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Endocrine Pathology Mar 2022This review summarizes the changes in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the thyroid gland. The new... (Review)
Review
This review summarizes the changes in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the thyroid gland. The new classification has divided thyroid tumors into several new categories that allow for a clearer understanding of the cell of origin, pathologic features (cytopathology and histopathology), molecular classification, and biological behavior. Follicular cell-derived tumors constitute the majority of thyroid neoplasms. In this new classification, they are divided into benign, low-risk, and malignant neoplasms. Benign tumors include not only follicular adenoma but also variants of adenoma that are of diagnostic and clinical significance, including the ones with papillary architecture, which are often hyperfunctional and oncocytic adenomas. For the first time, there is a detailed account of the multifocal hyperplastic/neoplastic lesions that commonly occur in the clinical setting of multinodular goiter; the term thyroid follicular nodular disease (FND) achieved consensus as the best to describe this enigmatic entity. Low-risk follicular cell-derived neoplasms include non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), thyroid tumors of uncertain malignant potential, and hyalinizing trabecular tumor. Malignant follicular cell-derived neoplasms are stratified based on molecular profiles and aggressiveness. Papillary thyroid carcinomas (PTCs), with many morphological subtypes, represent the BRAF-like malignancies, whereas invasive encapsulated follicular variant PTC and follicular thyroid carcinoma represent the RAS-like malignancies. This new classification requires detailed subtyping of papillary microcarcinomas similar to their counterparts that exceed 1.0 cm and recommends not designating them as a subtype of PTC. The criteria of the tall cell subtype of PTC have been revisited. Cribriform-morular thyroid carcinoma is no longer classified as a subtype of PTC. The term "Hürthle cell" is discouraged, since it is a misnomer. Oncocytic carcinoma is discussed as a distinct entity with the clear recognition that it refers to oncocytic follicular cell-derived neoplasms (composed of > 75% oncocytic cells) that lack characteristic nuclear features of PTC (those would be oncocytic PTCs) and high-grade features (necrosis and ≥ 5 mitoses per 2 mm). High-grade follicular cell-derived malignancies now include both the traditional poorly differentiated carcinoma as well as high-grade differentiated thyroid carcinomas, since both are characterized by increased mitotic activity and tumor necrosis without anaplastic histology and clinically behave in a similar manner. Anaplastic thyroid carcinoma remains the most undifferentiated form; squamous cell carcinoma of the thyroid is now considered as a subtype of anaplastic carcinoma. Medullary thyroid carcinomas derived from thyroid C cells retain their distinct section, and there is a separate section for mixed tumors composed of both C cells and any follicular cell-derived malignancy. A grading system for medullary thyroid carcinomas is also introduced based on mitotic count, tumor necrosis, and Ki67 labeling index. A number of unusual neoplasms that occur in the thyroid have been placed into new sections based on their cytogenesis. Mucoepidermoid carcinoma and secretory carcinoma of the salivary gland type are now included in one section classified as "salivary gland-type carcinomas of the thyroid." Thymomas, thymic carcinomas and spindle epithelial tumor with thymus-like elements are classified as "thymic tumors within the thyroid." There remain several tumors whose cell lineage is unclear, and they are listed as such; these include sclerosing mucoepidermoid carcinoma with eosinophilia and cribriform-morular thyroid carcinoma. Another important addition is thyroblastoma, an unusual embryonal tumor associated with DICER1 mutations. As in all the WHO books in the 5th edition, mesenchymal and stromal tumors, hematolymphoid neoplasms, germ cell tumors, and metastatic malignancies are discussed separately. The current classification also emphasizes the value of biomarkers that may aid diagnosis and provide prognostic information.
Topics: Adenocarcinoma, Follicular; Carcinoma, Neuroendocrine; Carcinoma, Papillary; DEAD-box RNA Helicases; Humans; Ribonuclease III; Thyroid Neoplasms; World Health Organization
PubMed: 35288841
DOI: 10.1007/s12022-022-09707-3 -
JAMA Feb 2024Approximately 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... (Review)
Review
IMPORTANCE
Approximately 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.
OBSERVATIONS
Papillary 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.
