Fine needle aspiration outcomes of masses detected by positron emission tomography: correlation with standard uptake value

OBJECTIVES: To characterize the cytopathologic outcome of lesions detected on positron emission tomography (PET) scan. STUDY DESIGN: Cases with fine needle aspiration (FNA) performed because of a PET-positive lesion over an 18-month period were reviewed. Correlation with the standard uptake value (SUV) (using 2.5 as a cutoff value) was carried out. RESULTS: A total of 112 FNAs were found, of which 83 had adequate tissue for evaluation and available corresponding SUVs to be included in the final study. Fisher's exact test was carried out for correlation between FNA diagnosis and SUV Sixty-one (73.5%) lesions had an SUV > or = 2.5, 53 (87%) ofwhich were malignant and 8 (13%) benign on cytology. Twenty-two (26.5%) lesions had an SUV < 2.5, of which 12 (54.5%) showed benign and 10 (45.5%) showed malignant cytology. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of SUV were 84%, 60%, 87%, 56% and 78%, respectively. CONCLUSION: Our data show that FNA procedures performed for PET-positive lesions have high PPV, but low NPV. Therefore interpretation of PET SUV values < 2.5 as benign should be made with extreme caution.     

Posters. P13 Cytohistological correlation in 212 FNAs of thyroid: analysis of discordant cases

Aim To detect major pitafalls in thyroid FNA and to confirm its in a clinical sensitivity and specificity. Methods A total of 9251 fine needle aspirations biopsy carried out at Bellaria Hospital in Bologna from 1991 to 2000 by a pathologist in the FNA Clinic or by a clinician under ultrasonic guidance using a small needle (25–27 G); at least two passes have been made for each nodule. The specimen was considered satisfactory if at least five groups of follicular cells with at least 10 cells each, were seen. The cytological results were tiered in a four categories classification: inadequate, negative, suspicious and positive. Cyto‐histological correlations were available in 212 cases: 127 benign lesions and 85 malignant lesions. An analysis of false positive cases and false negative cases was performed and discordant case reviewed according to the flowing criteria: architecture, cellularity, colloid, pseudoinclusions, nuclear groovings, chromatin pattern, nuclear membrane, cytoplasm, naked nuclei and lymphocytes. Results Diagnostic distribution in 9251 FNAs from the thyroid: 88.6% negatives, 2.8 suspicious, 2.4% positives and 6.2% inadequates. Specificity was 85.8% and sensitivity was 78.8%. Among the 18 false negative cases eight were papillary microcarcinomas, four papillary carcinomas, five follicular carcinoma and one a Hurtle cell carcinoma. Four false positive cases were found: three reported as papillary carcinomas and one as carcinoma NOS. Review of false positives showed that in three cases the colloid was fluid, in three cases nuclear grooving was rare or absent, in two cases degenerative vacuoles at MGG were interpreted as nuclear inclusions and in three cases benign naked nuclei were present in the background. Review of false negatives confirmed lack of malignant features in 13 (eight papillary microcarcinomas and five follicular carcinomas), five were interpretation errors (three papillary carcinomas, one follicular, one Hurtle cell). Conclusion FNAC of the thyroid is a sensitive and specific method of assessment for thyroid nodules but false negative and false positive cases do occur. Use of all and only few criteria enhances diagnostic accuracy.     

The UK Royal College of Pathologists Thyroid Fine-Needle Aspiration Diagnostic Classification Is a Robust Tool for the Clinical Management of Abnormal Thyroid Nodules

