However, some three dimensional structures that resemble the epithelial tips of papillae without the fibrovascular cores can be seen[35]. The interpretation of follicular cell atypia is hindered by sample preparation artifact, eg, Air-drying artifact with slight nuclear and cytoplasmic enlargement, pale and slightly smudgy chromatin, and/or mildly irregular nuclear contours. 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. 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. . Statistics . Go to: . In some cases psammoma bodies may be present[35,44]. specimen from ileal conduits Urine samples from these conduits contain a large number of degenerated intestinal epithelial cells, and They are then stained and processed much like the original core biopsy. Retrieved from https://www.hematology.org/education/trainees/fellows/trainee-news/2021/demystifying-the-bone-marrow-biopsy-a-hematopathology-primer. Map ; Apps; Tools . 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 its aggressive, infiltrative nature, patients with an undifferentiated carcinoma often require a tracheostomy as an emergency procedure. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. Each of these four specimens have their strengths and limitations; therefore, they should be assessed separately. This is particularly true of the follicular variant of PTC, which can be difficult to distinguish from a benign follicular nodule.28 Other PTCs may be incompletely sampled and yield only a small number of abnormal cells.29 If only 1 or 2 characteristic features of PTC are present, if they are only focal and not widespread throughout the follicular cell population, or if the sample is sparsely cellular, a malignant diagnosis cannot be made with certainty. Human immunodeficiency virus (HIV)-associated cystic lymphoepithelial lesions. 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 risk of malignancy for an AUS nodule is difficult to ascertain because only a minority of cases in this category have surgical follow-up. 92 0 obj <> endobj LiVolsi These can be highly useful when a core biopsy is suboptimal, demonstrates marked myelofibrosis, is a dry tap, or otherwise fails to provide adequate visual data for morphology, architecture, cellularity, and hematopoietic lineage assessments. JR Management of a solitary thyroid nodule. The same general principle applies to other thyroid malignancies like medullary carcinoma and lymphoma, but these are encountered less frequently than PTC. The NCI conference participants acknowledged the importance of developing a uniform terminology for reporting thyroid FNA results. Marchevsky AM, Walts AE, Bose S, Gupta R, Fan X, Frishberg D, Scharre K, Zhai J. Evidence-based evaluation of the risks of malignancy predicted by thyroid fine-needle aspiration biopsies. Teixeira GV, Chikota H, Teixeira T, Manfro G, Pai SI, Tufano RP. It is important to note that only nodules with atypia of undetermined significance should be placed in the AUS category. The nuclear chromatin is similar to that seen in other neuroendocrine tumors, i.e., salt and pepper type (Figure (Figure7).7). III For a thyroid FNA specimen to be satisfactory for evaluation (and benign), 6 . That said, this specimen (if involved by a disease process) can be sent for genetic testing such as polymerase chain reaction and does not present the issue of being postdecalcification (which may hinder some genetic tests). 2023 ,https://www.hematology.org/education/trainees/fellows/trainee-news/2021/demystifying-the-bone-marrow-biopsy-a-hematopathology-primer. 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]. 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]. , eds. AA Lymphoepithelial cyst. However, in almost 20% to 28% of AUS/FLUS cases, a repeat thyroid FNA will again be characterized as AUS/FLUS[27,28]. Q: Can flow cytometry be used for assessment of morphologic dysplasia? When evaluating an undifferentiated carcinoma using immunocytochemistry a basic immunopanel should include cytokeratins, calcitonin, leucocyte common antigen, carcinoembryonic antigen, thyroglobulin, chromogranin, and TTF-1. This variant is sometimes difficult to diagnose, because in some cases the characteristic neoplastic cells are sparsely evident in the mass. The 6 general diagnostic categories are shown in bold type in Table 1. {t+[O-]:KtJE]+ZhoZo$ZfqemI,W69l]g]EuGnWMGow" elP~G>6?{LsTY?R+-jW:E#x( xtT} . 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]. At low magnification, aspirates of PTC are typically cellular, epithelium-rich structures. The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. The isolated cyst-lining cells in thyroid aspirates are often difficult to distinguish from PTC. Every thyroid FNA must be evaluated for adequacy. The molecular diagnosis and management of thyroid neoplasms. Such changes may represent atypical but benign cyst lining cells, but a papillary carcinoma cannot be entirely excluded (ThinPrep, Papanicolaou stain). Taken together, the study results confirmed several tenets of TBSRTC approach to adequacy: 1) A sample should be considered ND/UNS if it is sparsely cellular, even if there are a few groups of. 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). ME 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). A: No. Chronic sialadenitis: sparsely cellular specimen with fewer lymphocytes and germinal center fragments; no characteristic lymphoepithelial islands. Note: Please review ASHs disclaimerregarding the use of the information contained in these articles. The clot sections, core biopsy, marrow aspirate, and touch preps all contribute to the overall assessment of patients collected marrow. 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]. (10%) RA 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). 