Comparison of palpation-guided fine-needle aspiration biopsy to ultrasound-guided fine-needle aspiration biopsy in the evaluation of thyroid nodules.

OBJECTIVE: Although fine-needle aspiration biopsy (FNAB) of thyroid nodules is a reliable and simple method, the diagnostic value may be limited by inadequate and false-negative results. In this prospective study, we compared palpation-guided FNAB (PGFNAB) with ultrasound-guided FNAB (UGFNAB) to establish the rates of inadequate material and cost-effectiveness. DESIGN: A total of 285 thyroid nodules in 215 patients were included in the study. Palpable nodules with the greatest diameter between 1 and 2.5 cm were included in the study. PGFNAB and UGFNAB techniques were applied to the same nodule by the same operator. Cytologic evaluations were performed by the same cytologist in a blinded fashion. To provide cost analysis, the prices obtained from different hospitals were evaluated. MAIN OUTCOME: The rates of inadequate material for PGFNAB and UGFNAB were significantly different as 32.3% and 21.4%, respectively (p = 0.004). There was significantly higher inadequate material rate in PGFNAB group for small-sized nodules (greatest nodule diameter between 10 and 15 mm) (p = 0.009), despite inadequate material rate was not significant for both procedures for larger sized nodules. False-negative results were 15.8% for PGFNAB and 5.6% for UGFNAB. Regarding cost analysis, the difference between the two methods was 20 dollars on average for each patient. CONCLUSIONS: We consider UGFNAB to be superior to PGFNAB for obtaining adequate material especially for small-sized nodules, as well as providing more accurate cytologic evaluation. Indeed, the difference between the costs of two procedures might be acceptable.     

Hydatic cyst in the thyroid gland diagnosed by fine-needle aspiration biopsy.

A 33-year-old man was admitted with a swelling in the right lobe of the thyroid gland of 1 years duration. Laboratory investigations and thyroid function tests were normal. Thyroid scanning showed a cold nodule in the lower pole of the right thyroid lobe. Thyroid ultrasonography showed multiple cystic nodules in the thyroid gland. To make a differential diagnosis of the thyroid nodule, fine-needle aspiration biopsy (FNAB) was performed and hydatic cyst of the thyroid gland was diagnosed. Subtotal thyroidectomy was carried out and histopathologic examination confirmed the diagnosis. During aspiration biopsy, the patient did not present a clinical picture of anaphylactic reaction. To our knowledge, this is the first case of thyroid hydatic cyst diagnosed by FNAB reported in the literature.     

Diagnosis of medullary thyroid carcinoma by calcitonin measurement in fine-needle aspiration biopsy specimens.

Medullary thyroid carcinoma (MTC) is a thyroid malignancy originating from C cells. To date, serum calcitonin measurement and fine-needle aspiration biopsy (FNAB) have been prominent diagnostic approaches to these lesions. Although an elevated serum calcitonin level strongly suggests the presence of MTC, this examination cannot identify the origin of the calcitonin overexpression, especially in patients demonstrating multiple thyroid nodules. For the treatment planning, it is important to know which nodule is MTC, especially in nonhereditary MTC. In this study, we propose calcitonin measurement in the washout of FNAB needles after sampling each tumor (FNAB-CT) as a new approach to diagnosis of MTC. We performed FNAB-CT for five MTC cases. Although only one of these cases was definitively diagnosed as having MTC by FNAB cytology, FNAB-CT values ranged from 17,000 to 560,000 pg/mL, which were exceedingly higher than those of 11 controls (seven papillary carcinomas, two adenomatous nodules, one chronic thyroiditis, and one normal thyroid), which showed values ranging from <10 to 67 pg/mL. In patients with MTC, FNAB-CT values were 74 to 1888 times greater than serum calcitonin values. These findings suggest that FNAB-CT can be an additional approach to diagnosis of MTC.     

Efficacy of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of complex thyroid nodules.

