Presentation on theme: "ATA Guideline in Thyroid Nodule Management"— Presentation transcript:
1 ATA Guideline in Thyroid Nodule Management Zohreh MousaviEndocrine Research CenterMashhad university of Medical SciencesIsfahan 4th International Congress of Endocrine & Metabolism Updates April 2017
3 Scope of ProblemThyroid nodules are extremely common. An estimated 4% of the population have a palpable thyroid nodule, and more than 50% have a nodule detectable by ultrasonography. With the frequent use of computed tomographic scans and carotid ultrasound studies, many thyroid nodules are found in asymptomatic patients. In my practice, this has generated more than one-third of referrals for consultation regarding a thyroid nodule. Each of the guidelines addresses which nodules necessitate a biopsy and which can be safely monitored or ignored
4 Thyroid Nodules:Palpable thyroid nodules: 5% of general population and up to 30-40% above age 50.Thyroid incidentalomas on autopsy: 8-65%.Thyroid US depicts nodules in up to 67% of the population and % of childrenThyroid cancer is present in 5-15% of thyroid nodules.
5 A. Overdetection: 4 cancers An epidemic of diagnosis, not an epidemic of cancer!Prostate CancerThyroid CancerBreast CancerMelanomaRecommendations are likely to continue to evolve as detection rates of thyroid cancers rise, adding to the pressing need for more evidence to help guide clinical decision making, Dr Bible stressed."There is an 'epidemic' of papillary thyroid cancer noted worldwide, particularly in developed countries, apparently arising primarily due to increased detection of minute papillary cancers, either from intentional thyroid-cancer screening (for instance, in South Korea) or by incidental detection from the increasing use of medical imaging (for instance, in the United States)," he explained."Available data suggest that the vast majority of these micropapillary cancers would not have previously been recognized and furthermore suggest that most appear to be indolent and not requiring of aggressive therapy — but more evidence is required to define how to respond most appropriatelySource: AIHW
6 Too much testing?The discovery of a thyroid nodule, should prompt a careful history taking and physical examination, measurement of thyrotropin levels, and an ultrasonographic examination“A normal person is someone who has not had enough tests” Dean at John Hopkins Medical School
7 A. Overdetection: thyroid cancer Thyroid cancer tripled in 25 years; no more deaths
8 Guide the decision to perform fine-needle aspiration Nodule sizeClinical contextUltrasonographic characteristicsNodule size, clinical context, and ultrasonographic characteristics guide the decision to perform fine-needle aspiration
9 Strategies and Evidence Pertinent History and Physical ExaminationLaboratory StudiesImaging StudiesFine-Needle Aspiration of the ThyroidMolecular Analysis of Thyroid Fine-Needle AspirationManagement
10 Clinical Findings Associated with an Increased Risk That a Thyroid Nodule Is Malignant. Table 1 Clinical Findings Associated with an Increased Risk That a Thyroid Nodule Is Malignant.Burman KD, Wartofsky L. N Engl J Med 2015;373:
11 Evaluation History Physical Examination Rapid growth Family history IrradiationCancer syndromesPhysical ExaminationFixed, hard massVocal cord paralysisCervical lymphadenopathyObstructive symptomsIrradiation as a child of head and neck or total body irradiation from bone marrow transplant
12 KSTR : Korean Society of Thyroid Radiology ATAAACEKSTR : Korean Society of Thyroid RadiologyThree sets of guidelines regarding management of thyroid nodules have been published during the past 3 years. The first set was issued by the American Thyroid Association (ATA), the second was by the American Association of Clinical Endocrinologists (AACE), in collaboration with the Associazione Medici Endocrinologi (AME) and the European Thyroid Association (ETA), and the most recent was by the Korean Society of Thyroid Radiology (KSTR). These guidelines have many similarities, but each set takes a slightly different approach to recommending which nodules should undergo biopsy
