Contemporary Management of Thyroid Nodules.

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance.

Assessing the Frequency of Deferrable Thyroid Nodule Biopsies to De-escalate Low-Value Care.

OBJECTIVE: Thyroid nodules are common, yet fewer than 1 in 10 harbors malignancy. When present, thyroid cancer is typically indolent with excellent survival. Therefore, patients who are not candidates for thyroid cancer treatment due to comorbid disease may not require further thyroid nodule evaluation. The goal of this study was to determine the rate of deferrable thyroid nodule biopsies in patients with limited life expectancy. METHODS: We identified patients who underwent thyroid fine needle aspiration (FNA) between 2015 and 2018 at our institution. The primary outcome was the number of deferrable FNAs, defined as FNAs performed in patients who died within 2 years after biopsy. Secondary outcomes included cytologic Bethesda score, procedure costs, and final diagnosis on surgical pathology. Multivariable logistic and Cox proportional hazards regressions were used to evaluate factors associated with FNA in patients with limited life expectancy. RESULTS: A total of 2565 FNAs were performed. Most patients were female (79%), and 37 (1.5%) patients died within 2 years. Nonthyroid specialists were significantly more likely to order deferrable FNAs (odds ratio 4.13, P < .001). Of the patients who died within 2 years, most (78%) had a concomitant diagnosis of nonthyroid cancer, and 4 went on to have thyroid surgery (Bethesda scores: 3, 4, 4, and 6). Spending associated with deferrable FNAs and subsequent surgery totaled over $98 000. CONCLUSIONS: Overall, the rate of deferrable thyroid nodule biopsies was low. However, there is an opportunity to reduce low-value biopsies in patients with a concurrent nonthyroid cancer by partnering with oncology providers.

International Expert Consensus on US Lexicon for Thyroid Nodules.

Multiple US-based systems for risk stratification of thyroid nodules are in use worldwide. Unfortunately, the malignancy probability assigned to a nodule varies, and terms and definitions are not consistent, leading to confusion and making it challenging to compare study results and craft revisions. Consistent application of these systems is further hampered by interobserver variability in identifying the sonographic features on which they are founded. In 2018, an international multidisciplinary group of 19 physicians with expertise in thyroid sonography (termed the International Thyroid Nodule Ultrasound Working Group) was convened with the goal of developing an international system, tentatively called the International Thyroid Imaging Reporting and Data System, or I-TIRADS, in two phases: (phase I) creation of a lexicon and atlas of US descriptors of thyroid nodules and (phase II) development of a system that estimates the malignancy risk of a thyroid nodule. This article presents the methods and results of phase I. The purpose herein is to show what has been accomplished thus far, as well as generate interest in and support for this effort in the global thyroid community.

Racial and Ethnic Disparities in Appropriate Thyroid Cancer Treatment, Before and After the Release of the 2015 American Thyroid Association Guidelines.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines reduced the recommended extent of therapy for low-risk thyroid cancers. Little is known about the impact of these changes on overall treatment patterns and on previously described racial/ethnic disparities in guideline-concordant care. This study aimed to assess trends in thyroid cancer care before and after release of the 2015 guidelines, with particular attention to racial/ethnic disparities. METHODS: Patients with well-differentiated thyroid cancer were identified from the National Cancer Database (2010-2018). An interrupted time series design was used to assess trends in treatment before and after the 2015 guidelines. Appropriateness of surgical and radioactive iodine (RAI) treatment was determined based on the ATA guidelines, and the likelihood of receiving guideline-concordant treatment was compared between racial/ethnic groups. RESULTS: The study identified 309,367 patients (White 74%, Black 8%, Hispanic 9%, Asian 6%). Between 2010 and 2015, the adjusted probability of appropriate surgery was lower for Black (- 2.1%; p < 0.001), Hispanic (- 1.0%; p < 0.001), and Asian (- 2.1%; p < 0.001) patients than for White patients. After 2015, only Hispanic patients had a lower probability of undergoing appropriate surgical therapy (- 2.6%; p = 0.040). Similarly, between 2010 and 2015, the adjusted probability of receiving appropriate RAI therapy was lower for the Hispanic (- 3.6%; p < 0.001) and Asian (- 2.4%; p < 0.001) patients than for White patients. After 2015, the probability of appropriate RAI therapy did not differ between groups. CONCLUSIONS: Between 2010 and 2015, patients from racial/ethnic minority backgrounds were less likely than White patients to receive appropriate surgical and RAI therapy for thyroid cancer. After the 2015 guidelines, racial/ethnic disparities in treatment improved.

