Cystic degeneration also is often found. French As a result they may be not diagnosed through the FNA test, resulting in a false-negative test[44]. Figure 6. et al. Maybe a routine peripheral smear caught some circulating blasts. and transmitted securely. See more. Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. Aldinger KA, Samaan NA, Ibanez M, Hill CS. Q: Can flow cytometry be used for assessment of morphologic dysplasia? The recommended management is clinical correlation and a repeated FNA at an appropriate interval.2,15 In most cases, a repeated FNA results in a more definitive interpretation; only about 20% of nodules are repeatedly AUS.2 In some cases, however, the physician may choose not to repeat the FNA but observe the nodule clinically or, alternatively, to refer the patient for surgery because of concerning clinical and/or sonographic features. 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. Any specimen that contains abundant colloid is adequate (and benign), even if 6 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. The Bethesda System for Reporting Thyroid cytopathology. The molecular diagnosis and management of thyroid neoplasms. Deveci FNA is diagnostic of many thyroid conditions (eg, papillary carcinoma, lymphocytic thyroiditis), but, with regard to follicular carcinoma, it is better considered a screening test. View an interactive bone marrow clot specimen online. Quick tip: Flow cytometry cannot be performed on the clot section after the clot has set and after fixation in formalin. The benefit of thyroid FNA derives in large part from the ability to make a reliably benign interpretation that avoids unnecessary surgery. the contents by NLM or the National Institutes of Health. LiVolsi The significance and clinical value of a CFO result depend in large part on sonographic correlation. Several systems have been proposed for the cyropathologic diagnosis of the thyroid nodules. )TEgX>T|*Q0%K5P- HVe t 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]. The National Cancer Institute Thyroid FNA State of the Science Conference: Wrapped up. TBSRTC provides a uniform 6-tier system on thyroid FNA for pathologists to communicate with clinicians. 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). Should atypical follicular cells in thyroid fine-needle aspirates be subclassified? The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. I 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. They found that apart from the TIR III category, for the TIR 1/DCI(unsatisfactory/nondiagnostic) category the percentage of cases in the 5-tiered system was greater than twice the percentage of cases in the 6-tiered system (7.5% vs 3%). The management of each case derives from the category that is classified. Fine-needle aspiration (FNA) has an essential role in the evaluation of euthyroid patients with a thyroid nodule. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. The hallmark of this diagnostic category is a disturbed cytoarchitecture: follicular cells are arranged predominantly in microfollicular or trabecular arrangements. $AJ !b``3iK Auger M, Stelow EB, Yang GCH. Thyroid aspiration cytology: current status. 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. Q: Can flow cytometry be performed on the core biopsy? Moses W, Weng J, Sansano I, Peng M, Khanafshar E, Ljung BM, Duh QY, Clark OH, Kebebew E. Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy. In conclusion, patients who require repeated FNAs for indeterminate diagnoses will be resolved by repeat FNA in a percentage of 72%-80%. In part, each component is analyzed and interpreted in correlation together for a final report. . A review of the English literature was conducted, and data were analyzed and summarized and integrated from the authors perspective. It usually behaves as an indolent malignant tumor; however, an aggressive clinical course with decreased survival has been reported in some histologic variants of PTC[41]. 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. Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any. In this pattern the nuclear enlargement is generalized in mild-to-moderate degree with evident nuclear grooves and mild nuclear pallor. van Heerden Rathan Statistics . 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.. 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]. In such laboratories, macrophages only often constituted the great majority of ND/UNS cases, with rates that ranged from 15% to 30%.2,9,11,12 Other laboratories considered the risk of a false-negative result negligible and reported macrophages only as benign.10,11 At the 2007 NCI Conference, it was decided that cyst-fluid-only (CFO) cases should be considered a clearly identified subset of ND/UNS. 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: Post Anesthesia Care Unit. Primary angiosarcoma of breast: A case report and literature review. J et al. Palpation-guided FNA can be performed when a thyroid nodule is easily palpable (> 1.0 cm in diameter) and rather solid. Phenotyping hematopoietic cells. Renshaw AA. 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 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. Centrifuge each specimen, and resuspend the cell concentrate in about 5 mL balanced electrolyte solution. This interpretation applies to cellular samples that are composed exclusively (or almost exclusively) of Hrthle cells. hbbd``b`$Ks ^ T 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. 144 0 obj <>stream However, in almost 25%-30% of cases, MTC is inherited, and is associated with one of three familial syndromes: Multiple endocrine neoplasia (MEN) syndrome type 2A (Sipples syndrome), MEN type 2B (mucosa neuroma syndrome or Gorlins syndrome), and familial MTC[35]. 