13 Evaluation Low Thyroid scintigraphy TSHLow Thyroid scintigraphyNot low US to select for FNA biopsy; evaluate for hypothyroidismUltrasoundHigh risk of cancer: hypoechoic, microcalcifications, increased central vascularity, irregular margins, taller than wide, documented enlargement, size >3cmLow risk of cancer: hyperechoic, peripheral vascularity, pure cyst, comet-tail shadowingHigher TSH = higher rate of malignancy and more advanced stage of cancer
14 Patient #148 yo male incidental 8 mm thyroid nodule Suspicious sonographic pattern, no abnormal LN
22 Composition Solid Predominantly solid Predominantly cystic Cystic Spongiform : predominately of tiny cystic spacesThe echogenicity of the solid component of a nodule should be compared with normal-appearing thyroid tissue, usually immediately adjacent to the nodule. In the setting of background abnormal thyroid tissue echogenicity, such as in Hashimoto’s thyroiditis, the echogenicity of the solid component should still be described relative to the adjacent thyroid tissue, but it may be noted that the background tissue is of altered echogenicity
23 What is the malignancy risk of the nodule Most of the malignant thyroid tumors are solid (81.6–93%)malignancy risk of the solid nodules is higher (24.1–34.7%)than that of the partially cystic nodules (3.3–7.1%)*Isoechoic Spongiform Nodule is benignWhen a spongiform nodule was defined as“the aggregation of multiple microcystic componentsin more than 50% of the volume of the nodule,”only one in 52 spongiform nodules was malignant. When a spongiform nodule was defined as tiny cystic spaces involving the entire nodule, all 210 spongiform nodules were benign on FNA biopsy.
24 Echogenicity Hyperechoic Isoechoic Hypoechoic Very hypoechoic * If the nodule is of mixed echogenicity, it can be described as“predominantly” hyperechoic, isoechoic, or hypoechoicThe echogenicity of the solid component of a noduleshould be compared with normal-appearing thyroid tissue, usually immediately adjacent to the nodule. Inthe setting of background abnormal thyroid tissue echogenicity, such as in Hashimoto’s thyroiditis, theechogenicity of the solid component should still be
25 Would you biopsy this nodule? Thyroid Nodule: 2.7 cm, predominantly solid, hypoechoic, circumscribed, marked vascularity, wider than tall, no microcalcificationsWould you biopsy this nodule?What do guidelines say?
26 Would you biopsy this nodule? Thyroid Nodule: 1.7 cm, mixed solid and cystic, isoechoic, circumscribed, vascular, wider than tall, no microcalcificationsWould you biopsy this nodule?What do guidelines say?
27 Would you biopsy this nodule? Thyroid Nodule: 3.5 cm, spongiform, isoechoic, circumscribed, peripheral vascularity, wider than tall, no microcalcificationsWould you biopsy this nodule?What do guidelines say?
28 Shape Term: taller-than wide A taller-than-wide shape is defined as a ratio of >1 in the anteroposterior diameter to the horizontal diameter when measured in the transverse planeSuspicious or suggestive of malignancyThis finding is seen in 12% of thyroid nodulesSensitivity: 40-68%specificity: 82-93%Taller-than-wide shape is a major feature for the ratio of >1categorization of thyroid nodules that are suspiciou or suggestive of malignancy. The correspondingpathologic feature leading to this appearance isthought to be decreased compressibility. This findingis seen in 12% of thyroid nodules . Sensitivity ranges between 40% and 68%, specificity between82% and 93%, positive predictive value between 0.58 and 0.73, and negative predictive value between 0.77and 0.88
