False-negative Fine-needle Aspiration Research Articles

The Utility of ACR TI-RADS in Predicting False-Negative Fine Needle Aspiration for Thyroid Cancer.

Thyroid nodule fine needle aspiration (FNA) biopsies are associated with a low false-negative rate. There is limited data regarding the predictive value of American College of Radiology Thyroid Imaging Reporting and Data System for false-negative FNA. This single-center retrospective study evaluated 119 patients who underwent thyroidectomy. The association of TR category, along with other clinical variables, with false-negative FNA was evaluated. The overall false-negative rate of FNA was 10.8% (n = 9). False-negative FNAs were associated with younger age (mean 42years vs 50.6years, P = .04), larger nodule size (mean 4.4cm vs 3.2cm, P = .03), and a lower TR category (median 3 v 4, P = .01). Lower TR category, younger age, and larger nodule size were associated with false-negative FNA of thyroid nodules. These findings should be taken into context when counseling patients with thyroid nodules who have a benign FNA.

SAT571 When Two Is Too Few: Bethesda IV Pathology On Repeat Thyroid Fine Needle Aspiration

Abstract Disclosure: C.M. Godar: None. A.J. Spiro: None. M.K. Shakir: None. T.D. Hoang: None. Background: The 2015 American Thyroid Association Guidelines for Adult Patients with Thyroid Nodules provide a strong recommendation against routine ultrasound surveillance of thyroid nodules for which two benign fine needle aspiration (FNA) cytology results have been previously obtained. Strict adherence to these guidelines may hinder detection of malignancy, especially in large nodules where there is potential to miss heterogeneous pathology based on sampling technique. Clinical Case: A 36-year-old female was evaluated for surveillance of a large non-toxic multinodular goiter. Thyroid ultrasound demonstrated a dominant right thyroid nodule greater than 7 centimeters in size. The patient had undergone FNA of this nodule in 2014 and 2019 with Bethesda II (benign) cytopathology results. A chest x-ray showed tracheal deviation without evidence of narrowing. She noted a sensation of neck pressure without dysphagia or shortness of breath. She denied fatigue, heat or cold intolerance, hand tremor, or pretibial myxedema. She denied a family history of thyroid cancer or any history of neck irradiation. Due to new compressive symptoms a repeat FNA was performed. Three passes were performed with adequate samples, and the final FNA cytopathology demonstrated a Hurthle cell oncocytic-type follicular neoplasm with Bethesda IV classification. The sample was submitted for ThyGeNEXTTM and ThyraMIRv2TM molecular testing, which returned with NRAS q61R mutation of moderate-to-high risk of malignancy (65-75%). The patient was subsequently referred for total thyroidectomy with pending surgery date. Discussion: The current ATA guidelines offer a cost-effective surveillance strategy for the vast majority of patients with thyroid nodules. False negative FNA results are rare and are reported to occur in about 1% of cases1. As in this vignette, it is reasonable to perform an additional FNA after two consecutive Bethesda II results in nodules with clinically significant growth, new compressive symptoms, or if there is concern for incomplete sampling in nodules of large size. During an FNA, care should be taken to gently move the needle at various angles to capture follicular cells from different areas within a nodule. Large nodules should be sampled via multiple, separate skin entry points when feasible. Judicious use of repeat FNA along with these sampling techniques may help to prevent under-diagnosis in nodules containing multifocal areas of heterogeneous pathology. Reference: 1) Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S, Attard M, Lamartina L, Nicolucci A, Filetti S. 2015. The natural history of benign thyroid nodules. JAMA 313:926-935 Presentation: Saturday, June 17, 2023

Mesenchymal neoplasms of the parotid gland and parapharyngeal space: an FNA cytologic study of 22nonlipomatous tumors.

