Cellular crowding and overlapping are conspicuous, and the follicular cells are usually larger than normal. Open in a separate window The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. Since there is a considerable proportion of patients with a thyroid nodule who remain undiagnosed with FNA, molecular biology could be very helpful at that point. The molecular testing proved to have a high specificity, although the sensitivity was quite low (60%). Hematopathologists can assess morphology, histologic architecture, and immunologic and phenotype profiles (Figure 2) across all four components to create a comprehensive report for your patient. The cytological diagnosis of PTC is based mainly on the characteristic nuclear morphology. 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. A moderately or markedly cellular sample is composed of a virtually exclusive population of Hrthle cells, yet the clinical setting suggests a benign Hrthle cell nodule, eg. Therefore, it is not prudent to remove every thyroid nodule we encounter in our medical practice. 2023 ,https://www.hematology.org/education/trainees/fellows/trainee-news/2021/demystifying-the-bone-marrow-biopsy-a-hematopathology-primer. Enter your ZIP Code, or City and State below to find the stores nearest you and a listing of the device models available within each. Johnson 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. JR 4';KiRQ5S&. As with the Bethesda System for cervical cytology, it is expected that subsequent workshops will lead to further refinements to this framework. 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. Proposal of the SIAPEC-IAP Italian Consensus Working Group. These indeterminate aspirates may present with architectural atypia or nuclear atypia[21]. However, the percentage of the cases classified into the TIR 3/DC IV (follicular proliferation/neoplasm) category was substantially smaller (4.6%) in the 5-tiered system compared with the 6-tiered system (23.8%). Lymphoepithelial cyst. et al. . Careers, Unable to load your collection due to an error. 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. For a thyroid FNA specimen to be satisfactory for evaluation (and benign), 6 . Fleisher To collect as many cells as possible from sparsely cellular urine, the specimen should have which of the following techniques applied? The malignancy rate of the AUS/FLUS category is estimated to be between 5% and 15%[10], which is intermediate between that of the benign category (0%-3%) and that of the SFN category (15%-30%). Due to the decalcification and need for fixation, bone core biopsy slides are usually not available to review until the following day. 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]. Two-dimensional fixed tissue specimens from the biopsy and clot are easily stained with immunohistochemical methods while three-dimensional, liquid cellular content can be assessed with flow cytometry. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Even neurons of the same type show various subtle process characteristics to fit into the diverse neural circuits. "Demystifying the Bone Marrow Biopsy: A Hematopathology Primer." Unless specified as ND/UNS, the FNA specimen is considered adequate for evaluation. 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. Remedy: The supernatant may not have been completely poured off resulting in dilution of the cell pellet. Primary angiosarcoma of breast: A case report and literature review. The neoplastic cells show a greater cell height than the tall cell variant and lack the obvious nuclear features of PTC. It is important to note that only nodules with atypia of undetermined significance should be placed in the AUS category. 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 Warthin's tumor : the presence of oncocytic epithelium. The contribution of intraoperative frozen section after a suspicious FNA diagnosis is questionable, as Lee et al[38] have demonstrated that preoperative FNA has a higher sensitivity than frozen section in detecting PTC. Sarasota Memorial Health Care System. While their individual turnaround times vary, these specimens are usually reported together to make sure all aspects are accounted for, which can take approximately three days on average. Cibas The significance and clinical value of a CFO result depend in large part on sonographic correlation. For example, increased serum calcitonin levels and/or strong immunoresponce of chromogranin which is disclosed after multiple FNA tests can indicate the diagnosis of a medullary carcinoma. Patients with sporadic MTC present with a solitary, circumscribed thyroid nodule, usually in the middle to upper-outer half of the thyroid gland. In some cases more diffuse but mild nuclear changes may exist with nuclear enlargement, crowding, and pallor, but without other characteristics, such as nuclear contour irregularities, grooves and nuclear pseudoinclusions, suggestive of a PTC. Top Users Networks Stats . Wasserman Additional descriptive comments (beyond such subcategorization) are optional and left to the discretion of the cytopathologist. The nucleoli are usually small and eccentric; however, rare oncocytic variants of PTC can show prominent nucleoli. There are cyst-lining cells that may appear atypical owing to the presence of nuclear grooves, prominent nucleoli, elongated nuclei and cytoplasm, and/or intranuclear cytoplasmic inclusions in an otherwise predominantly benign-appearing sample.16. Experience of over 18,000 FNAs reported at the same institution during 1998-2007. )TEgX>T|*Q0%K5P- HVe t {t+[O-]:KtJE]+ZhoZo$ZfqemI,W69l]g]EuGnWMGow" elP~G>6?