Nondiagnostic Fine-needle Aspiration Research Articles

Detection of ALK mRNA Transcripts in Liquid-based NSCLC ThinPrep Cytology Slides

Introduction: Endobronchial ultrasound (EBUS)-guided sampling of the mediastinum has traditionally been performed by fine needle aspiration (FNA) for cytologic evaluation. The ProCore fine needle biopsy, used primarily to obtain intra-abdominal tissue core biopsies, has not been widely used for EBUS. The aim of this study was to evaluate our experience with EBUS-Procore of mediastinal nodes, and to compare its diagnostic utilization to that of conventional EBUS-FNA. Material and Methods: A retrospective review of all EBUS cases of mediastinal masses using a ProCore needle from December 2013 to March 2014 was performed. Patient demographics, anatomic site, number of procedure passes, on-site immediate evaluation, final pathology reports, and ancillary test results were recorded. All specimen slides and cell blocks were evaluated scoring lesion and contamination cellularity (0 Z acellular, 1 Z scant, 2 Z moderate, and 3 Z abundant). Results: There were 18 EBUS cases of mediastinal lymph nodes using Procore in patients (12 female, 6 male) of average age 57 years (range, 3380 years). FNA was followed by Procore biopsy in all cases, except one where only Procore was performed. Cases included benign (granulomas), atypical, and malignant (carcinoma) diagnoses. More FNAs were satisfactory (with 2 unsatisfactory cases) than Procores (with 7 unsatisfactory cases). The 2 non-diagnostic FNA cases remained unsatisfactory with subsequent Procore. More passes were performed with FNA (4/case) than Procore (2.6/case). On average, FNA provided greater cellularity of lesional material (smear score Z 2; cell block score Z 1.4) than Procore (smear score Z 1.4; cell block score Z 1.4). However, FNAs contained more bronchial contamination (smear score Z 1.6; cell block score Z 1) than Procore (smear score Z 1; cell block score Z 0.4). Both sample types contained similar bronchial and blood contamination. Ancillary studies (special stains, immunostains, FISH, molecular) were equally successful using cell blocks from both specimen types. Conclusions: Our preliminary experience shows that EBUS-guided Procore sampling of mediastinal lymph nodes is feasible. Although FNA samples appear to provide more diagnostic cellular material in this pilot series, fewer subsequent Procore passes were required to achieve satisfactory specimens. Procore specimens also contained less obscuring bronchial contamination. Evaluation of more cases and more experience with this new technique is necessary to determine if the diagnostic yield using Procore during EBUS can be improved.

Endobronchial Ultrasound-Guided (EBUS) Procore Sampling: Comparison to Fine Needle Aspiration for Mediastinal Lymph Nodes

Introduction: Endobronchial ultrasound (EBUS)-guided sampling of the mediastinum has traditionally been performed by fine needle aspiration (FNA) for cytologic evaluation. The ProCore fine needle biopsy, used primarily to obtain intra-abdominal tissue core biopsies, has not been widely used for EBUS. The aim of this study was to evaluate our experience with EBUS-Procore of mediastinal nodes, and to compare its diagnostic utilization to that of conventional EBUS-FNA. Material and Methods: A retrospective review of all EBUS cases of mediastinal masses using a ProCore needle from December 2013 to March 2014 was performed. Patient demographics, anatomic site, number of procedure passes, on-site immediate evaluation, final pathology reports, and ancillary test results were recorded. All specimen slides and cell blocks were evaluated scoring lesion and contamination cellularity (0 Z acellular, 1 Z scant, 2 Z moderate, and 3 Z abundant). Results: There were 18 EBUS cases of mediastinal lymph nodes using Procore in patients (12 female, 6 male) of average age 57 years (range, 3380 years). FNA was followed by Procore biopsy in all cases, except one where only Procore was performed. Cases included benign (granulomas), atypical, and malignant (carcinoma) diagnoses. More FNAs were satisfactory (with 2 unsatisfactory cases) than Procores (with 7 unsatisfactory cases). The 2 non-diagnostic FNA cases remained unsatisfactory with subsequent Procore. More passes were performed with FNA (4/case) than Procore (2.6/case). On average, FNA provided greater cellularity of lesional material (smear score Z 2; cell block score Z 1.4) than Procore (smear score Z 1.4; cell block score Z 1.4). However, FNAs contained more bronchial contamination (smear score Z 1.6; cell block score Z 1) than Procore (smear score Z 1; cell block score Z 0.4). Both sample types contained similar bronchial and blood contamination. Ancillary studies (special stains, immunostains, FISH, molecular) were equally successful using cell blocks from both specimen types. Conclusions: Our preliminary experience shows that EBUS-guided Procore sampling of mediastinal lymph nodes is feasible. Although FNA samples appear to provide more diagnostic cellular material in this pilot series, fewer subsequent Procore passes were required to achieve satisfactory specimens. Procore specimens also contained less obscuring bronchial contamination. Evaluation of more cases and more experience with this new technique is necessary to determine if the diagnostic yield using Procore during EBUS can be improved.