Mesenchymal neoplasms of the parotid gland (PG) and para-pharyngeal (PP) space are distinctly uncommon. Fine-needle aspiration (FNA) biopsy experience with nonlipomatous neoplasms from this site is reviewed. Cytopathology and surgical pathology files were examined for mesenchymal PG and PP space neoplasms. FNA biopsy was performed using standard technique. Twenty-two PG and/or PP aspirates from 20 adults (male:female = 1.1:1; age range, 19-84 years, mean age, 50 years) and a 10-week-old infant met inclusion criteria. Biopsy sites included PG (17, 77%) or PP space (5, 23%). Five of 6 malignant neoplasms (83%) were called malignant cytologically. Only 7 of 11 (63%) benign neoplasms were recognized as a benign neoplasm. None of 5 solitary fibrous tumor (SFT) cases were correctly recognized. Conversion to the Milan classification showed 8 (36%) FNA cases diagnosed as benign neoplasm, 6 (27%) malignant neoplasm, 4 (18%) neoplasm of uncertain malignant potential, 2 (9%) nondiagnostic, and single cases of suspicious for malignancy and nonneoplastic. There was 1 false-positive and no false-negative FNA diagnoses. Ancillary testing in 10 (45%) aspirates helped substantiate a correct specific diagnosis in 3 malignant and 3 benign cases. FNA biopsy of nonlipomatous mesenchymal SG neoplasms is particularly challenging. Less than half (9 of 11, 41%) had specific FNA diagnoses that correctly matched the tissue diagnoses or clinical outcome. Accurate Milan categorization was superior for malignant neoplasms (5 of 6, 83%) in contrast to benign neoplasms (7 of 11, 63%), or neoplasms of uncertain malignant potential (SFT) (2 of 5, 40%).

Axillary lymph node metastasis: Fine-needle aspiration biopsy sensitivity as a function of node size, percent replacement of lymph node by tumor and tumor deposit size.

Fine-needle aspiration (FNA) is commonly used to investigate lymphadenopathy of suspected metastatic origin. While diagnostic accuracy of FNA for lymph node disease is well described, the relationship between node size, percent tumor replacement, and size of metastatic deposit with diagnostic accuracy is less well documented. All axillary lymph nodes undergoing ultrasound-guided FNA for suspected breast metastases were correlated with subsequent surgical excision specimens. FNAs were judged as positive or negative for malignancy and the percent of false negative FNAs was correlated with node size, percent tumor replacement and size of metastatic deposit RESULTS: Sensitivities were calculated for nodes greater than 15 mm (92%), nodes 11 to 14.9 mm (83%), nodes 7 to 10.9 mm (61%), and for nodes less than 7 mm (60%). Sensitivity increases with increasing node size (P = .001). Percent tumor replacement correlated with sensitivity: 90% or greater replacement (85%) 60% to 89.9% replacement (75%), 40% to 59.9% replacement (75%) and less than 39.9% replacement (64%)(P < .001). Metastases size correlated with sensitivity: metastases greater than 10 mm (94%), 6 to 9.9 mm (70%), 4 to 5.9 mm (54%), and less than 4 mm (72%). Percentage of false negative FNAs associate with investigation of metastatic disease correlates with node size, size of metastatic deposit and percentage of nodes replaced by tumor. Lymph nodes smaller than 7 mm, deposit diameter less than 6 mm and percentage replacement of less than 40% have the highest percentage of false negative results.

False‐negative ultrasound‐guided fine‐needle aspiration of axillary lymph nodes in breast cancer patients

The purpose of this study was to clarify the clinicopathological features of patients with false-negative fine needle aspiration cytology (FNAC) and to determine the factors associated with negative FNAC. Patients with negative FNAC from January 2010 to December 2019 were included. The patients with positive sentinel nodes (SN) were divided into two groups: micrometastasis (≤2mm) group and macrometastasis (>2mm) group. The clinicopathological characteristics were compared between the two groups using the χ2 test. A total of 165 patients with negative FNAC were included; 52 (31.5%) had positive SNs. Of the 52 patients, 13 (25%) had micrometastasis and the remaining 39 (75%) had macrometastasis. Of the 113 patients with negative SNs, none had metastases found in non-SNs. No significant differences were observed in age, cT stage or subtype, and preoperative ultrasound findings between the two groups. The false-negative rate of FNAC was high (31.5%). Micrometastatic disease was seen in patients with negative FNAC, and this might be the cause of false-negative FNAC results.