{LsTY?R+-jW:E#x( xtT} . Figure 3. Chemotherapy or radiotherapy usually cannot change the dismal prognosis of this cancer. Fine-needle aspiration (FNA) cytology is an important diagnostic tool in patients with thyroid lesions. The differential diagnosis for the latter includes hyperplastic adenomatoid nodule with Hurthle cell change, Hurthle cell adenoma, and Hurthle cell carcinoma; (5) DC V Suspicious for malignancy. Note the trabecular bone (*) with trilineage hematopoiesis including megakaryocytes, granulocytic precursors, and erythroid islands presented in 2D following formalin fixation and paraffin processing. Q: Can your pathologist tell you what the core biopsy shows on the same day as the procedure? VA Interestingly all predicted cancer proved to be papillary thyroid carcinoma in the final histology[59]. V Cytologic preparations typically have high cellularity, and colloid is scant or absent. SL The site is secure. Fine-needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Anaplastic carcinoma of the thyroid. Alexander Grant Evangelos P Misiakos, Dimitrios Schizas, Konstantinos Petropoulos, Anastasios Machairas, 3, Niki Margari, Christos Meristoudis, Aris Spathis, Petros Karakitsos, Department of Cytopathology, Attikon University Hospital, University of Athens School of Medicine, Attica, 12462 Athens, Greece. This category includes specimens with unequivocal cytologic evidence of a malignant neoplasm. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. The prognosis of this tumor is good; death due to PTC is rare. Horn RC. You order a bone marrow analysis for your patient. Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle aspiration biopsies of thyroid nodules: a survey of clinicians and pathologists. . ES 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. The FNA aspirates of an MTC are usually composed of numerous cells, either presenting in cell aggregates or as a mixture of non-cohesive cells. Filie AC, Asa SL, Geisinger KR, Logani S, Merino M, Nikiforov YE, Clark DP. 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. These small tumors may be incidentally discovered in glands removed for other reasons, they are treated with thyroidectomy; these patients usually do not need systemic 131I therapy and do not require a second-stage completion thyroidectomy. The management of cases with papillary microcarcinomas, i.e., tumors less than 1.0 cm in diameter, is still controversial. H Last but not least, repeated FNAs will lead to a diagnosis in 72%-80% of indeterminate cases where repeated FNAs were needed. Every thyroid FNA must be evaluated for adequacy. Copyright 2023 American Society for Clinical Pathology. This conference established the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), a 6-tiered diagnostic classification system based on a probabilistic approach[8,9]. Rosen LiVolsi hb```f``jg`e`bf@ a=TbO>9\!@)s\2q F)}w38|)0KQD[Vi>Rc@8[@5ii` .Q@q!d - `' }i@&QAz@%,700g& pL`r, l|Bj2"BTg]((@G@{2L2xVWA0Kk3\2 Ii The above panel correctly identified cancer in 78.2%, whereas cytology identified 58.9% of the thyroid cancers. 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). Deveci LiVolsi LiVolsi Core tip: Fine-needle aspiration (FNA) cytology is widely used for the diagnosis of thyroid nodules, although cases with indeterminate results are not rare. L Since the malignancy rate of this category is quite high, TBSRTC recommends that most patients undergo a repeat thyroid FNA within 3 to 6 mo, in order to define the nature of atypia[24,26]. Baloch ZW, LiVolsi VA. Fine-needle aspiration of thyroid nodules: past, present, and future. However, in almost 20% to 28% of AUS/FLUS cases, a repeat thyroid FNA will again be characterized as AUS/FLUS[27,28]. Benign follicular nodules often have a small population of microfollicles and crowded groups. This resulted in diagnostic inconsistencies among different laboratories and difficulty in communicating the implications of thyroid fine-needle aspiration (FNA) results both to clinicians (endocrinologists and endocrine surgeons) and laboratory doctors (pathologists and radiologists)[6]. 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. Describing methods to: i. 