The past two decades have seen numerous developments in the understanding of the origins and biology of papillary thyroid carcinoma. Advances in molecular biology, clinicopathologic studies of new ...entities, facility with fine-needle aspiration biopsy, and new radiologic imaging techniques have allowed for earlier diagnosis of these tumors. However, these advances have also caused controversies in cytologic and histopathologic diagnoses as well as therapy decisions. This paper will focus on several pathologic aspects of papillary carcinoma, which impact on its biology and prognosis.
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
2
). 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.
Special types of thyroid carcinoma Baloch, Zubair W; LiVolsi, Virginia A
Histopathology,
January 2018, 2018-Jan, 2018-01-00, 20180101, Letnik:
72, Številka:
1
Journal Article
Recenzirano
This article reviews the small percentage of thyroid tumours that are not classified as classic papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma. It includes ...subtypes of papillary thyroid carcinoma, including, tall‐cell, hobnail/micropapillary, columnar cell, diffuse sclerosing and solid variants. Poorly differentiated carcinoma, high‐grade carcinoma and anaplastic thyroid carcinoma are reviewed. Also discussed are entities that are unusual but need to be recognized as primary thyroid neoplasms, i.e. mucoepidermoid carcinoma, sclerosing mucoepidermoid carcinoma with eosinophilia, and mammary analogue secretory carcinoma/secretory carcinoma. The pathological features and prognostic factors are described; a brief review of molecular correlates of these neoplasms is included.
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formalized in October 2007 by experts in thyroidology at the National Institute of Health in Bethesda, Maryland. The first edition ...of the TBSRTC book was published in 2010 and the second edition in 2018. The TBSRTC is widely employed in cytology practices in the United States and has also served as a model for similar tiered classification schemes for reporting thyroid cytopathology specimens. The tremendous success of TBSRTC cannot be underscored, it has provided a diagnostic framework which is well aligned with the present and the future of thyroid nodule management.
Currently, there is no uniform classification scheme available for reporting of salivary gland fine‐needle aspiration (FNA) specimens. Recently, an International group of pathologists has recommended ...a tiered classification scheme for reporting of salivary gland FNA results known as the “Milan System for Reporting Salivary Gland Cytopathology (MSRSGC).” We performed a comprehensive review of the published literature on FNA of salivary gland lesions by employing the diagnostic categories of the MSRSGC to evaluate their reliability in the management of salivary gland lesions. A comprehensive review of the literature was carried out through PubMed from 1987 to 2015 to identify studies which categorized the cytologic diagnoses and included surgical follow‐up. Only cases with histopathologic follow‐up were included in the analysis. Twenty‐nine studies comprising 4514 cases of salivary gland FNAs with surgical follow‐up were included in this study. The cytologic diagnoses were categorized into the following categories proposed by MSRSGC. The number of cases in each diagnostic category and the risk of malignancy (ROM) were as follows: Non‐Diagnostic—100 cases (ROM‐ 25.0% ± 16.7%), Non‐Neoplastic—587 cases (ROM: 10.2% ± 5.5%), Benign Neoplasm −2673 cases (ROM: 3.4% ± 1.3%), Salivary Gland Neoplasm of Undetermined Malignant Potential (SUMP)—64 cases(ROM: 37.5% ± 24.7%), Suspicious for Malignant neoplasm—70 cases(ROM: 58.6% ± 19.5%), and Malignant—1012 cases(ROM: 91.9% ± 3.5%). A tiered classification scheme as proposed by MSRSGC may prove helpful in effectively guiding clinical management of patients with salivary gland lesions.
This paper will review neuroendocrine lesions of the thyroid and the differential diagnosis with the most significant such tumor of the thyroid, that is, medullary thyroid carcinoma. A brief overview ...of the understanding of this tumor's identification as a lesion of C cells and its familial and syndromic associations will be presented. Then, a discussion of the various mimics of medullary carcinoma will be given with an approach to the types of tests that can be done to arrive at a correct diagnostic conclusion. This review will focus on practical “tips” for the practicing pathologist.
The past half century has seen a number of advances in pathology of thyroid diseases, especially neoplastic lesions. These include the description of new entities, the definition of prognostically ...important lesions, the incorporation of fine needle aspiration biopsy and its functional risk stratification of diagnoses into the clinical evaluation and therapeutic recommendations of the patient with thyroid nodules and the understanding of thyroid neoplastic development, diagnostic and prognostic parameters by use of molecular analysis so that such techniques are becoming standard of care for patients with thyroid tumors. The histopathologist and cytopathologist have been and continue to be at the forefront in the definition and understanding of these areas of thyroid disease. This review describes many of the most important advances in this area in an attempt bring the practicing pathologist up to date in these developments.
To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy.
Surgical management of thyroid disease has evolved considerably over several decades leading to ...variability in rendered care. Over 100,000 thyroid operations are performed annually in the US.
The medical literature from 1/1/1985 to 11/9/2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content.
These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches to Thyroidectomy, Laryngology, Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation.
Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
Use of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery.
To ...measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules.
A blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States. All patients underwent surgery without genomic information and were assigned a histopathology diagnosis by an expert panel blinded to all genomic information. There were 210 potentially eligible thyroid biopsy samples with Bethesda III or IV indeterminate cytopathology that constituted a cohort previously used to validate the gene expression classifier. Of these, 191 samples (91.0%) had adequate residual RNA for validation of the genomic sequencing classifier. Algorithm development and independent validation occurred between August 2016 and May 2017.
Thyroid nodule surgical histopathology diagnosis by an expert panel blinded to all genomic data.
The primary end point was measurement of genomic sequencing classifier sensitivity, specificity, and negative and positive predictive values in biopsies from Bethesda III and IV nodules. The secondary end point was measurement of classifier performance in biopsies from Bethesda II, V, and VI nodules.
Of the 183 included patients, 142 (77.6%) were women, and the mean (range) age was 51.7 (22.0-85.0) years. The genomic sequencing classifier had a sensitivity of 91% (95% CI, 79-98) and a specificity of 68% (95% CI, 60-76). At 24% cancer prevalence, the negative predictive value was 96% (95% CI, 90-99) and the positive predictive value was 47% (95% CI, 36-58).
The genomic sequencing classifier demonstrates high sensitivity and accuracy for identifying benign nodules. Its 36% increase in specificity compared with the gene expression classifier potentially increases the number of patients with benign nodules who can safely avoid unnecessary diagnostic surgery.
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