Objective: To compare the outcomes and evaluate the relative risk of thyroid cancer by using the UK thyroid fine-needle aspiration (FNA) cytological diagnostic categories, with the main objective being the clarity of patient management. Study Design: Results of thyroid FNA reported as Thy3a, Thy3f, Thy4, and Thy5 were correlated with histological outcomes. The specificity and positive predictive value (PPV; risk of malignancy) for each reporting category was assessed. Results: Of a total of 873 thyroid FNAs, 237 (27%) were reported as 'abnormal': 40 (4.6%) as Thy3a, 119 (13.6%) as Thy3f, 20 (2.2%) as Thy4, and 58 (6.6%) as Thy 5. The final outcomes were available in 136 (57%) cases which underwent surgical resection (25, 60, 55, and 74% of Thy3a, Thy3f, Thy4, and Thy5, respectively). The known outcomes of the Thy3a category were too low to be statistically significant. The specificity and PPV of the Thy3f, Thy4, and Thy5 (equivalent to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) IV, V, and VI) categories were 50, 50, and 100% and 28, 64, and 100%, respectively. The PPV of Thy3f for diagnosis of 'neoplasms' (benign and malignant) was 63%. Conclusion: The current thyroid FNA classification system used in the UK, which is comparable to TBSRTC, offers a sound basis for clear communication on which the management of patients with abnormal thyroid FNA findings can be based. Categories Thy3f, Thy4, and Thy5 carry a progressively rising risk of malignancy, justifying their continuing use. Diagnostic category Thy5 'malignant' is robust and can be used as a sure indication of a definitive surgical management.     

Do all Thyroid Nodules >4 cm need to be Removed? An Evaluation of Thyroid Fine-Needle Aspiration Biopsy in Large Thyroid Nodules

Objective: Controversy exists regarding the ability of fine-needle aspiration (FNA) biopsy to rule out malignancy when thyroid nodules exceed 4 cm in diameter. The goal of this study was to provide data regarding FNA accuracy in a clinical setting for detecting/ruling out malignancy in large thyroid nodules (≥4 cm) and discuss FNA utility in guiding surgical decisions.Methods: All thyroid FNA cases performed at Marshfield Clinic from 1/1/2000 to 12/31/2010 followed by complete or partial thyroidectomy on nodules of at least 4 cm were identified. Demographics, medical history, nodule biopsy characteristics, surgical procedures, and diagnosis data were abstracted. FNA was compared to histologic evaluation of surgical specimens.Results: A total of 198 patients with large thyroid nodules were identified. Most had a single large nodule, but ~40% were multinodular, and 206 total nodules were assessed. Females outnumbered males, and the mean age was ~50 years. After surgery, cancer was histologically identified in 49/206 (23.8%) nodules, including 9/123 nodules that had been categorized as benign by FNA, corresponding to a false-negative rate of 7.3%. Sensitivity/specificity for detecting malignancy by FNA was ~80%. The positive predictive value (PPV) was just below 60%, and the negative predictive value (NPV) was 93% but rose to 96% when papillary microcarcinomas were excluded.Conclusion: While FNA sensitivity in large nodules was relatively low, NPV was high, especially if incidental papillary microcarcinomas were excluded. When cancer prevalence and NPV are known, FNA can be a reliable “rule out” test in nodules ≥4 cm. This information is critical and can help guide the surgery decision, especially in high-risk patients. The decision for surgery should not be solely based on nodule size but should consider additional factors including cancer prevalence, clinical history, ultrasound features, surgical risk, and life expectancy.Abbreviations:FNA = fine-needle aspirationNPV = negative predictive valuePPV = positive predictive value     

Evaluation of HMFG2 and thyroglobulin in the diagnosis of thyroid fine needle aspiration (FNA)

In order to appraise the usefulness of HMFG₂ and thyroglobulin (Tg) as specific markers for the diagnosis of thyroid disease, we studied 63 FNA smears. Cases tested included 30 benign (nine colloid goitres, six cases of Hashimoto's thyroiditis, six Hürthle cell adenomas, nine follicular adenomas) and 33 malignant lesions (nine follicular carcinomas, 12 papillary carcinomas, nine anaplastic carcinomas, three medullary carcinomas). All cases with malignant lesions except the anaplastic carcinomas were positive for HMFG₂. Immunoreactive cells to HMFG₂ were also found in 15 adenomas out of 30 benign cases. Positive Tg reaction was found in benign and malignant thyroid lesions, except six cases of Hashimoto's thyroiditis, nine anaplastic and three medullary carcinomas. The results obtained indicate that morphology paired with immunocytochemistry can usually depict a more specific profile of thyroid lesions for better evaluation of the pathology.     

