Quick tip: A cellular aspirate smear is crucial to an adequate differential count and assessment of morphologic dysplasia. et al. Examine microscopically and determine the number of drops that will produce satisfactory cellularity on the slide. H A full molecular panel of BRAF, RAS, RET/PTC and PAX8PPAR offer additional diagnostic value[58]. Correspondence to: Evangelos P Misiakos, MD, FACS, Associate Professor of Surgery, Attikon University Hospital, University of Athens School of Medicine, 76 Aigeou Pelagous Street, Agia Paraskevi, 15 341, Attica, 12462 Athens, Greece. Renshaw noted that a Hurthle cell neoplasm demonstrating one of the following features: Small cell dysplasia, large cell dysplasia, severe nuclear crowding, and dishesive cellular pattern is usually associated with a high risk of malignancy[33]. The risk of malignancy in the HCLUS category was significantly lower than in the other subtypes of AUS. Ramzy Presence of cell group with nuclear crowding, increased nuclear-cytoplasmic ratio, irregularities in nuclear membrane and micro-nuclei ( 40 pap stain on ThinPrep slide) (diagnostic categories V). Neutrophils are the same as WBCs, and as you know, it is normal to gave some WBCs in the urine. Remedy: The supernatant may not have been completely poured off resulting in dilution of the cell pellet. Hay It allows classification of nodules as benign or malignant, and patients with malignant nodules are scheduled for surgery. LiVolsi Asa Additional descriptive comments (beyond such subcategorization) are optional and left to the discretion of the cytopathologist. Accessibility Cystic degeneration also is often found. These include hypocellular smears with extensive cystic degeneration with rare follicular cells with nuclear atypia indicative of PTC. It is critical that cytopathologists communicate thyroid FNA interpretations to referring physicians in terms that are succinct, unambiguous, and clinically helpful. These formalin specimens are embedded in paraffin blocks and sectioned by histotechnologists to provide a two-dimensional cross-section of the clotted tissue. View an interactive bone marrow core biopsy online. ?K !o J The Bethesda System for Reporting Thyroid cytopathology. Literature reviews were limited to English language publications dating back to 1995, using PubMed as the search engine, with key words determined by the committee members. The Bethesda System for Reporting Thyroid Cytopathology is the most preferred system for the diagnosis of FNA specimens, which also contains guidelines for the diagnosis and treatment of indeterminate cases. Undifferentiated (anaplastic) thyroid carcinoma (UTC) is an extremely aggressive thyroid malignancy with a very poor prognosis. Cibas ES, Ali SZ. Faquin Furthermore, the clot section, like the core biopsy, can be used for immunohistochemical stains. The molecular diagnosis and management of thyroid neoplasms. The recommended management is clinical correlation and a repeated FNA at an appropriate interval.2,15 In most cases, a repeated FNA results in a more definitive interpretation; only about 20% of nodules are repeatedly AUS.2 In some cases, however, the physician may choose not to repeat the FNA but observe the nodule clinically or, alternatively, to refer the patient for surgery because of concerning clinical and/or sonographic features. Hematology.org.https://www.hematology.org/education/trainees/fellows/trainee-news/2021/demystifying-the-bone-marrow-biopsy-a-hematopathology-primer(label-accessed May 01, 2023). PU Listing the acceptable fixatives for use in cytology 5. Walfish Aspirates where malignancy is suspected but cannot be determined due to: Overlapping cytological features with other thyroid lesions, Specimens suspicious for a follicular or Hrthle cell neoplasm (see, Specimens with a minor degree of atypia, primarily cytologic or architectural (see, Frozen section has limited utility for suspicious for malignancy nodules (, 55 year old man with colon cancer metastasis within a NIFTP which was cytologically suspected of PTC (, 58 year old woman with mammary analogue secretory carcinoma of the thyroid which was cytologically suspected of PTC (, 63 year old man with follicular variant of papillary thyroid carcinoma presenting as a toxic nodule which was cytologically suspected of follicular variant of PTC (, 63 year old woman with hyalinizing trabecular tumor which was cytologically suspected of hyalinizing trabecular tumor (, 71 year old man with mixed medullary and follicular cell carcinoma of the thyroid which was cytologically suspected of thyroid carcinoma (, Pattern A (patchy nuclear changes): moderate to high cellularity, nuclei showing enlargement, pallor, grooves, irregularity or molding but absence of nuclear pseudoinclusions, psammoma bodies and papillary architecture, Pattern B (incomplete nuclear