Follow up Analysis of Non-diagnostic Fine Needle Aspiration of the Thyroid in the African-American Population

Introduction: It has been suggested that African Americans (AA) suffer from a more aggressive thyroid disease despite a lower rate of thyroid malignancies. The aim of this study is to analyze non-diagnostic (ND) aspirates and their follow up pathology diagnosis and compare the implied risk of malignancy in the African American (AA) versus non-African American (NAA) population. Materials and Methods: Thyroid FNA cytology reports and corresponding follow up findings were retrospectively reviewed between March 2006 and December 2012. 179 patients met our inclusion criteria. The patients were categorized as AA and NAA. Aspirates were labeled as ND based on adequacy criteria listed in the in the Bethesda System for Reporting Thyroid Cytolopathology (TBS-Thy). The follow-up cytology and surgical pathology diagnosis were used for the final categorization. Results: We studied 179 patients with ND aspirates: 85 AA and 94 NAA. The mean age of AA and NAA was not significantly different (AA 56.5 13.9 yrs. vs. NAA 56.3 15.2, pZ0.95). 91.8% of AA were females compared to 85.1% of NAA (pZ0.17). With respect to the outcomes of ND aspirates, loss of follow up was comparable in both AA and NAA: 71.8% and 77.7%, respectively. Two patients in the NAA group (2.1%) were diagnosed with papillary thyroid carcinoma (PTC) upon follow up compared to 0% in AA. The incidence of benign and atypical thyroid lesions was comparable between these two populations (Table 1). The distribution of benign versus malignant diagnosis on follow up cytology and surgical pathology was examined across TBS-Thy classes. Table 1

Do repeatedly nondiagnostic fine needle aspirations of thyroid nodules predict malignancy risk?

Fine needle aspiration biopsy (FNAB) is a common, minimally invasive, cost-effective, and rapid method to manage thyroid nodules, but nondiagnostic FNAB (ND-FNAB) is still a common problem due to high prevalence (2%-20%). Our purpose in this study is to investigate risk of malignancy of repeating ND-FNABs and correlation between clinical and ultrasound findings. Our cohort study included 75 patients who had 2 or more times ND-FNABs and, finally, undergone surgical resection. We evaluated demographic, clinical, ultasonographic, and pathologic features. Fifty-seven patients were female, and 22 patients were male. Seventy-five patients' histopathologic results were 76% (n=57) benign and 24% (n=18) malignant. Of malignant nodules, 94.4% (n=17) were papillary carcinoma, whereas 5.6% (n=1) were follicular carcinoma. We did not find any predictive factor for malignancy and any differences associated with clinical and ultrasonographic features between benign and malignant nodules. Reaspiration followed by surgery for appropriate patients is recommended.

Management of nodules with initially nondiagnostic results of thyroid fine-needle aspiration: can we avoid repeat biopsy?

To identify demographic and ultrasonographic (US) features associated with malignancy after initially nondiagnostic results of fine-needle aspiration (FNA) to help clarify the role of repeat FNA, surgical excision, or serial US in these nodules. This study was HIPAA compliant and institutional review board approved; informed consent was waived. Thyroid nodules (n = 5349) that underwent US-guided FNA in 2004-2012 were identified; 393 were single nodules with nondiagnostic FNA results but adequate cytologic, surgical, or US follow-up. Demographic information and diameters and volume at US at first biopsy were modeled with malignancy as outcome through medical record review. Exact logistic regression was used to model malignancy outcomes, demographic comparisons with age were made (Student t test, Satterthwaite test), and proportion confidence intervals (CIs) were estimated (Clopper-Pearson method). Of 393 nodules with initially nondiagnostic results, nine malignancies (2.3%) were subsequently diagnosed with repeat FNA (n = 2, 0.5%) or surgical pathologic examination (n = 7, 1.8%), 330 (84.0%) were benign, and 54 (13.7%) were stable or decreased in size at serial US (mean follow-up, 3.0 years; median, 2.5 years; range, 1.0-7.8 years). Patients with malignancies were significantly older (mean age, 62.7 years; median, 64 years; range, 47-77 years) than those without (mean age, 55.4 years; median, 57 years; range, 12-94 years; P = .0392). Odds of malignancy were 4.2 times higher for men versus women (P = .045) and increased significantly for each 1-cm increase in anteroposterior, minimum, and mean nodule diameter (1.78, 2.10, and 1.96, respectively). In 393 nodules, no malignancies were detected in cystic or spongiform nodules (both, n = 11, 2.8%; 95% CI: 1.4%, 5.0%), nodules with eggshell calcifications (n = 9, 2.3%; 95% CI: 1.1%, 4.3%), or indeterminate echogenic foci (n = 39, 9.9%; 95% CI: 7.2%, 13.3%). Very few malignancies were diagnosed with repeat FNA following nondiagnostic FNA results (two of 336, 0.6%); therefore, clinical and US follow-up may be more appropriate than repeat FNA following nondiagnostic biopsy results.

