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). To collect as many cells as possible from sparsely cellular urine, the specimen should have which of the following techniques applied? The most common malignant diagnosis made after surgery in cases initially classified as AUS/FLUS is PTC, usually of the follicular variant (PTC-FV)[24,25]. Figure 1. For patients with large tumors (> 4 cm), the best approach could be a total thyroidectomy, considering the fact that large tumors have an elevated risk of malignancy[40]. 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. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. (General, Ortho . Sparsely cellular specimens: Sample w/ not many cells in suspension can be made more conc'd by Cytospin or centrifugation preparation: 1mL properly prepared cell suspension in funnel of cytospin, centrifuge, cells will be deposited on slide & fluid absorbed by filter paper: Problem: bloody specimens: 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 In this study the AUS category was further subdivided into HCLUS (atypical cells rule out Hurthle cell neoplasm) and FLUS. Rabaglia JL, Kabbani W, Wallace L, Holt S, Watumull L, Pruitt J, Snyder WH, Nwariaku FE. Unlike the core biopsy, decalcification is not required for the clot section. Megakaryocytes (yellow circles) can be seen at low power. Role of repeat fine-needle aspiration biopsy (FNAB) in the management of thyroid nodules. Histologic trends in thyroid cancer 1969-1993: a clinico-pathologic analysis of the relative proportion of anaplastic carcinoma of the thyroid. If the nodule is almost entirely cystic, with no worrisome sonographic features, an endocrinologist might proceed as if the CFO were a benign result. . Additional benign findings (eg, black thyroid, reactive changes, radiation changes, cyst lining cells) can be mentioned as descriptive diagnoses at the discretion of the cytopathologist. Extra smeared slides are kept unstained for possible subsequent ancillary staining (e.g., MPO, PAS, esterases). This category also includes cases with a predominant population of Hurthle cells; these cases are labelled Hurthle cell neoplasm (Figure (Figure3).3). We thank Diane Solomon, MD, for review of the manuscript and helpful comments. As such, the redundancies in place discussed here and the compound output of the four major components have synergistic effects on diagnostic evaluation. . 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]. Whenever a specific diagnosis (eg, lymphocytic thyroiditis) can be rendered and whenever there is any atypia, the specimen is, by definition, adequate for evaluation. Cytopreparatory Techniques | SpringerLink Determination of cellular phenotype (what the cell expresses on its surface, or in its cytoplasm) on an aspirate is carried out by flow cytometry. Preparations for the conference began 18 months earlier with the designation of a steering committee, coordination with cosponsoring organizations, and the establishment of a dedicated, permanent Web site. A: Probably, yes. . Review of the literature suggests a malignancy rate of 55%-75% for the suspicious category[8]. Such patients were followed clinically with periodic physical and sonographic examinations. Since it is a two-dimensional specimen and reveals cells in cut section, it is not ideal for assessment of dysplasia (a marrow aspirate is preferred), but it is extremely useful in identifying possible reasons for a dry tap (a term for when liquid marrow cannot be aspirated during the bone marrow procedure), since the architecture can show fibrosis, sheets of cohesive plasma cells, or metastatic tumor which could result in a dry tap. MTC was first described by Horn et al[45] in 1951, and it was first recognized as a unique clinicopathological entity by Hazard et al[46], in 1959. It allows classification of nodules as benign or malignant, and patients with malignant nodules are scheduled for surgery. et al. Schnadig 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. Proposal of the SIAPEC-IAP Italian Consensus Working Group. ( a) In this sparsely cellular specimen, some cells have abundant cytoplasm, enlarged nuclei, and prominent nucleoli. Cantara S, Capezzone M, Marchisotta S, Capuano S, Busonero G, Toti P, Di Santo A, Caruso G, Carli AF, Brilli L, et al. Deveci Because of the densely cellular composition of bone marrow, the imprints impart many cells directly on the slides. The impact of atypia/follicular lesion of undetermined significance on the rate of malignancy in thyroid fine-needle aspiration: evaluation of the Bethesda System for Reporting Thyroid Cytopathology. Inadequate samples are reported as nondiagnostic (ND) or unsatisfactory (UNS). The use of molecular markers can further increase the diagnostic value of FNA samples for the detection of thyroid cancer. PTC accounts for 80% of all thyroid malignancies and occurs more often in women with a 3:1 female-to-male ratio, with a mean age at presentation 30-40 years. 