Indeterminate Fine-needle Aspiration Research Articles

Genomic Profiling of Thyroid Nodules: Current Role for ThyroSeq Next-Generation Sequencing on Clinical Decision-Making.

In recent years there has been an increased awareness of the genetic alterations underlying both benign and malignant neoplasms of the thyroid. Next-generation sequencing (NGS) is an emerging technology that allows for rapid detection of a large number of genetic mutations in thyroid fine-needle aspiration (FNA) specimens. NGS for targeted mutational analysis in thyroid tumors has been proposed as a tool to assist in the diagnosis of thyroid nodules with indeterminate FNA cytology. Results of genomic testing of thyroid nodules and thyroid cancers could also have prognostic implications and play a role in determining optimal treatment strategies including targeted therapies. We provide a critical review of existing studies assessing the performance of the ThyroSeq NGS test for the diagnosis and management of patients with thyroid nodules with indeterminate cytopathology and discuss the applicability of findings from these studies to clinical practice. While there are early indications to suggest a possible utility of data obtained from NGS to aid in prognostication and therapeutic decision-making in thyroid cancer, we recommend judicious use and cautious interpretation of such molecular testing until results of ongoing clinical trials become available. Lastly, we discuss recommendations provided from clinical practice guidelines regarding the use of mutation detection via NGS in the diagnostic evaluation of thyroid nodules.

Cost comparison of initial lobectomy versus fine-needle aspiration for diagnostic workup of thyroid nodules in children

BackgroundThough uncommon in children, pediatric thyroid nodules carry a higher risk of malignancy than adult nodules. While fine-needle aspiration (FNA) has been well established as the initial diagnostic test in adults, it has been more slowly adopted in children. The purpose of this study was to examine the comparative cost of FNA versus initial diagnostic lobectomy (DL) in the pediatric patient with an ultrasound-confirmed thyroid nodule. MethodsA decision tree model was created using an adolescent with an asymptomatic thyroid nodule as the reference case. Probabilities were defined based on review of the pediatric and adult literature. Costs were determined from previous literature and the publicly available Medicare physician fee schedule. Tornado plot and sensitivity analyses were performed to assess sources of cost variation. ResultsUsing decision analysis, FNA was less costly than DL with an estimated cost of $2529 vs. $5680. Tornado analysis demonstrated that the probability of an initial indeterminate FNA result contributed most to cost variation. On sensitivity analysis, when probability of an indeterminate FNA result was increased to 35%, the maximum value found in the literature, FNA remained less costly. In Monte Carlo simulation set to 10,000 iterations, FNA was superior to DL in 74% of cases. ConclusionsIn this theoretical model based on available literature and costs, FNA is less costly than DL for initial diagnostic workup of thyroid nodules in children. Securing resources to offer FNA in the work-up of thyroid nodules may be financially beneficial to hospitals and patients. Level of evidenceLevel 1 cost effectiveness study - using reasonable costs and alternatives used in study with values obtained from many studies, study used multi-way sensitivity analysis.

Two-miRNA classifiers differentiate mutation-negative follicular thyroid carcinomas and follicular thyroid adenomas in fine needle aspirations with high specificity.