Surgical Utility of Afirma: Effects of High Cancer Prevalence and Oncocytic Cell Types in Patients with Indeterminate Thyroid Cytology

ObjectiveThe Afirma Gene Expression Classifier (GEC) molecular marker assay was developed for the purpose of improving surgical decision-making with indeterminate fine-needle aspiration (FNA) biopsies of thyroid nodules. In this paper, we analyze the performance of the GEC over 27 months in a community hospital-based thyroid surgery practice.MethodsWe began using GEC and Thyroid Cytopathology Partners (TCP) exclusively for thyroid FNA analysis in January 2011, shortly after the Afirma GEC became commercially available. In this paper, we focus on patients with indeterminate FNA results and the outcomes of GEC analysis, with particular attention paid to the calculation of the negative predictive value (NPV) of the Afirma test.ResultsWe performed 645 FNAs in 519 patients over 27 months. Overall, 58 FNAs (9%) were read as indeterminate, with 36 of these classified as suspicious by GEC (62%), 20 characterized as GEC benign (34%), and 2 determined to be inadequate due to low mRNA content. Of the 36 suspicious GEC patients, 30 underwent thyroidectomy, and 21 of the 30 had malignant final pathology. Of the 20 benign GEC patients, 5 underwent thyroid surgery, and 2 were discovered to have malignancies. The NPV for the Afirma GEC in our practice environment was 89.6%.ConclusionIn a practice with a high incidence of thyroid cancer in patients with indeterminate FNAs (33% for our practice), the NPV of the Afirma GEC test may not be as robust as suggested in the existing literature. (Endocr Pract. 2014;20:364-369)     

Benign follicular thyroid lesions versus follicular variant of papillary carcinoma: differentiation by architectural pattern

Differentiation between benign and malignant follicular lesions is one of the difficult diagnostic areas in thyroid fine needle aspiration (FNA). Nuclear criteria are usually used to distinguish between them. In this study the microarchitectural pattern of common benign follicular lesions, namely nodular hyperplasia (NH) and follicular adenoma (FA) were analysed in comparison with those of follicular variant of papillary carcinoma (FVPC) in order to aid in their differentiation. The FNA smears of histologically proven cases of FVPC, NH and FA were reviewed and compared. The microarchitectural features of FVPC, NH and FA were described. Three cytological features--multi-layered rosettes, branching monolayered sheets and balls of thick pinkish colloid--were exclusively observed in FVPC. Hyperplastic papillae with intact follicles and colloid were frequently seen in NH, 83% and 100%, respectively. Albeit less frequently, they were also noted in FVPC, 25% and 75% of cases, respectively. These overlapping features make the distinction between FVPC and NH sometimes difficult; however, assessing the smears for the specific features of FVPC may help in their differentiation. None of the aforementioned microscopic findings with the exception of the seldom presence of colloid were documented in FA. The crowded clusters of follicular cells were seen both in FA and FVPC; however, they were complex and branching in the latter and round to oval in the former. Finally, smears with good recovery of material are indispensable for the identification of these helpful microarchitectural patterns.     

