sparsely cellular specimen

CA Correspondence to: Evangelos P Misiakos, MD, FACS, Associate Professor of Surgery, Attikon University Hospital, University of Athens School of Medicine, 76 Aigeou Pelagous Street, Agia Paraskevi, 15 341, Attica, 12462 Athens, Greece. Edmund S. Cibas, MD, and Susan J. Mandel, MD, MPH, served as moderators. Rabaglia JL, Kabbani W, Wallace L, Holt S, Watumull L, Pruitt J, Snyder WH, Nwariaku FE. Prognosis is dismal with a mean survival of 2.5 to 6 mo and an overall 5-year survival of 0% to 14%. The AUS/FLUS category in the Bethesda system, represents aspirates that contain follicular, lymphoid, or other cell types with architectural and/or nuclear atypia that is more pronounced than that observed in benign lesions yet not sufficient to be characterized as suspicious for follicular neoplasm (SFN), or suspicious for malignancy[10]. Ghossein In several countries the Cytological Communities have adopted the first system or the other, as there is still an ongoing dispute on whether the 5-tiered system or the 6-tiered system is more efficient[12]. The cells have abundant pink cytoplasm, basally located nuclei and nuclear features of conventional PTC. In addition, obtaining adequate material at FNA is a very important issue, as the rates of malignancy observed in the nondiagnostic categories of both reporting systems are very high[14]. Despite the fact that not all PTC were detected by this panel, a positive molecular test helped to refine the FLUS cases into high-risk and low-risk categories[61]. Descriptive comments that follow are used to subclassify the malignancy and summarize the results of special studies, if any. Several patterns of nuclear atypia may be also present without being quantitatively and/or qualitatively sufficient for the interpretation of suspicious for malignancy. These cells constitute more than 50% of tumor volume[44]. 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]. [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 . Yang J, Schnadig V, Logrono R, Wasserman PG. Centrifuge the specimen again and decant the entire supernatant. In FNA specimens of this variant, the cancer cells appear more profuse, granular or vacuolated compared to regular PTC. Neutrophils are the same as WBCs, and as you know, it is normal to gave some WBCs in the urine. For that reason these findings are best interpreted as SFM. IB Its clinical utilization is significant, as it can define whether a recently emerged thyroid nodule should be managed expectantly or surgically, and can assist in selecting the appropriate surgical procedure when necessary[3]. Therefore, it is not prudent to remove every thyroid nodule we encounter in our medical practice. The nuclei are hyperchromatic, uniform in size and shape, and with indinstinct nucleoli. This system allows patients with FNAs showing focal atypia to undergo repeat aspiration prior to surgery. Nuclear grooves become an important diagnostic feature when associated with an oval, enlarged nucleus with fine chromatin[41]. JR 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%. Chung Utilization of ancillary studies in thyroid fine needle aspirates: a synopsis of the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Thyroid FNA specimen a. Therefore the diagnosis SFM, suspicious for thyroid carcinoma is an indication for surgery. The inherited forms are characterized by an autosomal dominant mode of inheritance and are associated with point mutations in the RET proto-oncogene on chromosome 10. et al. R The most common sites are the lungs, bone, liver and brain. These specimens typically show sheets of bland thyroid follicular cells, which represent flattened macrofollicles. Different cell types of neurons form complicated circuits in the brain. This variant is sometimes difficult to diagnose, because in some cases the characteristic neoplastic cells are sparsely evident in the mass. LiVolsi The site is secure. lobectomy). Gharib 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. Hay %PDF-1.6 % Based on the findings (MRI, gross and histopathology) cysticercosis was confirmed. This is an aggressive variant of PTC characterized by the presence of crowded, stratified clusters of elongated cells resembling cells from a colonic adenoma. LiVolsi Broome JT, Solorzano CC. Conspicuous cellularity alone does not qualify the nodule for a suspicious interpretation.23 If the sample is cellular but mostly macrofollicular (intact spheres and flat fragments of evenly spaced follicular cells), a benign interpretation is appropriate. Patients with the sporadic forms of MTC or the familial MTC are most often middle-aged (mean age 50 years old), except in familial cases, in which they are relatively younger. The atypical thyroid fine-needle aspiration: past, present, and future. Q: Can the core biopsy determine the blast count? Almost all patients with MTC have a significantly elevated serum calcitonin level, and in some cases these tumors can produce substances that can lead to paraneoplastic syndromes[35,44]. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. The differential diagnosis includes hyperplastic adenomatous nodules, follicular adenoma, follicular carcinoma, and follicular variant of PTC, where the nuclear features remain ill defined. Of those that prove to be malignant, many are FCs, but a significant proportion are follicular variants of papillary carcinoma.2,8,11,19. . Description of a distinctive morphological variant and report of 7 cases. LiVolsi However, this requires additional FNA passes or residual cellular material from the cytologic sample. Zubair W. Baloch, MD, PhD, served as chair of the Terminology and Morphologic Criteria committee. For clarity of communication, TBSRTC recommends that each report begin with 1 of 6 general diagnostic categories. In: Ali SZ, Cibas ES, editors. Note the trabecular bone (*) with trilineage hematopoiesis including megakaryocytes, granulocytic precursors, and erythroid islands presented in 2D following formalin fixation and paraffin processing. Other benign subcategories include consistent with lymphocytic (Hashimoto) thyroiditis in the proper clinical context and consistent with granulomatous (subacute) thyroiditis. This is a partial list and does not include a variety of other benign conditions like infections and amyloid goiter that are occasionally sampled by FNA. qA;`Yb]@b,@ "~Xbqs8J The many faces and mimics of papillary thyroid carcinoma. In a study by Teixeira et al[29] the overall incidence of malignancy in the FNA-biopsied nodules characterized as FLUS was 16.2%, a higher value than the suggested 5% to 15%[10,29-31]. Distant metastases seldom occur, but may develop in 20% of cases in late stage. The specimen is fixed in paraffin and cut for slide preparation. . For a thyroid FNA specimen to be satisfactory for evaluation (and benign), 6 . Figure 4. Lin Descriptive comments that follow are used to subclassify the benign interpretation. Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ, et al. Cantara S, Capezzone M, Marchisotta S, Capuano S, Busonero G, Toti P, Di Santo A, Caruso G, Carli AF, Brilli L, et al. A minor population of macrofollicles (intact spheres and fragments) can be present. 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]. 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. . 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]. 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. RT 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]. 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. What is one to do with the sparsely cellular specimen consisting mostly of microfollicles? Medullary carcinoma is highly metastatic, as tumor cells can be disseminated through hematogenous and metastatic routes to numerous sites, including cervical lymph nodes, liver, lung, bone, and adrenal glands. Piana S, Frasoldati A, Ferrari M, Valcavi R, Froio E, Barbieri V, Pedroni C, Gardini G. Is a five-category reporting scheme for thyroid fine needle aspiration cytology accurate? The main purpose of thyroid FNA is to stratify higher risk patients for surgery, and to prevent unnecessary surgeries for benign conditions. 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). 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. Cystic degeneration also is often found. ZW 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. Agrawal S, Rao RS, Parikh DM, Parikh HK, Borges AM, Sampat MB. Cochand-Priollet Dottorini The following breakdown shines some light inside the black box of hematologic diagnostics and may provide insight into what the hematopathology report tells you. V Ultrasound guidance is preferable than palpation-guided FNA for small nodules (< 1 cm), cystic lesions and when a prior FNA is nondiagnostic[13]. Rubenfeld The https:// ensures that you are connecting to the VA 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 Lloyd Heitz 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 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]. Patients with sporadic MTC present with a solitary, circumscribed thyroid nodule, usually in the middle to upper-outer half of the thyroid gland. The method could also be applicable to other sparsely cellular samples such as cerebrospinal fluid (CSF) samples, or eye vitreous fluid samples. S van Heerden The phenotypic composition of the various marrow components is key to understanding their utility for further investigative diagnostic studies. C Note granulocytic precursors (arrows) and erythroid cells (arrow heads). Due to the decalcification and need for fixation, bone core biopsy slides are usually not available to review until the following day. Inadequate samples are reported as nondiagnostic (ND) or unsatisfactory (UNS). Picture of four bone marrow specimens in a slide tray. But the nuclear and architectural changes of some PTCs are subtle and focal. It reduces the rate of unnecessary thyroid surgery for patients with benign nodules and appropriately triages patients with thyroid cancer to appropriate surgery. Handle sparsely cellular specimens ii. Kinematic comparison between the knee after bicruciate stabilized total knee arthroplasty and the native knee: A cadaveric study. Goellner 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]. 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. McHenry The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer. Quick tip: Flow cytometry cannot be performed on the clot section after the clot has set and after fixation in formalin. (2021).Demystifying the Bone Marrow Biopsy: A Hematopathology Primer. Unless specified as ND/UNS, the FNA specimen is considered adequate for evaluation. 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). Warthin's tumor : the presence of oncocytic epithelium. A moderately or markedly cellular sample is composed of a virtually exclusive population of Hrthle cells, yet the clinical setting suggests a benign Hrthle cell nodule, eg. Top Users Networks Stats . Pathology and Genetics of Tumours of Endocrine Organs, Genetic and biological subgroups of low-stage follicular thyroid cancer. Determination of cellular phenotype (what the cell expresses on its surface, or in its cytoplasm) on an aspirate is carried out by flow cytometry. This category is reserved for aspirates with borderline cellularity and is subdivided into two subcategories. The documents underwent revision after each comment period before reposting on the Web. 2nd ed. 