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). Gharib 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. Broome JT, Solorzano CC. 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. 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. Literature reviews were limited to English language publications dating back to 1995, using PubMed as the search engine, with key words determined by the committee members. A syringe with applied negative pressure gently removes approximately 5 mL of deep red, semi-liquid marrow content. RV Fadda G, Basolo F, Bondi A, Bussolati G, Crescenzi A, Nappi O, Nardi F, Papotti M, Taddei G, Palombini L. Cytological classification of thyroid nodules. It allows classification of nodules as benign or malignant, and patients with malignant nodules are scheduled for surgery. The tumor cells show nuclear elongation, chromatin clearing, but nuclear grooves and inclusions are rare[40]. Your patients cytopenias remain unexplained. DA 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]. Patients with sporadic MTC present with a solitary, circumscribed thyroid nodule, usually in the middle to upper-outer half of the thyroid gland. Even neurons of the same type show various subtle process characteristics to fit into the diverse neural circuits. Pedro Patricio de Agustin, MD, PhD, Department of Pathology, University Hospital 12 de Octubre, Madrid, Spain, Erik K. Alexander, MD, Department of Medicine, Brigham and Womens Hospital, Boston, MA, Sylvia L. Asa, MD, PhD, Department of Pathology and Laboratory Medicine, University of Toronto; University Health Network and Toronto Medical Laboratories; Ontario Cancer Institute, Toronto, Canada, Kristen A. Atkins, MD, Department of Pathology, University of Virginia Health System, Charlottesville, Manon Auger, MD, Department of Pathology, McGill University Health Center and McGill University, Montreal, Canada, Zubair W. Baloch, MD, PhD, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Katherine Berezowski, MD, Department of Pathology, Virginia Hospital Center, Arlington, Massimo Bongiovanni, MD, Department of Pathology, Geneva University Hospital, Geneva, Switzerland, Douglas P. Clark, MD, Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, Batrix Cochand-Priollet, MD, PhD, Department of Pathology, Lariboisire Hospital, University of Paris 7, Paris, France, Barbara A. Crothers, DO, Department of Pathology, Walter Reed Army Medical Center, Springfield, VA, Richard M. DeMay, MD, Department of Pathology, University of Chicago, Chicago, IL, Tarik M. Elsheikh, MD, Ball Memorial Hospital/PA Labs, Muncie, IN, William C. Faquin, MD, PhD, Department of Pathology, Massachusetts General Hospital, Boston, Armando C. Filie, MD, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, Pinar Firat, MD, Department of Pathology, Hacettepe University, Ankara, Turkey, William J. Frable, MD, Department of Pathology, Medical College of Virginia Hospitals, Virginia Commonwealth University Medical Center, Richmond, Kim R. Geisinger, MD, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, Hossein Gharib, MD, Department of Endocrinology, Mayo Clinic College of Medicine, Rochester, MN, Ulrike M. Hamper, MD, Department of Radiology and Radiological Sciences, The Johns Hopkins Medical Institutions, Baltimore, MD, Michael R. Henry, MD, Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN, Jeffrey F. Krane, MD, PhD, Department of Pathology, Brigham and Womens Hospital, Boston, MA, Lester J. Layfield, MD, Department of Pathology, University of Utah Hospital and Clinics, Salt Lake City, Virginia A. LiVolsi, MD, Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Britt-Marie E. Ljung, MD, Department of Pathology, University of California San Francisco, Claire W. Michael, MD, Department of Pathology, University of Michigan Medical Center, Ann Arbor, Ritu Nayar, MD, Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, Yolanda C. Oertel, MD, Department of Pathology, Washington Hospital Center, Washington, DC, Martha B. Pitman, MD, Department of Pathology, Massachusetts General Hospital, Boston, Celeste N. Powers, MD, PhD, Department of Pathology, Medical College of Virginia Hospitals, Virginia Commonwealth University Medical Center, Richmond, Stephen S. Raab, MD, Department of Pathology, University of Colorado at Denver, UCDHSC Anschutz Medical Campus, Aurora, Andrew A. Renshaw, MD, Department of Pathology, Baptist Hospital of Miami, Miami, FL, Juan Rosai, MD, Dipartimento di Patologia, Instituto Nazionale Tumori, Milano, Italy, Miguel A. Sanchez, MD, Department of Pathology, Englewood Hospital and Medical Center, Englewood, NJ, Vinod Shidham, MD, Department of Pathology, Medical College of Wisconsin, Milwaukee, Mary K. Sidawy, MD, Department of Pathology, Georgetown University Medical Center, Washington, DC, Gregg A. Staerkel, MD, Department