Galectin-3 is not useful in thyroid FNA

INTRODUCTION: Previous studies have suggested that galectin-3 immunohistochemistry may be useful in the fine needle aspiration (FNA) diagnosis of thyroid carcinoma as it has been reported to selectively stain carcinomas and not adenomas or goitres. METHODS: Fifty-one patients were included in a prospective study of galectin-3 in thyroid FNA; 88.2% were female and 11.8% male, mean age 53 years, range 25-87 years. Cell blocks were prepared and stained for galectin-3 if any cells were present in needle washings from the respective FNAs. RESULTS: Twelve of 51 (23.5%) of cell blocks contained epithelial cells. One benign and one inadequate FNA were negative for galectin-3 staining. One of five non-diagnostic FNA cases, a papillary carcinoma on final histology showed positive staining. Four follicular neoplasm/suspicious of carcinoma cases showed negative staining. One malignant FNA case, a papillary carcinoma showed positive staining with galectin-3 but three further carcinomas, two papillary and one follicular were galectin-3 negative. CONCLUSION: Galectin-3 immunohistochemistry does not appear to be a useful adjunct to diagnosis in thyroid FNA as it does not reliably distinguish malignant and benign lesions. Many thyroid aspirates are of low cellularity and are not suitable for cell block immunohistochemistry.     

The bethesda terminology for reporting thyroid cytopathology: from theory to practice in europe

Objectives: A 2007 conference held at the National Cancer Institute, Bethesda, Md., USA, proposed a new terminology for classifying the results of thyroid fine-needle aspiration (FNA) - The Bethesda System for Reporting Thyroid Cytology (TBSRTC). The need to standardize thyroid FNA terminology was emphasized during the 35th European Congress of Cytology in 2009. An interobserver review study to assess the new terminology for analyzing the results of thyroid FNA was organized by the scientific committee of the European Federation of Cytology Societies. Study Design: Four experts in thyroid FNA examined and classified 116 FNAs according to the 6 levels of TBSRTC which are: nondiagnostic (ND); benign; atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN), with those of Hürthle cell type reported as follicular neoplasm, Hürthle cell type/suspicious for a follicular neoplasm, Hürthle cell type (FNHCT/SFNHCT); suspicious (SUS), and malignant. Results: The total consensus was 62.1%; the cytopathologists disagreed on 44 cases, including 8 cases of AUS/FLUS and 18 of FN/SFN; 59% of the cases had no consensus. They agreed on 73 and 80% of the cases classified as benign and malignant, respectively, and on 58.3% of the SUS cases. The percentage of no consensus for each expert was between 32 and 39%. Conclusions: Disagreement regarding the use of TBSRTC terminology for classifying the results of thyroid FNA mainly occurred in the most-often criticized categories of AUS/FLUS and FN/SFN.     

Fine needle aspiration biopsy in the diagnosis of thyroid nodules

The fine needle aspiration (FNA) biopsies performed on thyroid nodules at Turku University Central Hospital from 1983 to 1988 were reviewed. Of the 1,054 total aspirated nodules, 194 were investigated histologically after thyroid surgery (191 cases) or at autopsy (3 cases). Two cases with an insufficient FNA sample, 4 with an incidental occult papillary carcinoma and 2 cases with carcinoma outside the nodule investigated by FNA biopsy were excluded from the series, leaving 186 histologically confirmed nodules in the final analysis. Three (3%) of the 107 cases with an FNA biopsy diagnosis of benign, 4 (8%) of the 52 with an FNA diagnosis of equivocal, 3 (20%) of the 15 with an FNA diagnosis of suspicious and all 12 (100%) with an FNA diagnosis of malignant were histologically malignant. If only an unequivocally malignant cytologic finding is considered positive, FNA biopsy had a diagnostic specificity of 100%, a sensitivity of 55% and an accuracy of 95% among the histologically confirmed cases. Follow-up revealed no cases of cancer among the 863 thyroids that were not explored surgically. It is concluded that FNA biopsy is a practical method with considerable diagnostic value in the evaluation of thyroid nodules.     