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. The benefit of thyroid FNA derives in large part from the ability to make a reliably benign interpretation that avoids unnecessary surgery. 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. Bethesda guidelines suspicious for malignancy, Ali: The Bethesda System for Reporting Thyroid Cytopathology - Definitions, Criteria and Explanatory Notes, 2nd Edition, 2018, Head Neck Pathol 2019 Oct 17 [Epub ahead of print], Noninvasive follicular thyroid neoplasm with papillary-like nuclear features, invasive follicular variant of papillary thyroid carcinoma, Bethesda category V suspicious for malignancy (SM) is used when some cytologic features are strongly suspected of malignancy but are not sufficient for a conclusive diagnosis (, Higher suspicion of malignancy than atypia of undetermined significance / follicular lesion of undetermined significance (AUS / FLUS) but lower suspicion than malignant, Molecular testing with mutation panels may be useful, particularly for potential noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) cases, Purpose of separating suspicious for malignancy from malignant is to preserve the very high positive predictive value of the malignant category without compromising the overall sensitivity of fine needle cytology aspiration, Used when cytology is strongly suspected of malignancy but is not sufficient for a conclusive diagnosis, Frequency < 5%, resection rate 70%, risk of malignancy 80% (NIFTP = malignant), 45 - 60% (NIFTP malignant), Most common histological diagnosis is papillary thyroid carcinoma (PTC) (, Risk of malignancy: 80% (NIFTP = malignant), 45 - 60% (NIFTP malignant) (, Suspicious for malignancy interpretation allows for more conservative management options (e.g. Cerutti JM. A significant proportion of these cases (16%25%) prove not to be neoplasms but rather hyperplastic proliferations of Hrthle cells in nodular goiter or lymphocytic thyroiditis.26,27 About 15% to 45% of nodules are malignant, and the remainder of the neoplasms prove to be Hrthle cell adenomas.22,26,27, Many thyroid cancers, most especially papillary thyroid carcinoma (PTC), can be diagnosed with certainty by FNA. Jing X, Michael CW, Pu RT. Regardless the staining method used, all slides with diagnostic material are used for the evaluation and clarification of each case. 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. Royal College of Physicians. The heterogeneity of this category precludes outlining all scenarios for which an AUS interpretation is appropriate. CS If the nodule is almost entirely cystic, with no worrisome sonographic features, an endocrinologist might proceed as if the CFO were a benign result. et al. The cytotechnologist is specially trained and certified to examine cellular samples under a microscope, evaluating the slides for specific abnormalities in the cell's shape, color, or size which could signal a cancerous process or other disease. et al. 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). Highly cellular specimens are ideal for smeared preparations, whereas sparsely cellular specimens will require multiple centrifugation steps and special cell concentration methods. It is expected that the many benefits, clinical and investigational, of the Bethesda cervical terminology will also apply to the Bethesda thyroid terminology. SL Atypical cells in fine-needle aspiration biopsy specimens of benign thyroid cysts. Incidence of malignancy in thyroid nodules determined to be follicular lesions of undetermined significance on fine-needle aspiration. et al. 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. et al. 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). Highly cellular specimens are ideal for smeared preparations, whereas sparsely cellular specimens will require multiple centrifugation steps and special cell consolidation processing. View an interactive bone marrow core biopsy online. The adequacy of a thyroid FNA is defined by both the quantity and quality of the cellular and colloid components. (A) A representative case classified as diagnostic category (DC) III (atypia of undetermined significance) showing sparsely cellular specimen (x15; scale bar, 200 m). Mazzaferri EL. 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. et al. Deveci Unlike the core biopsy, decalcification is not required for the clot section. We reviewed the English literature regarding Thyroid Cytopathology systems in order to identify the most suitable methodology, taking into account our prospective as well. Since recurrent PTC typically secretes thyroglobulin, serum monitoring of thyroglobulin serves as a useful tumor marker for recurrent PTC[35]. Clark This category applies to specimens that are unsatisfactory owing to obscuring blood, overly thick smears, air drying of alcohol-fixed smears, or an inadequate number of follicular cells. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. L However cases with indeterminate cytological findings still remain a matter of debate. According to the Bethesda system for reporting thyroid cytopathology, a specimen . 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.

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