Cystic thyroid nodules are considered to be one of the major causes of nondiagnostic and false-negative results on conventional fine-needle aspiration biopsy, thus limiting the potential of this method for the evaluation of complex (solid-cystic) thyroid nodules. Although ultrasound-guided fine-needle aspiration biopsy has emerged as a highly effective diagnostic method for the assessment of nonpalpable and difficult to palpate nodules, its role in complex nodules has not yet been carefully evaluated. In this study, we report the efficacy of ultrasound-guided fine-needle aspiration biopsy in 124 complex nodules in 113 patients. This method proved to be highly effective, yielding a satisfactory specimen for cytological evaluation in 94% of the nodules, suggesting that it is an excellent modality for the evaluation of complex nodules and also for the reevaluation of those nodules with a nondiagnostic result on conventional fine-needle aspiration biopsy.     

The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer.

A total of 1076 patients with thyroid nodules were reviewed. The accuracy of fine needle aspiration biopsy (FNAB) and frozen section (FS) were compared and clinical risk factors were analyzed. Our results indicate that 67.9% are benign and 32.1% are malignant with the predominance of papillary thyroid cancer (75.1%). Overall diagnostic accuracy for FNAB and FS were 90.8%-91.2% and 89.1%-90.5%, respectively. There were no significant differences between the diagnostic accuracy on FNAB and FS in all tumors except the follicular adenoma and carcinoma. The diagnostic accuracy of FS was higher than FNAB in patients with follicular adenoma (89.3% vs. 58.9%, p < 0.001) and but lower than FNAB in patients with follicular carcinoma (46.2% vs. 92.3%, p < 0.001). In conclusion, FNAB is cost effective in the preoperative evaluation of thyroid nodule. FS could be eliminated in most cases except with follicular and Hürthle cell neoplasms. FS is valuable when result of FNAB is suspicious or unavailable. FS is more appropriate in deciding the extent of thyroidectomy in follicular neoplasm and FNAB is more reliable initial approach to surgery in patients with Hürthle cell neoplasm. Clinical risk factors may help in selecting patients for surgery but cannot exceed FS in deciding the extent of thyroidectomy in patients with follicular and Hürthle cell neoplasms.     

Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma

Ten to fifteen percent of fine-needle aspiration biopsy (FNAB) of thyroid nodules are indeterminate. Galectin-3 (Gal-3) and the oncogene BRAFV600E are markers of malignancy useful to improve FNAB accuracy. The objective of this study was to determine whether the combined analysis of Gal-3 and BRAFV600E expression in thyroid aspirates could improve the diagnosis in FNAB with suspicious cytological findings. Two hundred and sixty-one surgical thyroid tissues and one hundred and forty-four thyroid aspirates were analyzed for the presence of the two markers. In surgical specimens, Gal-3 expression was present in 27.4% benign nodules, 91.9% papillary (PTC) and 75% follicular (FTC) thyroid carcinomas. BRAFV600E was not detected in 127 benign nodules, as well as in 32 FTCs, while was found in 42.9% PTC. No correlation was found between BRAF mutation and Gal-3 expression. Forty-seven consecutive FNAB suspicious for PTC were analyzed for the presence of the two markers. Of these nodules, 23 were benign at histology, 6 were positive for Gal-3, none displayed BRAFV600E, and 17 were negative for both the markers. Twenty suspicious nodules were diagnosed as PTC and four FTCs at histology. Of these 24 carcinomas, 9 resulted positive for BRAFV600E, 17 for Gal-3, and 22 for one or both the markers. The sensitivity, specificity, and accuracy for the presence of Gal-3 and/or BRAFV600E were significantly higher than those obtained for the two markers alone. Notably, the negative predictive value increased from 70.8 to 89.5%. In conclusion, the combined detection of Gal-3 and BRAFV600E improves the diagnosis in FNAB with cytological findings suspicious for PTC and finds clinical application in selected cases.     

Twenty-one-gauge needles provide more cellular samples than twenty-five-gauge needles in fine-needle aspiration biopsy of the thyroid but may not provide increased diagnostic accuracy.