Insurance-Based Disparities in Guideline-Concordant Thyroid Cancer Care in the Era of De-escalation.

INTRODUCTION: Prior studies have demonstrated insurance-based disparities in the treatment of well-differentiated thyroid cancer. However, it remains unclear whether these disparities have persisted in the era of the 2015 American Thyroid Association (ATA) management guidelines. The goal of this study was to assess whether insurance type is associated with the receipt of guideline-concordant and timely thyroid cancer treatment in a modern cohort. METHODS: Patients diagnosed with well-differentiated thyroid cancer between 2016 and 2019 were identified from the National Cancer Database. Appropriateness of surgical and radioactive iodine treatment (RAI) was determined based on the 2015 ATA guidelines. Multivariable logistic regression and Cox proportional hazard regression analyses, stratified at age 65, were used to evaluate the associations between insurance type and appropriateness and timeliness of the treatment. RESULTS: 125,827 patients were included (private = 71%, Medicare = 19%, Medicaid = 10%). Compared to privately insured patients, patients with Medicaid more frequently presented with tumors >4 cm in size (11% versus 8%, P < 0.001) and regional metastases (29% versus 27%, P < 0.001). However, patients with Medicaid were also less likely to undergo appropriate surgical treatment (odds ratio 0.69, P < 0.001), less likely to undergo surgery within 90 d of diagnosis (hazard ratio 0.80, P < 0.001), and more likely to be undertreated with RAI (odds ratio 1.29, P < 0.001). There were no differences in the likelihood of guideline-concordant surgical or medical treatment by insurance type in patients ≥65 y old. CONCLUSIONS: In the era of the 2015 ATA guidelines, patients with Medicaid remain less likely to receive guideline-concordant, timely surgery and more likely to be undertreated with RAI compared to privately insured patients.

Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

Safety and Benefit of Transesophageal Echocardiography in Liver Transplant Surgery: A Position Paper From the Society for the Advancement of Transplant Anesthesia (SATA).

More anesthesiologists are routinely using transesophageal echocardiography (TEE) during liver transplant surgery, but the effects on patient outcome are unknown. Transplant anesthesiologists are therefore uncertain if they should undergo additional training and adopt TEE. In response to these clinical questions, the Society for the Advancement of Transplant Anesthesia appointed experts in liver transplantation and who are certified in TEE to evaluate all available published evidence on the topic. The aim was to produce a summary with greater explanatory power than individual reports to guide transplant anesthesiologists in their decision to use TEE. An exhaustive search recovered 51 articles of uncontrolled clinical observations. Topics chosen for this study were effectiveness and safety because they were a major or minor topic in all articles. The pattern of clinical use was a common topic and was included to provide contextual information. Summarized observations showed effectiveness as the ability to make a new and unexpected diagnosis and to direct the choice of clinical management. These were reported in each stage of liver transplant surgery. There were observations that TEE facilitated rapid diagnosis of life-threatening conditions difficult to identify with other types of monitoring commonly used in the operating room. Real-time diagnosis by TEE images made anesthesiologists confident in their choice of interventions, especially those with a high risk of complications such as use of anticoagulants for intracardiac thrombosis. The summarized observations in this systematic review suggest that TEE is an effective form of monitoring with a safety profile similar to that in cardiac surgery patients.

The Diagnosis and Management of Thyroid Nodules: A Review.