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]. Gharib In this study the AUS category was further subdivided into HCLUS (atypical cells rule out Hurthle cell neoplasm) and FLUS. Contribution of molecular testing to thyroid fine-needle aspiration cytology of follicular lesion of undetermined significance/atypia of undetermined significance. Tumor cells with distinct granules with eccentric nuclei. In FNA specimens of this variant, the cancer cells appear more profuse, granular or vacuolated compared to regular PTC. In other cases it is sparsely cellular and contains atypical lymphoid cells. The nuclei have conventional PTC nuclear features that distinguish it from Hurthle cell neoplasms[35]. In the World Health Organization classification, Hrthle cell adenoma and Hrthle cell carcinoma are considered oncocytic variants of FA and FC, respectively.24 Studies suggest, however, that follicular and Hrthle cell tumors have different underlying genetics.4,25 For this reason, and because they have such distinctive morphologic features, it is helpful to specify that a sample raises the possibility of a Hrthle cell rather than a follicular neoplasm. (10%) 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). Renshaw AA. Thyroid aspiration cytology: current status. For that reason the aspirate is then classified as AUS/FLUS to indicate the uncertainty of the findings. Results: We evaluated 5030 thyroid FNAs. LiVolsi The National Cancer Institute Thyroid FNA State of the Science Conference: Wrapped up. et al. See more. Within these sections, there are often small areas of hematopoietic material preserved from their original marrow environment. 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. moc.oohay@sokaisime. Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, et al. We thank Diane Solomon, MD, for review of the manuscript and helpful comments. The Bethesda System for Reporting Thyroid Cytopathology is the most widely used system for the diagnosis of thyroid FNA specimens. The management of each case derives from the category that is classified. If these constitute the minority of the follicular cells, they have little significance and the FNA can be interpreted as benign. Figure 1. Megakaryocytes (yellow circles) can be seen at low power. Cibas ES. Yang J, Schnadig V, Logrono R, Wasserman PG. Hay Wright-Giemsa staining of the marrow aspirate smear. 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]. Grant Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any. 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: FVPTC is characterized cytologically by the paucity of diagnostic nuclear features. "Sparse" is not a medical term. 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. Half of patients present with significant compression of the upper respiratory and the digestive tract in the neck, resulting in dyspnea, hoarseness, dysphagia, and pain. ZW The isolated cyst-lining cells in thyroid aspirates are often difficult to distinguish from PTC. Cytological diagnosis of paucicellular variant of anaplastic carcinoma of thyroid: report of two cases. Inadequate samples are reported as nondiagnostic (ND) or unsatisfactory (UNS). Although these nuclear alterations are usually disseminated, they are mild and incomplete. of value in acquiring a cellular sample, possibly due to increasing hemodilution. 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. BRAF mutation detection in indeterminate thyroid cytology specimens: underlying cytologic, molecular, and pathologic characteristics of papillary thyroid carcinoma. 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]. , eds. Goellner VA 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. . 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. Highly cellular specimens are ideal for smeared preparations, whereas sparsely cellular specimens will require multiple centrifugation steps and special cell concentration methods. In a study that segregated CFO cases and analyzed them separately, the risk of malignancy for a CFO sample was 4%.9 The risk of malignancy for ND/UNS (not including CFO) is 1% to 4%.810, The Bethesda System for Reporting Thyroid Cytopathology: Recommended Diagnostic Categories*, The Bethesda System for Reporting Thyroid Cytopathology: Implied Risk of Malignancy and Recommended Clinical Management, A repeated aspiration with ultrasound guidance is recommended for ND/UNS and clinically or sonographically worrisome CFO cases and is diagnostic in 50% to 88% of cases,2,6,9,11,13,14 but some nodules remain persistently ND/UNS. 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. Rabaglia JL, Kabbani W, Wallace L, Holt S, Watumull L, Pruitt J, Snyder WH, Nwariaku FE. The diagnosis of MTC can be confirmed by simply measuring serum calcitonin levels, which are markedly elevated in the majority of cases (> 10 pg/mL)[48]. . 