Thyroid Cytology and Risk of Thyroid Cancer: Differences Among Indeterminate Specimens

ObjectiveTo assess the potential for stratification of indeterminate cytologic findings on fine-needle aspiration (FNA) of thyroid nodules in an effort to improve therapeutic strategies.MethodsWe attempted to determine the malignant risk associated with various indeterminate FNA cytologic patterns by correlation of specimens with the final histologic diagnosis. For this analysis, we identified 294 computerized medical records of surgically treated thyroid nodules during a 5-year period at our institution with the corresponding FNA cytology reports available.ResultsOf the 294 surgical cases, 162 with a positive or indeterminate cytologic report were selected, reviewed, and classified. Of 52 patients with positive cytologic findings on FNA, 51 (98%) had a final histologic report of a malignant thyroid nodule. Of 110 patients with indeterminate specimens, 30 (27%) had a final histologic diagnosis of thyroid carcinoma. The presence of nuclear atypia was predictive of thyroid carcinoma in 75% of patients, a Hürthle cell cytologic pattern was associated with a malignant thyroid nodule in 33%, and a hypercellular smear was suggestive of malignant involvement in 26% of cases. The lowest rate of malignant potential was associated with cytologic microfollicular and scant colloid alone subtype (6%).ConclusionThe results of this study show that indeterminate thyroid cytologic specimens can be subdivided into groups with different malignant risks. A microfollicular cytologic pattern in the absence of a hypercellular smear or nuclear atypia does not support a recommendation of surgical treatment. A malignant cytologic diagnosis has a high positive predictive value for detection of thyroid cancer. (Endocr Pract. 2004;10:330-334)     

Diagnostic value of qualitative and quantitative variables in thyroid lesions

Two hundred and thirty-three thyroid lesions were studied by fine needle aspiration (FNA) cytology using standard cytologic criteria available in the literature. These included 114 cases of nodular colloid goitre (NCG), 47 cases of Hashimoto's thyroiditis (HT), 12 follicular adenomas (FAd), five cases of subacute thyroiditis and three cases of thyrotoxicosis among the benign lesions. The malignant lesions seen were 30 cases of papillary carcinoma (PCa), 16 follicular carcinomas (FCa), three cases with double lesions, e.g. papillary carcinoma with coexisting NCG, and three of papillary carcinoma with HT. Emphasis was given to eight qualitative and quantitative (morphometric) variables in these various thyroid lesions. Cell measurements were done using a Visopan Lux projection microscope. The three qualitative variables included type of nuclear membrane (regular/irregular), type of nuclear chromatin and the presence or absence of conspicuous nucleoli. The quantitative variables studied were nuclear diameter, nuclear area, cytoplasmic diameter, cytoplasmic area & N/C ratio. Statistical analysis was performed in order to know whether the standard cytologic criteria used at FNA cytology in the literature (increased cellularity, microfollicles, increased N/C ratio, absence of significant haemosiderin-laden macrophages and scanty colloid) could differentiate a follicular adenoma from a follicular carcinoma. A statistical analysis was also performed to establish the utility of the qualitative and quantitative variables. The results showed that none of the standard cytologic criteria applied could differentiate follicular adenoma from a follicular carcinoma. With regard to qualitative variables, irregularity of nuclear membrane and presence of conspicuous nucleoli were most significant in papillary carcinoma, followed by follicular carcinoma, then by follicular adenoma; these features being hardly evident in nodular colloid goitre and Hashimoto's thyroiditis. A coarse nuclear chromatin was most significant in follicular carcinomas followed by follicular adenomas. It was less obvious in the benign conditions, but more prominent in Hashimoto's thyroiditis compared with a goitre. It was also not obvious in a papillary carcinoma. Of the quantitative variables, all measurements were greatest in PCa > FCa > FAd > NCG = HT. When differentiating follicular adenoma from follicular carcinoma the qualitative variables of significance were the presence or absence of nucleoli, the chromatin pattern and regularity/irregularity of nuclear membrane; the nuclear area was the most important feature among quantitative variables.     

Can the American Thyroid Association,K-Tirads,and Acr-Tirads Ultrasound Classification Systems Be Used to Predict Malignancy in Bethesda Category IV Nodules?