The technique of fine-needle aspiration (FNA) biopsy of the thyroid is important to evaluate malignancy in thyroid nodules. Eighty-five percent of thyroid FNA procedures lead to sufficient cellular material for diagnosis. With more cells aspirated, the chance of sufficiency for diagnosis increases. Large-bore needles lead to more cellular material being aspirated but bloodier specimens that may interfere with cytologic interpretation. Small-bore needles may result in too few cells for diagnosis. We conducted a randomized prospective study contrasting 21-gauge and 25-gauge needles in the evaluation of 50 consecutively enrolled nodules at our institution. In our investigation, 21-gauge needles more frequently provided superior biopsy specimens (50%) than did 25-gauge needles (18%). In the remaining specimens (32%), the 21-gauge and 25-gauge needles provided similar cellular material. The rate of sufficient samples was the same. We conclude that use of 21-gauge needles results in more cellular specimens but may not result in increased diagnostic accuracy.     

Detection of recurrent papillary thyroid carcinoma by thyroglobulin assessment in the needle washout after fine-needle aspiration of suspicious lymph nodes.

To evaluate an efficient method of surveillance of low-risk patients with thyroid cancer, ultrasound was performed on 74 postoperative patients being followed for stage I and II papillary carcinoma. All patients were clinically free of cancer 1-43 years after a total thyroidectomy, and were screened with ultrasound and thyroglobulin (Tg) measurement while taking thyroid hormone suppression. Ultrasound revealed findings suspicious of recurrent disease in the lymph nodes of the neck in 21 patients. An ultrasound-guided fine-needle aspiration (FNA) to obtain material for cytology and Tg analysis was done on these 21 patients, 7 of whom tested positive for Tg in their needle washout. Only 3 of the 7 had detectable Tg in their serum, and only 5 of the 7 had positive cytology. Ultrasound (with FNA-Tg analysis of needle washout of suspicious lymph nodes) is proposed as an effective and efficient method of surveillance in these low-risk patients. Presence of Tg in the needle washout proved to be more sensitive than cytology in diagnosing cancer in the lymph nodes and was not affected by positive anti-Tg antibodies in the serum.     

The impact of assessing specimen adequacy and number of needle passes for fine-needle aspiration biopsy of thyroid nodules.

Fine-needle aspiration biopsy (FNAB) of thyroid nodules is a safe, cost-effective procedure but the rates of inadequate cytology specimens range from approximately 1% to 15%. This study tests the hypothesis that ultrasonographically (US) guided FNAB and onsite assessment of cytology improves the adequacy rate of FNAB. A retrospective analysis was performed on 693 thyroid FNAB specimens obtained with and without ultrasound guidance and with or without onsite cytology assessment. Overall, 29 specimens (4%) were inadequate for diagnosis. Among 163 cystic nodules and 530 solid nodules, inadequacy rates were 15% (n = 24) and 1% (n = 5) respectively (p = 0.0001). An onsite assessment of cytology for adequacy was done in 550 cases (83%), which was more accurately performed by a cytopathologist (97%) than a cytotechnologist (93%, p = 0.015). With US-guided FNAB, 3% of the cytology specimens were inadequate, compared to a 7% rate when US was not done (p = 0.003). The mean number of needle punctures necessary for an adequate specimen was 3.8 +/- 0.06 (median, 3.0; range, 1-11), which was different among various types of doctors, ranging from 3.2 +/- 0.07 to 5.4 +/- 0.12 (p = 0.001 analysis of variance [ANOVA]). The fewest number of needle passes to achieve an adequate specimen were required by university endocrinologists and pathologists working together (average, 3.2 +/- 0.07; median, 3.0; range, 1-11). Sample inadequacy rate varied significantly among physician groups, ranging from 3% to 18% (p = 0.0001 ANOVA). Stepwise regression analysis showed that onsite assessment of cytology, US-guided FNAB (p = 0.16), and cystic nature of the nodule (p < 0.0001 for all) correlated with adequacy of the specimen. We conclude that US-guided FNAB with onsite evaluation of cytology specimens substantially increases the adequacy of cytology specimens and decreases the number of required needle passes, which ultimately reduces patient discomfort and diagnostic errors, thus raising the question as to whether this should eventually become the standard of care. We believe this is a goal that training programs should strive to achieve.     