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]. Grant Within these sections, there are often small areas of hematopoietic material preserved from their original marrow environment. 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. Wright-Giemsa staining of the marrow aspirate smear. The main purpose of thyroid FNA is to stratify higher risk patients for surgery, and to prevent unnecessary surgeries for benign conditions. {t+[O-]:KtJE]+ZhoZo$ZfqemI,W69l]g]EuGnWMGow" elP~G>6?{LsTY?R+-jW:E#x( xtT} . Horn RC. It reduces the rate of unnecessary thyroid surgery for patients with benign nodules and appropriately triages patients with thyroid cancer to appropriate surgery. Ancillary testing (eg, immunohistochemical analysis, flow cytometry) in borderline cases is usually more helpful with medullary carcinoma and lymphoma than with PTC. 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. We reviewed the English literature regarding Thyroid Cytopathology systems in order to identify the most suitable methodology, taking into account our prospective as well. Reduce red blood cells in smears iii. Amrikachi Ravetto The 2-day live conference in October 2007, attended by 154 registrants including pathologists, endocrinologists, surgeons, and radiologists, gave the committees an in-depth opportunity to present their conclusions and debate controversial areas. FNAs contain oncocytic cells with abundant granular cytoplasm, conventional nuclei, a papillary architecture, and a lymphoplasmacytic background. 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. AS moc.oohay@sokaisime. Benson 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]. This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases. Chronic sialadenitis: sparsely cellular specimen with fewer lymphocytes and germinal center fragments; no characteristic lymphoepithelial islands. Lin 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. A: Ideally, blasts should be calculated on the aspirate smear differential count; however, in cases where blasts express CD34, then a CD34 count on the core biopsy might be possible. CR 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. Prognosis is dismal with a mean survival of 2.5 to 6 mo and an overall 5-year survival of 0% to 14%. V 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. This category includes the diagnoses of nodular goiter, nodular goiter with hyperplastic nodules, colloid nodules, cyst contents with/without benign follicular cells, and lymphocytic thyroiditis; (3) DC III Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance (Figure (Figure2).2). Seventeen . ND/UNS results occur in 2% to 20% of cases but ideally should be limited to no more than 10% of thyroid FNAs, excluding samples composed exclusively of macrophages.810, Specimens that consist only of cyst contents (macrophages) are problematic. . The site is secure. Q: Can your pathologist tell you what the core biopsy shows on the same day as the procedure? Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle aspiration biopsies of thyroid nodules: a survey of clinicians and pathologists. Surgical intervention consisted of a 15 7 7-cm segmental mastectomy specimen that contained a large, ill-defined, irregular pink-tan . A: No. This category refers to cellular specimens with abundant follicular cells arranged in a microfollicular pattern with minimal colloid. ( a) In this sparsely cellular specimen, some of the cells had abundant cytoplasm and enlarged nuclei, some with prominent nucleoli. et al. It is important to note that only nodules with atypia of undetermined significance should be placed in the AUS category. [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 . Pan-keratin is the most reliable positive immunostain in UTCs, acquiring an expression ranging from 50% to 100%. Histogenesis of medullary carcinoma of the thyroid. Cellularity may in part be due to the LBC technique in comparison with smears made after sedimentation, . For a thyroid FNA specimen to be satisfactory for evaluation (and benign), 6 . DP Report of the Thyroid Cancer Guidelines Update Group. Aspirates where malignancy is suspected but cannot be determined due to: Overlapping cytological features with other thyroid lesions, Specimens suspicious for a follicular or Hrthle cell neoplasm (see, Specimens with a minor degree of atypia, primarily cytologic or architectural (see, Frozen section has limited utility for suspicious for malignancy nodules (, 55 year old man with colon cancer metastasis within a NIFTP which was cytologically suspected of PTC (, 58 year old woman with mammary analogue secretory carcinoma of the thyroid which was cytologically suspected of PTC (, 63 year old man with follicular variant of papillary thyroid carcinoma presenting as a toxic nodule which was cytologically suspected of follicular variant of PTC (, 63 year old woman with hyalinizing trabecular tumor which was cytologically suspected of hyalinizing trabecular tumor (, 71 year old man with mixed medullary and follicular cell carcinoma of the thyroid which was cytologically suspected of thyroid carcinoma (, Pattern A (patchy nuclear changes): moderate to high cellularity, nuclei showing enlargement, pallor, grooves, irregularity or molding but absence of nuclear pseudoinclusions, psammoma bodies and papillary architecture, Pattern B (incomplete nuclear changes): nuclei showing enlargement with mild pallor and grooves, absence of nuclear irregularity, nuclear molding, nuclear pseudoinclusions, psammoma bodies and papillary architecture, Pattern C (sparsely cellular specimen): poor cellularity, presence of many findings suggesting papillary thyroid carcinoma, Pattern D (cystic degeneration): cystic degeneration