Such changes may represent atypical but benign cyst lining cells, but a papillary carcinoma cannot be entirely excluded (ThinPrep, Papanicolaou stain). Layfield 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]. Your patients cytopenias remain unexplained. Psammoma bodies are occasionally seen in some aspirates, most possibly arising from calcification of epithelial tips. Cytological diagnosis of paucicellular variant of anaplastic carcinoma of thyroid: report of two cases. Demystifying the Bone Marrow Biopsy: A Hematopathology Primer et al. Ravetto Chemotherapy or radiotherapy usually cannot change the dismal prognosis of this cancer. Almost all patients with MTC have a significantly elevated serum calcitonin level, and in some cases these tumors can produce substances that can lead to paraneoplastic syndromes[35,44]. Due to the fact that the nuclei of this variant are darker than those of the regular PTC, the neoplastic cells of this variant may be mistaken for benign respiratory epithelial cells, or a colorectal neoplasm. The same general principle applies to other thyroid malignancies like medullary carcinoma and lymphoma, but these are encountered less frequently than PTC. $AJ !b``3iK If the nodule is almost entirely cystic, with no worrisome sonographic features, an endocrinologist might proceed as if the CFO were a benign result. Preoperative diagnostic categories of fine needle aspiration - PLOS Thyroid FNA is a well established procedure used in the preoperative diagnosis of thyroid nodules. In a large study with 1382 cases in a community practice setting, in the United States, Wu et al[32] diagnosed AUS in 27% of cases, ranging from 10% to 47% among pathologists participating in the study. The interpretation should provide clinically relevant information that will assist referring physicians in the management of patients. (A) A representative case classified as diagnostic category (DC) III (atypia of undetermined significance) showing sparsely cellular specimen (x15; scale bar, 200 m). Some cases may present with diagnostic difficulty if the specimen consists mainly of necrotic debris or if the tumor is extremely sclerotic (the paucicellular variant)[40,53]. Cytopreparatory Techniques | SpringerLink ZW After patient preparation, sedation, and the procedure itself, a bone marrow investigation provides four specimen types for pathologist review (Figure 1): the bone marrow core biopsy, the bone marrow touch imprint, the bone marrow aspirate smear, and the bone marrow clot particle. We also evaluated aspects of specimen quality that differed according to the use of ROSE. Hematoxylin-eosinstained sections of the clot particle. Oncocytic cells with nuclear features of papillary carcinoma are excluded from this interpretation. 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]. et al. Medullary carcinoma is highly metastatic, as tumor cells can be disseminated through hematogenous and metastatic routes to numerous sites, including cervical lymph nodes, liver, lung, bone, and adrenal glands. IB Megakaryocytes (yellow circles) can be seen at low power. Benson Benign cyst-lining cells are typically polygonal or fusiform with abundant cytoplasm, well-defined cellular borders, sometimes enlarged, grooved nuclei, and small distinct nucleoli. The diagnosis of this variant as a PTC is relatively easy, due to the numerous papillae and the coexisting intranuclear inclusions. In: Clark DP, Faquin WC, editors. Aspirate slides are also used for cytochemical and iron stains. The main purpose of thyroid FNA is to stratify higher risk patients for surgery, and to prevent unnecessary surgeries for benign conditions. Historically, terminology for thyroid FNA has varied significantly from one laboratory to another, creating confusion in some cases and hindering the sharing of clinically meaningful data among multiple institutions. Of those that prove to be malignant, many are FCs, but a significant proportion are follicular variants of papillary carcinoma.2,8,11,19. Highly cellular specimens are ideal for smeared preparations, whereas sparsely cellular specimens will require multiple centrifugation steps and special cell consolidation processing. 119 0 obj <>/Filter/FlateDecode/ID[<80B644DBD03A284F83277CD8A09960C6><94D1BF37A2B04B428378CFB47946E293>]/Index[92 53]/Info 91 0 R/Length 121/Prev 842357/Root 93 0 R/Size 145/Type/XRef/W[1 2 1]>>stream There are also sheets of follicular cells with large pale nuclei and some with nuclear grooves, but without intranuclear inclusions. Fine-needle aspiration in the work-up of thyroid nodules. Modified Bethesda system informing cytopathologic adequacy - Nature The general category FN/SFN is a self-sufficient interpretation; narrative comments that follow are optional. Report of the Thyroid Cancer Guidelines Update Group. Colombo H Gharib When this panel was used for specimens with indeterminate cytology, sensitivity was 27%, specificity was 95%, positive predictive value