IMPORTANCE: Thyroid nodules are common, being detected in up to 65% of the general population. This is likely due to the increased use of diagnostic imaging for purposes unrelated to the thyroid. Most thyroid nodules are benign, clinically insignificant, and safely managed with a surveillance program. The main goal of initial and long-term follow-up is identification of the small subgroup of nodules that harbor a clinically significant cancer (≈10%), cause compressive symptoms (≈5%), or progress to functional disease (≈5%). OBSERVATIONS: Thyroid function testing and ultrasonographic characteristics guide the initial management of thyroid nodules. Certain ultrasound features, such as a cystic or spongiform appearance, suggest a benign process that does not require additional testing. Suspicious sonographic patterns including solid composition, hypoechogenicity, irregular margins, and microcalcifications should prompt cytological evaluation. Additional diagnostic procedures, such as molecular testing, are indicated only in selected cases, such as indeterminate cytology (≈20%-30% of all biopsies). The initial risk estimate, derived from ultrasound and, if performed, cytology report, should determine the need for treatment and the type, frequency, and length of subsequent follow-up. Management includes simple observation, local treatments, and surgery and should be based on the estimated risk of malignancy and the presence and severity of compressive symptoms. CONCLUSIONS AND RELEVANCE: Most thyroid nodules are benign. A diagnostic approach that uses ultrasound and, when indicated, fine-needle aspiration biopsy and molecular testing, facilitates a personalized, risk-based protocol that promotes high-quality care and minimizes cost and unnecessary testing.

Preoperative diagnosis of benign thyroid nodules with indeterminate cytology.

BACKGROUND: Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment. METHODS: We performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed. RESULTS: Of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule. CONCLUSIONS: These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).

A prospective assessment defining the limitations of thyroid nodule pathologic evaluation.

BACKGROUND: Clinical management of thyroid neoplasms is based on light microscopic diagnosis, but its accuracy and precision are poorly defined. OBJECTIVE: To assess inter- and intraobserver variability of preoperative cytopathologic and postoperative histopathologic thyroid diagnoses. DESIGN: Samples were collected in a prospective, multicenter trial validating a gene expression classifier between June 2009 and December 2010. SETTING: 14 academic and 35 community clinical sites. PATIENTS: 653 patients with 776 surgically resected thyroid nodules of 1 cm or greater. MEASUREMENTS: Intraobserver concordance among 2 or more central histopathologists who independently read histopathology slides was calculated. Interobserver concordance between the diagnoses made by the central histopathologists and those made by local pathologists were calculated. Intra- and interobserver concordance for cytopathology was similarly calculated by comparing diagnoses made by local pathologists with those made by a central panel of 3 cytopathologists. RESULTS: Concordance on the histopathologic distinction between benign and malignant diagnoses was 91% comparing local with central histopathologists and 90% comparing 2 central histopathologists. Using the 6-category Bethesda System, 64.0% of diagnoses made by local and central cytopathologists and 74.7% of intraobserver diagnoses were concordant. Central cytopathologists made fewer indeterminate diagnoses than local pathologists (41.2% vs. 55.0%). LIMITATIONS: Many local pathologists did not use the Bethesda System, so their reports were translated to allow comparison. The study required histopathology, and the study population and specimens did not encompass all newly evaluated patients with a thyroid nodule. CONCLUSION: Substantial inter- and intraobserver variability exists in the cytopathologic and histopathologic evaluation of thyroid nodules, confirming an inherent limitation of visual microscopic diagnosis. PRIMARY FUNDING SOURCE: Veracyte.

Effects of music therapy on patient satisfaction and health-related quality of life of hospital inpatients.

The matched-case control study investigated the effect of inpatient music therapy (MT), including the gift of a compact disc, on patient satisfaction and quality of life. Overall rating of the hospital and likelihood to recommend it (n = 210), and SF-12 quality of life scores (n = 160) were compared between groups. Although no significant difference in overall hospital rating was found, MT patients' recommendation scores were higher (p =.02). The MT patients had marginally better quality of life pain scores (p =.06). Integration of MT with inpatient care can improve the likelihood that patients will recommend the hospital and may impact their perception of pain.

Revisiting the Relationship between Tumor Size and Risk in Well-Differentiated Thyroid Cancer.