Objective: Management of thyroid nodules with Bethesda category III and IV cytology on fine needle aspiration (FNA) is challenging as they cannot be adequately classified as benign or malignant. Ultrasound (US) patterns have demonstrated the utility in evaluating the risk of malignancy (ROM) of Bethesda category III nodules. This study aims to evaluate the value of 3 well-established US grading systems (American Thyroid Association &lsqb;ATA], Korean Thyroid Imaging Reporting and Data System &lsqb;Korean-TIRADS], and The American College of Radiology Thyroid Imaging Reporting and Data System &lsqb;ACR-TIRADS]) in determining ROM in Bethesda category IV nodules.Methods: Ninety-two patients with 92 surgically resected thyroid nodules who had Bethesda category IV cytology on FNA were identified. Nodule images were retrospectively graded using the 3 systems in a blinded manner. Associations between US risk category and malignant pathology for each system were analyzed.Results: Of the 92 nodules, 56 (61%) were benign and 36 (39%) were malignant. Forty-seven per cent of ATA high risk nodules, 53% of K-TIRADS category 5 nodules, and 50% of ACR-TIRADS category 5 nodules were malignant. The ATA high-risk category had 25% sensitivity, 82% specificity, 47% positive predictive value (PPV) for malignancy. K-TIRADS category 5 had 25% sensitivity, 85% specificity, 53% PPV for malignancy. ACR-TIRADS category 5 had 25% sensitivity, 84% specificity, 50% PPV for malignancy. None of the 3 grading systems yielded a statistically significant correlation between US risk category and the ROM (P = .30, .72, .28).Conclusion: The ATA, Korean-TIRADS, and ACR-TIRADS classification systems are not helpful in stratifying ROM in patients with Bethesda category IV nodules. Clinicians should be cautious of using ultra-sound alone when deciding between therapeutic options for patients with Bethesda category IV thyroid nodules.     

Predictive power of cytomorphological features in equivocal (C3, C4) breast FNAC

Definitive immediate diagnosis in breast fine needle aspiration cytology (FNAC) remains the aim for cytopathologists. We reviewed 72 consecutive equivocal (C3 and C4) aspirates with respect to 16 cytomorphological criteria. We assessed the power of each criterion at predicting either a malignant [positive predictive value (PPV)] or a benign [negative predictive value (NPV)] diagnosis by correlation with follow-up histology. Blind review led to 34% of cases being correctly definitively diagnosed. Eccentrically placed epithelial cell nuclei (PPV = 88%, sensitivity = 67%, specificity = 87%) and coarse nuclear chromatin (PPV = 81%, sensitivity = 72%, specificity = 83%) are the features that are most useful in predicting malignancy in this selected series. The presence of myoepithelial cells within epithelial groups is not a good indicator of a benign diagnosis (NPV = 24%, sensitivity = 80%, specificity = 53%).     

Utility of Ultrasound Versus Gene Expression Classifier in Thyroid Nodules with Atypia of Undetermined Significance

Objective: Thyroid nodules with fine-needle aspiration (FNA) cytology categorized as atypia of undetermined significance (AUS) often undergo additional diagnostic analysis with the Afirma Gene Expression Classifier (GEC), which classifies these as either high probability of being benign (GEC-B) or suspicious for malignancy (GEC-S). Our goal was to assess the clinical validity and utility of GEC in the evaluation of AUS cytology and evaluate the performance of ultrasonography (USG) for predicting malignancy in this subset.Methods: We conducted a study with a retrospective cohort of patients from January 2012 to January 2014 who had FNA of thyroid nodules >1 cm in size with AUS cytology.Results: Cleveland Clinic Florida has an overall prevalence of AUS of 5%. A total of 119 cases with nodules >1 cm in size were reported as AUS. Forty-eight (40.3%) had a GEC performed after the first FNA (AUS-1), and 27 of these were GEC-S. Of those 27, 21 went for surgery and 14 (66.6%) had thyroid cancer on histopathology. The remaining 71 with AUS-1 were sent for a second FNA: 19 nodules were benign and did not undergo further evaluation, while the remaining 52 were reported as AUS for the second consecutive time (AUS-2). AUS-2 samples were sent for GEC. Of these 52 AUS-2, 38 (73.1%) were reported as GEC-S. Thirty-five went for surgery and 32 (91.4%) had confirmed malignancy on histopathology. Positive predictive value (PPV) was 91.4% for AUS-2 and 66.6% for AUS-1. Moreover, AUS-2 nodules that were hypoechoic and solid on USG showed a PPV of 92% for malignancy.Conclusion: In our practice, the diagnostic accuracy to predict malignancy with GEC for AUS-1 nodules was poor (PPV, 66.6%). The PPV of GEC testing was markedly higher at 91.4% performed after two consecutive AUS cytologies. AUS-2 nodules that were solid and hypoechoic on USG also had a high probability to be malignant (PPV, 92%). We recommend repeat FNA on AUS-1 nodules rather than proceeding directly to GEC testing. Also, we suggest that among AUS-2 nodules, surgery can be recommended when USG shows solid and hypoechoic features with GEC testing reserved for the remainder.Abbreviations:AUS = atypia of undetermined significanceFNA = fine-needle aspirationGEC = gene expression classifierGEC-B = GEC-benignGEC-S = GEC-suspicious for malignancyNPV = negative predictive valuePPV = positive predictive valueUSG = ultrasonography     