was 66%, and negative predictive value was 78%[60]. Anderson Cancer Center, Houston, Edward B. Stelow, MD, Department of Pathology, University of Virginia Health System, Charlottesville, Jerry Waisman, MD, Department of Pathology, New York University of Medicine, New York, Helen H. Wang, MD, DrPH, Department of Pathology, Beth Israel-Deaconess Medical Center, Boston, MA, Philippe Vielh, MD, PhD, Department of Pathology, Institut de Cancerologie Gustave Roussy, Villejuif, France, Grace C. H. Yang, MD, Department of Pathology, Weill Medical College of Cornell University, New York, NY, Matthew A. Zarka, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale. Notes and recommendations are not required but can be useful in certain circumstances. A As a two-dimensional section of islands of preserved marrow content, the same stains applied to the core biopsy can be applied to the clot sections. Mazzaferri EL. Venkatesh YS, Ordonez NG, Schultz PN, Hickey RC, Goepfert H, Samaan NA. H Gharib Rossi moc.oohay@sokaisime. In such laboratories, macrophages only often constituted the great majority of ND/UNS cases, with rates that ranged from 15% to 30%.2,9,11,12 Other laboratories considered the risk of a false-negative result negligible and reported macrophages only as benign.10,11 At the 2007 NCI Conference, it was decided that cyst-fluid-only (CFO) cases should be considered a clearly identified subset of ND/UNS. Clark The significance and clinical value of a CFO result depend in large part on sonographic correlation. Describing methods to: i. O The benefit of thyroid FNA derives in large part from the ability to make a reliably benign interpretation that avoids unnecessary surgery. . Employing genetic markers to improve diagnosis of thyroid tumor fine needle biopsy. ME Hazard JB, Hawk WA, Crile G. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. Review of the literature suggests a malignancy rate of 55%-75% for the suspicious category[8]. Every thyroid FNA must be evaluated for adequacy. 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. et al. A cellular specimen composed of Hrthle cells arranged in loosely cohesive sheets or isolated in a case diagnosed as Hrthle cell adenoma ( 40 pap stain on ThinPrep slide) (diagnostic categories IV). The atypia of undetermined significance/follicular lesion of undetermined significance: malignant ratio: a proposed performance measure for reporting in The Bethesda System for thyroid cytopathology. The AUS/FLUS category in the Bethesda system, represents aspirates that contain follicular, lymphoid, or other cell types with architectural and/or nuclear atypia that is more pronounced than that observed in benign lesions yet not sufficient to be characterized as suspicious for follicular neoplasm (SFN), or suspicious for malignancy[10]. Approximately 3% to 7% of thyroid FNAs have conclusive features of malignancy, and most are papillary carcinomas.1013 Malignant nodules are usually removed by thyroidectomy, with some exceptions (eg, metastatic tumors, non-Hodgkin lymphomas, and undifferentiated carcinomas). To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted the NCI Thyroid FNA State of the Science Conference. 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. The .gov means its official. In this pattern the nuclear enlargement is generalized in mild-to-moderate degree with evident nuclear grooves and mild nuclear pallor. An AUS result is obtained in 3% to 6% of thyroid FNAs.2,10 Higher rates likely represent overuse of this category when other interpretations are more appropriate. The risk of malignancy of AUS/FLUS was only 6%, a quite lower value than the one reported elsewhere. These specimens demonstrate inadequate cellularity, poor fixation and preservation, obscuring blood or ultrasound gel, or a combination of the above factors. In several countries the Cytological Communities have adopted the first system or the other, as there is still an ongoing dispute on whether the 5-tiered system or the 6-tiered system is more efficient[12]. {t+[O-]:KtJE]+ZhoZo$ZfqemI,W69l]g]EuGnWMGow" elP~G>6?{LsTY?R+-jW:E#x( xtT} . Redman R, Yoder BJ, Massoll NA. Oxford University Press is a department of the University of Oxford. The tumor cells show nuclear elongation, chromatin clearing, but nuclear grooves and inclusions are rare[40]. et al. Melton Bukhari MH, Niazi S, Hanif G, Qureshi SS, Munir M, Hasan M, Naeem S. An updated audit of fine needle aspiration cytology procedure of solitary thyroid nodule. See more. Q: Can flow cytometry be used for assessment of morphologic dysplasia? Frequency Calculator eNB ID Calculator . In this pattern benign follicular cells are detected, along with cells with nuclear enlargement, nuclear grooves, nuclear membrane irregularity, and/or nuclear molding, usually without any trace of intranuclear inclusions. Kinematic comparison between the knee after bicruciate stabilized total knee arthroplasty and the native knee: A cadaveric study. Touch