Diagnosis of thyroid by fine needle aspiration is challenging for the "indeterminate" category and can be supported by molecular testing. We set out to identify miRNA markers that could be used in a diagnostic setting to improve the discrimination of mutation-negative indeterminate fine needle aspirations. miRNA high-throughput sequencing was performed for freshly frozen tissue samples of 19 RAS and PAX8/PPARG mutation-negative follicular thyroid carcinomas, and 23 RAS and PAX8/PPARG mutation-negative follicular adenomas. Differentially expressed miRNAs were validated by quantitative polymerase chain reaction in a set of 44 fine needle aspiration samples representing 24 follicular thyroid carcinomas and 20 follicular adenomas. Twenty-six miRNAs characterized by a significant differential expression between follicular thyroid carcinomas and follicular adenomas were identified. Nevertheless, since no single miRNA had satisfactory predictive power, classifiers comprising two differentially expressed miRNAs were designed with the aim to improve the classification. Six two-miRNA classifiers were established and quantitative polymerase chain reaction validated in fine needle aspiration samples. Four out of six classifiers were characterized by a high specificity (≥94 %). The best two-miRNA classifier (miR-484/miR-148b-3p) identified thyroid malignancy with a sensitivity of 89 % and a specificity of 87 %. The high-throughput sequencing allowed the identification of subtle differences in the miRNA expression profiles of follicular thyroid carcinomas and follicular adenomas. While none of the differentially expressed miRNAs could be used as a stand-alone malignancy marker, the validation results for two-miRNA classifiers in an independent set of fine needle aspirations are very promising. The ultimate evaluation of these classifiers for their capability of discriminating mutation-negative indeterminate fine needle aspirations will require the evaluation of a sufficiently large number of fine needle aspirations with histological confirmation.

Office-Based Ultrasound-Guided FNA with Molecular Testing for Thyroid Nodules.

Ultrasound-guided fine-needle aspiration (FNA) biopsy is the primary method of evaluating thyroid nodules. Up to one-third of FNA results are reported to be of "indeterminate" cytology, which carries a 25% malignancy risk. Most of these patients are referred for diagnostic surgery, which results in many unnecessary interventions. We implemented an FNA protocol combining expert thyroid cytopathology and molecular testing of indeterminate lesion in our community practice. This study is a report of the outcomes from this protocol as compared with historical data in the same setting over a similar period. Case series with planned data collections and retrospective chart reviews. A large community-based practice with multiple satellite offices. A total of 264 thyroid nodules (196 patients) were evaluated under the new protocol from January to December 2014, and data were collected in a prospective manner. Historical data for a similar period (2012), obtained by chart review, included 164 nodules (134 patients) biopsied in a hospital setting by a number of radiologists, with cytologic interpretations completed by community-based pathologists. Statistical analyses included χ(2) and Fischer's exact tests. Based on the new protocol, the rate of indeterminate lesion diagnosis was reduced from 24% to 10% (P = .006) and the rate of diagnostic surgery from 24% to 6% (P < .001). Of the patients who underwent diagnostic surgery, 58% had evidence of malignancy, as compared with 12% in our previous experience (P = .04). Expert cytopathologic analysis combined with molecular testing of indeterminate FNA samples significantly reduced unnecessary operations.

Frozen section analysis in the post-Bethesda era

BackgroundThe utility of frozen section (FS) for indeterminate thyroid nodules is controversial. In 2009, the Bethesda System for Reporting Thyroid Cytopathology was established to further subcategorize indeterminate fine-needle aspiration results (follicular lesions, FL) into Bethesda category 3 (BC3) and Bethesda category 4 (BC4). We hypothesize that FS will have less utility in the evaluation of BC3 lesions when compared to BC4. Materials and methodsA total of 479 patients who underwent thyroid lobectomy from January 2008 to July 2014 were retrospectively reviewed. Patients without appropriate Bethesda categorization were excluded. A total of 135 patients (65 FL, 45 BC3, 25 BC4) comprised the study groups. The sensitivity and specificity of FS within these three categories were determined. ResultsIn the FL group, 6 of 65 patients were found to have thyroid cancer. Three were identified on frozen section (FS) resulting in a sensitivity and specificity of 50% and 100%, respectively. Thus, FS changed the operation in 3 of 65 cases (4.6%). In the BC3 group, 5 of 45 patients were found to have cancer. One was identified on FS resulting in a sensitivity and specificity of 20% and 100%, respectively. Thus, FS changed the operation in 1 of 45 patients (2.2%). In the BC4 group, 4 of 25 patients were found to have cancer. Two were identified on FS resulting in a sensitivity and specificity of 50% and 100% respectively. Thus, FS changed the operation in 2 of 25 patients (8%). ConclusionsThere is improved utility of FS in BC 4 patients as 8% avoided reoperation. However, this benefit hinges on surgeon practice regarding the management of differentiated thyroid cancer >1 cm and <4 cm.