changes): nuclei showing enlargement with mild pallor and grooves, absence of nuclear irregularity, nuclear molding, nuclear pseudoinclusions, psammoma bodies and papillary architecture, Pattern C (sparsely cellular specimen): poor cellularity, presence of many findings suggesting papillary thyroid carcinoma, Pattern D (cystic degeneration): cystic degeneration based on foamy histiocytes, scattered clusters of follicular cells with the nuclei showing enlargement, pallor, grooves, absence of nuclear pseudoinclusions, psammoma bodies and papillary architecture, large, atypical, histiocytoid cells with enlarged nuclei and without abundant vacuolated cytoplasm (, Monomorphic population of isolated small or medium sized cells with a high nuclear cytoplasmic ratio, Nuclei are eccentrically located, with smudged chromatin, Numerous monomorphic small to intermediate sized lymphoid cells, Sparsely cellular and contains atypical lymphoid cells, Suspicious for malignancy, not otherwise specified, Other primary thyroid malignancies like anaplastic carcinoma and poorly differentiated carcinoma, Suboptimal cellularity or preservation can lead to uncertainty and result in a suspicious for malignancy interpretation, Usually surgical management similar to that of malignant nodules (, In suspicious for papillary thyroid carcinoma cases with low risk features ( 1 cm, without extrathyroidal extension and clinical metastasis), active surveillance is an option (, Molecular testing with high positive predictive value (, For suspicious for medullary thyroid carcinoma, Measuring serum calcitonin level or calcitonin immunostaining are recommended (, Repeat fine needle aspiration to obtain cells for flow cytometry (, A few follicular cells showing nuclear enlargement, pale and powdery chromatin and nuclear grooves are present, Correlation with serum calcitonin level or immunostaining might be helpful for definitive diagnosis if clinically indicated, Re-aspiration for flow cytometry might be helpful to better characterize the lymphocyte population if clinically indicated, Microfollicular architecture with minimal nuclear features of, Trabecular growth pattern of the cells with nuclear grooves and abundant nuclear pseudoinclusions, intratrabecular hyaline material, Nuclear changes of follicular cells with focal enlargement, grooves, prominent nucleoli and chromatin clearing in the lymphocytic background, An abundance of lymphocytes and plasma cells does not exclude the possibility of a coexisting, Numerous lymphocytes, few follicular cells, Elongated cells with pale chromatin, nuclear grooves and relatively large nucleoli, Spindle shaped morphology of the cell and nucleus, reminiscent of reparative epithelium in cervical Pap smears, Follicular variant of papillary thyroid carcinoma. et al. After these initial assessments, immunostains often aim to assess architecture, fibrosis, lymphoid aggregates, myeloid lineage maturity, and other related potential pathologies. , eds. It generally affects elderly patients presenting as a firm mass rapidly growing in the neck infiltrating extrathyroidal tissues, such as muscle, trachea, esophagus, skin, bone and cartilage[49]. Yassa Preparation Methods FNAs contain oncocytic cells with abundant granular cytoplasm, conventional nuclei, a papillary architecture, and a lymphoplasmacytic background. Inclusion in an NLM database does not imply endorsement of, or agreement with, LiVolsi Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. government site. Q: Can the core biopsy determine the blast count? An explicit statement of adequacy is optional. There are several exceptions to the numeric requirement of benign follicular cells. Layfield IR The atypical thyroid fine-needle aspiration: past, present, and future. 4';KiRQ5S&. PG Liquid-based preparation can also be made after a FNA pass, with the needle been rinsed in normal saline or ThinPrep solutions. Any specimen that contains abundant colloid is adequate (and benign), even if 6 groups of follicular cells are not identified; a sparsely cellular specimen with abundant colloid is, by implication, a predominantly macrofollicular nodule and therefore almost certainly benign. VA You order a bone marrow analysis for your patient. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. a. crush method b. cytocentrifuge c. fine needle aspiration d. liquid-based b. cytocentrifuge cytocentrifugation is the most common method of handling sparsely cellular specimens such as urine or spinal fluid For a thyroid FNA specimen to be satisfactory for evaluation (and benign), 6 . If these constitute the minority of the follicular cells, they have little significance and the FNA can be interpreted as benign. qA;`Yb]@b,@ "~Xbqs8J The main difference between the 5-tiered system and the 6-tiered system is that the DC III [atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)] category is included only in the 6-tier system, a category with considerable prevalence, as it is calculated 6%-7% according to various statistics[14]. The authors of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommended that the DC III (AUS/FLUS) category should not exceed 7% of the thyroid FNA diagnoses, and the risk of malignancy in this category should be in the range of 5% to 15%[23]. Cibas Zubair W. Baloch, MD, PhD, served as chair of the Terminology and Morphologic Criteria committee. As with the Bethesda System for cervical cytology, it is expected that subsequent workshops will lead to further refinements to this framework. FCs have cytomorphologic features that distinguish them from benign follicular nodules. Characteristically, distinct granules (calcitonin granules) are spotted in the cytoplasm of the cancer cells, as well as eccentric nuclei, indicating a plasmacytoid appearance to the tumor cells. Cases that demonstrate the nuclear features of papillary carcinoma are excluded from this category. Inadequate cellularity is defined as the presence of less than 6 groups of well-preserved follicular cells on each of at least two slides; (2) DC II Benign (Figure (Figure1).1). et al. To address terminology and other issues related to thyroid FNA, the National Cancer Institute (NCI) hosted the NCI Thyroid Fine Needle Aspiration State of the Science Conference. The meeting was organized by Andrea Abati, MD, and took place on October 22 and 23, 2007, in Bethesda, MD. Gharib The molecular testing proved to have a high specificity, although the sensitivity was quite low (60%). Q: Can flow cytometry be used for assessment of morphologic dysplasia? The method could also be applicable to other sparsely cellular samples such as cerebrospinal fluid (CSF) samples, or eye vitreous fluid samples. Hazard JB, Hawk WA, Crile G. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. The first draft of the committees summary documents was posted on the Web site and open for online discussion from May 1 to June 30, 2007. Quick tip: If the bone marrow is involved by metastatic carcinoma or clusters of cohesive plasma cells, these abnormal cells may not be amenable to aspiration and may cause a dry tap; however, a bone core biopsy will identify them. Before the specimen is transferred to a container with anticoagulant, some of the already clotted specimen may be submitted for permanent histology in formalin. The bone marrow aspirate smear. AA Baloch Lee TI, Yang HJ, Lin SY, Lee MT, Lin HD, Braverman LE, Tang KT. Any specimen that contains abundant colloid is considered adequate (and benign), even if 6 groups of follicular cells are not identified: A sparsely cellular specimen with abundant colloid is, by implication, a predominantly macrofollicular nodule and, therefore, almost certainly benign. Some thyroid FNAs are not easily classified into the benign, suspicious, or malignant categories. 2. This category includes the diagnoses of nodular goiter, nodular goiter with hyperplastic nodules, colloid nodules, cyst contents with/without benign follicular cells, and lymphocytic thyroiditis; (3) DC III Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance (Figure (Figure2).2). Management of a solitary thyroid nodule. But the nuclear and architectural changes of some PTCs are subtle and focal. Piana S, Frasoldati A, Ferrari M, Valcavi R, Froio E, Barbieri V, Pedroni C, Gardini G. Is a five-category reporting scheme for thyroid fine needle aspiration cytology accurate? B) 600 view of trilineage hematopoiesis. Histogenesis of medullary carcinoma of the thyroid. Explaining the use and composition of pre-fixatives and their effect on cellular morphology 4. Additionally, since the cells are smeared, they are technically three-dimensional, and morphology can be assessed. Results: We evaluated 5030 thyroid FNAs. The preparation of a "cell block" (a formalin-fixed, paraffin-embedded sediment of the urine sample) can be particularly useful because small pieces of tumor are often easier to evaluate with this preparation method. ES Specifically, the ultrasound image of the malignant nodule, as well as the patients general condition and age and other comorbidities should be taken into account when planning surgery. The cancer cells are also elongated, with a height-to-weight ratio of at least 3:1. It usually behaves as an indolent malignant tumor; however, an aggressive clinical course with decreased survival has been reported in some histologic variants of PTC[41]. Incidence of malignancy in thyroid nodules determined to be follicular lesions of undetermined significance on fine-needle aspiration. After this therapy the patients serum thyroglobulin levels should fall to undetectable levels. Mazzaferri EL. Consequently it is essential to distinguish this form of atypical calcification