EUS-Guided FNA: Tips and Tricks

AbstractThe development of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) technique has been proved to be a great armamentarium to gastroenterologists and other branches including surgery, oncology, hepatology, pulmonary medicine, and internal medicine. EUS-FNA is quite safe and allows tissue acquisition from difficult anatomical locations like retroperitoneum, pancreas, and mediastinum. The current review discusses basic techniques steps of EUS-FNA including tips and tricks. Also, false negative FNA and EUS-FNA in difficult locations are discussed. We also discussed about EUS-guided fine needle biopsy.

Clinical analysis of false-negative fine needle aspiration cytology of head and neck cancers

ABSTRACTBackground: Fine-needle aspiration (FNA) cytology is frequently used for initial and/or preoperative diagnosis of tumors in the head and neck region. However, false-negative results can lead to misdiagnosis. The aim of this study was to investigate the diagnostic results of FNA in the head and neck region and the reasons for false-negative cases.Methods: The study population comprised 1,341 patients with pathologically confirmed head and neck tumors in whom FNA was performed before surgery or biopsy in the Otolaryngology Department at Numazu City Hospital between 2002 and 2016. We evaluated the false-negative FNA cytology rate as well as the site of the primary nodule, patient age and sex, sensitivity, accuracy, specificity, positive predictive value, negative predictive value, and the pathologic diagnosis after resection.Results: The rate of false-negative FNA results was 5.9% (78/1,315 cases). The main sites of false-negative cases were the thyroid gland (n = 50), the lymph nodes (n = 16), and the salivary glands (n = 9). The sensitivity of FNA for head and neck tumors was 82.0%, with specificity and accuracy rates of 94% and 92.0%, respectively.Conclusions: We have assessed the quality of preoperative FNA cytology in head and neck tumors. To avoid misdiagnosis by FNA, it is important that the target tumor is punctured accurately. If the specimen obtained is too small, FNA should be repeated.

Large Cytologically Benign Thyroid Nodules Do Not Have High Rates of Malignancy or False-Negative Rates and Clinical Observation Should be Considered: A Meta-Analysis.

Background: Management of large thyroid nodules is controversial, as data are conflicting regarding overall rates of malignancy (ROM) in all nodules and frequency of false-negative fine-needle aspiration results (FNR) in cytologically benign nodules. This meta-analysis aimed to evaluate and compare ROM and FNR in small versus large nodules published in the literature. Methods: Articles indexed in PubMed, written in English, published electronically or in print on or prior to December 8 2017 were searched for "false negative thyroid size or cm" and "malignancy rates benign thyroid nodules." Three hundred fifty-two unique citations were identified. Multiple reviewers selected a final set of 35 articles that contained nodules stratified by size (3, 4, or 5 cm), with benign or all cytologic diagnoses, and with postsurgical histologic diagnoses. Multiple observers extracted data, including numbers of total, cytologically benign, and histologically malignant nodules. Size cutoffs of 3, 4, and/or 5 cm were analyzed in 14, 24, and 1 article, respectively. Results: ROM in all nodules ≥3 cm (13.1%) and ≥4 cm (20.9%) was lower than those <3 cm (19.6%) and <4 cm (19.9%; odds ratio [OR] = 0.72 [confidence interval (CI) 0.64-0.81] and OR = 0.85 [CI 0.77-0.95]). FNR in nodules ≥3 cm (7.2%) was not different from smaller nodules (5.7%; OR = 1.47 [CI 0.80-2.69]). FNR in nodules ≥4 cm (6.7%) was slightly higher than those <4 cm (4.5%; OR = 1.38 [CI 1.06-1.80]). The most frequently reported false-negative diagnosis was papillary thyroid carcinoma. Conclusions: Rates of malignancy and false-negative FNA results vary but, in most studies, are not higher in larger nodules. Patients with large, cytologically benign thyroid nodules need not undergo immediate surgical resection, as false-negative FNA rates are low and are expected to decrease in light of nomenclature revision of a subset of follicular variants of papillary thyroid carcinoma.