Noninvasive Follicular Variant of Papillary Thyroid Carcinoma and the Afirma Gene-Expression Classifier.

It is now recognized that noninvasive follicular variant of papillary thyroid carcinoma (NFVPTC) is a distinct subset of FVPTC with an exceedingly indolent clinical course. The Afirma gene-expression classifier (GEC) helps guide clinicians in the management of thyroid nodules with indeterminate fine-needle aspiration (FNA) results. Thyroid surgery is recommended for nodules with a suspicious Afirma result, whereas observation is deemed reasonable for most nodules with a benign result. The aim of this study was to confirm that the Afirma test detects NFVPTCs and to determine how many carcinomas detected by the Afirma GEC represent NFVPTCs. From a database of 249 FNAs sent for Afirma testing between January 2012 and October 2014, a search was conducted for cases with a preceding FNA diagnosis of atypia/follicular lesion of undetermined significance (AUS/FLUS) or suspicious for a follicular neoplasm (SFN), a suspicious Afirma result, and a corresponding resection specimen reviewed at Brigham and Women's Hospital. The diagnoses of the prior FNAs and subsequent resection specimens were recorded. Slides for all resection specimens with a diagnosis of FVPTC were reviewed to identify NFVPTCs. Sixty-three cases met the inclusion criteria. The preceding FNA diagnosis was AUS/FLUS in 34 (54%) cases and SFN in 29 (46%) cases. The surgical resection specimen demonstrated 16 (25%) FVPTCs, five (8%) follicular thyroid carcinomas, one (2%) classical type PTC, and 41 (65%) benign tumors/nodules. Of the 16 FVPTCs, 14 (88%) were NFVPTCs. Thus, NFVPTCs accounted for 64% of the carcinomas in the cohort. These results indicate that the Afirma GEC detects NFVPTCs and that many of the carcinomas detected by Afirma are NFVPTCs. While all care should be individualized and include clinical and sonographic assessment, these results suggest lobectomy as opposed to total thyroidectomy should be considered for nodules with a preceding AUS/FLUS or SFN on cytology and a suspicious Afirma result.

Impact of Afirma gene expression classifier on cytopathology diagnosis and rate of thyroidectomy.

The Afirma gene expression classifier (GEC) assesses malignancy risk in patients with indeterminate thyroid nodules. Afirma putatively reduces costs by classifying certain nodules as benign and thereby avoiding unnecessary surgery. Prior studies have evaluated its impact exclusively on GEC-tested nodules. The objective of the current study was to analyze the effect of Afirma on 1) cytopathology diagnosis, 2) the rate of surgery, and 3) the rate of malignancy on all indeterminate nodules at a high-volume thyroid center. A retrospective cohort analysis of indeterminate (Bethesda III/IV) thyroid nodules from 2012 through 2014 was performed. Cases were evaluated from January 2012 to July 2013 (pre-Afirma), and from July 2013 to December 2014 (post-Afirma). Of 4292 fine-needle aspirations (FNAs) performed, 13.2% were classified as indeterminate. The GEC was used in 45.3% of post-Afirma cases, with the GEC-Benign call rate at 37.1%. In comparing pre-Afirma and post-Afirma cohorts, a significant increase in Bethesda III (10.7% vs 13.4%; P<.005) and Bethesda IV (1.8% vs 2.9%; P<.01) rates were observed. Conversely, the incidence of Bethesda II was found to be significantly decreased (74.6% vs 68.8%; P<.001). The rate of surgery did not change significantly between pre-Afirma and post-Afirma cohorts (37.7% vs 45.1%; P = .11), nor did the malignancy rate (25.3% vs 36.0%; P = .12). The incidence of indeterminate FNA diagnoses significantly increased after Afirma became routinely available, whereas the incidence of benign diagnoses significantly decreased. These data suggest that Afirma may shift FNA interpretation toward Bethesda III/IV, in which molecular testing is used. Moreover, the institutional rates of surgery and malignancy did not appear to change, raising uncertainty regarding the benefits of molecular assay risk stratification. Afirma may produce unintended collateral effects, increasing the number of indeterminate FNA diagnoses while not affecting the institutional thyroidectomy rate or malignancy yield. Cancer Cytopathol 2016;124:722-8. © 2016 American Cancer Society.