preps can be imprinted, rolled, or crushed between glass to provide similar information. The specimen is fixed in paraffin and cut for slide preparation. The nuclear chromatin is similar to that seen in other neuroendocrine tumors, i.e., salt and pepper type (Figure (Figure7).7). MS Vimentin immunoexpression is also a common finding[52]. BRAF is not usually found in the follicular variant of papillary thyroid carcinoma, but is increasingly detectable in each step of dedifferentiation, including tall cell tumors and anaplastic cancer. Specimen Adequacy and Non-diagnostic Thyroid Nodules III B DA The disc is then wrapped in tissue paper and paraffin processed as for a biopsy specimen. et al. The Bethesda System for Reporting Thyroid cytopathology. Understanding the capabilities and potential within each component may explain both the process and usefulness of obtaining optimal specimens and elucidate exactly how tissue is evaluated. Almost simultaneously, in Europe, the British Thyroid Association-Royal College of Physicians and the Italian Society for Anatomic Pathology and Cytopathology-International Academy of Pathology (SIAPEC-IAP) thyroid reporting systems, each comprised of 5 diagnostic classes, have been introduced[10,11]. 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 Quick tip: Flow cytometry cannot be performed on the clot section after the clot has set and after fixation in formalin. LJ In FNA specimens of this variant, the cancer cells appear more profuse, granular or vacuolated compared to regular PTC. The sensitivity of thyroid FNA for medullary thyroid carcinoma (MTC) is considered high, actually it is higher than the sensitivity of FNA for PTC[36]. This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases. Chung Goellner 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]. BRAF testing has been coupled successfully with the Bethesda Thyroid FNA classification system to offer molecular quality assurance on positive samples, as well as a diagnostic upgrade on samples of indeterminate diagnostic categories, such as AUS/FLUS and SFN/SHN[54]. The nuclear chromatin appears as salt and pepper type in a medullary carcinoma case ( 40 pap stain on ThinPrep slide) (diagnostic categories VI). PDF The Bethesda System for Reporting Thyroid Cytopathology This variant is sometimes difficult to diagnose, because in some cases the characteristic neoplastic cells are sparsely evident in the mass. We thank Diane Solomon, MD, for review of the manuscript and helpful comments. Albores-Saavedra J, Wu J. Nuclear grooves become an important diagnostic feature when associated with an oval, enlarged nucleus with fine chromatin[41]. Papaparaskeva K, Nagel H, Droese M. Cytologic diagnosis of medullary carcinoma of the thyroid gland. VanderLaan PA, Marqusee E, Krane JF. Before The risk of malignancy for an AUS nodule is difficult to ascertain because only a minority of cases in this category have surgical follow-up. The specimen is usually cellular with polygonal cells in loose papillary clusters with abundant eosinophilic cytoplasm. LiVolsi . Anaplastic carcinoma of the thyroid. Comparative findings of lymphocytic thyroiditis and thyroid lymphoma. 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). The majority of the thyroid FNA specimens, in the range of 60% to 70%, are classified as benign, whereas approximately 20% to 30% fall into the 3 categories of suspicious for follicular neoplasm, suspicious for malignancy, and malignant[19]. Palpation-guided FNA can be performed when a thyroid nodule is easily palpable (> 1.0 cm in diameter) and rather solid. Ancillary testing (eg, immunohistochemical analysis, flow cytometry) in borderline cases is usually more helpful with medullary carcinoma and lymphoma than with PTC. The spindle-shaped morphology of these cells is helpful in distinguishing these cells from PTC[24,34]. 2023 ,https://www.hematology.org/education/trainees/fellows/trainee-news/2021/demystifying-the-bone-marrow-biopsy-a-hematopathology-primer. On the other hand, it might be clinically equivalent to an ND result if the sonographic features are worrisome and the endocrinologist is not convinced that the sample is representative. The nuclei are hyperchromatic, uniform in size and shape, and with indinstinct nucleoli. Remedy: The supernatant may not have been completely poured off resulting in dilution of the cell pellet. While there are advantages and disadvantages to each component regarding turnaround time, comprehensiveness, and diagnostic utility (Table), their synergism provides ample information for your consultant hematopathologists. The morphology is similar to that seen on the core biopsy. Author contributions: Misiakos EP, Margari N, Meristoudis C, Petropoulos K, and Spathis A contributed significantly in preparation, collection of data, writing and critically revising the manuscript; Machairas N, Schizas D, Karakitsos P and Machairas A contributed in data analysis, and writing the manuscript. CellMapper is a crowd-sourced cellular tower and coverage mapping service. 