from true psammomatous calcifications with their concentrically laminated microscopic appearance[35]. This interpretation applies to cellular samples that are composed exclusively (or almost exclusively) of Hrthle cells. A) 20 view of the clot. L Whatever the cause, you have reason to request a hematopathology workup and investigative studies. Figure 3. Bongiovanni M, Crippa S, Baloch Z, Piana S, Spitale A, Pagni F, Mazzucchelli L, Di Bella C, Faquin W. Comparison of 5-tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology: a multi-institutional study. . Bongiovanni M, Krane JF, Cibas ES, Faquin WC. Faquin WC, Cibas ES, Renshaw AA. If the tumor is small and confined to the thyroid, thyroidectomy may be feasible; however, in most cases the tumor extends outside the thyroid gland preventing adequate resection[35]. EK It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Extra smeared slides are kept unstained for possible subsequent ancillary staining (e.g., MPO, PAS, esterases). A: Ideally, blasts should be calculated on the aspirate smear differential count; however, in cases where blasts express CD34, then a CD34 count on the core biopsy might be possible. Comparative findings of lymphocytic thyroiditis and thyroid lymphoma. ED Amyloid can be observed in close association with tumor cells, and can be distinguished from the thick colloid of PTC by performing a Congo-red stain. Logrono Last but not least, repeated FNAs will lead to a diagnosis in 72%-80% of indeterminate cases where repeated FNAs were needed. Deveci Bethesda, MD 20894, Web Policies In this selected population, 20% to 25% of patients with AUS prove to have cancer after surgery, but this is undoubtedly an overestimate of the risk for all AUS interpretations.2,10 The risk of malignancy is certainly lower and probably closer to 5% to 15%. Its clinical utilization is significant, as it can define whether a recently emerged thyroid nodule should be managed expectantly or surgically, and can assist in selecting the appropriate surgical procedure when necessary[3]. It is expected that the many benefits, clinical and investigational, of the Bethesda cervical terminology will also apply to the Bethesda thyroid terminology. The inherited forms are characterized by an autosomal dominant mode of inheritance and are associated with point mutations in the RET proto-oncogene on chromosome 10. On the other hand, these polarized spermatids also align across the plane of seminiferous epithelium, mimicking planar cell polarity (PCP . Immunohistochemistry test for specific biomarkers (i.e., calcitonin, thyroglobulin) will easily distinguish MTC from other thyroid malignancies. The most common sites are the lungs, bone, liver and brain. Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, et al. Aldinger KA, Samaan NA, Ibanez M, Hill CS. What happens after you place the orders, though? . Thyroid nodules is a very usual clinical problem, as it is diagnosed in approximately 60% of the general population in Western countries[1]. Because of the densely cellular composition of bone marrow, the imprints impart many cells directly on the slides. Three of the 28 specimens (11%) were sparsely cellular, and the rest (89%) were at least moderately cellular. LiVolsi et al. Fadda We reviewed the English literature regarding Thyroid Cytopathology systems in order to identify the most suitable methodology, taking into account our prospective as well. Edmund S. Cibas, MD, Syed Z. Ali, MD, The Bethesda System for Reporting Thyroid Cytopathology, American Journal of Clinical Pathology, Volume 132, Issue 5, November 2009, Pages 658665, https://doi.org/10.1309/AJCPPHLWMI3JV4LA. Employing genetic markers to improve diagnosis of thyroid tumor fine needle biopsy. This document summarizes several years of work, begun as a Web-based discussion, followed by a live conference, and culminating in the production of a print and online atlas. Many laboratories have traditionally considered a macrophages-only sample unsatisfactory and included them in the ND/UNS category, with the understanding that, because the parenchyma of the nodule has not been sampled, one cannot exclude a cystic papillary carcinoma. et al. CA Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, et al. A: No. Schnadig There was also a great difference regarding the percentage of the cases classified into the TIR 2/ DC II (benign) category (83.9%) compared with approximately half (55.4%) of the cases in the 6-tiered system. For that reason the aspirate is then classified as AUS/FLUS to indicate the uncertainty of the findings. Heitz Patients with the sporadic forms of MTC or the familial MTC are most often middle-aged (mean age 50 years old), except in familial cases, in which they are relatively younger. Cerutti JM. V Therefore, detailed neuronal morphology is required to understand normal