Impact of the Afirma Gene Expression Classifier Result on the Surgical Management of Thyroid Nodules with Category III/IV Cytology and Its Correlation with Surgical Outcome

Objective: The Afirma gene expression classifier (GEC) is a molecular test to further classify indeterminate fine-needle aspiration (FNA) as benign or suspicious for malignancy. Study Design: A total of 158 FNAs with Bethesda category III/IV cytology were sent for an Afirma GEC test. We correlated the Afirma GEC results with surgical outcome and also compared the data after Afirma's implementation with the data before. Results: Among the 158 FNAs, the Afirma result was benign in 63 (40%), suspicious in 85 (54%) and unsatisfactory in 10 (6%). In total, 73 (86%) suspicious Afirma cases had surgery and 28 (38%) showed carcinoma. In contrast, only 8 (13%) benign Afirma cases had surgery and all of them were benign. The sensitivity, specificity, negative predictive value and positive predictive value (PPV) of Afirma were 100, 15, 100 and 38%, respectively. The PPV was 20% in cases with follicular lesion of undetermined significance, but was 50% in cases suspicious for follicular neoplasm (SFN). The surgical excisional rate was significantly decreased in SFN cases after the Afirma test. Conclusions: The Afirma GEC is useful for further risk stratifying SFN cases.

Analytical validity of a microRNA-based assay for diagnosing indeterminate thyroid FNA smears from routinely prepared cytology slides.

BACKGROUNDThe majority of thyroid nodules are diagnosed using fine‐needle aspiration (FNA) biopsies. The authors recently described the clinical validation of a molecular microRNA‐based assay, RosettaGX Reveal, which can diagnose thyroid nodules as benign or suspicious using a single stained FNA smear. This paper describes the analytical validation of the assay.METHODSMore than 800 FNA slides were tested, including slides stained with Romanowsky‐type and Papanicolaou stains. The assay was examined for the following features: intranodule concordance, effect of stain type, minimal acceptable RNA amounts, performance on low numbers of thyroid cells, effect of time since sampling, and analytical sensitivity, specificity, and reproducibility.RESULTSThe assay can be run on FNA slides for which as little as 1% of the cells are thyroid epithelial cells or from which only 5 ng of RNA have been extracted. Samples composed entirely of blood failed quality control and were not classified. Stain type did not affect performance. All slides were stored at room temperature. However, the length of time between FNA sampling and processing did not affect assay performance. There was a high level of concordance between laboratories (96%), and the concordance for slides created from the same FNA pass was 93%.CONCLUSIONSThe microRNA‐based assay was robust to various physical processing conditions and to differing sample characteristics. Given the assay's performance, robustness, and use of routinely prepared FNA slides, it has the potential to provide valuable aid for physicians in the diagnosis of thyroid nodules. Cancer Cytopathol 2016;124:711–21. © 2016 Rosetta Genomics. Cancer Cytopathology published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Correlating thyroid cytology and histopathology: Implications for molecular testing.

A gene expression classifier (GEC) has been advocated in management of some indeterminate nodules without surgery. We assessed the potential negative predictive value (NPV) of the GEC at our academic center. Retrospectively, all cytologically indeterminate fine-needle aspirates (FNAs) diagnosed by University of Iowa cytopathologists over a 3-year period were identified. Histopathologic findings were recorded. Using published sensitivity and specificity, NPVs were calculated. Of 178 nodules (17, 135, and 26 in classes III, IV, and V, respectively), 71 (40%) were malignant. Prevalence of malignancy was 41%, 29%, and 96% for classes III, IV, and V, respectively. Using sensitivities and specificities for the GEC, NPVs were 91% for the cohort: 88%, 92%, and 26% for classes III, IV, and V, respectively. Molecular testing should be associated with an NPV no lower than that from clinical criteria alone. With the prevalences reported, GEC use may result in more missed cancer diagnoses. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1104-1106, 2016.