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]. Immunohistochemistry test for specific biomarkers (i.e., calcitonin, thyroglobulin) will easily distinguish MTC from other thyroid malignancies. Hay 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. If resected, virtually all benign follicular nodules turn out to be nodules of a multinodular goiter or follicular adenomas. Most primary thyroid malignancies with the exception of follicular and Hurthle cell carcinomas have unique cytological features which can differentiate primary malignancies from other thyroid lesions. Flat sheets showing enlarged, pale nuclei with finely granular chromatin of a papillary Ca case ( 40 pap stain on ThinPrep slide) (diagnostic categories VI). CA Processing A collection method should harvest well-preserved cells that reliably represent any urinary tract lesion that might be present. et al. McHenry Apart from imaging studies, serological or immunohistochemical studies can be used to secure diagnosis, when the FNA indicated suspicious for MTC or suspicious for lymphoma. These specimens are differentially used to study morphology, assess lineage, perform cell counts and differentials, triage and send for appropriate immunohistochemical stains, perform flow cytometry, and send ancillary cytogenetic and molecular genetic studies. The double needle from the same aspirate procedure is used to cut a core biopsy of optimal length (longer is better; i.e., more data). Such changes may represent atypical but benign cyst-lining cells, but a papillary carcinoma cannot be entirely excluded (ThinPrep, Papanicolaou stain). 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. Venkatesh YS, Ordonez NG, Schultz PN, Hickey RC, Goepfert H, Samaan NA. These formalin specimens are embedded in paraffin blocks and sectioned by histotechnologists to provide a two-dimensional cross-section of the clotted tissue. Ravetto sharing sensitive information, make sure youre on a federal gynecologic cytology specimens 3. 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. Crowded macrofollicles with mild irregularities in nuclear membrane and prominent nucleoli in a specimen with scant colloid ( 40 pap stain on ThinPrep slide) (diagnostic categories III). JA Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, et al. View an interactive bone marrow clot specimen online. Because the nuclear changes of FVPTC are subtle, the majority of cytologic samples are often diagnosed as suspicious for PTC. Deshpande AH, Munshi MM, Bobhate SK. As with the Bethesda System for cervical cytology, it is expected that subsequent workshops will lead to further refinements to this framework. The reason is that in approximately 10%-30% of cases, cytology is indeterminate and nondiagnostic[4]. Nuclear grooves become an important diagnostic feature when associated with an oval, enlarged nucleus with fine chromatin[41]. Unlike complete blood counts (CBCs), which produce fast results, a bone marrow analysis requires a more in-depth analysis and, as a more invasive procedure, necessitates built-in redundancies to ensure the highest-quality results. A) 20 view of the clot. "American Society of Hematology. KH LiVolsi According to the Bethesda system for reporting thyroid cytopathology, a specimen . Preparation Methods They can be sparsely cellular, because of the marked fibrosis and hyalinization encountered in some cases[19,51]. H Single neurons, as the basic unit of the brain, consist of a cell body and processes, including dendrites and axons. Low and high power of clot particle. The tall cell variant of PTC is an important subtype with a potentially aggressive clinical course. Rubenfeld ID See more. et al. Yang Warthin's tumor : the presence of oncocytic epithelium. Guidelines for management of thyroid cancer. Three of the 28 specimens (11%) were sparsely cellular, and the rest (89%) were at least moderately cellular. Lymphadenopathy is also present in one quarter to half of patients, whereas the lungs is the most common site of metastases[49,50]. CB Without individual cells to analyze through flow cytometric methods, the clot section is limited to only tissue-type immunostaining. It usually affects the elderly population, and often presents as a large and bulky tumor with extrathyroidal extension and metastases. 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. Filie AC, Asa SL, Geisinger KR, Logani S, Merino M, Nikiforov YE, Clark DP. Assisted nurses with recovering over 70 post-surgical patients daily. LJ The thyroid FNAs can be performed either by direct puncture after palpating the thyroid nodule, or more commonly under ultrasound guidance by dedicated thyroid specialists (endocrinologists, radiologists, or pathologists). 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: Aldinger KA, Samaan NA, Ibanez M, Hill CS. Williams ED. The neoplastic cells resemble Hurthle cells but have diagnostic nuclear features of PTC. Determination of cellular phenotype (what the cell expresses on its surface, or in its cytoplasm) on an aspirate is carried out by flow cytometry. Therefore the diagnosis SFM, suspicious for thyroid carcinoma is an indication for surgery. 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 H The diagnosis of this variant as a PTC is relatively easy, due to the numerous papillae and the coexisting intranuclear inclusions. 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. (A) A representative case classified as diagnostic category (DC) III (atypia of undetermined significance) showing sparsely cellular specimen (x15; scale bar, 200 m). CS et al. FCs have cytomorphologic features that distinguish them from benign follicular nodules. For most cases surgical resection is not an effective treatment and only palliative therapies are used. 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). This category refers to cellular specimens with abundant follicular cells arranged in a microfollicular pattern with minimal colloid. 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. The heterogeneity of this category precludes outlining all scenarios for which an AUS interpretation is appropriate. Seventeen . 