Fine-needle aspiration biopsy of thyroid nodules: Is routine ultrasound-guidance necessary?

Current guidelines recommend either ultrasound-guided or palpation-guided fine-needle aspiration biopsy for evaluation of a thyroid nodule. However, it has been suggested that ultrasound-guided fine-needle aspiration biopsy should be used routinely in all patients to reduce the rate of nondiagnostic and false negative results. The purpose of this study was to determine whether any difference exists in nondiagnostic and false negative rates between the two methods of fine-needle aspiration biopsy at our institution. A retrospective review of a prospectively maintained thyroid database was completed to determine the rates of nondiagnostic and false negative fine-needle aspiration biopsy in patients with nodular thyroid disease evaluated during the period 1990-2017. From 1990 to 2017, a total of 2,322 patients underwent fine-needle aspiration biopsy for evaluation of nodular thyroid disease, 1,123 (48%) underwent ultrasound-guided fine-needle aspiration biopsy and 1,199 (52%) underwent palpation-guided fine-needle aspiration biopsy. Ultrasound-guided fine-needle aspiration biopsy was nondiagnostic in 4.5% and had a 5.2% false negative rate, compared with palpation-guided fine-needle aspiration biopsy, which was nondiagnostic in 5.0% and had a 2.6% false negative rate (P = .53 and .14, respectively). The rate of nondiagnostic and false negative fine-needle aspiration biopsy results is similar whether US guidance is used or not. To minimize resource utilization, ultrasound-guided fine-needle aspiration biopsy can be used selectively for nonpalpable, predominantly cystic, or previously nondiagnostic nodules.

The Efficacy of Touch Smear Cytology in the Diagnosis of Salivary Gland Cancers

Methods for cytologic diagnosis, such as fine-needle aspiration (FNA) and touch smear (TS) cytology, have been frequently used for malignant tumor screening; however, false-negative cases often result in misdiagnosis. The purpose of this study was to investigate the causes of false-negative cases and methods to decrease the false-negative rate in salivary gland tumor TS cytology. In this cross-sectional study, the authors examined pathologically confirmed salivary gland tumors in 127 cases in which FNA and TS cytology were performed before the operation or open biopsy at Numazu City Hospital (Numazu, Japan) from 2002 to 2016. The authors evaluated the false-negative rates of TS and FNA cytology separately and when used in combination and other variables, such as age, gender, sensitivity, accuracy, specificity, and overall pathologic diagnosis by resection. The overall false-negative rate of postoperative pathologic diagnosis was lower when TS and FNA were combined (1 of 127 cases; 0.8%) compared with FNA cytology alone (10 of 127 cases; 7.9%; P=.034). Suggested causes of a false-negative FNA (or TS) result include cytologic difficulties present in certain malignancies, such as mucoepidermoid carcinoma, adenoid cystic carcinoma, and others. False-negative cases were decreased when a combination of preoperative FNA and intraoperative TS cytology was performed. TS cytology appears to be a useful method to avoid misdiagnosis in salivary gland diseases.

Size and Ultrasound Features Affecting Results of Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules.

