Before the specimen is transferred to a container with anticoagulant, some of the already clotted specimen may be submitted for permanent histology in formalin. The false-negative rate of a benign interpretation is low (0%3%),2,12 but patients are nevertheless followed up with repeated assessment by palpation or ultrasound at 6- to 18-month intervals.15 If the nodule shows significant growth or suspicious sonographic changes, a repeated FNA is considered. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. Research is directed to the identification of molecular markers that, in conjunction with FNA, can identify patients with a malignant nodule. CellMapper is a crowd-sourced cellular tower and coverage mapping service. 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]. et al. 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]. Since recurrent PTC typically secretes thyroglobulin, serum monitoring of thyroglobulin serves as a useful tumor marker for recurrent PTC[35]. Jing X, Michael CW, Pu RT. H To address terminology and other issues related to thyroid FNA, the National Cancer Institute (NCI) hosted the NCI Thyroid Fine Needle Aspiration State of the Science Conference. The meeting was organized by Andrea Abati, MD, and took place on October 22 and 23, 2007, in Bethesda, MD. van Heerden Zubair W. Baloch, MD, PhD, served as chair of the Terminology and Morphologic Criteria committee. There were several subsequent drafts and online discussion periods (August 15 to September 30, 2007, and November 30 to December 15, 2007). "Demystifying the Bone Marrow Biopsy: A Hematopathology Primer." The bone marrow aspirate is arguably the most straightforward aspect of the bone marrow workup. A print atlas, with more than 40 contributing authors Appendix 1, is in press.3. Wright-Giemsa staining of the marrow aspirate smear. Enlarged follicular cells arranged in monolayer sheets and follicular groups with nuclear elongation and chromatin clearing in a follicular variant of PTC case ( 40 pap stain on ThinPrep slide) (diagnostic categories VI). Chronic sialadenitis: sparsely cellular specimen with fewer lymphocytes and germinal center fragments; no characteristic lymphoepithelial islands. . R Rosen 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. It was apparent from the discussions at the conference and the Web postings that the primary purpose of terminology is clarity of communication. et al. Redman R, Yoder BJ, Massoll NA. (iii) Cytologic and architectural atypia: Cerutti JM. The site is secure. Royal College of Physicians. A: Probably, yes. Krane JF, Vanderlaan PA, Faquin WC, Renshaw AA. Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology. Most (60%75%) prove to be papillary carcinomas, and the rest are usually FAs.2,10,12,30. 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. 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). The National Cancer Institute Thyroid FNA State of the Science Conference: Wrapped up. Several systems have been proposed for the cyropathologic diagnosis of the thyroid nodules. 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. 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. In conclusion, patients who require repeated FNAs for indeterminate diagnoses will be resolved by repeat FNA in a percentage of 72%-80%. The Bethesda System for Reporting Thyroid Cytopathology: Definitions, Criteria and Explanatory Notes. . To collect as many cells as possible from sparsely cellular urine, the specimen should have which of the following techniques applied? Aldinger KA, Samaan NA, Ibanez M, Hill CS. The cancer cells are also elongated, with a height-to-weight ratio of at least 3:1. The management of each case derives from the category that is classified. The discs are 2 mm thick in the unprocessed state, but less thick when processed, and sometimes slightly . Explaining the use and composition of pre-fixatives and their effect on cellular morphology 4. The general category malignant is used whenever the cytomorphologic features are conclusive for malignancy. The rate of malignancy in FNA-BRAF positive nodules has been shown to be 99.8%[55]. 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]. The cells have abundant pink cytoplasm, basally located nuclei and nuclear features of conventional PTC. 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). The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer. Cibas ES. 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]. Baloch The many faces and mimics of papillary thyroid carcinoma. Figure 1. Single neurons, as the basic unit of the brain, consist of a cell body and processes, including dendrites and axons. Baloch Z, LiVolsi VA, Jain P, Jain R, Aljada I, Mandel S, Langer JE, Gupta PK. 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. Open in a separate window Like the marrow aspirate smear, touch imprint preparations provide a quick turnaround time (i.e., do not need decalcification) and great morphologic detail (if the aspirate smears are paucispicular or hemodiluted). Melton Whenever a specific diagnosis (eg, lymphocytic thyroiditis) can be rendered and whenever there is any atypia, the specimen is, by definition, adequate for evaluation. The isolated cyst-lining cells in thyroid aspirates are often difficult to distinguish from PTC. Note granulocytic precursors (arrows) and erythroid cells (arrow heads). View an interactive bone marrow clot specimen online. VanderLaan PA, Marqusee E, Krane JF. The first draft of the committees summary documents was posted on the Web site and open for online discussion from May 1 to June 30, 2007. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. Highly cellular specimens are ideal for smeared preparations, whereas sparsely cellular specimens will require multiple centrifugation steps and special cell concentration methods. Federal government websites often end in .gov or .mil. 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. It is critical that cytopathologists communicate thyroid FNA interpretations to referring physicians in terms that are succinct, unambiguous, and clinically helpful. 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. Does the fine-needle aspiration diagnosis of Hrthle-cell neoplasm/follicular neoplasm with oncocytic features denote increased risk of malignancy? 2nd ed. specimen from ileal conduits Urine samples from these conduits contain a large number of degenerated intestinal epithelial cells, and In: Clark DP, Faquin WC, editors. The core biopsy is useful for assessing overall marrow cellularity, trilineage hematopoiesis, and marrow architecture. Conflict-of-interest statement: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases. The risk of malignancy in the HCLUS category was significantly lower than in the other subtypes of AUS. The difficulties in securing diagnosis of a diffuse large B-cell lymphoma derive from the inadequate sampling technique and/or insufficient preservation of the specimen. 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. Cibas D Deveci Moreover, a lower percentage of cases in the European system was placed into the TIR 4 and TIR 5 categories as well, compared with the American system. These specimens demonstrate inadequate cellularity, poor fixation and preservation, obscuring blood or ultrasound gel, or a combination of the above factors. 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. 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]. As a library, NLM provides access to scientific literature. The morphologic findings are very similar to that of the aspirate smear, with the caveat that it only represents the cells that slough off. Cellular crowding and overlapping are conspicuous, and the follicular cells are usually larger than normal. ED Wasserman 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 III 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. Pu 8600 Rockville Pike 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. ID The diagnosis of this variant as a PTC is relatively easy, due to the numerous papillae and the coexisting intranuclear inclusions. Note: Please review ASHs disclaimerregarding the use of the information contained in these articles. Description of a distinctive morphological variant and report of 7 cases. ?K !o "Sparse" is not a medical term. Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any. 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 adequacy of a thyroid FNA is defined by both the quantity and quality of the cellular and colloid components. 4';KiRQ5S&. et al. Cellularity may in part be due to the LBC technique in comparison with smears made after sedimentation, . Fadda Clark DP, Faquin WC. 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. Lloyd Furthermore, spermatid development is likely supported by planar cell polarity (PCP) proteins since polarized spermatids are aligned across the plane of seminiferous epithelium in an orderly fashion, analogous to hair cells in the cochlea of the inner ear. . the contents by NLM or the National Institutes of Health. Palpation-guided FNA can be performed when a thyroid nodule is easily palpable (> 1.0 cm in diameter) and rather solid. Quick tip: A cellular aspirate smear is crucial to an adequate differential count and assessment of morphologic dysplasia. Distant metastases seldom occur, but may develop in 20% of cases in late stage. 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. Fine-needle aspiration cytology (FNAC) has been widely adopted as a meticulous, secure and cost-effective method for the diagnosis of non-toxic thyroid nodules[1,2]. V G Because the nuclear changes of FVPTC are subtle, the majority of cytologic samples are often diagnosed as suspicious for PTC. Cibas H B) 600 view of trilineage hematopoiesis. 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]. As a result they may be not diagnosed through the FNA test, resulting in a false-negative test[44]. 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). Gharib Reduce red blood cells in smears iii. For a thyroid FNA specimen to be satisfactory for evaluation (and benign), 6 . McHenry This interpretation applies to cellular samples that are composed exclusively (or almost exclusively) of Hrthle cells. Papillary thyroid carcinoma. Hematoxylin-eosinstained section of the bone core biopsy (100). Edmund S. Cibas, MD, and Susan J. Mandel, MD, MPH, served as moderators. This variant is sometimes difficult to diagnose, because in some cases the characteristic neoplastic cells are sparsely evident in the mass. Although these nuclear alterations are usually disseminated, they are mild and incomplete. In this review we analyze all literature regarding Thyroid Cytopathology Reporting systems trying to identify the most suitable methodology to use in clinical practice for the preoperative diagnosis of thyroid nodules. What happens after you place the orders, though? 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). Inclusion in an NLM database does not imply endorsement of, or agreement with, The Bethesda system for reporting thyroid cytopathology: An experience of 1,382 cases in a community practice setting with the implication for risk of neoplasm and risk of malignancy. Agarwal A, Kocjan G. FNAC thyroid reporting categories: value of using the British Thyroid Association (Thy 1 to Thy 5) thyroid FNAC reporting guidelines. Unless specified as ND/UNS, the FNA specimen is considered adequate for evaluation. Report of the Thyroid Cancer Guidelines Update Group. Go to: . Prepares and stains all specimen types (gyn, medical cytology, fna) for cytologic examination. Atypical cells in fine-needle aspiration biopsy specimens of benign thyroid cysts. CA Teixeira GV, Chikota H, Teixeira T, Manfro G, Pai SI, Tufano RP. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. 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. RV If no aspirate is collected, then an extra core biopsy specimen can be agitated to release cells for flow cytometry; however, this is not ideal. Gough Fleisher SL A review of the English literature was conducted, and data were analyzed and summarized and integrated from the authors perspective. 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. 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]. TBSRTC provides a uniform 6-tier system on thyroid FNA for pathologists to communicate with clinicians. Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Pitman MB, Abati A. However, in almost 20% to 28% of AUS/FLUS cases, a repeat thyroid FNA will again be characterized as AUS/FLUS[27,28]. Note extensive red blood cells in the background. The term benign follicular nodule applies to the most common benign pattern: an adequately cellular specimen composed of varying proportions of colloid and benign follicular cells arranged as macrofollicles and macrofollicle fragments. Q: Can your pathologist tell you what the core biopsy shows on the same day as the procedure? Rabaglia JL, Kabbani W, Wallace L, Holt S, Watumull L, Pruitt J, Snyder WH, Nwariaku FE. Yang J, Schnadig V, Logrono R, Wasserman PG. ES Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. Ohori NP, Singhal R, Nikiforova MN, Yip L, Schoedel KE, Coyne C, McCoy KL, LeBeau SO, Hodak SP, Carty SE, et al. We welcome suggestions or questions about using the website. An explicit statement of adequacy is optional. Benson Touch preps can be imprinted, rolled, or crushed between glass to provide similar information. L H If these constitute the minority of the follicular cells, they have little significance and the FNA can be interpreted as benign. Quick tip: If the bone marrow is involved by metastatic carcinoma or clusters of cohesive plasma cells, these abnormal cells may not be amenable to aspiration and may cause a dry tap; however, a bone core biopsy will identify them. Another pitfall encountered with cystic thyroid nodules are the atypical cyst-lining cells[24]. Horn RC. Because of the densely cellular composition of bone marrow, the imprints impart many cells directly on the slides. Click, Copyright PathologyOutlines.com, Inc. Click, 30150 Telegraph Road, Suite 119, Bingham Farms, Michigan 48025 (USA). Guidelines for management of thyroid cancer. 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. 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). Any specimen that contains abundant colloid is adequate (and benign), even if six groups of follicular cells are not identified: a sparsely cellular specimen with abundant colloid is, by implication, a predominantly macrofollicular nodule and therefore almost certainly benign. Accessibility In this selected population, 20% to 25% of patients with AUS prove to have cancer after surgery, but this is undoubtedly an overestimate of the risk for all AUS interpretations.2,10 The risk of malignancy is certainly lower and probably closer to 5% to 15%. 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]. 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. Layfield LJ, Cibas ES, Gharib H, Mandel SJ. VA 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]. Auger M, Stelow EB, Yang GCH. 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]. Thyroid nodules is a very usual clinical problem, as it is diagnosed in approximately 60% of the general population in Western countries[1]. In FNA specimens of this variant, the cancer cells appear more profuse, granular or vacuolated compared to regular PTC. Liquid-based preparation can also be made after a FNA pass, with the needle been rinsed in normal saline or ThinPrep solutions. FOIA 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. Within these sections, there are often small areas of hematopoietic material preserved from their original marrow environment. 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]. IB Carcinoma of the thyroid. Theoharis C, Roman S, Sosa JA. Experience of over 18,000 FNAs reported at the same institution during 1998-2007. A benign result is obtained in 60% to 70% of thyroid FNAs. Intranuclear inclusions and multinucleated cells have been reported. 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. In order to establish a standardized diagnostic terminology/classification system for reporting thyroid FNAC results, the National Cancer Institute (NCI) in the United States sponsored the NCI Thyroid FNA State of the Science Conference with a group of experts at Bethesda, MD, in October 2007[7]. Grant Ravetto C et al. 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]. Rathan (General, Ortho . et al. Oncocytic cells with nuclear features of papillary carcinoma are excluded from this interpretation. Listing the acceptable fixatives for use in cytology 5. et al. ES Every thyroid FNA must be evaluated for adequacy. For that reason these findings are best interpreted as SFM. Aspirate slides are also used for cytochemical and iron stains. Anaplastic carcinoma of the thyroid. Hypocellular or paucispicular smears preclude these assessments, which are not easily (or accurately) performed on the core biopsy (Table). 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. See more. Leibowitz What is one to do with the sparsely cellular specimen consisting mostly of microfollicles? 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.