Diagnostic value of pyrosequencing for the BRAFV600E mutation in ultrasound-guided fine-needle aspiration biopsy samples of thyroid incidentalomas

Context Dideoxy sequencing is the most commonly used method for detecting the BRAF^V600E mutation in thyroid cancer and melanoma. However, this gold standard method often makes less definite results in detecting the BRAF ^V600E mutation when there are relatively low amounts of the mutant template in biopsy specimens, which are invariably contaminated with normal tissues. Pyrosequencing, which measures the incorporation of each of the four nucleotides at each template position and indicates the amounts of mutant template present, may be more useful in such situations. Objective To investigate the diagnostic efficiency of pyrosequencing for the mutant BRAF allele in ultrasound (US)‐guided fine needle aspiration biopsies (FNABs) of thyroid incidentalomas. Design, setting and subjects A total of 101 thyroid incidentaloma cases were included prospectively. Cytological diagnoses of the FNAB samples were made according to the American Thyroid Association (ATA) guidelines, 2006. The presence of the BRAF ^V600E mutation was investigated by pyrosequencing and dideoxy sequencing. Results On the basis of cytological analysis, the thyroid incidentalomas were classified into benign (n = 43), malignant (n = 30), indeterminate or suspicious neoplasm (n = 24), and nondiagnostic (n = 4) categories. Pyrosequencing detected the BRAF ^V600E mutation in 30 cases: 22 malignant cases, 7 indeterminate cases, and 1 nondiagnostic case. Dideoxy sequencing also detected the BRAF ^V600E mutation in 28 of the same cases but failed to clearly distinguish the mutant allele from the wild‐type allele in one indeterminate case and one nondiagnostic case. Histopathological analysis ascertained that all BRAF ^V600E ‐positive cases were papillary thyroid carcinomas. Conclusions Pyrosequencing may be suitable for detecting the BRAF ^V600E mutation in thyroid incidentaloma and may be superior to dideoxy sequencing when low amounts of the mutant template are present in the biopsy.     

Systematic inclusion of clinical and laboratory data improves diagnostic accuracy of fine-needle aspiration biopsy in solitary thyroid nodules.

In this study, we identified clinical and laboratory markers of malignant thyroid nodules and determined whether systematic inclusion of these data could improve diagnostic accuracy of fine-needle aspiration biopsy in solitary thyroid nodules. The patients were 24 men and 105 women who underwent surgical removal of solitary thyroid nodules and had adequate fine-needle aspiration biopsy performed prior to surgery. Including fine-needle aspiration biopsy's diagnosis of suspected of malignancy in the same category as malignancy, the sensitivity and specificity of fine-needle aspiration biopsy were 71.4% and 85.1%, respectively, with an accuracy of 82.2%. Using stepwise linear regression analysis, clinical data, i.e. increasing age, irregular nodule surface, hard consistency of nodule, and high serum thyroglobulin concentration, were associated with an increased risk of malignancy when the cytological result was excluded. When cytology was also considered, male sex, irregular nodule surface and high serum thyroglobulin concentration were found to be associated with an increased risk of malignancy. The diagnostic value of clinical data alone, even in combination with cytology or laboratory data, was inferior to that of fine-needle aspiration biopsy alone. The specificity and accuracy of fine-needle aspiration biopsy could be increased to 98.0% and 90.7%, respectively, whereas its sensitivity was decreased to 64.3% when these variables were considered in combination. Therefore, of fine-needle aspiration biopsy, clinical and laboratory data, fine-needle aspiration biopsy alone has the highest diagnostic value, which can be increased only when both clinical characteristics and serum thyroglobulin concentration are systematically included.     

High frequency of incidental diagnosis of extrathyroidal neoplastic diseases at the fine-needle aspiration biopsy of laterocervical lymph nodes in patients with thyroid nodules.