Role of core needle biopsy for patients with indeterminate, fine-needle aspiration cytology

In this journal of Endocrine, Nasrollah et al. [1] reported a new core needle biopsy (CNB) technique for thyroid nodules classified as indeterminate in fine-needle aspiration (FNA) cytology. This new technique obtains core samples consisting of nodular tissue, extranodular parenchyma, and the nodule’s capsule when it is present. They concluded that this technique is helpful to discern the nature of thyroid nodules classified as indeterminate on FNA. In 1930s, large-needle biopsy using 14-gauge needle without ultrasound (US) had been used for diagnosis of thyroid nodules [2], but it showed no benefit in terms of its safety and efficacy as compared with those of FNA [3]. Therefore, in 1980s, FNA has been used as the standard technique for diagnosing thyroid cancer [4]. CNB has recently been reconsidered for use in the diagnosis of thyroid cancer because modern type, spring-activated CNB under US guidance improved both the safety and efficacy of this technique [5]. The patient comfort during and after CNB or tolerability of this procedure is well reported [6]. The majority of the recent guidelines have recommended CNB for patients with thyroid nodules with previously non-diagnostic FNA results [7–9] and in patients with suspicious lymphoma or anaplastic cancer [8, 9]. However, the American Thyroid Association guidelines recommend repeat FNA for patients with previously nondiagnostic FNA results instead of CNB [10]. Recently, Yeon et al. [11] retrospectively studied a large group of patients with non-diagnostic FNA results and concluded that CNB could reduce both the non-diagnostic and inconclusive results. Their results also showed that CNB could prevent unnecessary diagnostic surgery in 96 % of the patients with repeated, non-diagnostic FNA results. For indeterminate FNA results, F18-FDG-PET/CT or (99 m)Tc-MIBI scan may be helpful in patients with thyroid nodules in which malignancy is suspected on the basis of conventional diagnostic techniques [3, 4]. There are no guidelines recommending CNB. Therefore, repeated, indeterminate results of FNA cause patients to undergo diagnostic surgery [8]. As thyroid FNA has become widely used, unnecessary surgery has increased. In a recent study by Park et al. [12], they retrospectively reported the role of CNB for indeterminate thyroid nodules. Their results showed that CNB is superior to repeat FNA for previously non-diagnostic or indeterminate nodules. In another report on this topic by Na et al. [13], they again prospectively evaluated and suggested that CNB can effectively reduce inconclusive results compared with repeat FNA in nodules with previously non-diagnostic or atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) FNA results. This may be related to the larger tissue sample and the additional histological information obtained by CNB as compared with FNA. Choi et al. [14] verified the value of CNB in a large study population (N = 191) of patients with AUS and FLUS seen in previous FNA results. In a recent study by Nasrollah et al. [1], 20 patients were diagnosed as follicular neoplasm without false negative results by new CNB technique including nodular tissue, extranodular parenchyma, and the nodule’s capsule. On histology, all but one patient was diagnosed as having follicular adenoma, while the other patient was diagnosed with follicular carcinoma. Adenomatous nodules lack or have a thin fibrous capsule, while follicular neoplasms usually manifest as thick, encapsulated lesions [15]. In W. J. Choi J. H. Baek (&) Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-Gil, Songpa-Gu, Seoul 138-736, Korea e-mail: radbaek@naver.com

Diagnostic Value of FNA‐BRAF Mutation Analysis in Papillary Thyroid Cancer: A Systematic Review and Meta‐analysis