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. et al. We reviewed the English literature regarding Thyroid Cytopathology systems in order to identify the most suitable methodology, taking into account our prospective as well. ZW You can now find us in many convenient retail stores, including select Walmart and Target locations. Flat sheets showing enlarged, pale nuclei with finely granular chromatin of a papillary Ca case ( 40 pap stain on ThinPrep slide) (diagnostic categories VI). After the aspirate, the most expected informative component of a bone marrow workup is likely the core needle biopsy. Some thyroid FNAs are not easily classified into the benign, suspicious, or malignant categories. PG government site. Quick tip: Flow cytometry cannot be performed on the clot section after the clot has set and after fixation in formalin. FCs have cytomorphologic features that distinguish them from benign follicular nodules. The separation of these four components allows for multiple sources of data collection and offers insurance against otherwise compromised specimens. Statistics . Teixeira GV, Chikota H, Teixeira T, Manfro G, Pai SI, Tufano RP. 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]. View an interactive bone marrow aspirate online. Benson Such cases represent a minority of thyroid FNAs and in the Bethesda System are reported as atypia of undetermined significance (AUS) or follicular lesion of undetermined significance. The necessity for this category was debated at the NCI conference, after which a vote (limited to the clinicians in attendance) was taken, and the majority voted in favor of this category. 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 clot sections, core biopsy, marrow aspirate, and touch preps all contribute to the overall assessment of patients collected marrow. Faquin WC, Cibas ES, Renshaw AA. Several systems have been proposed for the cyropathologic diagnosis of the thyroid nodules. Krane JF, Vanderlaan PA, Faquin WC, Renshaw AA. Deveci A malignant thyroid FNA diagnosis accounts for 4%-8% of all thyroid FNAs, the majority of which are PTCs, and these patients will require thyroidectomy[53]. VanderLaan PA, Marqusee E, Krane JF. They can be sparsely cellular, because of the marked fibrosis and hyalinization encountered in some cases[19,51]. Gough 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. A minor population of macrofollicles (intact spheres and fragments) can be present. The individual tumor cells are enlarged, oval in shape with eosinophilic cytoplasm; the nuclei show elongation, oval shape, membrane thickening, chromatin clearing, grooves, and inclusions. A suspicious interpretation is rendered only when the majority of the follicular cells are arranged in abnormal architectural groupings (microfollicles, crowded trabeculae). The prepared core biopsy slides can be used for immunohistochemical (IHC) investigations (phenotyping the cells using IHC stains), and an initial standard hematoxylin and eosin stain is done to assess baseline histology. HHS Vulnerability Disclosure, Help 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]. Because of the mixture of oncocytes with lymphocytes on smears, this tumor should be distinguished from Hashimoto thyroiditis or a follicular lesion with oncocytic changes[44]. Neither of these patterns fits comfortably into the benign category, but the changes are insufficient for any of the more . Assisted nurses with recovering over 70 post-surgical patients daily. Mazzaferri EL. We welcome suggestions or questions about using the website. AS Schnadig Lee TI, Yang HJ, Lin SY, Lee MT, Lin HD, Braverman LE, Tang KT. Without individual cells to analyze through flow cytometric methods, the clot section is limited to only tissue-type immunostaining. The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer. However, nuclear grooves can be seen also in several thyroid diseases such, as Hashimotos thyroiditis, multinodular goiter, Hurthle cell tumors and medullary carcinoma[42,43]. After this therapy the patients serum thyroglobulin levels should fall to undetectable levels. 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]. 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. ( a) In this sparsely cellular specimen, some of the cells had abundant cytoplasm and enlarged nuclei, some with prominent nucleoli. A) 20 view of the bone marrow aspirate reveals a deeply basophilic smear of cells. Three of the 28 specimens (11%) were sparsely cellular, and the rest (89%) were at least moderately cellular. 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]. The heterogeneity of this category precludes outlining all scenarios for which an AUS interpretation is appropriate. Bongiovanni et al[14] analyzed the differences between the 5-tiered and the 6-tiered diagnostic systems for reporting thyroid cytopathology, based in a large series of 7686 thyroid FNA specimens, collected from 3751 patients from several institutions from Italy, Switzerland, and the United States. From each FNA pass one to three smears are prepared and fixed in alcohol for Papanicolaou staining and air dried for Giemsa staining.
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