neuronal function . Hahn SY, Shin JH, Han BK, Ko EY, Ko ES. Single neurons, as the basic unit of the brain, consist of a cell body and processes, including dendrites and axons. SL HHS Vulnerability Disclosure, Help What is one to do with the sparsely cellular specimen consisting mostly of microfollicles? Table: Comparative advantages and drawbacks of the marrow aspirate versus the core biopsy. The adequacy of a thyroid FNA is defined by both the quantity and quality of the cellular and colloid components. Giorgadze The cellular sample is typically monomorphic, although some specimens may appear pleomorphic; the cells are usually small or medium-sized, noncohesive, and contain an eccentrically located nuclei[35]. Experience of over 18,000 FNAs reported at the same institution during 1998-2007. Furthermore, various other thyroid FNA reporting systems have been created, in which the experiences of the pathologists and/or associated risks of malignancy have been taken into account. This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases. Clark There are three main methods of sample preparation; smears, liquid-based preparations, and cell block--these preparation methods may be used singly or in . Bethesda guidelines suspicious for malignancy, Ali: The Bethesda System for Reporting Thyroid Cytopathology - Definitions, Criteria and Explanatory Notes, 2nd Edition, 2018, Head Neck Pathol 2019 Oct 17 [Epub ahead of print], Noninvasive follicular thyroid neoplasm with papillary-like nuclear features, invasive follicular variant of papillary thyroid carcinoma, Bethesda category V suspicious for malignancy (SM) is used when some cytologic features are strongly suspected of malignancy but are not sufficient for a conclusive diagnosis (, Higher suspicion of malignancy than atypia of undetermined significance / follicular lesion of undetermined significance (AUS / FLUS) but lower suspicion than malignant, Molecular testing with mutation panels may be useful, particularly for potential noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) cases, Purpose of separating suspicious for malignancy from malignant is to preserve the very high positive predictive value of the malignant category without compromising the overall sensitivity of fine needle cytology aspiration, Used when cytology is strongly suspected of malignancy but is not sufficient for a conclusive diagnosis, Frequency < 5%, resection rate 70%, risk of malignancy 80% (NIFTP = malignant), 45 - 60% (NIFTP malignant), Most common histological diagnosis is papillary thyroid carcinoma (PTC) (, Risk of malignancy: 80% (NIFTP = malignant), 45 - 60% (NIFTP malignant) (, Suspicious for malignancy interpretation allows for more conservative management options (e.g. There are focal features suggestive of papillary carcinoma, including nuclear grooves, enlarged nuclei with pale chromatin, and alterations in nuclear contour and shape in an otherwise predominantly benign-appearing sample (especially in patients with Hashimoto thyroiditis or with abundant colloid and other benign-appearing follicular cells). Yang An official website of the United States government. Should atypical follicular cells in thyroid fine-needle aspirates be subclassified? Since the PTC-FV variant represents one of the most common causes of a false negative diagnosis of PTC, it is important to distinguish this PTC variant from other benign conditions, such as a follicular neoplasm or adenomatous nodule. Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle aspiration biopsies of thyroid nodules: a survey of clinicians and pathologists. The FNA specimens should be immediately processed for cytomorphologic analysis. JR 2023 ,https://www.hematology.org/education/trainees/fellows/trainee-news/2021/demystifying-the-bone-marrow-biopsy-a-hematopathology-primer. Leibowitz Layfield LJ, Cibas ES, Gharib H, Mandel SJ. Many of the HCLUS cases did not show any of the above features and were proved to be benign adenomas. Your patients cytopenias remain unexplained. LJ ES The management of cases with papillary microcarcinomas, i.e., tumors less than 1.0 cm in diameter, is still controversial. As a library, NLM provides access to scientific literature. Most (60%75%) prove to be papillary carcinomas, and the rest are usually FAs.2,10,12,30. The heterogeneity of this category precludes outlining all scenarios for which an AUS interpretation is appropriate. Benign cyst-lining cells are typically polygonal or fusiform with abundant cytoplasm, well-defined cellular borders, sometimes enlarged, grooved nuclei, and small distinct nucleoli. DeLellis It is the hope of all contributors to this project that this terminology proposal will be a valuable first step toward uniformity and consensus in the reporting of thyroid FNA interpretations.

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