Objectives: Fine needle aspiration (FNA) with cytological analysis is an initial step in investigating thyroid nodules. We systematically reviewed the diagnostic value of adding B-type Raf kinase (BRAFV600E) gene mutation analysis to the conventional FNA in the diagnosis of papillary thyroid cancer (PTC). Methods: Studies reporting BRAFV600E mutation analysis following FNA for evaluation of thyroid nodules were identified through searching electronic databases (eg, MEDLINE, EMBASE) through 1948-2011, scanning reference lists of relevant studies, and contacting experts. Two independent reviewers screened literature results, abstracted data, and appraised study quality. Meta-analysis of sensitivity and specificity was performed using bivariate random effects models. Results: Forty-two studies met our inclusion criteria after screening 787 citations and 117 full-text articles. The included studies enrolled approximately 7,676 patients with 8,196 FNA samples evaluated for BRAFV600E mutation. Bivariate-pooled sensitivity and specificity results from 29 included studies that examined BRAFV600E mutation among cytologically confirmed PTC samples were 72.6% (95% confidence interval [CI] 66.1-78.3%) and 50.8% (95% CI; 32.3-69.1%), respectively. For samples that were diagnosed cytologically as suspicious for PTC, and confirmed by histology as PTC, bivariate-pooled sensitivity and specificity results were 52.1% (95% CI; 36.3-67.4%) and 85.3% (95% CI; 55.2-96.5%), respectively. Eleven studies reported non-diagnostic FNA samples. The pooled sensitivity and specificity results for these samples were 50.5% (95% Cl; 31-69.8%) and 92.9% (95% Cl; 74.2-98.3%), respectively. Conclusions: BRAFV600E mutation analysis is associated with increase specificity and moderate increase in the sensitivity of FNA in the diagnosis of papillary thyroid cancer.

The impact of implementing the bethesda system for reporting of thyroid FNA at an academic center

Recently, a six-tiered diagnostic risk classification system was created based on the recommendations of the National Cancer Institute (NCI) sponsored NCI Thyroid Needle Aspiration State of the Science Conference at Bethesda, MD in October 2007. The objective of the current study was to compare the frequency distribution of the various diagnostic categories to evaluate its diagnostic performance before and after implementation of The Bethesda System (TBS). A total of 5,897 thyroid Fine needle aspirations (FNAs) were reviewed; 3,207 were from 2008 after TBS implementation, and 2,690 were from 2007 immediately before TBS implementation. Follow-up consisted of reviewing corresponding histologic results. The rates of "Nondiagnostic" specimens and cases with a diagnosis of "Follicular Neoplasm" decreased from 13.1 to 11.1% and 8.6 to 5.5%, respectively, after implementation of TBS, while the rate of negative specimens increased from 68.2 to 73.8%. The other categories remained relatively stable. In addition, there also was a significant decrease in the use of noncommittal descriptive diagnoses. The diagnostic performance of thyroid FNA in identifying a neoplastic process as measured by area under the receiver operating characteristic curve increased from 0.88 to 0.89; the difference was statistically significant (P=0.03). Implementation of TBS showed a significant reduction of: nondiagnostic thyroid FNAs, of FNAs with a diagnosis of "Follicular Neoplasm," as well as cases with descriptive noncommittal diagnoses. TBS results in improved diagnostic performance and therefore more consistent and uniform reporting of thyroid FNA.

Nondiagnostic fine-needle aspirations of the thyroid: is the risk of malignancy higher?

BackgroundNondiagnostic fine-needle aspirations (FNAs) pose a dilemma in the management of patients with thyroid nodules. In most cases, these patients undergo either repeat FNA or surgical resection. However, a significant number of patients will only be observed, assuming that the risk of malignancy is low. Therefore, the purpose of this study was to determine whether the risk of malignancy is higher in patients with thyroid nodules and nondiagnostic FNAs. MethodsWe reviewed reports from 4286 consecutive FNA biopsies performed on patients with thyroid nodules at our institution between 2002 and 2010. We divided FNAs into two categories: diagnostic and nondiagnostic. We collected demographic, follow-up, and pathology data from both groups and then analyzed them with analysis of variance and chi-square tests. ResultsOf the 4286 FNAs, 259 were classified as nondiagnostic (6%). We saw no significant differences in age or gender between patients with diagnostic versus nondiagnostic FNAs. Of the patients with nondiagnostic FNAs, 62 underwent diagnostic thyroidectomy (24%), 74 had a repeat FNA (29%), and 123 had observation only (47%); thus, 136 patients had a cytologic or pathologic diagnosis. Patients with nondiagnostic FNAs had a significantly higher rate of all types of thyroid cancer, compared with those with diagnostic FNAs (12% versus 5%, respectively; P < 0.001). Impressively, the chance of papillary thyroid cancer was twofold higher in patients with nondiagnostic FNAs. ConclusionsThe percentage of nondiagnostic FNA at our institution during this period (6%) was relatively low. However, the incidence of malignancy in these patients was significantly higher. Therefore, we recommend that patients with thyroid nodules and nondiagnostic FNAs undergo either repeat biopsy or diagnostic thyroidectomy.