of Pathology, the University of Texas M.D. Deveci A serum protein electrophoresis might have even shown a monotypic expansion. JA Several patterns of nuclear atypia may be also present without being quantitatively and/or qualitatively sufficient for the interpretation of suspicious for malignancy. First Time Setup Tested phones Android App Settings Estimated Band FAQ Translate . However, this requires additional FNA passes or residual cellular material from the cytologic sample. Gharib EK Deshpande AH, Munshi MM, Bobhate SK. "Demystifying the Bone Marrow Biopsy: A Hematopathology Primer." Statistics . This website is intended for pathologists and laboratory personnel but not for patients. Palpation-guided FNA can be performed when a thyroid nodule is easily palpable (> 1.0 cm in diameter) and rather solid. These indeterminate aspirates may present with architectural atypia or nuclear atypia[21]. Explaining the use and composition of pre-fixatives and their effect on cellular morphology 4. The above panel correctly identified cancer in 78.2%, whereas cytology identified 58.9% of the thyroid cancers. 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. ZW 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. H Some categories have 2 alternative names; a consensus was not reached at the NCI conference on a single name for these categories. D Lin Histogenesis of medullary carcinoma of the thyroid. Giorgadze 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 Additionally, since the cells are smeared, they are technically three-dimensional, and morphology can be assessed. In 1966 Williams demonstrated that this tumor derives from the parafollicular cells, known also as calcitonin-producing C cells, which have an ectodermal neural crest origin[47]. Cases that demonstrate the nuclear features of papillary carcinoma are excluded from this category. 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]. The bone marrow aspirate smear. , eds. These features could be intranuclear inclusions, nuclear grooves, or psammoma calcifications; (6) DC VI Malignant (Figures (Figures55--7).7). hbbd``b`$Ks ^ [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 . Walfish The thyroid nodules are aspirated 3 to 5 times with a 22-gauge or 25-gauge needle. 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. Conflict-of-interest statement: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. In this review we analyze current literature regarding Thyroid Cytopathology Reporting systems trying to identify the most suitable and practical methodology to use in everyday clinical practice. 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. Mazzaferri EL. Map ; Apps; Tools . 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. Note: Please review ASHs disclaimerregarding the use of the information contained in these articles. Gharib Deveci Oral Cysticercosis- A Diagnostic Dilemma - PMC - National Center for Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, et al. LiVolsi 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]. Figure 6. The nuclei have conventional PTC nuclear features that distinguish it from Hurthle cell neoplasms[35]. J ZW DeLellis et al. ES 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. 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. Therefore the diagnosis SFM, suspicious for thyroid carcinoma is an indication for surgery. R 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? BRAF testing has been coupled successfully with the Bethesda Thyroid FNA classification system to offer molecular quality assurance on positive samples, as well as a diagnostic upgrade on samples of indeterminate diagnostic categories, such as AUS/FLUS and SFN/SHN[54]. When evaluating an undifferentiated carcinoma using immunocytochemistry a basic immunopanel should include cytokeratins, calcitonin, leucocyte common antigen, carcinoembryonic antigen, thyroglobulin, chromogranin, and TTF-1. 8600 Rockville Pike Chemotherapy or radiotherapy usually cannot change the dismal prognosis of this cancer. et al. However, there are cases with diagnostic uncertainty due to suboptimal sampling or preservation, and overlapping cytomorphologic features with other thyroid conditions. Free Histology Flashcards about Cytology - StudyStack Note the trabecular bone (*) with trilineage hematopoiesis including megakaryocytes, granulocytic precursors, and erythroid islands presented in 2D following formalin fixation and paraffin processing. The discs are 2 mm thick in the unprocessed state, but less thick when processed, and sometimes slightly . Assisted nurses with recovering over 70 post-surgical patients daily. S Cellularity may in part be due to the LBC technique in comparison with smears made after sedimentation, . Therefore, detailed neuronal morphology is required to understand normal