INTRODUCTION: Large tumor size is associated with poorer outcomes in well-differentiated thyroid cancer (WDTC), yet it remains unclear whether size >4 cm alone confers increased risk, independent of other markers of aggressive disease. The goal of this study was to assess the relationship between tumor size, other high-risk histopathologic features, and survival in WDTC, and to evaluate the significance of 4 cm as a cutoff for management decisions. METHODS: Patients with WDTC were identified from the National Cancer Database (2010-2015) and categorized by tumor size [i.e., small (≤4 cm) or large (>4 cm)] and presence of high-risk histopathologic features (e.g., extrathyroidal extension). First, propensity score matching was used to identify patients who were similar across all other observed characteristics except for small vs. large tumor size, and a multivariable Cox proportional hazards model was used to estimate the relationship between tumor size and survival. Second, we assessed whether the presence of high-risk features demonstrate conditional effects on survival based on the presence of tumor size >4 cm using an interaction term. Finally, additional models assessed the relationship between incremental 1 cm increases in tumor size and survival. Analyses were repeated using a validation cohort from the Surveillance, Epidemiology, and End Results Program (2008-2013). RESULTS: Of 193,133 patients in the primary cohort, 7.9% had tumors >4 cm, and 30% had at least one high-risk feature. After matching, tumor size >4 cm was independently associated with worse survival (HR 1.63, p<0.001). However, tumor size >4 cm and one or more other high-risk features together yielded worse survival than either size >4 cm alone (MMD: 0.70, p<0.001) or other high-risk features alone (MMD: 0.49, p<0.001). When assessed in 1 cm increments, the largest increases in hazard of death occurred at 2 cm and 5 cm, not 4 cm. Results from the validation cohort were largely consistent with our primary findings. CONCLUSIONS: Concomitant high-risk features confer worse survival than large tumor size alone, and a 4 cm cutoff is not associated with the greatest increase in risk. These findings support a more nuanced approach to tumor size in the management of WDTC.

A Reappraisal of Suspicious Sonographic Features of Thyroid Nodules: Shape Is Not an Independent Predictor of Malignancy.

CONTEXT: For the correct clinical application of the sonographic risk-stratification systems, the definition of independent risk features that are foundational to each system is crucial. OBJECTIVE: The aim of this study was to identify the gray-scale sonographic features independently associated with malignancy, and to compare different definitions. METHODS: This prospective, diagnostic accuracy study took place in a single thyroid nodule referral center. All patients consecutively referred to our center for fine-needle aspiration cytology of a thyroid nodule between November 1, 2015 and March 30, 2020, were enrolled before cytology. Each nodule was examined by 2 experienced clinicians to record the sonographic features on a rating form. Histologic (when available) or cytologic diagnosis was used as the reference standard. For each single sonographic feature and definition, the sensitivity, specificity, positive and negative predictive values, and diagnostic odds ratios (DOR) were calculated. The significant predictors were then included in a multivariable regression model. RESULTS: The final study cohort consisted of 903 nodules in 852 patients. A total of 76 nodules (8.4%) were malignant. Six features were independent predictors of malignancy: suspicious lymph node (DOR 16.23), extrathyroidal extension (DOR 6.60), irregular or infiltrative margins (DOR 7.13), marked hypoechogenicity (DOR 3.16), solid composition (DOR 3.61), and punctate hyperechoic foci (including microcalcifications and indeterminate foci; DOI 2.69). Taller-than-wide shape was not confirmed as an independent predictor. CONCLUSION: We identified the key suspicious features of thyroid nodules and provided a simplified definition of some debated ones. Malignancy rate increases with number of features.

Unraveling the significance of TSHR mutations in indeterminate thyroid cytology specimens.