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. LiVolsi 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. Fadda Core tip: Fine-needle aspiration (FNA) cytology is widely used for the diagnosis of thyroid nodules, although cases with indeterminate results are not rare. Immediately after the core biopsy is obtained, the procured tissue is "touched" several times onto glass slides. A Amrikachi Recognizably benign cellular changes (eg, typical cyst lining cells, focal Hrthle cell change, changes ascribed to radioiodine therapy, black thyroid) should not be interpreted as AUS. Consequently it is essential to distinguish this form of atypical calcification from true psammomatous calcifications with their concentrically laminated microscopic appearance[35]. MTC represents 3%-12% of thyroid cancers, the majority of which are sporadic. A uniform reporting system for thyroid FNA will facilitate effective communication among cytopathologists, endocrinologists, surgeons, radiologists, and other health care providers; facilitate cytologic-histologic correlation for thyroid diseases; facilitate research into the epidemiology, molecular biology, pathology, and diagnosis of thyroid diseases, particularly neoplasia; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies. Thyroid FNA is a well established procedure used in the preoperative diagnosis of thyroid nodules. Different cell types of neurons form complicated circuits in the brain. The 2017 Bethesda System for Reporting Thyroid Cytopathology McHenry Thyroid nodules is a very usual clinical problem, as it is diagnosed in approximately 60% of the general population in Western countries[1]. It is important to note that only nodules with atypia of undetermined significance should be placed in the AUS category. Top Users Networks Stats . 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. An effort should be made to use this category as a last resort and limit its use to approximately 7% or fewer of all thyroid FNAs. 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. FVPTC is characterized cytologically by the paucity of diagnostic nuclear features. Federal government websites often end in .gov or .mil. Giorgadze Cyst lining cells are usually elongated, containing pale chromatin, with sparsely found intranuclear grooves, large nucleoli, and always associated with hemosiderin-laden macrophages and benign-appearing macrofollicle fragments. Clinical outcome for atypia of undetermined significance in thyroid fine-needle aspirations: should repeated fna be the preferred initial approach? A specimen is considered as suspicious for malignancy (SFM), when some features of malignancy (usually PTC features) exist, but the findings are not sufficient for a definitive diagnosis[9]. Baloch ZW, LiVolsi VA. Cytologic and architectural mimics of papillary thyroid carcinoma. Logrono The Bethesda System for Reporting Thyroid Cytopathology - OUP Academic 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. Moses W, Weng J, Sansano I, Peng M, Khanafshar E, Ljung BM, Duh QY, Clark OH, Kebebew E. Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. et al. Last but not least, repeated FNAs will lead to a diagnosis in 72%-80% of indeterminate cases where repeated FNAs were needed. ND/UNS results occur in 2% to 20% of cases but ideally should be limited to no more than 10% of thyroid FNAs, excluding samples composed exclusively of macrophages.810, Specimens that consist only of cyst contents (macrophages) are problematic. A minor population of macrofollicles (intact spheres and fragments) can be present. The 2-day live conference in October 2007, attended by 154 registrants including pathologists, endocrinologists, surgeons, and radiologists, gave the committees an in-depth opportunity to present their conclusions and debate controversial areas. Benign follicular nodules often have a small