29 Suspicious US features: Solid hypoechoic nodule with non-parallel orientation.
30 MarginsSmooth: Uninterrupted, well-defined, curvilinear edge typically forming a spherical or elliptical shapeIrregular margin: The outer border of the nodule is spiculated, jagged, or with sharp angles with or without clear soft tissue protrusions into the parenchymaLobulated: Border has focal rounded soft tissue protrusions that extend into the adjacent parenchymaIll-defined: Border of the nodule is difficult to distinguish from thyroid parenchyma; the nodule lacks irregular or lobulated marginsHalloExtrathyroidal extensionHalo: Border consists of a dark rim around the peripheryof the nodule. The halo can be described ascompletely or partially encircling the nodule. In theliterature, halos have been further characterized asuniformly thin, uniformly thick, or irregular in thickness
31 Suspicious US features: Solid hypoechoic nodule with spiculated/microlobulated margin.
33 Echogenic FociPunctate echogenic foci: “Dot-like” foci having no posterior acoustic posterior artifactsMacrocalcificationsPeripheral calcificationsComet-tail artifacts
34 Colloid cyst: mostly cystic nodule with punctate echogenicities that show posterior ring-down artifact, indicating colloid crystals and a high likelihood that the nodule is benign
35 High-Risk Ultrasound Features ATA 2015 • Marked hypoechogenicity• Microcalcifications• Irregular (speculated) margins• More tall than wide ( AP>TR )• Extracapsular growth• Suspicious regional lymph node
36 Ultrasonographic Images of Thyroid Nodules. Figure 2 Ultrasonographic Images of Thyroid Nodules. Panel A shows a papillary thyroid carcinoma with hypoechogenicity. The other panels show nodular features that raise suspicion for cancer. Panel B shows a thyroid nodule with blurred or indistinct margins. Panel C shows a nodule that is higher (2.5 cm) than it is wide (1.6 cm). Panel D shows a nodule with microcalcifications.Burman KD, Wartofsky L. N Engl J Med 2015;373:
37 Large cystic nodal mass. Small focal cystic change and hyperechogenicity in lymph node.Hyperechogenicity and macrocalcifications in lymph node.D. Multifocal hyperechogenicity (black arrows) and microcalcification (white arrow) in lymph nodeA. Large cystic nodal mass. B. Small focal cystic change and hyperechogenicity in lymph node. C. Hyperechogenicity and macrocalcificationsin lymph node. D. Multifocal hyperechogenicity (black arrows) and microcalcification (white arrow) in lymph node. E. Hyperechogenicity,microcalcification, and abnormal hypervascularity in lymph node. Diagnosis: metastatic papillary carcinoma
39 A. Solid hypoechoic nodule without suspicious US features A. Solid hypoechoic nodule without suspicious US features. Diagnosis: benign follicular nodule. B. Solid isoechoic (predominantly isoechoic)nodule with microcalcification. Diagnosis: benign follicular nodule. C. Predominantly solid hypoechoic nodule with multiple microcalcifications.Diagnosis: papillary carcinoma. D. Predominantly cystic hypoechoic nodule with microcalcification (arrow). Diagnosis: papillary carcinoma. (intermediate suspicion
40 Low Risk NoduleA.Solid isoechoic nodule. Diagnosis: follicular variant papillary carcinoma. B. Predominantly solid and isoechoic nodule. Diagnosis: benign follicularnodule. C. Predominantly solid and hypoechoic nodule. Diagnosis: benign follicular nodule. D. Predominantly cystic and isoechoic nodule.Diagnosis: benign follicular nodule low suspicious
42 Spongiform noduleA. Spongiform nodule. Diagnosis: benign (FNA not performed). B. Spongiform nodule with tiny microcystic changes. Diagnosis: benign follicularnodule. C. Predominantly cystic nodule with multiple comet tail artifacts. Diagnosis: benign follicular nodule with colloid. D. Cyst with comet-tailartifact. Diagnosis: benign (colloid cyst, FNA not performed) Benign
43 cystic nodule with multiple comet tail artifacts
44 Algorithm of K-TIRADS for malignancy risk stratification based on solidity and echogenicity of thyroid nodulesNa et al. Thyroid 2016;26: (25)
45 Algorithm of K-TIRADS for malignancy risk stratification based on solidity and echogenicity of thyroid nodules