Interim results of a screening protocol for early detection of pancreatic cancer in asymptomatic high-risk patients.

223 Background: Pancreatic cancer (PC) is the 4th leading cause of cancer deaths in the US but is rarely diagnosed at an early curable stage. Early detection of PC will have measurable improved outcomes in affected patients. This study sets out to evaluate if EUS can detect early stage pre-cancerous or cancerous changes in the pancreas of high risk (HR) patients. Methods: After IRB review, a clinical trial (NCT01662609) to evaluate HR patients was opened to accrual. Study subjects met specified inclusion and exclusion criteria as defined by the protocol. Enrolled subjects underwent EUS followed by screening as defined by study protocol: subjects with normal EUS underwent repeat EUS at 1 year; subjects with abnormal EUS underwent fine needle aspiration (FNA) if a mass or cyst was found and measured ≥ 5mm and did not undergo FNA if the lesion measured &lt; 5mm. Those with indeterminate or benign FNA underwent pancreatic CT scan with repeat EUS/FNA at 3 or 6 months respectively. Those with positive FNA were treated appropriately based on findings. Patients with mass/cyst &lt; 5mm underwent repeat EUS/FNA at 3 months. Targeted follow-up is 5 years. Results: Of the 52 subjects accrued thus far, 41 were available for interim analysis. Twenty-seven (67%) subjects had a normal EUS while 14 (34%) subjects had abnormal findings. Two patients had large cysts with FNA consistent with an intraductal papillary mucinous neoplasms (IPMN). These 2 subjects ultimately underwent surgical resection. The 12 remaining subjects had at least 1 subcentimeter lesion and are being routinely screened per the outlined protocol. Conclusions: EUS screening of asymptomatic individuals who are at high risk for pancreatic cancer as defined by our inclusion criteria frequently detects abnormal lesions in the pancreas. These lesions include high risk IPMNs that warrant surgical resection. Our results validate the results of other high risk screening protocols and support the screening of individuals who are at high risk for development of pancreatic cancer. Clinical trial information: NCT01662609.

Pediatric thyroid surgery and management of thyroid nodules - an institutional experience over a 10-year period.

BackgroundWe reviewed our institutional experience in the diagnosis and management of pediatric thyroid nodules and well-differentiated thyroid carcinoma (WDTC), highlighting the unique challenges in this population.MethodsIRB approved retrospective chart review was conducted on patients who underwent fine needle aspiration (FNA) or thyroid surgery from 1/1/2001 to 12/31/2010 at Rady Children’s Hospital San Diego, a tertiary referral center in Southern California. Patients thus identified who completed their initial treatment at our institution were included.ResultsTotal of 79 subjects qualified; 20 had FNA only, and 59 underwent thyroid surgery. Of the latter, 29 had benign histology and 30 had WDTC. Average age was 14.5 years with a female: male ratio of 4:1 for WDTC versus 1.6:1 for benign nodules. When compared to final pathology, malignancy rate was high in indeterminate FNA cytology at 60 %. Neck metastasis was noted in 40 % and pulmonary spread in 10 % of patients. There was a 2.75 fold increase in malignant cases (n = 22) treated during 2006–2010 compared to 2001–2005 (n = 8) with more advanced disease at initial presentation. Ninety percent of WDTC patients received adjuvant I-131 treatment with an initial average dose of 132.4 mCi. Despite aggressive initial presentation, 26/30 patients had no evidence of disease at last follow-up, with an average length of 40.3 months.ConclusionsIn recent years, we are managing significantly more WDTC cases at our institution with advanced disease at the onset. Malignancy rate on indeterminate cytology is higher than reported in adults with an overall high rate of malignancy in thyroid nodules removed in this cohort. Disease control and short-term outcome is still excellent. The recently published pediatric guidelines for WDTC will further standardize management.

Role of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Evaluation of Cytologically Indeterminate Thyroid Nodules.