OBJECTIVES: We investigated the clinical significance of thyroid-stimulating hormone receptor (TSHR) mutations detected in thyroid fine needle aspiration (FNA) specimens. METHODS: The pathology archives at our institution were reviewed between 2018 and 2021 for indeterminate (Bethesda category III and IV) specimens with Thyroseq® analysis showing TSHR mutations. RESULTS: A total of 2184 cases diagnosed as atypia/follicular lesion of undetermined significance (AUS/FLUS), and 2625 diagnosed as follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) were identified. A total of 1735 AUS/FLUS and 2339 SFN/FN underwent Thyroseq® analysis; 69 showed TSHR mutations (1.6%, 59 female, 10 male, average age: 55 years). Ten cases showed oncocytic features. Twelve patients underwent radionuclide scans within 1 year of FNA:11 were hyperfunctioning. Nodule size and TSH levels were weakly correlated. Twenty-two different TSHR mutations were identified (most common: M453T). A second mutation was found in five cases (EZH1 n = 2, and EIF1AX n = 3). The expression of sodium-iodide transporter (NIS) mRNA was in the range of 0.01%-62.43% out of all sequencing reads, and was elevated in 49 (71%) cases. Surgical pathology follow-up was available in five cases (all benign except one). On follow-up available for 38 cases (mean: 24 months; range: 7-47 months), 34 (89.5%) nodules remained stable and 3 (8%) increased in size. CONCLUSIONS: TSHR mutations in thyroid FNA samples classified as indeterminate are rare, generally benign, and commonly associated with autonomy on scan if performed.

Ultrasound Follow-Up of Benign Thyroid Nodules: A Scoping Review.

Background: For cytologically benign thyroid nodules with very low to intermediate suspicion ultrasound patterns, optimal ultrasound follow-up intervals and outcomes of discontinuing follow-up are unclear. Methods: Ovid MEDLINE, Embase, and Cochrane Central were searched through August 2022 for studies comparing different ultrasound follow-up intervals and discontinuation versus continuation of ultrasound follow-up. The population was patients with cytologically benign thyroid nodules and very low to intermediate suspicion ultrasound patterns, and the primary outcome was missed thyroid cancers. Utilizing a scoping approach, we also included studies that were not restricted to very low to intermediate suspicion ultrasound patterns or evaluated additional outcomes such as thyroid cancer-related mortality rate, nodule growth, and subsequent procedures. Quality assessment was performed, and evidence was synthesized qualitatively. Results: One retrospective cohort study (n = 1254; 1819 nodules) compared different first follow-up ultrasound intervals for cytologically benign thyroid nodules. There was no difference between >4- versus 1- to 2-year intervals to first follow-up ultrasound in the likelihood of malignancy (0.4% [1/223] vs. 0.3% [2/715]), and no cancer-related deaths occurred. Follow-up ultrasound at >4 years was associated with increased likelihood of ≥50% nodule growth (35.0% [78/223] vs. 15.1% [108/715]), repeat fine needle aspiration (19.3% [43/223] vs. 5.6% [40/715]), and thyroidectomy (4.0% [9/223] vs. 0.8% [6/715]). The study did not describe ultrasound patterns or control for confounders, and analyses were based on interval to first follow-up ultrasound only. Other methodological limitations were not controlling for variability in follow-up duration and unclear attrition. The certainty of evidence was very low. No study compared discontinuation of ultrasound follow-up versus continuation. Conclusions: This scoping review found that evidence comparing different ultrasound follow-up intervals in patients with benign thyroid nodules is limited to one observational study, but suggests that the subsequent development of thyroid malignancies is very uncommon regardless of follow-up interval. Longer follow-up may be associated with more repeat biopsies and thyroidectomies, which could be related to more interval nodule growth that meets thresholds for further evaluation. Research is needed to clarify optimal ultrasound follow-up intervals for low to intermediate suspicion cytologically benign thyroid nodules and outcomes of discontinuing ultrasound follow-up for very low suspicion nodules.

What's in a Name? A Cost-Effectiveness Analysis of the Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features' Nomenclature Revision.