Fine-Needle Aspiration Biopsy of Thyroid Bed Lesions in Post-Thyroidectomy Patients

The purpose of this study was to determine the importance of nondiagnostic fine-needle aspiration biopsy results for post-thyroidectomy bed lesions in patients with thyroid cancer. The Institutional Review Board approved this retrospective Health Insurance Portability and Accountability Act-compliant study with a waiver for informed consent. Twenty-one patients with nondiagnostic fine-needle aspiration biopsy of a thyroid bed lesion after thyroidectomy with at least 1 year of follow-up with neck imaging were retrospectively enrolled in our study. The tumor type, local staging, radiotherapy, serum thyroglobulin levels, and imaging characteristics of the thyroid bed lesions were recorded. All patients underwent sonographically guided fine-needle aspiration biopsy of the thyroid bed lesion. The mean imaging follow-up ± SD was 46.3 ± 28.7 months. Lesions in 20 patients (95.2%) were stable on imaging. Most thyroid bed lesions were hypoechoic (80.9%), and none showed calcifications. The mean thyroid bed mass maximum diameter was 1.17 ± 0.6 cm (range, 0.3-2.9 cm). Thyroid bed lesions with nondiagnostic fine-needle aspiration biopsy results after thyroidectomy can be managed with imaging follow-up; 1-year imaging is a reasonable interval after biopsy.

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.

Axillary lymph node status in breast cancer staging: What patient and tumor factors affect the accuracy of ultrasound-guided fine needle aspiration?

1126 Background: The purpose of the study is to evaluate the accuracy of ultrasound-guided fine needle aspiration (FNA) of axillary lymph nodes(ALNs) in patients with breast cancer and to determine factors that influence accuracy of ultrasound-guided FNA. Methods: Retrospective review of patients with breast cancer who had FNA of ALNs as well as sentinel lymph node excision or complete axillary dissection. Patients treated with neoadjuvant chemotherapy were excluded. 55 axillary FNAs in 54 patients were included in the final analysis. Pathology reports were reviewed for size of the primary tumor, FNA results, number of positive ALNs, and greatest tumor size in ALNs. FNA was performed if a suspicious lymph node was identified. Surgical sentinel lymph node biopsy or full axillary dissection were the reference standard. Micrometastases (&lt; 0.2 mm) and isolated tumor cells in the lymph node were included in the negative group. Atypical and nondiagnostic FNA results were considered negative cytologic results. Significance was analyzed using the Mann-Whitney test. Results: Size of the primary cancer ranged from 0.3 mm to 8.5 cm. The sensitivity of FNA was 73%, with positive predictive value of 97% and negative predictive value of 52%. The NPV of FNA for primary tumors &lt;1 cm, 1.1-2, 2.1-5 and &gt;5 cm is 100%, 36%, 50% and 66% respectively. Correlation of primary tumor size with sensitivity of FNA was not statistically significant. The sensitivity of FNA for lymph nodes with metastatic deposit &lt; 5mm, 6-10mm, 11-15mm, 16-20mm, and 21mm+ is 0%, 57%, 59%, 89%, and 100%, which is statistically significant (p = 0.007). The number of positive ALNs at axillary dissection is not correlated to the sensitivity of FNA. The sensitivity of FNA for 1-3, 4-9 and 10+ positive ALNs is 78%, 64% and 80%. Conclusions: Our findings indicate that FNA of suspicious axillary lymph nodes is valuable even in small tumors, which differs from the literature. The overall negative predictive value of FNA is 52%, so sentinel lymph node biopsy is essential after negative FNA. Sensitivity of FNA increases with the size of the metastatic deposit in the lymph node, but is not correlated to the number of positive ALNs found at dissection.