IS MEASUREMENT OF CIRCULATING TUMOR DNA OF DIAGNOSTIC USE IN PATIENTS WITH THYROID NODULES?

Objective: Circulating tumor DNA (ctDNA), a subset of cell-free DNA (cfDNA), is a potential biomarker for thyroid cancer. We determined the performance of a ctDNA panel for detecting thyroid malignancy in patients with thyroid nodules.Methods: Sixty-six patients with thyroid nodules without a prior history of cancer enrolled in a prospective, 1-year study in which blood was drawn for ctDNA analysis prior to undergoing fine-needle aspiration biopsy (FNAB) of thyroid nodules. The ctDNA panel consisted of 96-mutations in 9 cancer driver genes. The primary outcome measures were the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of our ctDNA panel for the diagnosis of thyroid malignancy as determined by pathologic and/or molecular tissue examination.Results: Results from 10 subjects could not be determined due to inadequate volume or technical issues. The final classifications of the thyroid nodules were 13 malignant and 43 benign lesions. A KRAS G12V mutation was detected in the plasma of 1 patient with stage IVA papillary carcinoma whose tissue contained the same mutation. Two of the 43 patients with benign lesions also had ctDNA detected, giving a sensitivity of 7.7%, specificity of 95.35%, PPV of 33.33%, and NPV of 77.35%. There were no significant differences between benign or malignant lesions in cfDNA levels.Conclusion: Neither cfDNA measurements nor our panel of ctDNA mutations are sensitive or specific enough to provide valuable information over FNAB. An expanded panel and the inclusion of proteomics may improve sensitivity and specificity for thyroid cancer detection.Abbreviations: cfDNA = cell-free DNA; ctDNA = circulating tumor DNA; FNAB = fine-needle aspiration biopsy; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features     

Fine needle aspiration diagnosis of mycobacterial lymphadenitis. Sensitivity and predictive value in the United States

OBJECTIVE: Fine needle aspiration (FNA) has proven valuable in diagnosing tuberculous lymphadenitis in countries with endemic mycobacterial infection (MI). Its role in developed countries, where sensitivity and positive predictive value are likely to be lower, has not been adequately explored. STUDY DESIGN: This retrospective, five-year study from a public hospital in the United States examined the predictiveness of 238 nodal FNAs in patients with MI; 59% of patients were also HIV+. RESULTS: Diagnostic results (stainable acid-fast bacilli or positive culture) were present in nearly half the aspirates; sensitivity was 46%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 94%. If granulomatous inflammation (GI) was also considered a positive result, sensitivity increased to 53%; false positive cases of GI reduced PPV to 80%, while specificity (98%) and NPV (95%) changed little. Considered alone, GI had the lowest sensitivity (25%) and PPV (65%). CONCLUSION: FNA was useful in this U.S. population with MI, identifying almost half the affected patients. However, nondiagnostic results, such as granulomatous inflammation, should be interpreted with caution.     

