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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 -
Annals of Internal Medicine Apr 2020Thyrotoxicosis is a general term for excess circulating and tissue thyroid hormone levels, whereas hyperthyroidism specifically denotes disorders involving a hyperactive...
Thyrotoxicosis is a general term for excess circulating and tissue thyroid hormone levels, whereas hyperthyroidism specifically denotes disorders involving a hyperactive thyroid gland (Graves disease, toxic multinodular goiter, toxic adenoma). Diagnosis and determination of the cause rely on clinical evaluation, laboratory tests, and imaging studies. Hyperthyroidism is treated with antithyroid drugs, radioactive iodine ablation, or thyroidectomy. Other types of thyrotoxicosis are monitored and treated with β-blockers to control symptoms given that most of these conditions resolve spontaneously.
Topics: Adrenergic beta-Antagonists; Antithyroid Agents; Biomarkers; Diagnosis, Differential; Humans; Hyperthyroidism; Iodine Radioisotopes; Mass Screening; Risk Factors; Thyroid Hormones; Thyroidectomy; Thyrotoxicosis
PubMed: 32252086
DOI: 10.7326/AITC202004070 -
Gland Surgery Feb 2020Hyperthyroidism is a condition where the thyroid gland produces and secretes inappropriately high amounts of thyroid hormone which can lead to thyrotoxicosis. The... (Review)
Review
Hyperthyroidism is a condition where the thyroid gland produces and secretes inappropriately high amounts of thyroid hormone which can lead to thyrotoxicosis. The prevalence of hyperthyroidism in the United States is approximately 1.2%. There are many different causes of hyperthyroidism, and the most common causes include Graves' disease (GD), toxic multinodular goiter and toxic adenoma. The diagnosis can be made based on clinical findings and confirmed with biochemical tests and imaging techniques including ultrasound and radioactive iodine uptake scans. This condition impacts many different systems of the body including the integument, musculoskeletal, immune, ophthalmic, reproductive, gastrointestinal and cardiovascular systems. It is important to recognize common cardiovascular manifestations such as hypertension and tachycardia and to treat these patients with beta blockers. Early treatment of cardiovascular manifestations along with treatment of the hyperthyroidism can prevent significant cardiovascular events. Management options for hyperthyroidism include anti-thyroid medications, radioactive iodine, and surgery. Anti-thyroid medications are often used temporarily to treat thyrotoxicosis in preparation for more definitive treatment with radioactive iodine or surgery, but in select cases, patients can remain on antithyroid medications long-term. Radioactive iodine is a successful treatment for hyperthyroidism but should not be used in GD with ophthalmic manifestations. Recent studies have shown an increased concern for the development of secondary cancers as a result of radioactive iodine treatment. In the small percentage of patients who are not successfully treated with radioactive iodine, they can undergo re-treatment or surgery. Surgery includes a total thyroidectomy for GD and toxic multinodular goiters and a thyroid lobectomy for toxic adenomas. Surgery should be considered for those who have a concurrent cancer, in pregnancy, for compressive symptoms and in GD with ophthalmic manifestations. Surgery is cost effective with a high-volume surgeon. Preoperatively, patients should be on anti-thyroid medications to establish a euthyroid state and on beta blockers for any cardiovascular manifestations. Thyroid storm is a rare but life-threatening condition that can occur with thyrotoxicosis that must be treated with a multidisciplinary approach and ultimately, definitive treatment of the hyperthyroidism.
PubMed: 32206604
DOI: 10.21037/gs.2019.11.01 -
Endocrine-related Cancer Feb 2023The fifth edition of the Classification of Endocrine and Neuroendocrine Tumors has been released by the World Health Organization. This timely publication integrates... (Review)
Review
The fifth edition of the Classification of Endocrine and Neuroendocrine Tumors has been released by the World Health Organization. This timely publication integrates several changes to the nomenclature of non-neoplastic and neoplastic thyroid diseases, as well as novel concepts that are essential for patient management. The heterogeneous group of non-neoplastic and benign neoplastic lesions are now collectively termed as 'thyroid follicular nodular disease' to better reflect the clonal and non-clonal proliferations that clinically present as multinodular goiter. Thyroid neoplasms originating from follicular cells are distinctly divided into benign, low-risk and malignant neoplasms. The new classification scheme stresses that papillary thyroid carcinoma (PTC) should be subtyped based on histomorphologic features irrespective of tumor size to avoid treating all sub-centimeter/small lesions as low-risk disease. Formerly known as the cribriform-morular variant of PTC is redefined as cribriform-morular thyroid carcinoma since this tumor is now considered a distinct malignant thyroid neoplasm of uncertain histogenesis. The 'differentiated high-grade thyroid carcinoma' is a new diagnostic category including PTCs, follicular thyroid carcinomas and oncocytic carcinomas with high-grade features associated with poorer prognosis similar to the traditionally defined poorly differentiated thyroid carcinoma as per Turin criteria. In addition, squamous cell carcinoma of the thyroid is now considered a morphologic pattern/subtype of anaplastic thyroid carcinoma. In this review, we will highlight the key changes in the newly devised fifth edition of the WHO classification scheme of thyroid tumors with reflections on its applicability in patient management and future directions in this field.