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. Despite the fact that not all PTC were detected by this panel, a positive molecular test helped to refine the FLUS cases into high-risk and low-risk categories[61]. A) 20 view of the bone marrow aspirate reveals a deeply basophilic smear of cells. DP Giorgadze The main purpose of thyroid FNA is to identify patients with higher risk for malignancy, and to prevent unnecessary surgeries for benign conditions. Examine microscopically and determine the number of drops that will produce satisfactory cellularity on the slide. 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]. Figure 5. Those that are resected represent a selected population of patients with repeated AUS results or patients with worrisome clinical or sonographic findings. LiVolsi Cantara et al[59] evaluated this panel of tumor-associated mutations in thyroid FNA samples. Pu The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. Deveci A review of the English literature was conducted, and data were analyzed and summarized and integrated from the authors perspective. The FNA specimens show enlarged follicular cells arranged in monolayer sheets and follicular groups in a background of thin and thick colloid (Figure (Figure6).6). These cells constitute more than 50% of tumor volume[44]. See: http://creativecommons.org/licenses/by-nc/4.0/, P- Reviewer: Eilers SG, Li XL S- Editor: Qiu S L- Editor: A E- Editor: Liu SQ, National Library of Medicine Sparsely Definition & Meaning | Dictionary.com The rate of malignancy in FNA-BRAF positive nodules has been shown to be 99.8%[55]. Research is directed to the identification of molecular markers that, in conjunction with FNA, can identify patients with a malignant nodule. The clot sections, core biopsy, marrow aspirate, and touch preps all contribute to the overall assessment of patients collected marrow. Therefore, in the majority of patients in the AUS/FLUS category (72%-80%) the diagnosis will be resolved by repeat FNA, although 20%-28% of them will have AUS/FLUS on the repeat aspirate and thus require surgery. The above panel correctly identified cancer in 78.2%, whereas cytology identified 58.9% of the thyroid cancers. Since recurrent PTC typically secretes thyroglobulin, serum monitoring of thyroglobulin serves as a useful tumor marker for recurrent PTC[35]. Zubair W. Baloch, MD, PhD, served as chair of the Terminology and Morphologic Criteria committee. A suspicious interpretation is rendered only when the majority of the follicular cells are arranged in abnormal architectural groupings (microfollicles, crowded trabeculae). Gross specimen was measuring about 2x2x1.5 cm in size, soft in consistency, brownish black in color and roughly oval in shape [Table/Fig-4]. Ultrasound guidance is preferable than palpation-guided FNA for small nodules (< 1 cm), cystic lesions and when a prior FNA is nondiagnostic[13]. Alternatively, a more prominent than usual population of microfollicles may occur (and may be disproportionately apparent on a minority of smears) in a moderately or markedly cellular sample, but the overall proportion of microfollicles is not sufficient for a diagnosis of follicular neoplasm/suspicious for follicular neoplasm. Herein lies everything you were afraid to ask. In 2007 the Royal College of Pathologists introduced a new thyroid FNA reporting system, which was based on the existing United Kingdom terminology, but with some alterations, like new subcategories (i.e., c for cystic lesions, a for atypia, f for follicular neoplasm). The discussions and conclusions regarding terminology and morphologic criteria from the NCI meeting, summarized in the publications by Baloch et al,4,5 form the framework for the terminology presented here and in atlas form.3 It is intended as a flexible framework that can be modified to suit the needs of the particular laboratory and the patients it serves. Some thyroid FNAs are not easily classified into the benign, suspicious, or malignant categories. The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer. Therefore, the DC III (AUS/FLUS) cases are managed conservatively with repeat FNAs, whereas the DC IV, DC V, and DC VI cases, and TIR 3, TIR 4 and TIR 5 cases respectively, are managed operatively, with thyroid lobectomy or total thyroidectomy. Some laboratories, for example, may want to state the risk of malignancy associated with the general category, based on their own data or that found in the literature (Table 2). Contribution of molecular testing to thyroid fine-needle aspiration cytology of follicular lesion of undetermined significance/atypia of undetermined significance. Such cases occur with some regularity, and they are best classified as suspicious for malignancy, qualified as suspicious for papillary carcinoma. Nodules called suspicious for papillary carcinoma are resected by lobectomy or