ThyroSeq is reported to have a sensitivity of 90%, specificity of 93%, positive predictive value of 77–83%, and negative predictive value of 96–97%, with the ability to stratify risk based on the mutation detected.64,65 It is considered a test to “rule-in” malignancy.64 Since the newer classification of NIFTP, a recent study reports a decrease in positive predictive value with ThyroSeq of 42% and 33%, respectively when considering NIFTP as malignant or benign.66, BRAFV600E (BRAF) is an amino acid substitution at position 600 in BRAF, found in approximately 45–69% of all papillary thyroid carcinomas,67 with a 100% specificity for papillary thyroid carcinoma. Cite this article. Available at: www.cancer.gov (accessed: April 8, 2019). The initial assessment includes an evaluation of clinical risk factors and s onographic 9 examination of the neck. 2011;96(1):75–81. FNA should not be performed on thyroid nodules < 1 cm in diameter with some exceptions discussed later in this section. No microcalcifications or extrathyroidal extension. Appl Immunohistochem Mol Morphol. FNA evaluation of a hyperfunctioning nodule is not necessary as most hyperfunctioning nodules are benign [1]. Class 2 (intermediate-risk lesion): Nodules in this category have a 5–15% risk of malignancy. With the new developments in molecular testing, the approach to this category may change in the future. Haugen BR, Alexander EK, Bible KC, et al. The decision to repeat FNA or observe with repeat US is based on > 20 % growth in at least 2 nodule dimensions or > 50 % increase in nodule volume or the appearance of new suspicious US pattern. Article  By using this website, you agree to our Most of the assays are trained on classic papillary cancers and have limited data in follicular cancers. Eur J Endocrinol. Comprehensive history with focus on risk factors predicting malignancy (Table 1 [1, 3, 13]) should be part of the initial evaluation of a patient with thyroid nodule. These lesions have a 10–20 % risk of malignancy and FNA is recommended when nodule is ≥1.0 cm. Category V describes nodules suspicious for malignancy. Risk of malignancy in thyroid nodules 4 cm or larger.Â, Castro MR, Gharib H. Thyroid fine needle aspiration biopsy: progress, practice, and pitfalls.Â, Hwang SH, Sung JM, Kim EK, et al. A Bethesda I–III result was obtained in 91 nodule events (87.5%), in which 36 (39.6%) underwent operative management with a malignant result in 7 (19.4%); 4 (57.1%) were incidental malignancies. Also for these patients the frequency and duration of follow up will depend on the additional risk factors present. Ferris RL, Nikiforov Y, Terris D, et al. Category IV nodules may be assessed as follicular neoplasm or as suspicious for follicular neoplasm. Nodules with diameter < 1 cm with some exceptions require no FNA and can be observed with a follow up US. Molecular testing, previously difficult to attain due to cost restrictions and availability, now has a higher accuracy, reliability, availability, and affordability, making it easier to attain and interpret. J Clin Endocrinol Metab. Multicenter clinical experience with the Afirma gene expression classifier. The BSRTC is divided into six tiers (Table 4): I, nondiagnostic; II, benign; III, atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS); IV, follicular neoplasm (FN) and suspicious for FN (SFN); V, suspicious for malignancy; and VI, malignant.43 An important feature of this reporting system is the adequacy of the sample, defined as, no less than six groups of well-preserved thyroid epithelial cells consisting of at least 10 cells in each group. McCartney CR, Stukenborg GJ. Molecular markers in thyroid fine-needle aspiration biopsy: a prospective study. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. 2010;19(4):e130–9. Moon WJ, Jung SL, Lee JH, et al. Patients with surgical histology specimens showing benign follicular adenoma (absence of capsular or vascular invasion) do not require further treatment. This includes PTC (most common), MTC, anaplastic carcinoma, and high-grade metastatic cancers. The thyroid nodule. Cibas ES, Ali SZ. The interpretation of the features which comprise this category is based entirely on the observer which results in poor reproducibility and a second review by experienced high volume cytopathologist can be considered [99, 100]. PET positive nodules have a higher incidence of malignancy ~40–45 % and FNA is recommended in nodules > 1 cm [1, 57, 58]. Eur J Endocrinol. These are a common finding in the general population, majority being diagnosed incidentally during neck imaging. Suspicious for follicular J Clin Endocrinol Metab. Cersosimo E, Gharib H, Suman VJ, Goellner JR. “Suspicious” thyroid cytologic findings: outcome in patients without immediate surgical treatment. 2010;16 Suppl 1:1–43. A meta-analysis.Â, Moon HJ, Kwak JY, Kim MJ, et al. N Engl J Med. Cervical lymph nodes should be assessed. While this removes the tumor burden, in many cases surgery can lead to surgically associated complications, life-long thyroxine therapy for the patient, an increased overall cost burden with minimal to no changes in survival rates, in small localized or benign lesions.11 Over the years, our understanding of thyroid nodules and the natural progression of thyroid cancer has been a guiding force leading to a more standardized evaluation and management. Molecular tests have been developed in an attempt to determine whether an indeterminate nodule is benign or malignant. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. Thyroid incidentalomas detected on 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography: Thyroid Imaging Reporting and Data System (TIRADS) in the diagnosis and management of patients. 