Background:Thyroid nodules with indeterminate fine-needle aspiration biopsy (FNAB) results remain a diagnostic dilemma, because 70 - 85% of these nodules have been found to be benign after thyroid surgery.Objectives:The purpose of this study was to evaluate the usefulness of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the preoperative diagnosis of cytologically indeterminate nodules.Patients and Methods:Forty-six patients were included in this study. These individuals had undergone FDG PET/CTs for the preoperative evaluation of thyroid nodules with indeterminate FNAB results. The results of the preoperative PET/CT scans were compared with the postoperative pathological results and statistically analyzed.Results:Of the 46 patients included in our study, the histopathology of the surgical specimens revealed thyroid cancer in 17 individuals (37%, 17/46). The PET/CT scan showed a positive result in 27 patients. Of these, 16 patients (59.3%) were found to have thyroid carcinomas. In addition, the PET/CT scan was considered to be negative in 19 patients, 18 (94.7%) of whom had benign lesions. For the detection of malignant lesions, the values for the sensitivity and specificity, and the positive predictive and negative predictive values were 94%, 62%, 59%, and 95%, respectively.Conclusion:The FDG PET/CT showed a high sensitivity and a high negative predictive value for identifying malignancies in thyroid nodules with indeterminate FNAB results. Therefore, the FDG PET/CT may be a helpful tool in the clinical management of these nodules. When an FDG positive lesion is detected, further examination is recommended.

Role of gene expression profiling in defining indeterminate thyroid nodules in addition to BRAF analysis.

Fine-needle aspiration (FNA) is routinely used in the preoperative evaluation of thyroid nodules. However, 15% to 30% of aspirations yield indeterminate cytologic findings. Because the assessment of BRAF mutations seems to improve the diagnostic accuracy, this study evaluated BRAF mutations with Sanger sequencing and real-time methods in 650 consecutive thyroid aspirates. In addition, the expression of a large number of genes involved in basement membrane remodeling, extracellular matrix proteolysis, and cell adhesion was studied in both benign and malignant nodules to identify new diagnostic tools. In this prospective series, despite the use of a very sensitive BRAF mutational testing method, the frequency of a BRAF alteration being identified in indeterminate FNA samples was 3 of 68. Expression analysis revealed several genes that were differentially expressed between benign and malignant nodules (transforming growth factor, cadherin 1, collagen α1, catenin α1, integrin α3, and fibronectin 1 [FN1]), between follicular adenomas and follicular variant of papillary thyroid carcinoma (FN1, laminin γ1, integrin β2, connective tissue growth factor, catenin δ1, and integrin αV), and between BRAF-wild-type and BRAF-mutated papillary thyroid carcinomas (TIMP metallopeptidase inhibitor 1; catenin α1; secreted phosphoprotein 1; FN1; ADAM metallopeptidase with thrombospondin type 1 motif, 1; and selectin L). These data were partially confirmed with real-time polymerase chain reaction analysis and immunohistochemistry. When the cost/benefit ratio of the procedures was taken into account, BRAF mutational testing failed to increase diagnostic accuracy in cytologically indeterminate nodules. However, the additional analysis of the expression of specific molecular markers could have possible utility as a diagnostic tool, although further evidence based on a large series of samples is needed before definitive conclusions can be drawn. Cancer Cytopathol 2016;124:340-9. © 2015 American Cancer Society.

Decisional conflict in patients considering diagnostic thyroidectomy with indeterminate fine needle aspirate cytopathology.