Malignant teratoma of the thyroid with predominantly neuroepithelial differentiation. Fine needle aspiration cytologic, histologic and immunocytochemical features of a case

BACKGROUND: Teratoma of the thyroid in adults is extremely rare, and most are malignant. Only nine cases have been adequately documented in the English-language literature, and there are no reports detailing the fine needle aspiration (FNA) cytologic characteristics. CASE: A 32-year-old female presented with a left-sided nodular thyroid mass with left cervical lymphadenopathy. FNA cytology of the thyroid and lymph nodes was done. The cytologic and immunocytochemical features were that of a small round cell tumor with neuroepithelial (NE) differentiation, metastasizing to the cervical nodes. Microscopic study of the thyroidectomy specimen showed a tumor showing an NE pattern with occasional islands of squamous and cuboidal epithelium, leading to a diagnosis of malignant teratoma. CONCLUSION: Knowledge of FNA cytologic features of rare but highly malignant lesions like thyroid teratomas allow early recognition so that suitable and possibly aggressive treatment protocols can be adopted in the hope of prolonging survival.     

The Contribution of Qualitative CEUS to the Determination of Malignancy in Adnexal Masses,Indeterminate on Conventional US – A Multicenter Study

The aim of this study is to evaluate the efficacy of qualitative analysis of contrast-enhanced ultrasound (CEUS) in discrimination of adnexal masses which were undetermined by conventional ultrasound (US). A total of 120 patients underwent transabdominal CEUS. The initial enhancement time and intensity compared with the uterine myometrium, contrast agent distribution patterns and dynamic changes of enhancement were assessed. The sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC) and Youden’s index were calculated for contrast variables. The gold standard was the histological diagnosis. There were 48 malignant tumors and 72 benign tumors. The enhancement features of malignant masses were different from benign ones. Earlier or simultaneous enhancement with inhomogeneous enhancement yielded the highest capability in differential diagnosis, and Sen, Spe, PPV, NPV, ACC, Youden’s index was 89.6%, 97.2%, 93.2%, 95.6%, 93.3%, and 0.88, respectively. The qualitative evaluation of CEUS is useful in the differential diagnosis of adnexal masses where conventional US is indeterminate.     

Negative predictive value of pulmonary fine needle aspiration cytology.

Percutaneous fine needle aspiration (FNA) for cytologic examination is an accepted and reliable technique for diagnosing neoplasia. It is less useful, however, in excluding that diagnosis. We performed a retrospective analysis of a consecutive series of pulmonary FNA specimens at Memorial Sloan-Kettering Cancer Center to determine the negative predictive value (NPV) of this technique in the setting of a large cancer hospital. Fifty-seven cases were studied. Six cases (10.5%) were initially diagnosed as negative but acellular and were not further analyzed, and another 6 were lost to follow-up; 24 cases (42.1%) were subsequently confirmed negative by tissue or clinical follow-up, and 21 of the cases (36.8%) were proven positive for malignancy by repeat aspiration, tissue diagnosis or clinical means. Of these 21 cases, 1 was misdiagnosed as negative, and review demonstrated malignant cells on the slide; 3 of the 21 cases should have been initially rejected as unsatisfactory, and 18 of the 21 contained material sufficient for a cytologic diagnosis but not representative of the lesion. On follow-up the false-negative cases showed primary adenocarcinoma, epidermoid carcinoma, lymphoma, metastatic breast carcinoma and metastatic sarcoma. Specific benign diagnoses were made on the initial cytologic preparation in three cases. No benign tumors were found. The NPV in our series was 53.3%, comparable to values in previous reports. The single largest factor contributing to false-negative diagnoses is sampling error, and we recommend repeat aspiration when no specific benign diagnosis is made. In addition, we suggest that the diagnoses of negative for malignant cells and insufficient for diagnosis or acellular be considered separate categories.