinases that promote cell cycle transition and cell proliferation may be potential targets in the treatment of malignancy. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for papillary and follicular thyroid cancer (designated as well-differentiated thyroid cancer), were investigated in this study. Roniciclib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner. Roniciclib activated caspase-3 activity and induced apoptosis. Cell cycle progression was arrested in the G2/M phase. Roniciclib treatmentin vivoretarded the growth of two well-differentiated thyroid tumors in xenograft models in a dose-dependent fashion. Furthermore, the combination of roniciclib with sorafenib was more effective than either single treatment in a follicular thyroid cancer xenograft model. Acceptable safety profiles appeared in animals treated with either roniciclib alone or roniciclib and sorafenib combination therapy. These findings support roniciclib as a potential drug for the treatment of patients with well-differentiated thyroid cancer.
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Lal, Punita, and Prakash Kumar Swain. "Role of Radiotherapy in Differentiated Thyroid Cancer." World Journal of Endocrine Surgery 5, no. 3 (2013): 71–75. http://dx.doi.org/10.5005/jp-journals-10002-1132.
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ABSTRACT Differentiated thyroid cancers (i.e. papillary or follicular) account for majority of thyroid malignancies. Even though surgery has been the mainstay for these tumors, use of radioactive iodine (I131) therapy and thyroid hormone replacement therapy is common in most of these tumors in adjuvant setting. Radiotherapy is indicated in the presence of, gross residual disease after surgery, extra-capsular extension, and extensive lymph node involvement. As thyroid gland is located at the root of neck, sometimes with retrosternal extension and surrounded by critical structures, it is difficult to adequately cover the entire target volume with conventional radiotherapy technique. IMRT is a useful technique in these tumors, since it provides good dose distribution along with sparing of spinal cord while treating thyroid bed in adjuvant setting, and therefore it needs to be further standardized. Additionally palliative radiotherapy is effective in brain and bone metastasis. To conclude, external beam radiotherapy is an established and effective mode of therapy both in curative and palliative settings. How to cite this article Lal P, Swain PK. Role of Radiotherapy in Differentiated Thyroid Cancer. World J Endoc Surg 2013;5(3): 71-75.
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Lalountas, Miltiadis. "Skull metastasis from follicular thyroid cancer." Clinical Imaging and Case Reports 5, no. 1 (March 16, 2023): 1–4. http://dx.doi.org/10.52338/cicasrep.2022.1008.
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Differentiated thyroid cancers have indolent clinical course and good prognosis with an approximate 85–90% 10-year survival rate. Distant metastases from follicular thyroid cancer are uncommon but are one of the main causes of cancer-specific mortatily. Mainly involve the lung, bone, and brain. Bone metastasis most commonly occurs in the vertebrae, costas and hip bones
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Poolakkil, Prasanth, Sajith Babu Thavarool, Satheesan Balasubramanyam, and Kandathil Joseph Philip. "De-differentiation in thyroid cancer- an increasingly appreciated concept." International Surgery Journal 8, no. 2 (January 29, 2021): 757. http://dx.doi.org/10.18203/2349-2902.isj20210400.
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Thyroid cancer is the most common endocrine malignancy. In general, they are said to be of good prognosis, still there are a few aggressive variants. Differentiated carcinomas like papillary and follicular comprise of major proportion and have a less aggressive clinical behaviour, even though some of them tend to be otherwise. De-differentiated and undifferentiated cancers are more aggressive. There has been an already existing theory that these de-differentiated cancers arise from differentiated ones by a process of stepwise molecular changes. There are already reported cases of coexistence of multiple histologies. Appreciation of dedifferentiation and identification of the genetic changes may be of help in forming improved treatment strategies, including targeted therapy. This article is to report a rare case we came across, in which three different histologies coexisted and may be pointing towards graded de-differentiation pattern. This is a further support to the stepwise de-differentiation theory.
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Baldet, Line, Jean-Claude Manderscheid, Daniel Glinoer, Claude Jaffiol, Béatrice Coste-Seignovert, and Christine Percheron. "The management of differentiated thyroid cancer in Europe in 1988." Acta Endocrinologica 120, no. 5 (May 1989): 547–58. http://dx.doi.org/10.1530/acta.0.1200547.
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Abstract. In order to know how thyroid nodules and differentiated thyroid cancers are investigated and treated in 1988, an international inquiry was performed by mean of a questionnaire based on a well-defined case report of a 35-year-old female with a solitary small thyroid nodule. Clinicians were asked to indicate their diagnostic and therapeutic approaches to the reported case and to some variations. Analysis of the 157 responses from thyroid experts showed that three in vitro tests (sensitive-TSH, free T4 and total T4) and three in vivo tests (99mTc or radioiodide scintiscan, fine needle aspiration and ultrasonography) were performed most frequently. In the case of a solid and cold nodule and in the absence of fine needle aspiration results, 19% of respondents advocated suppressive therapy and 81% surgery. In the same clinical case, but whom fine needle aspiration had been performed and cytology was benign, surgery was advocated by 24%, suppressive therapy by 48% and a regular follow-up without treatment by 28% of respondents. When surgery was performed and the diagnosis was a differentiated thyroid cancer, (near) total thyroidectomy was more frequently chosen than partial thyroidectomy in both papillary (60 and 40%, respectively, of respondents) and follicular (74 and 26%, respectively, of respondents) cancers; 80% of clinicians did not change their surgical technique in relation to histological type of the tumour. Total thyroidectomy was more often recommended in most of the clinical or anatomical variations compared with the basic case report. Pre- or postoperative hormonal therapy was initiated with L-T4 and TSH suppression was controlled by sensitive-TSH and thyroglobulin determinations. After total thyroidectomy, 131I was used with similar modalities for papillary and follicular cancers to ablate a thyroid remnant.