BackgroundFine needle aspiration (FNA) cytopathology is the gold standard work-up for thyroid nodules. However, indeterminate lesions are encountered commonly and can lead to difficult treatment decisions. We sought to determine whether patients experienced decisional conflict surrounding management with diagnostic thyroidectomy in the setting of indeterminate FNA results.MethodsPatients with indeterminate results of thyroid nodule FNA were prospectively enrolled. All consultations were carried out by three otolaryngologists in a consistent manner. After consultation, participants completed a demographics form and the Decisional Conflict Scale (DCS) questionnaire.ResultsThirty-five patients (28 female) between the ages of 30 and 88 years (mean age 54.89) participated. The median total DCS score was 10.94 (interquartile range, 4.69–25.0). Twelve patients (34 %) scored at or above 25 on the DCS, indicating clinically significant level of decisional conflict. Patients reported feeling significantly more confident about their decision after the surgical consultation compared to before the consultation (p = 0.00). The total DCS score was significantly negatively correlated with self-reported confidence after the consultation (r = −0.421, p = 0.012).ConclusionMany patients experienced clinically significant decisional conflict when considering thyroidectomy for management of a thyroid nodule with indeterminate cytopathology. Future research should be directed at developing decision support tools for this patient group, and exploring the impact of decisional conflict on health outcomes.

Relationship Between Sonographic Characteristics and Afirma Gene Expression Classifier Results in Thyroid Nodules With Indeterminate Fine-Needle Aspiration Cytopathology.

The purpose of this article is to investigate whether specific clinical and sonographic characteristics are predictive of a benign Afirma test result. We conducted a retrospective study of Afirma gene expression classifier analysis performed in 44 patients with 45 indeterminate thyroid fine-needle aspiration (FNA) cytologic results between March 2013 and April 2014. Of these, 33 of 45 nodules (73.3%) were repeat atypia of undetermined significance (AUS) and follicular lesions of undetermined significance (FLUS), or follicular neoplasm (FN) and suspicious for a follicular neoplasm (SFN) before Afirma testing. Of the 45 nodules, 21 (46.7%) were cytologically diagnosed as FLUS, 16 (35.6%) were diagnosed as AUS, and eight (17.8%) were diagnosed as FN or SFN. By Afirma testing, 23 of the 45 nodules (51.1%) were benign, 21 (46.7%) were suspicious, and one (2.2%) had nondiagnostic results. The mean (± SD) nodule size was smaller in the Afirma-benign group than in the Afirma-suspicious group (1.8 ± 0.8 cm [95% CI, 1.4-2.1] vs 2.2 ± 0.8 cm [95% CI, 1.8-2.6]; p < 0.035). No sonographic feature was statistically significantly different between the Afirma-benign and -suspicious groups, including nodule solidity (p = 0.225), echogenicity (p = 0.543), calcification (p = 0.542), and hypervascularity (p = 0.976). All nodules were ovoid shaped and had circumscribed margins in both Afirma groups. Smaller nodule size was the only characteristic associated with a benign diagnosis on Afirma testing. Sonographic characteristics are not helpful in cases that had a repeat indeterminate FNA finding before Afirma testing.

The dilemma of "indeterminate" interpretations of pancreatic neuroendocrine tumors on fine needle aspiration.

Indeterminate (atypical/suspicious) fine needle aspiration (FNA) interpretation of Pancreatic Neuroendocrine Tumor (PanNET) can be frustrating for both pathologists and clinicians. Although published literature has often addressed the significance of indeterminate cytologic diagnoses in non-neuroendocrine epithelial lesions, the significance of indeterminate FNA results for PanNET is less established. The pathology records of The Johns Hopkins hospital were searched for histologic diagnoses of PanNET that had corresponding pre-operative FNA results. Cytopathologic diagnoses were categorized according to the index of suspicion described in the report (atypical, suspicious for PanNET and PanNET). Additionally, the exact reasons for the indeterminate nature of the diagnoses-such as lack of adequate cytologic features, unusual findings, or lack of confirmatory immunocytochemistry (ICC) were investigated. One hundred and twenty (120) cases of PanNET were identified. Of these, the FNA diagnoses were as follows: 78% (94/120) were PanNET, 9% (11/120) were suspicious for PanNET, 6% (7/120) were atypical, 4% (5/120) were benign, 2% (2/120) were non-diagnostic and 1% (1/120) was called a mucinous neoplasm. Of the 94 cases that were definitively PanNET, 74 (78%) required ICC for the diagnosis. Of the 26 cases that were not diagnosed definitively as PanNET, 73% (19/26) were morphologically suggestive of PanNET but did not have sufficient material for confirmatory ICC. ICC is commonly employed to confirm the cytologic suspicion for PanNET. The most common reasons for indeterminate diagnoses were a quantitative lack of lesional cells and lack of material for confirmatory ICC.