population of microfollicles and crowded groups. It is a point of great significance that Ohori et al[56] found a greater percentage of BRAF-mutated (V600E, K601E, and others) cases in the AUS/FLUS and SFN/SFN categories, rendering BRAF mutational testing a useful predictor of PTC diagnosis in these indeterminate cases. Cytologic features of histologically proven follicular adenoma and Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any. How do the different parts of a bone marrow workup relate to more in-depth analyses of morphology, markers, lineages, and overall diagnostic information? Papaparaskeva K, Nagel H, Droese M. Cytologic diagnosis of medullary carcinoma of the thyroid gland. V Kocjan G, Cochand-Priollet B, de Agustin PP, Bourgain C, Chandra A, Daneshbod Y, Deery A, Duskova J, Ersoz C, Fadda G, et al. 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. The neoplastic cells resemble Hurthle cells but have diagnostic nuclear features of PTC. Fine-needle aspiration biopsy (FNAB) showed sparsely cellular smears with a finely granular background and groups of cells arranged in 3-dimensional clusters and papillary formation (Figure 2, arrow). The 6 general diagnostic categories are shown in bold type in Table 1. However, in almost 25%-30% of cases, MTC is inherited, and is associated with one of three familial syndromes: Multiple endocrine neoplasia (MEN) syndrome type 2A (Sipples syndrome), MEN type 2B (mucosa neuroma syndrome or Gorlins syndrome), and familial MTC[35]. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Sherman SI, Tuttle RM. B) 1,000 view. 2021 L Street NW, Suite 900,Washington, DC 20036, Phone 202-776-0544Toll Free 866-828-1231Fax 202-776-0545, Copyright 2023 by American Society of Hematology, Support Opportunities|Privacy Policy|Terms of Service|Contact Us, Helping hematologists conquer blood diseases worldwide, Demystifying the Bone Marrow Biopsy: A Hematopathology Primer, https://www.hematology.org/education/trainees/fellows/trainee-news/2021/demystifying-the-bone-marrow-biopsy-a-hematopathology-primer, Relative quantity of different cell types, Provides material for flow and molecular studies. 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. 8600 Rockville Pike 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]. Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Pitman MB, Abati A. Vimentin immunoexpression is also a common finding[52]. Report of the Thyroid Cancer Guidelines Update Group. Baloch ZW, LiVolsi VA. Fine-needle aspiration of the thyroid: today and tomorrow. endstream endobj startxref "Demystifying the Bone Marrow Biopsy: A Hematopathology Primer, 01 May. 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). RT There are also sheets of follicular cells with large pale nuclei and some with nuclear grooves, but without intranuclear inclusions. Colombo In these SFN/SFN and AUS/FLUS cases with the K601E mutation, the cytomorphology of the PTC specimens prevented a more definitive diagnosis, in contrast to cases where the V600E mutation was observed, whether the diagnosis resolved to a classic (CL) subtype, tall cell variant (TCV) subtype, or a solid (SD) PTC diagnosis. Lymphadenopathy is also present in one quarter to half of patients, whereas the lungs is the most common site of metastases[49,50]. [2] First documented in HeLa cells, where there are generally 10-30 per nucleus, [3] Paraspeckles are now known to also exist in all human primary cells, transformed cell lines and . 2023 ,https://www.hematology.org/education/trainees/fellows/trainee-news/2021/demystifying-the-bone-marrow-biopsy-a-hematopathology-primer. Note granulocytic precursors (arrows) and erythroid cells (arrow heads). View an interactive bone marrow core biopsy online. Because the nuclear changes of FVPTC are subtle, the majority of cytologic samples are often diagnosed as suspicious for PTC. They can be readily classified as malignant due to nuclear pleomorphism, chromatin clumping, necrosis, atypical mitoses and other malignant features[40]. Additional descriptive comments (beyond such subcategorization) are optional and left to the discretion of the cytopathologist. 