thyroidectomy. Jan 2018 - Present5 years 4 months. A: Ideally, no. They can be readily classified as malignant due to nuclear pleomorphism, chromatin clumping, necrosis, atypical mitoses and other malignant features[40]. hbbd``b`$Ks ^ Cellularity may in part be due to the LBC technique in comparison with smears made after sedimentation, . Charge Nurse Job Denver Colorado USA,Research/Development Baloch The presence of true psammoma bodies with concentric laminations is highly suggestive of PTC; however the presence of psammoma bodies in cystic thyroid lesions is not diagnostic. Royal College of Physicians. et al. Schnadig The aspirates from anaplastic carcinoma do not pose any diagnostic difficulties. This technique is conclusive for the majority of cases suspicious for PTC, lymphoma, or follicular neoplasm after previous incomplete FNA results. , 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]. sparsely cellular sample but one that is comprised mostly of microfollicles. Planar cell polarity (PCP) proteins and spermatogenesis At low magnification, aspirates of PTC are typically cellular, epithelium-rich structures. This category also includes cases with a predominant population of Hurthle cells; these cases are labelled Hurthle cell neoplasm (Figure (Figure3).3). (iii) Cytologic and architectural atypia: 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. However; less than 10% of them represent malignant tumors. Suspicious for medullary thyroid carcinoma, Suspicious for papillary thyroid carcinoma, Vote for your favorite image from the PathologyOutlines.com Directory. The hallmark of this diagnostic category is a disturbed cytoarchitecture: follicular cells are arranged predominantly in microfollicular or trabecular arrangements. Since this is a liquid sample, it does not need to undergo decalcification, can be smeared onto a slide and stained relatively quickly, used for flow cytometry (which needs unfixed, liquid cells), and sent fresh for molecular analysis. VA This is the most common variant of PTC and is characterized by a predominantly follicular architecture. While the V600E and K601E mutations were almost equally observed in the AUS/FLUS category, there was a slight predominance of K601E mutation in SFN/SHN category. A benign follicular nodule is the most common benign pattern that is, an adequately cellular specimen composed of varying proportions of colloid and benign follicular cells arranged as macrofollicle and macrofollicle fragments. Pan-keratin is the most reliable positive immunostain in UTCs, acquiring an expression ranging from 50% to 100%. Determination of cellular phenotype (what the cell expresses on its surface, or in its cytoplasm) on an aspirate is carried out by flow cytometry. These include hypocellular smears with extensive cystic degeneration with rare follicular cells with nuclear atypia indicative of PTC. V However, there are cases with diagnostic uncertainty due to suboptimal sampling or preservation, and overlapping cytomorphologic features with other thyroid conditions. Before the routine use of thyroid FNA, the percentage of surgically resected thyroid nodules that were malignant was 14%.1 With current thyroid FNA practice, the percentage of resected nodules that are malignant surpasses 50%.2. ES C Because of its aggressive, infiltrative nature, patients with an undifferentiated carcinoma often require a tracheostomy as an emergency procedure. The four components of a routine bone marrow analysis. As a result they may be not diagnosed through the FNA test, resulting in a false-negative test[44]. Yang Due to the decalcification and need for fixation, bone core biopsy slides are usually not available to review until the following day. Sparsely definition, in a thinly distributed way; not thickly or densely: Michigan's Upper Peninsula is very sparsely populated, as more than 90% of it is forested. Walfish The clinical and diagnostic impact of using standard criteria of adequacy assessment and diagnostic terminology on thyroid nodule fine needle aspiration. The cells have abundant pink cytoplasm, basally located nuclei and nuclear features of conventional PTC. Issue: Non-Gyn specimen slide is sparsely cellular when ample specimen collected and centrifuged cell pellet is visibly adequate. . Papillary structures are not as common as it was believed, because intact papillae are often too large to enter the fine needle or are disrupted during the preparation of the smears. KH ES Immediately after the core biopsy is obtained, the procured tissue is "touched" several times onto glass slides. Chronic sialadenitis: sparsely cellular specimen with fewer lymphocytes and germinal center fragments; no characteristic lymphoepithelial islands. J After these initial assessments, immunostains often aim to assess architecture, fibrosis, lymphoid aggregates, myeloid lineage maturity, and other related potential pathologies.
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