Retrospective Assessment of the Utility of Imaging, Fine-Needle Aspiration Biopsy, and Intraoperative Frozen Section in the Management of Parotid Neoplasms: The Weill Cornell Medical College Experience

Background/Aims: Preoperative identification of malignant parotid lesions remains challenging, and thus, some surgeons use frozen section (FS) to assist them in their decision making. We evaluated the pathologic and cost benefit of FS after fine-needle aspiration (FNA) at our institution. Methods: We assessed medical data for 260 patients undergoing parotidectomy with FS. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for radiology, FNA, and FS. Results: The sensitivities, specificities, and accuracies of FNA and FS were 75.0, 96.4, and 93.2%, and 75.0, 100, and 96.8%, respectively. FS detected 0% of FNA false negatives and 80% of false positives. The additional pathology charge for FS alone per correctly identified benign lesion after a positive FNA was USD 1,443. Conclusion: FNA and FS are more reliable in the prognostication of the final pathology than radiology. At our center, FS appears to be of limited clinical use after benign FNAs, but may be more useful after positive, indeterminate, and nondiagnostic FNAs.

A Predictive Model for Selecting Malignant Thyroid Nodules in Patients With Nondiagnostic or Indeterminate Fine-Needle Aspiration Cytologic Findings.

The management of nodules with nondiagnostic or indeterminate fine-needle aspiration cytologic findings remains challenging. This study evaluated the clinical differences, conventional sonographic findings, elastographic findings, and cytologic findings for predicting thyroid malignancy. A total of 167 patients with a nondiagnostic or indeterminate thyroid fine-needle aspiration cytologic findings were enrolled in this study. The clinicopathologic and sonographic data from the patients were analyzed retrospectively to determine the independent predictive factors for thyroid malignancy. Then a scoring system was designed on the basis of statistically significant predictors. Fine-needle aspiration cytologic findings, Thyroid Imaging Reporting and Data System categorization, and elastographic findings were independent predictive factors for thyroid cancer on multivariate analysis. The index points were statistically significant, with a score higher than 3 favoring malignant nodules with sensitivity of 79.37%, specificity of 85.85%, a positive predictive value of 76.9%, and a negative predictive value of 87.3%. For patients with nondiagnostic or indeterminate fine-needle aspiration cytologic findings, our scoring system for prediction of thyroid malignancy can be another choice. We suggest surgery for nodules with index points higher than 3. For nodules with index points of 3 or lower, observation and regular follow-up are recommended.

American Thyroid Association Statement on Surgical Application of Molecular Profiling for Thyroid Nodules: Current Impact on Perioperative Decision Making

Recent advances in research on thyroid carcinogenesis have yielded applications of diagnostic molecular biomarkers and profiling panels in the management of thyroid nodules. The specific utility of these novel, clinically available molecular tests is becoming widely appreciated, especially in perioperative decision making by the surgeon regarding the need for surgery and the extent of initial resection. A task force was convened by the Surgical Affairs Committee of the American Thyroid Association and was charged with writing this article. This review covers the clinical scenarios by cytologic category for which the thyroid surgeon may find molecular profiling results useful, particularly for cases with indeterminate fine-needle aspiration cytology. Distinct strengths of each ancillary test are highlighted to convey the current status of this evolving field, which has already demonstrated the potential to streamline decision making and reduce unnecessary surgery, with the accompanying benefits. However, the performance of any diagnostic test, that is, its positive predictive value and negative predictive value, are exquisitely influenced by the prevalence of cancer in that cytologic category, which is known to vary widely at different medical centers. Thus, it is crucial for the clinician to know the prevalence of malignancy within each indeterminate cytologic category, at one's own institution. Without this information, the performance of the diagnostic tests discussed below may vary substantially.