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. Baloch The nuclei are enlarged, with usually an oval or irregular shape, and include intense nuclear grooves and inclusions. But the nuclear and architectural changes of some PTCs are subtle and focal. Figure 5. Lymphoepithelial cyst. Effect of the Bethesda system for reporting thyroid cytopathology on thyroidectomy rates and malignancy risk in cytologically indeterminate lesions. Theoharis C, Roman S, Sosa JA. Renshaw AA. The purpose of this diagnostic category is to identify a nodule that might be a follicular carcinoma (FC) and triage it for surgical lobectomy. Descriptive comments that follow are used to subclassify the benign interpretation. Nuclear grooves become an important diagnostic feature when associated with an oval, enlarged nucleus with fine chromatin[41]. These specimens typically show sheets of bland thyroid follicular cells, which represent flattened macrofollicles. Incidence of malignancy in thyroid nodules determined to be follicular lesions of undetermined significance on fine-needle aspiration. In other cases it is sparsely cellular and contains atypical lymphoid cells. Hypocellular or paucispicular smears preclude these assessments, which are not easily (or accurately) performed on the core biopsy (Table). et al. Cerutti JM. There were several subsequent drafts and online discussion periods (August 15 to September 30, 2007, and November 30 to December 15, 2007). Clark DP, Faquin WC. A: No. B Cibas ES. Without individual cells to analyze through flow cytometric methods, the clot section is limited to only tissue-type immunostaining. An explicit statement of adequacy is optional. (2021).Demystifying the Bone Marrow Biopsy: A Hematopathology Primer. The four components of a routine bone marrow analysis. The nuclei are hyperchromatic, uniform in size and shape, and with indinstinct nucleoli. 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]. The Paris System for Reporting Urinary Cytology tried lately to address adequacy. 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]. Therefore the diagnosis SFM, suspicious for thyroid carcinoma is an indication for surgery. Gupta Research is directed to the identification of molecular markers that, in conjunction with FNA, can identify patients with a malignant nodule. They can be sparsely cellular, because of the marked fibrosis and hyalinization encountered in some cases[19,51]. Sparsely Definition & Meaning | Dictionary.com Human immunodeficiency virus (HIV)-associated cystic lymphoepithelial lesions. 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. Cochand-Priollet As a result, 3 to 15 glass slides from each patient are taken and examined, which can be either Giemsa- or Papanikolaou-stained slides[14]. In this pattern cystic degeneration with hemosiderin-laden macrophages is present. For a thyroid FNA specimen to be satisfactory for evaluation (and benign), 6 . LiVolsi Lloyd 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. These specimens demonstrate inadequate cellularity, poor fixation and preservation, obscuring blood or ultrasound gel, or a combination of the above factors. Those that are resected represent a selected population of patients with repeated AUS results or patients with worrisome clinical or sonographic findings. Ultrasonography-guided core needle biopsy for the thyroid nodule: does the procedure hold any benefit for the diagnosis when fine-needle aspiration cytology analysis shows inconclusive results? Pathology and Genetics of Tumours of Endocrine Organs, Genetic and biological subgroups of low-stage follicular thyroid cancer. Loose cellular material can be held together to make into a cell block in all of the following EXCEPT a. agar b. albumin c. blood clot d. resin resin A slide of breast fluid has the cells washing off during staining. Heitz Demystifying the Bone Marrow Biopsy: A Hematopathology Primer The morphology is similar to that seen on the core biopsy. These features could be intranuclear inclusions, nuclear grooves, or psammoma calcifications; (6) DC VI Malignant (Figures (Figures55--7).7). 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. One subcategory includes cases with a microfollicular pattern and minimal colloid, that is, follicular lesion of undetermined significance (FLUS). . 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. When evaluating an undifferentiated carcinoma using immunocytochemistry a basic immunopanel should include cytokeratins, calcitonin, leucocyte common antigen, carcinoembryonic antigen, thyroglobulin, chromogranin, and TTF-1. (iii) Cytologic and architectural atypia:
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sparsely cellular specimen