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). A review of the English literature was conducted, and data were analyzed and summarized and integrated from the authors perspective. . The specimen is fixed in paraffin and cut for slide preparation. 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. Thyroid FNA is a well established procedure used in the preoperative diagnosis of thyroid nodules. The most common scenarios can be described as follows: There is a prominent population of microfollicles in an aspirate that does not otherwise fulfill the criteria for follicular neoplasm/suspicious for follicular neoplasm. This situation may arise when a predominance of microfollicles is seen in a sparsely cellular aspirate with scant colloid. Because of the densely cellular composition of bone marrow, the imprints impart many cells directly on the slides. 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]. 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. 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. Therefore, it is not prudent to remove every thyroid nodule we encounter in our medical practice. 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]. 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. Some categories have 2 alternative names; a consensus was not reached at the NCI conference on a single name for these categories. Additional descriptive comments (beyond such subcategorization) are optional and left to the discretion of the cytopathologist. Interestingly all predicted cancer proved to be papillary thyroid carcinoma in the final histology[59]. Grant The nuclear chromatin appears as salt and pepper type in a medullary carcinoma case ( 40 pap stain on ThinPrep slide) (diagnostic categories VI). Although these cytomorphologic features do not permit distinction from a follicular adenoma (FA), they are reportable as follicular neoplasm (FN) or suspicious for a follicular neoplasm (SFN), leading to a definitive diagnostic procedure, usually lobectomy.12,15,17 The term suspicious for a follicular neoplasm is preferred by some laboratories over follicular neoplasm for this category because a significant proportion of cases (up to 35%) prove not to be neoplasms but rather hyperplastic proliferations of follicular cells, most commonly those of multinodular goiter.10,1821 About 15% to 30% of cases called FN/SFN prove to be malignant.2,10,19,22 The majority of FN/SFN cases turn out to be FAs or adenomatoid nodules of multinodular goiter, both of which are more common than FC. Contribution of molecular testing to thyroid fine-needle aspiration cytology of follicular lesion of undetermined significance/atypia of undetermined significance. FVPTC is characterized cytologically by the paucity of diagnostic nuclear features. In adult mammalian testes, spermatids, most notably step 17-19 spermatids in stage IV-VIII tubules, are aligned with their heads pointing toward the basement membrane and their tails toward the tubule lumen. The hallmark of this diagnostic category is a disturbed cytoarchitecture: follicular cells are arranged predominantly in microfollicular or trabecular arrangements. Furthermore, the clot section, like the core biopsy, can be used for immunohistochemical stains. Ghossein CR An inspiration for the thyroid proposal was the Bethesda System for reporting cervical cytology interpretations, first developed at an NCI workshop in 1988 and widely adopted in the United States for reporting Papanicolaou test results. 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]. official website and that any information you provide is encrypted "Demystifying the Bone Marrow Biopsy: A Hematopathology Primer, 01 May. 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. A syringe with applied negative pressure gently removes approximately 5 mL of deep red, semi-liquid marrow content. The most common sites are the lungs, bone, liver and brain. 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]. 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. Intranuclear inclusions and multinucleated cells have been reported. You order a bone marrow analysis for your patient. Of those that prove to be malignant, many are FCs, but a significant proportion are follicular variants of papillary carcinoma.2,8,11,19. Fine-needle aspiration (FNA) has an essential role in the evaluation of euthyroid patients with a thyroid nodule. Based on the findings (MRI, gross and histopathology) cysticercosis was confirmed. 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. There are several exceptions to the numeric requirement of benign follicular cells. The neoplastic cells show a greater cell height than the tall cell variant and lack the obvious nuclear features of PTC. The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer. 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. Royal College of Physicians. 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. Top Users Networks Stats . The site is secure. Does Hrthle cell lesion/neoplasm predict malignancy more than follicular lesion/neoplasm on thyroid fine-needle aspiration? Fine-needle aspiration in the work-up of thyroid nodules. Research is directed to the identification of molecular markers that, in conjunction with FNA, can identify patients with a malignant nodule. One nucleus has an apparent intranuclear pseudoinclusion ( arrow ). CS A minor population of follicular cells show nuclear enlargement, often accompanied by prominent nucleoli, eg, Specimens from patients with a history of radioactive iodine, carbimazole, or other pharmaceutical agents, Repair due to involutional changes such as cystic degeneration and/or hemorrhage, There is an atypical lymphoid infiltrate (in which a repeated aspirate for flow cytometry is desirable), but the degree of atypia is insufficient for the general category suspicious for malignancy..
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