This study was undertaken to evaluate the frequency of the incidental diagnosis of extrathyroidal lymph node diseases at ultrasound-guided fine-needle aspiration biopsy/cytology (FNAB/C) being done to check the presence of metastatic thyroid cancer in 30 subjects with thyroid nodule (TN) and enlarged cervical lymph nodes (CLN). The patients in whom cytology suggested the presence of malignancy in the TN or in the CLN underwent surgical removal for histologic diagnosis. The spectrum of diseases revealed by this survey included: (1) 10 benign diseases including 1 case of Piringer-Kuchinka lymphadenitis with benign TN; (2) 10 metastatic thyroid cancers (2 anaplastic and 8 papillary cancers); (3) 3 benign TN associated with metastatic invasion of cervical lymph nodes from lung (2 cases) and breast (1 case) cancer; (4) 1 Hodgkin's lymphoma of the cervical lymph nodes with hyperplastic TN; (5) 3 nodal lymphomas with benign thyroid nodule and 2 cases of thyroid lymphoma with nodal invasion; and (6) 1 nodal sarcoidosis with benign TN. The results of this study demonstrate that important neoplastic and hematologic diseases affecting the cervical lymph nodes may frequently be incidentally detected using ultrasonography (US) and FNAB/C in the diagnostic procedure for thyroid nodule.     

Needle-free delivery of lidocaine for reducing the pain associated with the fine-needle aspiration biopsy of thyroid nodules: time-saving and efficacious procedure.

OBJECTIVE: Fine-needle aspiration biopsy (FNAB) is a mandatory procedure in evaluation of thyroid nodules. However, it is sometimes perceived as a painful procedure by the patients. Efficacy of the needle-free injection of local anesthesia for reducing the pain associated with other cutaneous procedures that involve needle insertion was previously reported. In this double-blind, placebo-controlled clinical trial, we evaluated the effectiveness of a needle-free injection of lidocaine in achieving satisfactory pain control in patients undergoing FNAB of thyroid nodules. DESIGN: Patients were allocated to receive either lidocaine administered by needle-free injection system (n = 55) or placebo (isotonic saline) (n = 52) 2-3 minutes before FNAB. A series of four aspirations of each nodule was performed. The patients rated pain associated with the procedure according to a 100-mm visual analog scale (VAS), an 11-point numeric rating scale (NRS), and a four-category verbal rating scale (VRS). MAIN OUTCOME MEASURE: The two groups studied were similar with respect to age, sex, thyroid volume, nodule size, and nodule site. When the effectiveness of lidocaine was compared with that of placebo, the mean VAS score was 11.4 +/- 13.6 mm versus 38.2 +/- 35.5 mm (p < 0.0001) and the mean NRS score was 1.4 +/- 1.5 points versus 3.9 +/- 2.6 points (p < 0.0001), respectively. The absolute numbers according to VRS score in each group was also significantly different (p < 0.0001). The percentage of patients with "no pain" or "mild pain" in the lidocaine group (90.9%) was significantly higher than that in the placebo group (44.2%) (p < 0.0001). Less than 10% of the patients in lidocaine group experienced moderate pain and none experienced severe pain. No adverse treatment-related effects were observed. CONCLUSIONS: To our knowledge, this is the first study demonstrating that the needle-free delivery of lidocaine is an effective, useful, and noninvasive method of providing local anesthesia for the FNAB of thyroid nodules.     

Plasma TARC concentration may be a useful marker for asthmatic exacerbation in children.