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Stewart, Latoya A., and Jennifer H. Kuo. "Advancements in the treatment of differentiated thyroid cancer." Therapeutic Advances in Endocrinology and Metabolism 12 (January 2021): 204201882110002. http://dx.doi.org/10.1177/20420188211000251.
Full textAbstract:
Derived from follicular epithelial cells, differentiated thyroid cancer (DTC) accounts for the majority of thyroid malignancies. The threefold increase in DTC incidence over the last three decades has been largely attributed to advancements in detection of papillary thyroid microcarcinomas. Efforts to address the issue of overtreatment have notably included the reclassification of encapsulated follicular variant papillary thyroid cancers (EFVPTC) to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). In the last 5 years, the overall management approach for this relatively indolent cancer has become less aggressive. Although surgery and radioiodine ablation remain the mainstay of DTC therapy, the role of active surveillance is being explored. Furthermore, the most recent American Thyroid Association (ATA) guidelines offer flexibility between lobectomy and total thyroidectomy for thyroid nodules between 1 cm and 4 cm in the absence of extrathyroidal extension or nodal disease. As our understanding of the natural history and molecular underpinnings of DTC evolves, so might our approach to managing low-risk patients, obviating the need for invasive intervention. Simultaneously, advances in interventional and systemic therapies have greatly expanded treatment options for high-risk surgical candidates and patients with widespread disease, and continue to be areas of active investigation. Continued research efforts are essential to improve our ability to offer effective individualized therapy to patients at all disease stages and to reduce the incidence of recurrent and progressive disease.
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Chan, Wai-Kin, Jui-Hung Sun, Miaw-Jene Liou, Yan-Rong Li, Wei-Yu Chou, Feng-Hsuan Liu, Szu-Tah Chen, and Syu-Jyun Peng. "Using Deep Convolutional Neural Networks for Enhanced Ultrasonographic Image Diagnosis of Differentiated Thyroid Cancer." Biomedicines 9, no. 12 (November 26, 2021): 1771. http://dx.doi.org/10.3390/biomedicines9121771.
Full textAbstract:
Differentiated thyroid cancer (DTC) from follicular epithelial cells is the most common form of thyroid cancer. Beyond the common papillary thyroid carcinoma (PTC), there are a number of rare but difficult-to-diagnose pathological classifications, such as follicular thyroid carcinoma (FTC). We employed deep convolutional neural networks (CNNs) to facilitate the clinical diagnosis of differentiated thyroid cancers. An image dataset with thyroid ultrasound images of 421 DTCs and 391 benign patients was collected. Three CNNs (InceptionV3, ResNet101, and VGG19) were retrained and tested after undergoing transfer learning to classify malignant and benign thyroid tumors. The enrolled cases were classified as PTC, FTC, follicular variant of PTC (FVPTC), Hürthle cell carcinoma (HCC), or benign. The accuracy of the CNNs was as follows: InceptionV3 (76.5%), ResNet101 (77.6%), and VGG19 (76.1%). The sensitivity was as follows: InceptionV3 (83.7%), ResNet101 (72.5%), and VGG19 (66.2%). The specificity was as follows: InceptionV3 (83.7%), ResNet101 (81.4%), and VGG19 (76.9%). The area under the curve was as follows: Incep-tionV3 (0.82), ResNet101 (0.83), and VGG19 (0.83). A comparison between performance of physicians and CNNs was assessed and showed significantly better outcomes in the latter. Our results demonstrate that retrained deep CNNs can enhance diagnostic accuracy in most DTCs, including follicular cancers.
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McAninch, Elizabeth A., Rossana M. Calderon, and Atil Y. Kargi. "A Cutaneous False Positive in Radioiodine Scintigraphy for Metastatic Thyroid Cancer." US Endocrinology 12, no. 01 (2016): 37. http://dx.doi.org/10.17925/use.2016.12.01.37.
Full textAbstract:
Contamination of external sites with secretions or excretory products can mimic metastases and yield false positives in radioiodine whole-body scintigraphy for thyroid cancer. We present a case of a 26-year-old woman with differentiated papillary thyroid carcinoma who received radioiodine 131 (I-131) for treatment of persistent upper mediastinal metastasis. Her post-treatment whole-body scintigraphy revealed an unexpected focus of increased uptake near the scalp in addition to the mediastinal lesion. Although the scalp is the most common site of cutaneous thyroid cancer metastasis, differentiated thyroid cancers rarely manifest with cutaneous thyroid cancer metastasis and thus it is prudent to consider etiologies of false positive I-131 uptake in such cases. Contamination of our patient’s hair from salivary secretions was confirmed on history and with coiffure repositioning during whole-body scintigraphy.