based on foamy histiocytes, scattered clusters of follicular cells with the nuclei showing enlargement, pallor, grooves, absence of nuclear pseudoinclusions, psammoma bodies and papillary architecture, large, atypical, histiocytoid cells with enlarged nuclei and without abundant vacuolated cytoplasm (, Monomorphic population of isolated small or medium sized cells with a high nuclear cytoplasmic ratio, Nuclei are eccentrically located, with smudged chromatin, Numerous monomorphic small to intermediate sized lymphoid cells, Sparsely cellular and contains atypical lymphoid cells, Suspicious for malignancy, not otherwise specified, Other primary thyroid malignancies like anaplastic carcinoma and poorly differentiated carcinoma, Suboptimal cellularity or preservation can lead to uncertainty and result in a suspicious for malignancy interpretation, Usually surgical management similar to that of malignant nodules (, In suspicious for papillary thyroid carcinoma cases with low risk features ( 1 cm, without extrathyroidal extension and clinical metastasis), active surveillance is an option (, Molecular testing with high positive predictive value (, For suspicious for medullary thyroid carcinoma, Measuring serum calcitonin level or calcitonin immunostaining are recommended (, Repeat fine needle aspiration to obtain cells for flow cytometry (, A few follicular cells showing nuclear enlargement, pale and powdery chromatin and nuclear grooves are present, Correlation with serum calcitonin level or immunostaining might be helpful for definitive diagnosis if clinically indicated, Re-aspiration for flow cytometry might be helpful to better characterize the lymphocyte population if clinically indicated, Microfollicular architecture with minimal nuclear features of, Trabecular growth pattern of the cells with nuclear grooves and abundant nuclear pseudoinclusions, intratrabecular hyaline material, Nuclear changes of follicular cells with focal enlargement, grooves, prominent nucleoli and chromatin clearing in the lymphocytic background, An abundance of lymphocytes and plasma cells does not exclude the possibility of a coexisting, Numerous lymphocytes, few follicular cells, Elongated cells with pale chromatin, nuclear grooves and relatively large nucleoli, Spindle shaped morphology of the cell and nucleus, reminiscent of reparative epithelium in cervical Pap smears, Follicular variant of papillary thyroid carcinoma. There are several exceptions to the numeric requirement of benign follicular cells. Gharib In FNA specimens of this variant, the cancer cells appear more profuse, granular or vacuolated compared to regular PTC. Once obtained, the core biopsy is used to make touch preps (discussed below) and then is transferred into a container with appropriate fixative (usually formalin) and sent to the laboratory for processing. A complete bone marrow biopsy examination usually involves the review of these four specimens noted here in a slide tray: A) marrow aspirate smear, B) marrow core biopsy, C) clot section, and D) touch imprint preparation. The most common sites are the lungs, bone, liver and brain. Figure 5. Pu It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Lerma E, Arguelles R, Rigla M, Otal C, Cubero JM, Bagu S, Carreras AM, Eulalia E, Gonzalez-Campora R, Galera H, et al. In cell biology, a paraspeckle is an irregularly shaped compartment of the cell, approximately 0.2-1 m in size, [1] found in the nucleus ' interchromatin space. By using redundancies across components, your consultant hematopathologists may offer insights into the architecture, morphology, immunostaining, and flow cytometry profiles of any identified hematologic entity. . Based on the findings (MRI, gross and histopathology) cysticercosis was confirmed. SL official website and that any information you provide is encrypted The 6 general diagnostic categories are shown in bold type in Table 1. Fine-needle aspiration (FNA) cytology is an important diagnostic tool in patients with thyroid lesions. The nuclei are enlarged, with usually an oval or irregular shape, and include intense nuclear grooves and inclusions. 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. FOIA VA We welcome suggestions or questions about using the website. Dottorini Bongiovanni M, Crippa S, Baloch Z, Piana S, Spitale A, Pagni F, Mazzucchelli L, Di Bella C, Faquin W. Comparison of 5-tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology: a multi-institutional study. It is expected that the many benefits, clinical and investigational, of the Bethesda cervical terminology will also apply to the Bethesda thyroid terminology. %%EOF Cibas Albores-Saavedra J, Wu J. Ramzy They are then stained and processed much like the original core biopsy. Each diagnostic category is associated with a specific risk of malignancy and a recommendation for management. Intussusception in an adult revealing a Vanek's tumor: A case report. The general category FN/SFN is a self-sufficient interpretation; narrative comments that follow are optional. , eds. It was apparent from the discussions at the conference and the Web postings that the primary purpose of terminology is clarity of communication. Fleisher Cytologic preparations typically have high cellularity, and colloid is scant or absent. Ultrasound guidance is preferable than palpation-guided FNA for small nodules (< 1 cm), cystic lesions and when a prior FNA is nondiagnostic[13]. The discs are 2 mm thick in the unprocessed state, but less thick when processed, and sometimes slightly . The morphology is similar to that seen on the core biopsy. 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. RA You order a bone marrow analysis for your patient. 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.