Our goal was to assess the diagnostic efficacy of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid nodules according to size and US features. A retrospective correlation was made with 1745 whole thyroidectomy and hemithyroidectomy specimens with preoperative US-guided FNA results. All cases were divided into 5 groups according to nodule size (≤5, 5.1-10, 10.1-15, 15.1-20, and >20 mm). For target nodules, static images and cine clips of conventional US and color Doppler were obtained. Ultrasound images were reviewed and evaluated by two radiologists with at least 5 years US working experience without knowing the results of pathology, and then agreement was achieved. The Bethesda category I rate was higher in nodules larger than 15 mm (P < .05). The diagnostic accuracy was best in nodules of 5 to 10 mm in diameter. The sensitivity, accuracy, PPV, and LR for negative US-guided FNA results were better in nodules with a size range of 5 to 15 mm. The specificity, negative predictive value (NPV), and LR for positive results and the Youden index rose with increasing nodule size. Seventeen false-positive and 60 false-negative results were found in this study. The false-negative rate rose with increasing nodule size. However, the false-positive rate was highest in the group containing the smallest nodules. Nodules with circumscribed margins and those that were nonsolid and nonhypoechoic and had no microcalcifications correlated with Bethesda I FNA results. Nodules with circumscribed margins and those that were nonsolid, heterogeneous, and nonhypoechoic and had increased vascularity correlated with false-negative FNA results. Borders correlated with Bethesda I false-negative and false-positive FNA results. Tiny nodules (≤5 mm) with obscure borders tended to yield false-positive FNA results. Large nodules (>20 mm) with several US features tended to yield false-negative FNA results.

False negative fine needle aspiration thyroid cytology: an institutional experience

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Diagnostic utility of fine-needle aspiration cytology of lesions involving bone.

Fine-needle aspiration (FNA) is utilized in the diagnostic work-up of bone lesions in a number of institutions, either in isolation or in conjunction with core biopsy. We report our experience with FNA of bone-based lesions, including comparison of this approach with concurrent core biopsy specimens. Retrospective review over a 5-year period (2011-2015) revealed 233 cases of bone FNAs. The most commonly encountered diagnosis was malignant neoplasm (160 cases, 68.7%); within this group of malignancies, 103 cases (64.4%) represented metastatic carcinoma. Benign lesions were encountered infrequently (9 cases, 3.9%). While 37 cases (15.9%) revealed "no evidence of malignancy," 12 cases (5.2%) showed atypical findings, 3 cases (1.3%) demonstrated inflammatory conditions, and 12 aspiration biopsies were deemed nondiagnostic (5.2%). In 202 cases, concurrent core biopsies were performed following FNA and rapid on-site evaluation (ROSE). Comparison of the FNA and core biopsy diagnoses among malignant neoplasms revealed 19 diagnostic discrepancies, including 16 cases with a false-negative FNA (7.9% of all FNAs with concurrent core biopsy) and 3 cases with a false-negative core biopsy (1.5% of all cases with corresponding FNA). Our findings indicate that FNA of bone lesions is a useful diagnostic technique with high sensitivity, particularly when the cytologic findings are interpreted in conjunction with the core biopsy and pertinent clinical and radiologic findings. In addition, ROSE followed by open, dynamic communication with the performing radiologist leads to an extremely low rate of inadequate core biopsy specimens, resulting in optimal patient diagnosis and management. Diagn. Cytopathol. 2017;45:608-613. © 2017 Wiley Periodicals, Inc.