2009;144(7):649–55. This field is evolving and many other molecular tests are being developed (mRNA markers, miRNA markers, etc.) Reports suggest that up to 5.0% in ATA, 3.0% in TI-RADS, and 2.6% in AACE/AME fall under this “unclassified” category,14,38 of which, malignancy rate reached 38.7% in TI-RADS group and 28.6% of the ATA group.38 For this reason, further research is needed to improve reporting systems in order to minimize missing possible malignant nodules. Niccoli P, Wion-Barbot N, Caron P, et al. Each cytopathological category is risk stratified for malignancy and corresponds to specific recommendations for patient management [11] , [12] , [22] . The role of BRAFV600E mutation and ultrasonography for the surgical management of a thyroid nodule suspicious for papillary thyroid carcinoma on cytology. This is one of the scenarios where a subcentimeter thyroid nodule associated with these abnormal cervical lymph nodes should undergo FNA. Near-total thyroidectomy is indicated in this category. With the molecular testing being available, it can be used to supplement the malignancy risk assessment again after considering the clinical and US risk factors and patient preference [68, 103]. 2011;165(3):447–53. ➢ Malignant. Article  Common and uncommon sonographic features of papillary thyroid carcinoma.Â. 1974;228(7):866–9. PubMed Central  Are there any specific ultrasound findings of nodular hyperplasia (“leave me alone” lesion) to differentiate it from follicular adenoma? This category includes cytologically inadequate specimen. Papillary thyroid carcinoma dominates this category. Prevalence by palpation and ultrasonography.Â, Hegedüs L. Clinical practice: the thyoid nodule.Â, Guth S, Theune U, Aberle J, et al. Endocr Relat Cancer. Pentagastrin is not available in the United States, and there is still an ambiguity about the sensitivity/specificity, threshold cut off values and cost-effectiveness [22–24]. Fine-needle aspiration cytology of the thyroid. Nikiforov YE, Ohori NP, Hodak SP, et al. Oertel YC, Miyahara-Felipe L, Mendoza MG, Yu K. Value of repeated fine needle aspirations of the thyroid: an analysis of over ten thousand FNAs. A recent study of 1,851 nodules, reported that irregular margins have a specificity for malignancy of around 83%. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. Solitary thyroid nodule. Thyrotropin versus thyroid hormone in regulating bone density and turnover in premenopausal women.Â, Bandeira-Echtler E, Bergerhoff K, Richter B. Levothyroxine or minimally invasive therapies for benign thyroid nodules.Â. Brito JP, Gionfriddo MR, Al Nofal A, et al. The problem of suspicious cytologic findings. Cervical lymph node assessment (anterior, central and lateral compartment) should be performed in all patients with thyroid nodule. FNA is considered the gold standard test for evaluating thyroid nodules. 1997;82(9):2862–6. Thyroid nodules (TNs) assigned to the Bethesda System categories III and IV include numerous clinical characteristics, which increase or decrease the risk of malignancy. 2010;148(6):1294–9. Thyroid. Due diligence has led to an increased incidence of thyroid cancer, followed by surgical intervention and radioactive ablation; much of which may be unwarranted or overly aggressive. Gharib H, Papini E, Garber JR, et al. Diagnostic accuracy of ultrasound-guided fine needle aspiration biopsy for thyroid malignancy: systematic review and meta-analysis. Also in patients with the clinical risk factors mentioned in Table 1 and with the high pretest likelihood for thyroid cancer associated with these features, FNA at sizes lower than those recommended can be considered [1, 13]. Thyroid. 1997;126(3):226–31. Bukjari MH, Niazi S, Hanif G, et al. The AACE Guidelines recommend neither for nor against their use in clinical practice [13]. When thyroid nodule fine-needle aspiration (FNA) cytologic results show follicular lesion of undetermined significance or atypia of undetermined significance (FLUS/AUS, Bethesda III) or follicular neoplasm (Bethesda IV), the results are often called indeterminate. 2014;170(5):659–66. an incidental finding of focal FDG uptake in a >1 cm thyroid nodule is concerning and FNA is warranted Petersen P, Hansen JM. vi. Thyroid nodules are common and carry a 4–6.5 % risk of malignancy. Nondiagnostic thyroid fine-needle aspiration cytology: management dilemmas. ➢ Nondiagnostic or Unsatisfactory. Lee S, Skelton TS, Zheng F, et al. Google Scholar. The evaluation of a thyroid nodule in a pregnant woman should be done in same way as one would in nonpregnant state. Clin Cancer Res. Sakorafas GH. The clinical and economic burden of a sustained increase in thyroid cancer incidence.Â, Gharib H, Papini E. Thyroid nodules: clinical importance, assessment, and treatment.Â, Alexander EK, Kennedy GC, Baloch ZW, et al. Diagn Cytopathol. ANZ J Surg. American Association of Clinical Endocrinologists. Afirma Genomic Sequencing Classifier & Xpression Atlas Molecular Findings in Consecutive Bethesda III-VI Thyroid Nodules. Although the overwhelming majority of them turn out to be benign, the small subset of cancerous nodules needs to be accurately identified for optimal and timely surgical management. According to a 1993 article, such nodules need to be treated only if they become toxic ; surgical excision ( thyroidectomy ), radioiodine therapy , or both may be used. 60–75 % predicted risk of malignancy. 2008;18(8):889–94. An updated audit of fine needle aspiration cytology procedure of solitary thyroid nodule. Non-diagnostic fine needle aspiration biopsy: a dilemma in management of nodular thyroid disease. Benign and malignant thyroid nodules: US differentiation--multicenter retrospective study.
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