Recent studies suggested the T-helper cells type-2 lymphocytes-specific thymus and activation-regulated chemokine (TARC) and monocyte-derived chemokine (MDC) are useful inflammatory markers for chronic asthma. However, their roles in assessing the severity of acute asthma are unknown. This study aims to evaluate the serial changes of plasma TARC and MDC concentrations in children with asthmatic exacerbation. All patients with acute asthma were treated with systemic corticosteroid for 5 days. The severity of asthmatic exacerbation was classified according to the Global Initiative for Asthma guidelines. Plasma TARC and MDC concentrations were measured by sandwich enzyme immunoassays. Sixteen children, with a median (interquartile range) age of 9.3 (7.2-10.6) yrs and asthmatic exacerbation, were recruited. Plasma TARC concentration showed inverse correlation with peak expiratory flow rate at presentation. The median plasma TARC concentration was highest during the acute attacks (46 pg x mL(-1)) as compared to those levels at 1 (31 pg x mL(-1)) and 5 weeks (32 pg x mL(-1)) following treatment. The median plasma MDC level similarly decreased from 698 pg x mL(-1) at baseline to 261 pg x mL(-1) 1 week later, but increased back to 574 pg x mL(-1) at 5 weeks. These results suggest that plasma T-helper cells type-2 lymphocytes-specific thymus and activation-regulated chemokine but not monocyte-derived chemokine concentration may be a useful inflammatory marker in assessing asthmatic exacerbation in children.     

Humoral and cellular immune monitoring might be useful to identify liver transplant recipients at risk for development of infection

Abstract: Orthotopic liver transplantation (OLT) is a successful therapy for patients with end‐stage liver disease, and infection remains a significant cause of morbidity and mortality for patients undergoing this procedure. To assess humoral and cellular immunity markers as potential risk factors for development of infection, 46 consecutive liver transplant recipients (hepatitis C virus cirrhosis [n=17], alcoholic liver disease [n=15], hepatocellular carcinoma [n=9], autoimmune hepatitis [n=2], and other [n=3]) performed at a single center were prospectively studied. Maintenance therapy included tacrolimus (n=37) or cyclosporine (n=9) and prednisone. During follow‐up, 27 patients had at least 1 episode of infection (58.7%). Pre‐OLT immunoglobulin G (IgG) hypergammaglobulinemia (relative risk [RR] 2.78; 95% confidence interval [CI], 1.17–6.60, P=0.02), pre‐OLT IgA hypergammaglobulinemia (RR 2.77, CI=1.24–6.19, P=0.012), and pre‐OLT C3 hypocomplementemia (RR 3.02, CI=1.21–7.55, P=0.018) were associated with an increased risk for development of infection. Monitoring of Ig and complement levels might help to identify the risk of developing infection in OLT.     

The role of fine-needle aspiration biopsy in the management of thyroid nodules in children, adolescents, and young adults: a multi-institutional study.

Thyroid nodules in children are extremely uncommon and in most cases present as asymptomatic neck masses. The significance of a thyroid nodule in a child involves the underlying risk of malignancy. The purpose of this study was to assess the validity of results of fine-needle aspiration biopsy (FNAB) of thyroid nodules in the pediatric population and its usefulness in pediatric patient management. FNAB was performed on a total of 57 thyroid nodules from 57 patients between 1992 and 1997. The patients included 46 females and 11 males ranging in age from 9 to 20 years (average 16.5 years). Surgical and/or clinical follow up was available in all patients. FNAB diagnoses included papillary thyroid carcinoma (PTC) (12.3% [7/57]), follicular neoplasm (FN) (15.8% [9/57]), atypical cytology (8.8% [5/57]) and nonneoplastic thyroid (63.2% [36/57]). Surgical follow-up available in all patients with cytological diagnoses of PTC, FN, and atypical cytology revealed malignancy in 13 cases. Of the 36 patients with nonneoplastic cytological diagnosis, surgical excision was performed in 3 patients and the rest were followed up clinically. Surgical excision in these 3 patients revealed follicular carcinoma (FC) (1 case) and multinodular goiter (2 cases). Overall, 14 patients (24.6%) had malignant thyroid lesions, including 11 PTC and 3 FC. In conclusion, the majority of pediatric thyroid nodules are benign. The prevalence of malignancy in pediatric patients with thyroid nodules in our series was 24.6%. High diagnostic accuracy of thyroid FNAB improves selection of pediatric patients requiring surgery.