Background: The noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (eFVPTC) has been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reflect the indolent behavior and favorable prognosis of this type of tumor. This terminology change has also de-escalated its management approach from cancer treatment to a more conservative treatment strategy befitting a benign thyroid neoplasm. Objective: To characterize the reduced health care costs and improved quality of life (QOL) from management of NIFTP as a nonmalignant tumor compared with the previous management as eFVPTC. Methods: A cost-effectiveness analysis was performed by creating Markov models to simulate two management strategies for NIFTP: (i) de-escalated management of the tumor as NIFTP involving lobectomy with reduced follow-up, (ii) management of the tumor as eFVPTC involving completion thyroidectomy/radioactive iodine ablation for some patients, and follow-up recommended for carcinoma. The model was simulated for 5 and 20 years following diagnosis of NIFTP. Aggregate costs and quality-life years were measured. One-way sensitivity analysis was performed for all variables. Results: Over a five-year simulation period, de-escalated management of NIFTP had a total cost of $12,380.99 per patient while the more aggressive management of the tumor as eFVPTC had a total cost of $16,264.03 per patient (saving $3883.05 over five years). Management of NIFTP provided 5.00 quality-adjusted life years, whereas management as eFVPTC provided 4.97 quality-adjusted life years. Sensitivity analyses showed that management of NIFTP always resulted in lower costs and greater quality-adjusted life years (QALYs) over the sensitivity ranges for individual variables. De-escalated management for NIFTP is expected to produce ∼$6-42 million in cost savings over a five-year period for these patients, and incremental 54-370 QALYs of increased utility in the United States. Conclusion: The degree of cost savings and improved patient utility of de-escalated NIFTP management compared with traditional management was estimated to be $3883.05 and 0.03 QALYs per patient. We demonstrate that these findings persisted in sensitivity analysis to account for variability in recurrence rate, surveillance approaches, and other model inputs. These findings allow for greater understanding of the economic and QOL impact of the NIFTP reclassification.

Macrocalcifications Do Not Alter Malignancy Risk Within the American Thyroid Association Sonographic Pattern System When Present in Non-High Suspicion Thyroid Nodules.

Background: The American Thyroid Association Sonographic Pattern System (ATASPS) depicts five levels of suspicion for malignancy based on the sonographic appearance of a thyroid nodule. However, 3-37% of nodules are non-classifiable when the combination of grayscale findings is not depicted by the ATASPS. The only calcifications included in the ATASPS are in solid hypoechoic high suspicion (HS) nodules and include both microcalcifications and peripheral interrupted calcifications with soft tissue extrusion. Non-hypoechoic nodules with these and other calcification patterns, which we defined as non-high suspicion calcifications (NHSC), are not classifiable by ATASPS. We assessed the effect of assigning an ATASPS risk level to nodules with NHSC based on analysis of their other grayscale features. Methods: A retrospective review of 728 consecutively biopsied nodules was performed. Nodules were classified by ATASPS as HS, intermediate suspicion (IS), low suspicion (LS), or very low suspicion (VLS); other nodules with patterns not described by ATASPS were non-classifiable (NC). If NC was due to NHSC, the nodule was assigned an ATASPS by analysis of grayscale features alone. Cytology and pathology results were correlated with assigned ATASPS level. Results: A NC pattern was observed in 144 of the 728 nodules (20%). Of these, 101/144 (70%) had NHSC and the assigned ATASPS was IS (n = 18), LS (n = 62) and VLS (n = 21). The distribution of cytology diagnoses within this group was similar to classifiable nodules (IS p = 0.13, LS p = 0.55, VLS p = 0.44). The majority of NHSC (n = 92, 91%) were macrocalcifications (large central or linear dystrophic calcifications); however, 9 LS pattern nodules had punctate echogenic foci, possibly representing microcalcifcations, with an estimated cancer prevalence of 19% (vs. 10% for total LS group, p = 0.24). The remaining NC nodules (43/144, 30%) included solid nodules with heterogeneous echogenicity (n = 30) or presence of a complete circumferential rim calcification, limiting further sonographic assessment (n = 13). Malignancy was identified in 11 out of 43 (26%) of these [9/30 (30%) heterogeneous solid and 2/13 (15%) with complete rim calcifications]. Conclusions: Macrocalcifications accounted for the majority of NHSC and these did not alter the expected ATASPS malignancy risk based on grayscale features.

ThyroSeq v3 for Bethesda III and IV: An institutional experience.