46 Quantification of cancer risk of each clinical and ultrasonographic suspicious feature of thyroid nodules: a systematic review and meta-analysisCampanella P, Ianni F, Rota CA, Corsello SM, et al Eur J Endocrinol 2014;170:R203-R211The highest risk was found for nodule height greater than width, absent halo sign, and microcalcifications forultrasonographic features and family history of thyroid carcinoma for clinical features.A meta-analysis-derived gradingsystem of TN malignancy risk, validated on a large prospective cohort, could be a useful tool in TN diagnostic work-up
49 Recommendation 8Nodules >1 cm in greatest dimension with high suspicion sonographic pattern(Strong recommendation, Moderate-quality evidence)
50 Recommendation 8Nodules > 1 cm in greatest dimension with intermediatesuspicion sonographic pattern.(Strong recommendation, Low-quality evidence)
51 Recommendation 8 Nodules > 1.5 cm in greatest dimension with low suspicion sonographic pattern.(Weak recommendation, Low-quality evidence)
52 Recommendation 8 Thyroid nodule diagnostic FNA may be considered for Nodules > 2 cm in greatest dimension with very lowsuspicion sonographic pattern (e.g., spongiform).*Observation without FNA is also a reasonable option.(Weak recommendation, Moderate-quality evidence)
53 Low-risk lesion ATA Benign Very low suspicion Low suspicion * Purely cystic nodules (no solid component)Very low suspicion*Spongiform or partially cystic nodules without any of the US features described in low-, intermediate- or high-suspicion patternsLow suspicion*Isoechoic or hyperechoic solid nodule, or partially cystic nodule with eccentric solid area without:• Microcalcifications• Irregular margin• Extrathyroidal extension• Taller than wide shape
54 Low-risk lesion AACE/ACE-AME • Mostly cystic nodules with reverberating artifacts and not associated with suspicious US signs• Isoechoic spongiform nodules, either confluent or with regular halo
55 Intermediate suspicion Hypoechoic solid nodule with smooth margins without:• Microcalcifications• Extrathyroidal extension• Or taller than wide shape
60 FNA Recommendations(Recommendation 8) Recommendations for diagnostic FNA based on sonographic features: A) Nodules > 1 cm with high suspicion sonographic pattern (Strong recommendation, Moderate-quality evidence)B) Nodules > 1cm with intermediate suspicion sonographic pattern (Strong recommendation, Low-quality evidence)C) Nodules > 1.5 cm with low suspicion sonographic pattern (Weak recommendation, Low-quality evidence)D) Nodules > 2 cm with very low suspicion sonographic pattern (e.g. - spongiform) (Weak recommendation, Moderate-quality evidence)E) FNA is not required for thyroid nodules that do not meet the above criteria, including all nodules < 1 cm (Strong recommendation, Moderate-quality evidence)F) FNA is not required for purely cystic nodules (Weak recommendation, Low- quality evidence)Ito Y, Thyroid 13:381-7, 2003 Ito Y, World J Surg 34:28-35, 2010
61 What is the role of fine-needle aspiration (FNA), cytology interpretation and molecular testing
62 Thyroid Fine-Needle Aspiration Specimens. Figure 3 Thyroid Fine-Needle Aspiration Specimens. The figure shows nodules in five different categories of the Bethesda System for Reporting Thyroid Cytopathology.29 Panel A shows a benign nodule. The thyroid follicular cells are evenly spaced and have a small and uniform nuclear size. Panel B shows atypia of undetermined significance. In an otherwise benign aspirate, rare groups of follicular cells show nuclear enlargement. The patient underwent a thyroidectomy, and final pathological analysis showed benign nodular hyperplasia. Panel C shows a follicular neoplasm. Smears contain a cellular aspirate with only scant colloid. The follicular cells are of normal size but form microfollicles (abnormal architecture). Final pathological analysis showed follicular adenoma. Panel D shows a nodule “suspicious for malignancy” (papillary carcinoma). Aspirate shows some features of papillary carcinoma, such as hypercellularity, nuclear enlargement, hyperchromasia, and an increased nuclear-to-cytoplasmic ratio. However, no definitive nuclear pseudoinclusions were identified. Thyroidectomy was performed, and the final pathological analysis showed a follicular variant of papillary carcinoma. Panel E shows a malignant nodule (papillary carcinoma). Smears show a cellular aspirate with numerous abnormal follicular cells containing enlarged hyperchromatic nuclei. Nuclear pseudoinclusions are present (arrow).Burman KD, Wartofsky L. N Engl J Med 2015;373:
63 Thyroid fine-needle aspiration (FNA) is the most useful screening test for evaluating a thyroid nodule and stratifying risk of malignancy. Unfortunately, the lack of a standardizedreporting format has caused confusion and ambiguity in inter-preting these results. To address this need, the 2007 NationalCancer Institute Thyroid Fine Needle Aspiration State of the Science Conferenceand the subsequent Bethesda Systemfor Reporting Thyroid Cytopathology proposed a uniformclassification scheme with 6 distinct diagnostic categories.
64 Bongiovanni M, et al. Acta Cytol 2012; 56:333-9. The Bethesda System for Reporting Thyroid Cytopathology: A Meta-AnalysisBongiovanni M, et al.Acta Cytol 2012; 56:333-9.
65 The Bethesda System for Reporting Thyroid Cytopathology: A Meta-Analysis
66 The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC ) Satisfactory for interpretation:89-95%Definitively benign :55-74%Definitively malignant : 2-5%AUS/FLUS : 2-18%FN : 2%–25%,SUSP : 1%–6%89%–95% of samples being satisfactory for interpretationand 55%–74% reported as definitively benign and2%–5% as definitively malignant (101–104). The remainingsamples are cytologically indeterminate, including AUS/FLUSin 2%–18% of nodules, FN in 2%–25%, and SUSP in 1%–6%. Ref
68 Diagnostic Categories of Thyroid Nodules and Risk of Cancer Table 2 Diagnostic Categories of Thyroid Nodules and Risk of Cancer.Burman KD, Wartofsky L. N Engl J Med 2015;373:
69 Recommendation 16 AUS/FLUS Repeat FNAMolecular testingDiagnostic surgeryActive surveillance* Consider : patient preference and feasibility(Weak recommendation, Moderate-quality evidence)Based on the Bethesda System, this diagnostic category is reserved for specimens thatcontain cells with architectural and/or nuclear atypia that is more pronounced than expected forbenign changes but not sufficient to be placed in one of the higher risk diagnostic categories(99;190). Although this diagnostic category has been recommended for limited use and has anexpected frequency in the range of 7%, recent reports based on the Bethesda System have foundthis cytologic diagnosis to be used in 1-27% of all thyroid FNA samples (105;191
70 Clinical Outcome for Atypia of Undetermined Significance in Thyroid Fine-Needle Aspirations Retrospective analysis yearsOf 4,691 thyroid FNAs, 512 (10.9%) had a diagnosis of AUSRepeat FNAFrom 331 cases (64.6%), of which 240 (72.5%) were benign91 (27.5%) were malignantVanderLaan Paul A et al, Am J Clin Pathol ;135:AbstractIn the Bethesda System for reporting thyroid fineneedle aspirations (FNAs), atypia of undetermined significance (AUS) is a category with limited reportedfollow-up and outcome data
71 No significant differences between groups single AUS diagnosis (37/90 [41%])2 successive AUS FNA diagnoses (22/51 [43%])and patients with a benign aspirate after AUS (2/7 [29%])We report canalysis of our institution’s experience duringnearly 4.5 years with a tiered classification schemeconforming to the Bethesda System in which repeatedFNA was recommended for most patients with an initialAUS diagnosis. Of 4,691 thyroid FNAs, 512 (10.9%)had a diagnosis of AUS. Cytologic or histologicoutcome data were available for 331 cases (64.6%), ofwhich 240 (72.5%) were benign and 91 (27.5%) weremalignant. Of patients with a surgical diagnosis, therewas no statistically significant difference in malignancyrate among patients who went directly to surgeryaftera single AUS diagnosis (37/90 [41%]), patients having2 successive AUS FNA diagnoses (22/51 [43%]),and patients with a benign aspirate after AUS (2/7[29%]). Although AUS confers an intermediate risk ofmalignancy, guidelines recommending repeated FNAfor most cases should be reevaluated.