Examining the Bethesda criteria risk stratification of thyroid nodules

BackgroundThe Bethesda criteria are proposed for appropriate stratification of malignancy risk in thyroid nodules, but controversy exists regarding their accuracy and reliability in decision making. Additionally, previous studies have suggested higher rates of both malignancy and false negative fine needle aspiration biopsy (FNA) associated with increasing nodule size. This study aims to determine the accuracy of ultrasound (US)-guided FNA using the current Bethesda criteria in surgical practice. We also aimed to investigate the relationship between nodule size and malignancy. MethodsA retrospective analysis of US-guided FNAs by a single surgeon during a 4.5 year period. FNA results using Bethesda criteria were compared to final surgical pathology. Results611 patients with thyroid nodules underwent US-guided FNA. FNA results in 375 subsequently excised thyroid nodules were recorded according to the Bethesda criteria: 192 (51%) benign, 65 (17%) atypia of unknown significance/follicular lesion of undetermined significance (AUS/FLUS), 42 (11%), suspicious for follicular neoplasm (SFN), 17 (5%) suspicious for malignancy (SM), 28 (8%) malignancy, and 31 (8%) non-diagnostic. Malignancy was confirmed by surgical pathology in 15%, 34%, 50%, 88%, 100%, and 39% of the above groups respectively. Sensitivity, specificity, and false-negative rate were 61%, 99%, and 15% respectively. No correlation existed between the size of nodules with indeterminate FNA results and malignancy rate (p=0.89), or size of nodules with non-diagnostic FNA and malignancy rate (p=0.50). ConclusionThe current Bethesda risk stratification system underestimated malignancy rates in benign, indeterminate and non-diagnostic cytopathologic categories in our experience. There was no positive linear correlation between nodule size and malignancy rate in these cytopathologic categories.

The Diagnostic Accuracy of Fine‐Needle Aspiration for Parotid Malignancy

Objectives: Determine the sensitivity and specificity of fine-needle aspiration (FNA) in the diagnosis of parotid malignancy and analyze those histologies most often associated with false negative and false positive results. Methods: A retrospective chart review was performed for all patients who had a parotidectomy at the University of Wisconsin from 1994 to 2013. Patients who underwent preoperative FNA were identified, and FNA results were categorized as benign, malignant, or indeterminate. Surgical pathology was utilized as the gold standard. Results: A total of 771 patients underwent parotidectomy from 1994 to 2013, and 280 patients (36.3%) had a preoperative FNA. Based on surgical pathology, 178 (63.6%) patients had benign disease and 102 (36.4%) had malignant parotid neoplasms. 174 (62.1%) FNAs were benign, 94 (33.6%) were malignant, and 12 (4.3%) were indeterminate. Excluding indeterminate cases, the sensitivity and specificity for FNA in the diagnosis of parotid malignancy were 83.7% (95% confidence interval [CI]: (74.8%, 90.4%)) and 93.0% (95% CI: (88.0%, 96.3%)), respectively. Moreover, FNA correctly categorized malignancy in 83.7% (n = 82) and benign in 92.9% (n = 158) of cases. There were 16 false negatives (16.3%) with mucoepidermoid carcinoma having a diagnostic accuracy of 60% and acinic cell carcinoma 50%. Both were most commonly mistaken for pleomorphic adenoma. There were 12 false positives (7.1%), most commonly pleomorphic adenoma (n = 4) and warthins (n = 3). Conclusions: This study demonstrates that FNA has high sensitivity (83.7%) and specificity (93.0%) for the diagnosis of parotid malignancy. However, mucoepidermoid carcinoma and acinic cell carcinoma are more commonly associated with a false negative FNA.

Molecular characterization of 54 cases of false-negative fine-needle aspiration among 1347 papillary thyroid carcinomas.

Fine-needle aspiration (FNA) has been widely accepted as the most crucial step in the preoperative assessment of thyroid nodules, but the false-negative rates are generally reported to be between 3.6% and 10.2%. To lower the overall incidence of this false-negative testing, new reporting systems encourage the molecular testing of thyroid nodules. However, to the authors' knowledge, the role of molecular testing in false-negative FNA has not yet been evaluated. In total, 1347 consecutive papillary thyroid carcinomas (PTCs) with both cytological and histological diagnoses were collected from the same center. A blinded revision of the false-negative cases was performed. An analysis of the BRAF and Ras genes in the false-negative cases was then performed. The false-negative rate at the time of primary FNA diagnosis was 4.8% (65 of 1347 cases). False-negative cases were 15 follicular variant PTCs, 2 classical variant, and 1 solid variant that lacked peculiar PTC cytomorphological features. Adequate cellular material for molecular analysis was available only in 54 of the 65 false-negative cases. Mutations were found in 6 cases (11%), and Ras alterations were present in 16 cases (29.6%). The addition of molecular analysis decreased the false-negative rate to 0.4% (5 of 1347 cases). The results of the current study confirm the feasibility of BRAF and Ras analysis in routine FNA. However, when the false-negative FNA rate is low, the cost-benefit analysis of the detection of BRAF and Ras mutations should be carefully evaluated. Consequently, the authors suggest that preoperative molecular assessment could be helpful for benign nodules, but only in the presence of clinical suspicion of malignancy.