neuronal function . Thyroid FNA is a well established procedure used in the preoperative diagnosis of thyroid nodules. However in doubtful cases definitive diagnosis can be made if sufficient material is available for immunocytochemical stains, or if it is known that the patient has an elevated serum calcitonin level. $AJ !b``3iK Careers, Unable to load your collection due to an error. Until recently there were no uniform criteria for the various diagnostic categories in thyroid cytopathology. Report of the Thyroid Cancer Guidelines Update Group. CB 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. Yang 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. Cytopreparatory Techniques | SpringerLink Tumor cells with distinct granules with eccentric nuclei. At low magnification, aspirates of PTC are typically cellular, epithelium-rich structures. specimens with obscuring blood, poor cell preservation, and an insufficient sample of follicular cells. 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. Renshaw AA. Role of repeat fine-needle aspiration biopsy (FNAB) in the management of thyroid nodules. Received 2015 May 24; Revised 2015 Nov 19; Accepted 2015 Dec 9. Moses et al[60] also examined the clinical utility of the above panel in thyroid FNA biopsies. Note granulocytic precursors (arrows) and erythroid cells (arrow heads). Atypical cells in fine-needle aspiration biopsy specimens of benign thyroid cysts. 119 0 obj <>/Filter/FlateDecode/ID[<80B644DBD03A284F83277CD8A09960C6><94D1BF37A2B04B428378CFB47946E293>]/Index[92 53]/Info 91 0 R/Length 121/Prev 842357/Root 93 0 R/Size 145/Type/XRef/W[1 2 1]>>stream The bone marrow aspirate is arguably the most straightforward aspect of the bone marrow workup. Grant Such atypia may result from a variety of benign cellular changes, but in some cases may reflect an underline malignancy which has been suboptimally sampled or has intermediate diagnostic features[20-22]. This variant is sometimes difficult to diagnose, because in some cases the characteristic neoplastic cells are sparsely evident in the mass. As a medical procedure, bone marrow collection may sometimes have limitations in obtaining adequate specimens. Remedy: The supernatant may not have been completely poured off resulting in dilution of the cell pellet. What is one to do with the sparsely cellular specimen consisting mostly of microfollicles? 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. Asa Yang Immediately after the core biopsy is obtained, the procured tissue is "touched" several times onto glass slides. If these constitute the minority of the follicular cells, they have little significance and the FNA can be interpreted as benign. Such patients were followed clinically with periodic physical and sonographic examinations. Logrono B These specimens demonstrate inadequate cellularity, poor fixation and preservation, obscuring blood or ultrasound gel, or a combination of the above factors. Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any. Redman R, Yoder BJ, Massoll NA. While the V600E and K601E mutations were almost equally observed in the AUS/FLUS category, there was a slight predominance of K601E mutation in SFN/SHN category. 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. A moderately or even highly cellular specimen by itself (without significant nuclear or architectural atypia) does not qualify a nodule for an AUS interpretation. 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. Hazard JB, Hawk WA, Crile G. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. However, some three dimensional structures that resemble the epithelial tips of papillae without the fibrovascular cores can be seen[35]. LiVolsi Inadequate samples are reported as nondiagnostic (ND) or unsatisfactory (UNS). Each of the categories has an implied cancer risk (ranging from 0% to 3% for the benign category to virtually 100% for the malignant category) that links it to a rational clinical management guideline Table 2. ID 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. Teixeira GV, Chikota H, Teixeira T, Manfro G, Pai SI, Tufano RP. 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. 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. Such changes may represent atypical but benign cyst-lining cells, but a papillary carcinoma cannot be entirely excluded (ThinPrep, Papanicolaou stain). Herein lies everything you were afraid to ask. 