CONCLUSIONS
Approximately 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.
Topics: Humans; Adenocarcinoma, Follicular; Carcinoma, Neuroendocrine; Imidazoles; Iodine Radioisotopes; Oximes; Phenylurea Compounds; Quinolines; Thyroid Neoplasms
PubMed: 38319329
DOI: 10.1001/jama.2023.26348 -
Endocrinology and Metabolism (Seoul,... Oct 2022The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes,... (Review)
Review
The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms "follicular nodular disease" and "differentiated high-grade thyroid carcinoma" are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term "Hürthle cells" is replaced with "oncocytic cells." Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term "variant" to describe a subclass of tumor has been replaced with the term "subtype." Instead, the term "variant" is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: "salivary gland-type carcinomas of the thyroid" and "thyroid tumors of uncertain histogenesis." This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.
Topics: Humans; Carcinoma, Papillary; Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary; World Health Organization
PubMed: 36193717
DOI: 10.3803/EnM.2022.1553 -
Expert Review of Anticancer Therapy 2023Medullary thyroid carcinoma (MTC) constitutes approximately 5-10% of all thyroid cancers. Although the tumor forms in the thyroid, it doesn't originate from thyroid... (Review)
Review
INTRODUCTION
Medullary thyroid carcinoma (MTC) constitutes approximately 5-10% of all thyroid cancers. Although the tumor forms in the thyroid, it doesn't originate from thyroid cells, but from the C cells or parafollicular cells which produce and release a hormone called calcitonin (CT). Starting from the second half of the 1900s, MTC was progressively studied and defined.
AREAS COVERED
This study aims to analyze the history, clinical presentation and biological behavior of MTC, bio-humoral and instrumental diagnosis, molecular profiling, genetic screening, preoperative staging and instrumental procedures, indispensable in expert and dedicated hands, such as high-resolution ultrasonography, CT-scan, MRI and PET/TC. We examine recommended and controversial surgical indications and procedures, prophylactic early surgery and multiple endocrine neoplasia surgery. Also, we discuss pathological anatomy classification and targeted therapies. The role of serum CT is valued both as undisputed and constant preoperative diagnostic marker, obscuring cytology and as early postoperative marker that predicts disease persistence.
EXPERT OPINION
With a complete preoperative study, unnecessary or useless, late and extended interventions can be reduced in favor of tailored surgery that also considers quality of life. Finally, great progress has been made in targeted therapy, with favorable impact on survival.
Topics: Humans; Carcinoma, Medullary; Quality of Life; Thyroidectomy; Thyroid Neoplasms
PubMed: 37646181
DOI: 10.1080/14737140.2023.2247566 -
Hormone and Metabolic Research =... Aug 2020The diagnostic modalities, stratification tools, and treatment options for patients with thyroid cancer have rapidly evolved since the development of the American... (Review)
Review
The diagnostic modalities, stratification tools, and treatment options for patients with thyroid cancer have rapidly evolved since the development of the American Thyroid Association (ATA) guidelines in 2015. This review compiles newer concepts in diagnosis, stratification tools and treatment options for patients with differentiated thyroid cancer (DTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid cancer (ATC). Newer developments apply precision medicine in thyroid cancer patients to avoid over-treatment in low risk disease and under-treatment in high risk disease. Among novel patient-tailored therapies are selective RET inhibitors that have shown efficacy in the treatment of MTC with limited systemic toxicity compared with non-specific tyrosine kinase inhibitors. The combination of BRAF and MEK inhibitors have revolutionized management of mutant ATC. Several immunotherapeutic agents are being actively investigated in the treatment of all forms of thyroid cancer. In this review, we describe the recent advances in the diagnosis and management of DTC, MTC, and ATC, with an emphasis on novel treatment modalities.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Disease Management; Humans; Interdisciplinary Communication; Mutation; Prognosis; Protein Kinase Inhibitors; Thyroid Neoplasms; Thyroidectomy
PubMed: 32040962
DOI: 10.1055/a-1089-7870 -
Endocrinology and Metabolism (Seoul,... Jun 2021Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular cells. The diagnostic and therapeutic strategies for the condition... (Review)
Review
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular cells. The diagnostic and therapeutic strategies for the condition are different from those used for well-differentiated thyroid cancer. Since the 2015 American Thyroid Association guidelines for the diagnosis and treatment of MTC, the latest, including the National Comprehensive Cancer Network and European Association for Medical Oncology guidelines have been updated to reflect several recent advances in the management of MTC. Advances in molecular diagnosis and postoperative risk stratification systems have led to individualized treatment and follow-up strategies. Multi-kinase inhibitors, such as vandetanib and cabozantinib, can prolong disease progression-free survival with favorable adverse effects. In addition, potent selective rearranged during transfection (RET) inhibitors (selpercatinib and pralsetinib) have shown a promising efficacy in recent clinical trials. This review summarizes the management of MTC in recent guidelines focused on sporadic MTC.