Role of [18F]Fluorodeoxyglucose Positron Emission Tomography—Computed Tomography, Sonography, and Sonographically Guided Fine–Needle Aspiration Biopsy in the Diagnosis of Axillary Lymph Nodes in Patients With Breast Cancer

The aim of this study was to compare the diagnostic performance of [(18)F]fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) with that of sonography and sonographically guided fine-needle aspiration (FNA) for determining the preoperative axillary lymph node (ALN) status and to evaluate the factors related to false-negative PET-CT, sonographic, and FNA results in ALN staging of invasive ductal carcinoma. From March 2009 to July 2012, 226 patients had a diagnosis of primary breast cancer. Among these patients, 107 constituted the study population after exclusion of transferred patients and patients with breast cancer other than invasive ductal carcinoma. The diagnostic performance of the modalities was compared with pathologic reports. Univariate and multivariate analyses were used to evaluate the relationship between clinicopathologic factors (symptoms, T stage, hormone receptors, and histologic grade), false-negative results, and true-negative results on PET-CT, sonography, and FNA. Of the 107 patients, 45 (42.1%) had positive results on final pathologic analysis of ALNs. Sonographically guided FNA had a significantly higher specificity, positive predictive value, accuracy, and area under the receiver operating characteristic curve than sonography and PET-CT (P < .01). When sonography and PET-CT were combined, the sensitivity was significantly improved (P = .019) compared with sonography alone. When FNA and PET-CT were combined, the sensitivity and negative predictive value were significantly increased compared with each modality (P < .01). Sonographically guided FNA was found to be an excellent diagnostic tool for preoperative evaluation of the ALN status. To obviate the step of sentinel lymph node biopsy for determining the ALN status, combined evaluation of ALNs by these modalities may be more complementary than the use of a single modality.

Assessing The Risk of False-Negative Fine-Needle Aspiration Cytology and of Incidental Cancer in Nodular Goiter

In cases of multinodular goiter with negative cytologic result, reasonable management options include surgical treatment, simple follow-up, or more recently introduced conservative therapies such as laser or radiofrequency ablation, and recombinant human thyroid-stimulating hormone-augmented radioiodine. For patients who are eligible for follow-up or nonsurgical treatments, the possibility that they may have an undiagnosed malignancy (false-negative [FN]-fine-needle aspiration cytology [FNAC] result or incidental thyroid cancer [ITC]) should be considered. The aim of our study was to assess the risk of malignancy in patients known to have presumably benign thyroid disease. Surgical series of patients who underwent total thyroidectomy for benign disease between 2000 and 2010 at two Italian centers were reviewed. Patients with any preoperative suspicion of malignancy were excluded. Histologic examination revealed that 84 of 970 (8.6%) thyroidectomized patients had malignancy (5% ITC and 3.6% FN-FNAC), with 89.8% of ITCs having a diameter <10 mm, and 65.7% of FN-FNAC cancers having a diameter >30 mm. Sixty-seven thyroid malignancy patients (79.8%) had stage I disease (American Joint Committee on Cancer criteria). The risk of FN-FNAC increases with increasing size of the nodule, while the risk of ITC increases as nodule size decreases. The risk of malignancy in presumably benign thyroid disease cannot be overlooked, but can be minimized through skillfully performed ultrasonography (US) examination and FNAC. Once a patient with multinodular goiter is referred for follow-up or nonsurgical therapy, careful US surveillance is mandatory.