Topics: Humans; Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary
PubMed: 36445235
DOI: 10.1530/ERC-22-0293 -
Journal of Nuclear Medicine : Official... Mar 2021Benign thyroid disorders, especially hyper- and hypothyroidism, are the most prevalent endocrine disorders. The most common etiologies of hyperthyroidism are autoimmune... (Review)
Review
Benign thyroid disorders, especially hyper- and hypothyroidism, are the most prevalent endocrine disorders. The most common etiologies of hyperthyroidism are autoimmune hyperthyroidism (Graves disease, GD), toxic multinodular goiter (TMNG), and toxic thyroid adenoma (TA). Less common etiologies include destructive thyroiditis (e.g., amiodarone-induced thyroid dysfunction) and factitious hyperthyroidism. GD is caused by autoantibodies against the thyroid-stimulating hormone (TSH) receptor. TMNG and TA are caused by a somatic activating gain-of-function mutation. Typical laboratory findings in patients with hyperthyroidism are low TSH, elevated free-thyroxine and free-triiodothyronine levels, and TSH-receptor autoantibodies in patients with GD. Ultrasound imaging is used to determine the size and vascularity of the thyroid gland and the location, size, number, and characteristics of thyroid nodules. Combined with lab tests, these features constitute the first-line diagnostic approach to distinguishing different forms of hyperthyroidism. Thyroid scintigraphy with either radioiodine or Tc-pertechnetate is useful to characterize different forms of hyperthyroidism and provides information for planning radioiodine therapy. There are specific scintigraphic patterns for GD, TMNG, TA, and destructive thyroiditis. Scintigraphy with Tc-sestamibi allows differentiation of type 1 from type 2 amiodarone-induced hyperthyroidism. The radioiodine uptake test provides information for planning radioiodine therapy of hyperthyroidism. Hyperthyroidism can be treated with oral antithyroid drugs, surgical thyroidectomy, or I-iodide. Radioiodine therapy is generally considered after failure of treatment with antithyroid drugs, or when surgery is contraindicated or refused by the patient. In patients with TA or TMNG, the goal of radioiodine therapy is to achieve euthyroid status. In GD, the goal of radioiodine therapy is to induce hypothyroidism, a status that is readily treatable with oral thyroid hormone replacement therapy. Dosimetric estimates based on the thyroid volume to be treated and on radioiodine uptake should guide selection of the I-activity to be administered. Early side effects of radioiodine therapy (typically mild pain in the thyroid) can be handled by nonsteroidal antiinflammatory drugs. Delayed side effects after radioiodine therapy for hyperthyroidism are hypothyroidism and a minimal risk of radiation-induced malignancies.
Topics: Clinical Laboratory Techniques; Humans; Hyperthyroidism; Nuclear Medicine
PubMed: 33008929
DOI: 10.2967/jnumed.120.243170 -
DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma.Modern Pathology : An Official Journal... Jan 2022DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common... (Review)
Review
DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in DICER1 provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in DICER1. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a DICER1-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a DICER1 mutation.
Topics: Causality; Germ-Line Mutation; Humans; Lung Neoplasms; Pleural Neoplasms; Pulmonary Blastoma; Ribonuclease III; Syndrome
PubMed: 34599283
DOI: 10.1038/s41379-021-00905-8 -
Iranian Journal of Pharmaceutical... 2019The thionamide drugs, carbimazole and its metabolite methimazole (MMI), and propylthiouracil (PTU) have extensively been used in the management of various forms of... (Review)
Review
The thionamide drugs, carbimazole and its metabolite methimazole (MMI), and propylthiouracil (PTU) have extensively been used in the management of various forms of hyperthyroidism over the past eight decades. This review aims to summarize different aspects of these outstanding medications. Thionamides have shown their own acceptable efficacy and even safety profiles in treatment of hyperthyroidism, especially GD in both children and adults and also during pregnancy and lactation. Of the antithyroid drugs (ATDs) available, MMI is the preferred choice in most situations taking into account its better efficacy and less adverse effects accompanied by once-daily dose prescription because of a long half-life and similar cost. Considering the more severe teratogenic effects of MMI, PTU would be the selected ATD for treatment of hyperthyroidism during pre-pregnancy months and the first 16 weeks of gestation. Recent studies have confirmed the efficacy and safety of long-term MMI therapy with low maintenance doses for GD and toxic multinodular goiter. Despite the long-term history of ATD use, there is still ongoing debate regarding their pharmacology and diverse mechanisms of action, viz. their immunomodulatory effects, and mechanisms and susceptibility factors to their adverse reactions.
PubMed: 32802086
DOI: 10.22037/ijpr.2020.112892.14005