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). Ravetto Abati A. Primary angiosarcoma of breast: A case report and literature review. FNAs contain oncocytic cells with abundant granular cytoplasm, conventional nuclei, a papillary architecture, and a lymphoplasmacytic background. Gross specimen was measuring about 2x2x1.5 cm in size, soft in consistency, brownish black in color and roughly oval in shape [Table/Fig-4]. Quick tip: A cellular aspirate smear is crucial to an adequate differential count and assessment of morphologic dysplasia. The Bethesda System for Reporting Thyroid Cytopathology is the most preferred system for the diagnosis of FNA specimens, which also contains guidelines for the diagnosis and treatment of indeterminate cases. . ES 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. DP The specimen is fixed in paraffin and cut for slide preparation. Figure 1. Kelman Ohori NP, Singhal R, Nikiforova MN, Yip L, Schoedel KE, Coyne C, McCoy KL, LeBeau SO, Hodak SP, Carty SE, et al. 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. Venkatesh YS, Ordonez NG, Schultz PN, Hickey RC, Goepfert H, Samaan NA. This category includes specimens with features characteristic of a malignant neoplasm, which are quantitatively or qualitatively insufficient to make a definitive diagnosis of malignancy (Figure (Figure4).4). 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. Nikiforov YE, Ohori NP, Hodak SP, Carty SE, LeBeau SO, Ferris RL, Yip L, Seethala RR, Tublin ME, Stang MT, et al. The nucleoli are usually small and eccentric; however, rare oncocytic variants of PTC can show prominent nucleoli. The Bethesda System for Reporting Thyroid cytopathology. The risk of malignancy in the HCLUS category was significantly lower than in the other subtypes of AUS. Bethesda System for Reporting Thyroid Fine-Needle Aspiration Specimens PK Cytologic features of histologically proven follicular adenoma and For clarity of communication, TBSRTC recommends that each report begin with 1 of 6 general diagnostic categories. If the nodule is almost entirely cystic, with no worrisome sonographic features, an endocrinologist might proceed as if the CFO were a benign result. The molecular testing proved to have a high specificity, although the sensitivity was quite low (60%). Fine-needle aspiration (FNA) has an essential role in the evaluation of euthyroid patients with a thyroid nodule. Cytological diagnosis of paucicellular variant of anaplastic carcinoma of thyroid: report of two cases. VA For that reason these findings are best interpreted as SFM. B) 600 view of trilineage hematopoiesis. 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 terms for reporting results should have an implied (or explicit) risk of malignancy on which recommendations for patient management (eg, annual follow-up, repeated FNA, surgical lobectomy, near total thyroidectomy) can be based. The diagnosis of a MALT lymphoma of the thyroid requires the use of immunophenotyping by flow cytometry or immunocytochemistry[9,37]. For some of the general categories, some degree of sub-categorization can be informative and is often appropriate; recommended terminology is shown in Table 1. 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. The TBSRTC classifies thyroid follicular lesions with microfollicle predominance and lack of colloid into the suspicious for follicular neoplasm category. et al. The molecular diagnosis and management of thyroid neoplasms. Chung Charge Nurse Job Denver Colorado USA,Research/Development 2. The six-tier diagnostic approach includes the following six categories[8,15]: (1) Disctrict of columbia (DC)INondiagnostic or Unsatisfactory. Pu Each diagnostic category is associated with a specific risk of malignancy and a recommendation for management. et al. 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. . Thus, our aim was to standardize a manual, simple, cost-effective innovative technique, namely, ACS to process clear/sparsely cellular specimens and also to compare ACS smears along with cytocentrifuged specimens which were used as control smears. Use freshly squeaky-cleaned slides. Wasserman Therefore, it is not prudent to remove every thyroid nodule we encounter in our medical practice. Aldinger KA, Samaan NA, Ibanez M, Hill CS. Nayar R, Ivanovic M. The indeterminate thyroid fine-needle aspiration: experience from an academic center using terminology similar to that proposed in the 2007 National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. 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). 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. 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]. It usually affects the elderly population, and often presents as a large and bulky tumor with extrathyroidal extension and metastases. We reviewed the English literature regarding Thyroid Cytopathology systems in order to identify the most suitable methodology, taking into account our prospective as well. PDF The Bethesda System for Reporting Thyroid Cytopathology This distinction cannot be made by FNA and is of no consequence to the patient. Fine-needle aspiration (FNA) cytology is an important diagnostic tool in patients with thyroid lesions.
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