False negatives in thyroid cytology: Impact of large nodule size and follicular variant of papillary carcinoma

Fine-needle aspiration (FNA) cytology is well established in the diagnosis of thyroid nodules. However, false-negative rates for malignancy of 3% to 10% are reported. The purpose of the present study was to investigate the impact of nodule size and follicular variant of papillary carcinoma (FVPTC) on false-negative FNA rates in thyroid nodules and on malignancy rates in nodules with indeterminate cytology. Retrospective study. A total of 765 consecutive ultrasound-guided FNAs were reviewed. Histological correlation was available in 262 cases. The overall sensitivity of FNA for malignancy was 84%, and the false-negative rate 9.1%. Nodules ≥ 3 cm were significantly more likely to ultimately be diagnosed as cancer by histology than nodules <3 cm (14% vs. 6.8%, P = .006); however, they were also significantly more likely to undergo surgery than smaller nodules (P < .0001). Among the surgical series, the false-negative rate was 10.9% in nodules ≥ 3 cm and 6.1% in nodules <3 cm (P = .71). Most false negatives were due to FVPTC. FVPTC was significantly more likely to be missed by preoperative cytology than conventional or other variants of papillary carcinoma (P < .001). Among cases with indeterminate cytology, nodule size and Thy-3f versus Thy-3a subclassification did not have any significant impact on likelihood of malignancy. The sensitivity of FNA for detection of FVPTC is reduced compared to conventional papillary carcinoma. The impact of nodule size is not significant. 4.

The Impact of Thyroid Nodule Size on the Risk of Malignancy and Accuracy of Fine-Needle Aspiration: A 10-Year Study from a Single Institution

False-negative rates for thyroid fine-needle aspiration (FNA) vary from 0.4% to 13%, but the effect of nodule size on the accuracy of thyroid FNA remains controversial. We hypothesized that large thyroid nodule size does not contribute to the risk of malignancy or the risk of a false-negative FNA. All thyroid FNAs performed at the Walter Reed Army Medical Center during September 2001-August 2011 were reviewed. A strict correlation between the biopsy site, location, and size of nodule on ultrasound (US) and pathology report was ensured. FNA results were classified as benign, atypical, follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy (SM), or malignant, and the pathology result was categorized as either benign or malignant. Nodules were analyzed by size: 0.5-0.9 cm (group A), 1.0-3.9 cm (group B), and ≥ 4 cm (group C). Incidental thyroid cancer was not included. Of 3013 patients undergoing FNA, 667 (22.1%) had surgery. Patients were excluded for nodules <0.5 cm, nondiagnostic FNA, or no preoperative US, leaving 540 patients with 695 nodules. Among patients referred for surgery, FNA results were benign in 417 nodules (60%), atypical in 22 (3.2%), FN/SFN in 122 (17.6%), SM in 77 (11.1%), and malignant in 57 (8.2%). Postoperative malignancy rates by FNA result were 7% if benign, 4.5% if atypical, 23% if FN/SFN, 33.8% if SM, and 78.9% if malignant. FNA accuracy was 60% in group A, 68.5% in group B, and 80.3% in group C (p=0.01). False-negative rates for FNA were 7.0% overall, 15.8% in group A, 6.3% in group B, and 7.1% in group C (p=0.25). Sensitivity and negative predictive value were highest in group B at 81.6% and 93.7%, respectively. The prevalence of malignancy was not different between groups. Our results show that the thyroid nodule size ≥ 4 cm increases neither the risk of false-negative FNA results, nor the overall risk of malignancy. We also show a tendency toward a higher false-negative rate in subcentimeter nodules. We conclude that a large nodule size should not prompt automatic referral for thyroidectomy. An increased awareness of potential sampling error in subcentimeter nodules is warranted.