72 AUS/FLUS: A second opinion review of the cytopathology slides by a high-volume cytopathologist Unfortunately, there is a relatively high intra-observer variability in this difficult diagnostic categoryAnn Intern Med. 2013;159:Ref 106
73 core-needle biopsy: requires further investigation and is not justified
74 Surgery for AUS Repeated AUS diagnosis Suspicious or malignant diagnosis on repeated FNA
75 What is the utility of 18FDG-PET scanning to predict malignant or benign disease when FNA cytology is indeterminate (AUS/FLUS, FN, SUSP)?Not routinely indicated RECOMMENDATION 1818FDG-PET imaging is not routinely recommended for the evaluation of thyroid nodules with indeterminate cytology.(Weak recommendation, 8 studies that subject of 2 meta analysis )
76 AUS/FLUSIf repeat FNA cytology and/or molecular testing are not performed or inconclusive,either surveillance or diagnostic surgical excision may be performed for an AUS/FLUS thyroidnodule, depending on clinical risk factors, sonographic pattern, and patient preference
77 MAPK and PI3K-AKT-MTOR pathways—genetic alterations
78 A hotly debated area: molecular markers And tests for molecular markers for thyroid cancer, a hotly debated area, are treated differently in the two guidelines, Dr Gharib noted. The ATA guidelines suggest that clinicians should order these tests if cytology findings are atypical, whereas the AACE guideline uses more cautious wording: "At present, no single cytochemical or genetic marker can definitely rule out malignancy in indeterminate nodules. Nevertheless, these tools should be considered together with clinical data.“More recently, molecular testing to improve the diag-nostic assessment of indeterminate nodules has becomecommercially available (14–16). The Afirma gene expres-sion classifier (GEC) (Veracyte, Inc) analyzes the mRNAexpression of 167 genes in aspiration material and pro-Vides a benign or suspicious result toimprove preoperativerisk stratification
79 Algorithm for management of thyroid nodules on the basis of FNAB and molecular marker tests Depending on the cytology categories, molecular tests with high sensitivity and NPV (eg, gene expression classifier) or high specificity and PPV (eg, BRAF mutation) are chosen. Extent of surgery should be decided on the basis of the combined assessment of clinical, imaging, cytological, and molecular marker data. FNAB=fine needle aspiration biopsy. AUS/FLUS=atypia of undetermined significance/follicular lesion of undetermined significance. FN/SFN=follicular neoplasm/suspicious for follicular neoplasm. PTC=papillary thyroid cancer. NPV=negative predictive value. PPV=positive predictive value. Tx=total/near total thyroidectomy. LND=lymph node dissectionXing M, et al.Lancet March 23; 381(9871): 1058–1069