Topics: Carcinoma, Neuroendocrine; Humans; Protein Kinase Inhibitors; Thyroid Neoplasms
PubMed: 34154310
DOI: 10.3803/EnM.2021.1082 -
Journal of the National Comprehensive... Aug 2022Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by...
Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).
Topics: Adenocarcinoma; Carcinoma, Neuroendocrine; Humans; Iodine; Iodine Radioisotopes; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms
PubMed: 35948029
DOI: 10.6004/jnccn.2022.0040 -
Annals of Oncology : Official Journal... Dec 2019
Topics: Humans; Adenocarcinoma, Follicular; Carcinoma, Neuroendocrine; Follow-Up Studies; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms
PubMed: 31549998
DOI: 10.1093/annonc/mdz400 -
Current Oncology (Toronto, Ont.) Oct 2019Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of... (Review)
Review
BACKGROUND
Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important.
METHODS
We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc.
RESULTS
A neuroendocrine tumour, mtc arises from parafollicular cells ("C cells"), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism.
SUMMARY
Although the initial diagnosis of a suspicious thyroid nodule is the same for differentiated thyroid carcinoma and mtc, the remainder of the workup and diagnosis for mtc is distinct.
Topics: Calcitonin; Carcinoembryonic Antigen; Carcinoma, Neuroendocrine; Germ-Line Mutation; Humans; Practice Guidelines as Topic; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms
PubMed: 31708652
DOI: 10.3747/co.26.5539 -
Frontiers in Endocrinology 2020The incidence of thyroid cancer (TC) has increased worldwide over the past four decades. TC is divided into three main histological types: differentiated (papillary and... (Review)
Review
The incidence of thyroid cancer (TC) has increased worldwide over the past four decades. TC is divided into three main histological types: differentiated (papillary and follicular TC), undifferentiated (poorly differentiated and anaplastic TC), and medullary TC, arising from TC cells. This review discusses the molecular mechanisms associated to the pathogenesis of different types of TC and their clinical relevance. In the last years, progresses in the genetic characterization of TC have provided molecular markers for diagnosis, risk stratification, and treatment targets. Recently, papillary TC, the most frequent form of TC, has been reclassified into two molecular subtypes, named -like and -like, associated to a different range of cancer risks. Similarly, the genetic characterization of follicular TC has been proposed to complement the new histopathological classification in order to estimate the prognosis. New analyses characterized a comprehensive molecular profile of medullary TC, raising the role of mutations. More recent evidences suggested that immune microenvironment associated to TC may play a critical role in tumor invasion, with potential immunotherapeutic implications in advanced and metastatic TC. Several types of ancillary approaches have been developed to improve the diagnostic value of fine needle aspiration biopsies in indeterminate thyroid nodules. Finally, liquid biopsy, as a non-invasive diagnostic tool for body fluid genotyping, brings a new prospective of disease and therapy monitoring. Despite all these novelties, much work remains to be done to fully understand the pathogenesis and biological behaviors of the different types of TC and to transfer this knowledge in clinical practice.
Topics: Carcinoma, Neuroendocrine; Genetic Predisposition to Disease; Humans; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-ret; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroid Nodule; Tumor Microenvironment
PubMed: 32231639
DOI: 10.3389/fendo.2020.00102