Initially non-diagnostic ultrasound-guided fine needle aspiration cytology of thyroid nodules: value and management

Ultrasound (US)-guided fine needle aspiration cytology (FNAC) is an accurate, reliable, and simple method to identify a thyroid nodule as benign or malignant. However, non-diagnostic cytology results for thyroid nodules are a major limitation of US-guided FNAC. To investigate the incidence of thyroid cancer among cases with non-diagnostic results on FNAC and to provide suggestions for the management of thyroid nodules that are initially non-diagnostic by FNAC according to ultrasonographic findings. From July 2006 to December 2009, 10,317 thyroid nodules in 6684 consecutive patients underwent US-guided FNAC at our institute. Among these, 871 thyroid nodules (8.4%) were diagnosed as non-diagnostic on initial cytologic evaluation and 196 underwent a second or third FNAC. Twenty-seven thyroid nodules (18.9%) underwent surgery, while 116 thyroid nodules were cytologically confirmed as benign with no remarkable change on follow-up US were included. We retrospectively reviewed the US findings for a total of 143 thyroid nodules (123 benign nodules and 20 malignant nodules). The US features that we compared included composition, echogenicity, margin, calcifications, shape, and underlying echogenicity. In total, thyroid cancer was diagnosed in 20 nodules (14.0%). The size of the nodule was significantly associated with malignancy (P < 0.05). Most of the sonographically probable benign nodules were found to be benign (97.6%). Suspicious nodules on US were thyroid cancer in 43.2% of cases. Marked hypoechogenicity, microlobulated or irregular margin, microcalcifications, and taller-than-wide shape were significant US findings that correlated with malignancy (P < 0.05). The diagnostic performance of ultrasound for initially non-diagnostic thyroid nodules was as follows: sensitivity of 90.0%, specificity of 65.0%, positive predictive value of 29.5%, and negative predictive value of 97.6%. In terms of management of thyroid nodules with non-diagnostic FNAC cytology, US evaluation is a feasible and useful method for predicting malignancy.

Seeking Help From ShadowsThe Author’s Reply

To the Editor The article by Renshaw1 expressed the views that nondiagnostic thyroid fine-needle aspiration should be followed by repeat aspiration and that patients with 2 sequential nondiagnostic aspirations have a very low risk of malignancy. We agree with this view. However, the difficulty arises in the case of cystic thyroid lesions. We are of the view that while doing a repeat aspiration it is better to correlate with ultrasonographic findings and better aspirate from a solid area under guidance. According to Moon et al,2 shape, margin, echogenicity, and presence of calcification are helpful ultrasound criteria for the discrimination of malignant …

Prevalence of Malignancy in Thyroid Nodules with an Initial Nondiagnostic Result After Ultrasound Guided Fine Needle Aspiration

The objective of this study was to determine the rate of malignancy in thyroid nodules with an initial nondiagnostic fine needle aspiration. From October 2001 to April 2007, biopsies were performed on 1344 thyroid nodules in our practice. Biopsies were performed on nodules using 25–27 gauge needles, ultrasound guidance and multiple passes using both suction and capillary action. We retrospectively reviewed the results of these biopsies as well as any further management of nodules that received nondiagnostic results (IRB HUM00006459). Following initial biopsy, 295/1344 (21.9%) of nodules received nondiagnostic pathologic results. Of this population, 39 nodules (13.1%) were lost to follow-up. Of the remaining 256 nodules that received a repeat FNA, surgical excision, or greater than 24 months of clinical and imaging follow-up, only five cancers were detected, representing only 2% of the population that received an initial nondiagnostic biopsy result. All of these cancers were papillary neoplasms. When rigorous, ultrasound-guided, fine needle aspiration of thyroid nodules is performed, a nondiagnostic histopathologic result should not be interpreted as suspicious for thyroid cancer. Given the low rate of malignancy in this population (2%), we suggest that clinical and imaging follow-up of these nodules, opposed to repeat sampling, is warranted.

Ultrasound-Guided Percutaneous Thyroid Nodule Core Biopsy: Clinical Utility in Patients with Prior Nondiagnostic Fine-Needle Aspirate