80 What are the principles of the molecular testing of FNA samples?
81 Molecular testing : NCCN Tumor Marker Task Force Analytic validity : accuracy and reproducibilityClinical validity : sensitivity, specificity, predictivelyClinical utility : decision making* “improves patient outcomes sufficiently to justify its incorporation into routine clinical practice”Ref : 158 ATA
82 Molecular testing using theAfirma GEC in AUS/FLUS 95% NPV (95% CI 79%-99%)37% PPV (95% CI 23%-52%)Alexander EK et al, 2012;N Engl J Med 367:
83 AUS/FLUS or FN, and ‘suspicious’167 GEC have an estimated 37-44% risk of malignancy which is slightly higher than the riskbased upon the Bethesda classification alone (Table 7) (163;171)
84 Summary ATA about molecular tests In summary, there is currently no single optimal molecular test that can definitively rule in or rule out malignancy in all cases of indeterminate cytology, and long-term outcome data proving clinical utility are needed.Page 43
85 based on a recent meta-analysis of performance of the Bethesda system) Ideal ‘‘rule-out’’ test : NPV similar to a benign cytologic diagnosis (96.3%) (predictive value estimatesbased on a recent meta-analysis of performance of the Bethesda system)Ideal ‘‘rule-in’’test would have a PPV for histopathologically proven malignancy similar to a malignant cytologic diagnosis (98.6%),Bongiovanni M et al 2012 The Bethesda System for ReportingThyroid Cytopathology: a meta-analysis. Acta Cytol 56:333–339.
86 Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology2. Expected surgical histopathology outcomes in thyroid nodules with AUS/FLUS or FN/SFN cytopathology after diagnostic surgery or after preoperative molecular testing. The size of each box and the associated percentages represent the expected proportions of benign/malignant outcomes (white/black boxes) or molecular results (white/dark gray boxes) at 32% (A) or 24% (B) thyroid cancer prevalence. The residual risk of malignancy (ROM) in nodules with negative/benign molecular results is [1-NPV] and the ROM in nodules with positive/malignant molecular results is PPV. The rate of unnecessary or potentially avoidable surgeries is the proportion of surgeries performed on nodules subsequently classified as benign by surgical histology. Abbreviations: B, benign; Mal, malignant.
87 Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology
88 New Platform"One of the key challenges is when you have a suspicious nodule, you have to determine whether it's benign or malignant to determine if the patient has to go to surgery. After fine-needle aspiration, about 20% to 30% are indeterminate. What we have done is come up with a new approach, which is a combination test — for the first time, we are able to both rule in and rule out malignancy," Dr Labourier told Medscape Medical News
89 Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate CytologyConclusions:Multiplatform testing for DNA, mRNA, and miRNA can accurately classify benign andmalignant thyroid nodules, increase the diagnostic yield of molecular cytology, and further improve the preoperative risk-based management of benign nodules with AUS/FLUS or FN/SFNLabourier E, et al 2015; J Clin Endocrinol Metab 100:
90 J Clin Endocrinol Metab. 2014;99(8):2674-2682 From: Cost-Effectiveness of Molecular Testing for Thyroid Nodules With Atypia of Undetermined Significance CytologyJ Clin Endocrinol Metab. 2014;99(8): doi: /jcJ Clin Endocrinol Metab. 2014;99(8):Figure Legend:Overview of cost-effectiveness model. The squares represent decision nodes, circles represent chance nodes, rectangles represent procedures, and ovals represent health states.J Clin Endocrinol Metab. 2014;99(8):90
91 "These tests are often very expensive and when used inappropriately add undue expense to an already burdened health care system"