BACKGROUND: The ThyroSeq v3 genomic classifier is a commercial molecular test that examines a wide spectrum of genomic alterations in a thyroid fine-needle aspiration (FNA) sample and reports test results as either negative or positive. The authors report their institutional experience with ThyroSeq v3. METHODS: Thyroid FNA specimens diagnosed as either atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) (Bethesda category III [Bethesda III] according to The Bethesda System for Reporting Thyroid Cytopathology) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) (Bethesda IV) that had ThyroSeq v3 results available from December 2017 through October 2019 were retrieved for analysis. FNA diagnoses were correlated with ThyroSeq v3 results and follow-up histopathology. RESULTS: In total, 415 cases (AUS/FLUS, n = 251; FN/SFN, n = 164) were retrieved: 294 (71%) were reported as ThyroSeq v3-negative, and 121 (29%) were reported as ThyroSeq v3-positive. The benign call rate (BCR) of ThyroSeq v3 for AUS/FLUS (82%; 206 of 251 cases) was significantly higher (P < .001) than that for FN/SFN (BCR, 54%; 88 of 164 cases). Histopathologic follow-up was available for 127 cases (ThyroSeq v3-positive, 96; ThyroSeq v3-negative, 31), of which 57 were benign and 70 were malignant (including noninvasive follicular thyroid neoplasm with papillary-like nuclear features). The negative predictive value of ThyroSeq v3 was significantly higher for AUS/FLUS (99.5%) than for FN/SFN (95.4%; P < .0294), given malignancy rates of 10% for AUS/FLUS and 30% for FN/SFN. Forty-five unique combinations of genetic alterations were detected in the operated ThyroSeq-positive cases, and there were only 5 false-negative cases, comprised of 4 low-risk neoplasms. CONCLUSIONS: The high BCR of ThyroSeq v3 for AUS/FLUS prevents surgery in a majority of patients. The ThyroSeq v3 genomic classifier reveals the complexity of the genetic signature of indeterminate nodules.

Do Ultrasound Patterns and Clinical Parameters Inform the Probability of Thyroid Cancer Predicted by Molecular Testing in Nodules with Indeterminate Cytology?

Background: Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further inform the risk of thyroid cancer in nodules predicted to be positive or negative by MT remains unknown. The aim of this study was to test if clinical parameters, including patient age, sex, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] vs. American College of Radiology Thyroid Image Reporting and Data System [TI-RADS] systems), radiation exposure, or family history of thyroid cancer can modify the probability of thyroid cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) predicted by MT. Methods: We studied 257 thyroid nodules in 232 patients from 10 study centers with indeterminate fine needle aspiration cytology and informative MT results using the ThyroSeq v3 genomic classifier (TSv3). Univariate and multivariate logistic regression was used for data analysis. Results: The presence of cancer/NIFTP was associated with positive TSv3 results (odds ratio 61.39, p < 0.0001). On univariate regression, patient sex, age, and Bethesda category were associated with cancer/NIFTP probability (p < 0.05 for each). Although ATA (p = 0.1211) and TI-RADS (p = 0.1359) US categories demonstrated positive trends, neither was significantly associated with cancer/NIFTP probability. A multivariate regression model incorporating the four most informative non-MT covariates (sex, age, Bethesda category, and ATA US pattern; Model No. 1) yielded a C index of 0.653; R2 = 0.108. When TSv3 was added to Model number 1, the C index increased to 0.888; R2 = 0.572. However, age (p = 0.341), Bethesda category (p = 0.272), and ATA US pattern (p = 0.264) were nonsignificant, and other than TSv3 (p < 0.0001), male sex was the only non-MT parameter that potentially contributed to cancer/NIFTP risk (p = 0.095). The simplest and most efficient clinical model (No. 3) incorporated TSv3 and sex (C index = 0.889; R2 = 0.588). Conclusions: In this multicenter study of thyroid nodules with indeterminate cytology and MT, neither the ATA nor TI-RADS US scoring systems further informed the risk of cancer/NIFTP beyond that predicted by TSv3. Although age and Bethesda category were associated with cancer/NIFTP probability on univariate analysis, in sequential nomograms they provided limited incremental value above the high predictive ability of TSv3. Patient sex may contribute to cancer/NIFTP risk in thyroid nodules with indeterminate cytology.