Five percent to 20% of thyroid nodule fine-needle aspiration (FNA) samples are nondiagnostic. The objective of this study was to determine whether a combination of FNA and core biopsy (CFNACB) would yield a higher proportion of diagnostic readings compared with FNA alone in patients with a history of one or more prior nondiagnostic FNA readings. We conducted a retrospective study of 90 core biopsies (CBs) performed in 82 subjects (55 women and 27 men) between 2006 and 2008 in an outpatient clinic. CFNACB yielded a diagnostic reading in 87%. The diagnostic reading yield of the CB component of CFNACB was significantly superior to the concurrent FNA component, with CB yielding a diagnosis in 77% of cases and FNA yielding a diagnosis in 47% (p<0.0001). The combination of CB and FNA had a higher diagnostic reading yield than either alone. In 69 nodules that had only one prior nondiagnostic FNA, CB was diagnostic in 74%, FNA was diagnostic in 52%, CFNACB was diagnostic in 87%, and CB performed significantly better than FNA (p=0.0135). In 21 nodules with two or more prior nondiagnostic FNAs, CFNACB and CB were diagnostic in 86%, FNA was diagnostic in 29%, and CB was significantly better than FNA (p=0.0005). Clinical, ultrasound, or histopathologic follow-up was available for 81% (73/90) of the CFNACB procedures. No subject with a benign CFNACB reading was diagnosed with thyroid malignancy in the follow-up period (range 4-37 months, mean 18 months), although one subject had minimal increase in nodule size and was awaiting repeat sonography at study conclusion. Thyroid nodule CFNACB is safe and clinically useful in selected patients when a prior FNA reading is nondiagnostic. CFNACB is superior to either CB or FNA alone. CFNACB should be strongly considered as an alternative to surgery in individuals with two prior nondiagnostic FNAs.

Repeatedly Nondiagnostic Thyroid Fine-Needle Aspirations Do Not Modify Malignancy Risk

Objective: Thyroid nodules with nondiagnostic (ND) fine-needle aspirations (FNA) typically undergo repeat sampling. While repeat FNA is often diagnostic, little is known regarding the significance of repeatedly ND aspirates. Limited data suggest there is very low, if any, risk of malignancy for repeatedly ND FNAs. Study Design: We performed a retrospective analysis of ND thyroid FNAs over a nearly 6-year period at our institution to further address this question. Results: There were 834 ND thyroid FNAs, representing 694 distinct thyroid nodules. Repeat FNA was performed after an initial ND aspirate in 52% of cases (363/694); 19% (70/363) had at least one additional ND diagnosis on repeat FNA. Surgical follow-up was available for 57 cases. Malignancy was identified histologically in 21% (9/42) of nodules after a single ND FNA and in 20% (3/15) of nodules with 2 or more repeatedly ND aspirates. Accounting for all benign cytologic follow-up, the overall risk of malignancy was 4% [12/303; 3.5% (9/255) following a single ND FNA and 6.3% (3/48) after repeated ND FNAs]. Conclusion: We observed no modification of malignancy risk when repeated FNAs were ND. Clinical management for an ND aspirate should remain repeat aspiration along with clinical and sonographic correlation.

Thyroid Fine-Needle Aspiration&lt;subtitle&gt;Does Case Volume Affect Diagnostic Yield and Interpretation?&lt;/subtitle&gt;

To evaluate the effect of case volume on the diagnostic yield and interpretation of thyroid fine-needle aspiration (FNA). Retrospective case series. An academic tertiary referral center and 2 community hospital centers. Data were retrospectively reviewed for all consecutive patients undergoing thyroid FNA at these institutions during the 2009 calendar year. Differences in diagnostic distribution and yield among pathologists and clinicians of differing case volume. A total of 790 patients underwent thyroid FNA, with the results interpreted as benign (479 [60%]), atypical (166 [22%]), malignant (9 [1%]), or nondiagnostic (136 [17%]). The FNAs were performed by 134 physicians and interpreted by 16 pathologists with varying case volumes. Low-volume pathologists (<50 FNAs interpreted) were more likely to report atypical FNAs (32% vs 13%; P<.001) and less likely to call FNAs benign (50% vs 70%; P<.001) compared with high-volume pathologists (≥50 FNAs interpreted), and compared with expected normative data (benign, P<.001; atypical, P<.001). Atypical FNA findings reported by low-volume pathologist were more likely to yield benign permanent results than those read by high-volume pathologists (64% vs 42%; P<.02). Low-volume clinicians (<20 FNAs performed) were not more likely to perform nondiagnostic FNAs compared with high-volume clinicians (≥20 FNAs performed) (16% vs 15%; P=.47). Case volume significantly influences the pathologic interpretation of thyroid FNA, as low-volume pathologists report more atypical and fewer benign FNA results. Case volume did not have a significant impact on diagnostic yield, because thyroid FNAs performed by low-volume clinicians did not result in more frequent nondiagnostic results compared with those performed by high-volume clinicians.