92 A 2015 Survey of Clinical Practice Patterns in the Management of Thyroid Nodules AUS/FLUS resulting in molecular testing (38.8% of respondents), repeat FNA cytology (31.5%), or immediate referral for thyroid surgery (24.4%)Fn/SFN : are referred for thyroid surgery by 61.2% of respondents (46.6 % lobectomy, 14.6 % total thyroidectomy) or molecular testing (29.0 %).SUSP : thyroid surgery (86.0%) and rarely undergo molecular testing (9.5%).J Clin Endocrinol Metab (2016) Burch H ,Burman K, Cooper D 101 (7):Respondents in general have a lower threshold for FNA of thyroid nodules than that recommended in the updated ATA CPG. Management depends on the FNA result, with follicular lesion of undetermined significance/atypia of undetermined significance resulting in molecular testing (38.8% of respondents), repeat FNA cytology (31.5%), or immediate referral for thyroid surgery (24.4%). Nodules showing follicular neoplasm by FNA are referred for thyroid surgery by 61.2% of respondents (46.6 % lobectomy, 14.6 % total thyroidectomy) or molecular testing (29.0 %). Nodules found suspicious but not conclusive for malignancy (Bethesda category V), are referred for thyroid surgery (86.0%) and rarely undergo molecular testing (9.5%). During pregnancy, only 47.6% of respondents would perform FNA in the absence of nodular growth, with most respondents deferring FNA until after pregnancy. Endocrinologists are 64.2% less likely to perform FNA in an octogenarian than a younger patient with a comparable thyroid nodule. Striking international differences were identified in the routine measurement of calcitonin and in the use of molecular testing of thyroid nodules
93 Diagnostic surgical excision is the long-established standard of care for the management FN/SFN
94 Patient #2 Case Vignette 40 yo woman presents with a thyroid nodule, 2.0 cm by 2.0 cm on palpation.No history of childhood radiation exposure or family history of thyroid abnormalities.No Suspicious sonographic pattern, no abnormal LN
98 The natural history of thyroid nodules is variable JAMA 2015The discovery of a thyroid nodule may be stressful for thepatient, but more than 90% of the detected nodules areclinically insignificant benign lesions. Fine-needle aspirationcytology is the procedure of choice to identify suspiciouslesions that require thyroid surgery. Established criteriafor initial biopsy include nodule size and sonographic characteristics. Nodules measuring less than 1 cm, the majorityof which are discovered incidentally, do not require initial aspiration unless they exhibit suspicious features on ultrasonography.
99 The Natural History of Benign Thyroid Nodules To resolve these questions, we conducted a prospectivemulticenter study of the natural history of cytologically benignand sonographically nonsuspicious thyroid nodules Wereportdata fromthe first 5years of follow-up, includingchangesin nodule size, baseline factors associatedwithnodule growth,the appearance of new thyroid nodules, and the incidence ofthyroid cancer diagnosis.Changes in Thyroid Nodule Size and Volume During the First 5 Years of Follow-upNodule growth occurred in 174 (11.1%) of the 1567 nodules present at baseline; 1188 (75.8%) remained stable and 205 (13.1%) shrank. Graphs represent the estimated mean with 95% CIs of the maximum diameters and volumes of thyroid nodules. An analysis of variance for repeated measures was carried out to evaluate the change in thyroid nodule size over 5 years of follow-up.JAMA. 2015;313(9):
100 Significant growth has been defined as an increase of 20% or more in at least 2 nodule diameters, with a minimum increase of 2mm
101 local compressive symptoms or cosmetic concerns
102 Would this patient be a candidate for medical therapy? IMPORTANCE Detection of asymptomatic thyroid nodules has increased. Consensus is lackingregarding the optimal follow-up of cytologically proven benign lesions and sonographicallynonsuspicious nodulesJAMA Current guidelines recommend serial ultrasound examinations andreassessment of cytology if significant growth is observed
104 Key Clinical PointsThyroid nodules are common; the majority are benign.• Thyroid ultrasonographic characteristics and especially the results of ultrasonographically guided fine needle aspiration are helpful in determining whether a nodule is likely to be benign or malignant.• The risk of cancer is approximately 14% for a thyroid nodule that is interpreted as atypia ofundetermined significance or follicular lesion of undetermined significance and approximately % for a nodule that is interpreted as follicular neoplasm or possible follicular neoplasm. Such nodules should be considered for molecular analysis.• In the absence of growth or suspicious clinical or radiologic findings, thyroid nodules with a benign finding on fine-needle aspiration can be managed by observation.• Patients whose fine-needle aspirates are interpreted as “suspicious for malignancy” or as malignant should be referred for a thyroidectomy