Parotid cancer treatment with surgery followed by radiotherapy

We read with interest the paper by Shah et al looking at the 15-year experience of parotid cancer in their centre. The review highlights the criticisms frequently aimed at fine needle aspiration (FNA), which often performs poorly outside specialist centres with high non-diagnostic rates. The diagnostic performance of FNA can be improved when undertaken by a cytologist, who can re-aspirate if needed, and with the use of imaging guidance1 and ancillary techniques, which are expensive and not widely available. We would suggest that all patients undergoing parotid surgery should ideally have an accurate preoperative cytological/histological diagnosis. We would agree with the authors that preoperative diagnosis is important for operative planning and informed consent of the patients. A non-diagnostic FNA is as unhelpful as a false negative or false positive result. In this paper an accurate preoperative diagnosis was obtained in only 18 of 27 patients. Four patients had a false positive and five patients had non-diagnostic FNA; these results seem high. Twenty-three patients had no preoperative diagnosis at all although this may to some extent reflect the changing trends in preoperative diagnosis. The authors do not mention the use of ultrasound guided core biopsy (USCB), which has recently been described in the diagnosis of parotid tumours.2,3 The procedure is safe, requiring only local anaesthetic, and can be performed on an outpatient basis. This technique utilises a spring loaded biopsy automated device to obtain a core of tissue, usually via an 18G or 20G needle inserted into the parotid lesion. USCB provides a diagnostic accuracy approaching 100% with the advantage over FNA that it provides a core of tissue that can be used for immuno/histochemical analysis, which will allow grading and typing of parotid malignancy (as well as lymphoma). As recognised by Shah et al, this ability is a crucial aspect of surgical management, allowing the operation to be tailored according to the tumour. Only 12 of 27 patients (44.4%) who had FNA were accurately subtyped in the study by Shah et al. USCB can be combined with diagnostic ultrasonography to facilitate lesion characterisation and also compartmentalisation (superficial vs deep lobe). Additionally, it can be used to obtain biopsies from the solid parts of necrotic lesions. We would suggest that USCB is the technique of choice for the diagnosis of parotid tumours. It not only informs the choice of operative intervention but also provides an accurate preoperative diagnosis for the vast majority of patients, which, combined with further staging investigations, should be a baseline requirement for the multidisciplinary team.

Think Zebra: An Unusual Cause of Nausea, Vomiting, and Abdominal Pain

Purpose: Case: A 42-year-old Hispanic male presented with nausea, vomiting, epigastric pain since March 2010. He was hospitalized with similar complaints in April 2010. A CT scan of abdomen and pelvis revealed cholelithiasis without associated cholecystitis. Due to his recurrent symptoms, he underwent laparoscopic cholecystectomy in May 2010. His symptoms partially improved following surgery, but recurred soon after. In February 2011, he presented to the emergency department with worsening nausea, vomiting, and epigastric pain. A repeat CT scan of abdomen and pelvis was unremarkable. Subsequently, an esophagogastroduodenoscopy (EGD) was done which demonstrated submucosal antral mass. An endoscopic ultrasound (EUS) revealed a 2.6 x 2.4 cm homogenous hypoechoic lesion arising from muscularis propria in the antrum. Fine needle aspiration (FNA) biopsy was obtained, but the final pathology report was non-diagnostic. The patient underwent partial gastrectomy. Pathologic examination of the tumor tissue was strongly positive for smooth muscle actin and negative for CD117, CD 34, CD 31, desmin, chromogranin, synaptophysin, and CAM 5.2. The immunohistochemical and histologic features support a diagnosis of gastric glomus tumor. Postoperatively, the radiologists were notified of the diagnosis and were asked to review the pre-operative CT scan images. Once again, the mass was not visualized on the images. Patient tolerated the surgery well and was discharged home. His symptoms never recurred, and he is waiting surveillance EGD in a year after surgery. Discussion: Gastric glomus tumor is a rare benign mesenchymal neoplasm that originated from neuromyoarterial glomus. The first case of gastric glomus tumor was reported in 1951, and the incidence is estimated to be only 1% out of all gastrointestinal stromal tumors. Patients may present with non-specific symptoms such as epigastric discomfort, nausea, vomiting or melena. Only a few cases of metastatic gastric glomus tumor were described in the literature, and the liver is the common site. Those tend to be size of greater than 2 cm, deep gastric location, and high mitotic activity. The preoperative diagnosis is challenging due to the insensitivity of CT scan, non-specific EGD findings, and non-diagnostic FNA biopsy result due to intramural localization of the mass. Conservative local resection is the gold standard for both diagnosis and treatment. However, endoscopic enucleation is also under consideration. Overall, gastric glomus tumor has favorable prognosis after resection. Although rare, gastric glomus tumor should be included in the differential diagnosis in patients presenting with non-specific upper gastrointestinal symptoms.