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BACKGROUND—Fine needle aspiration biopsy (FNA) is a routine diagnostic technique for evaluating thyroid nodules. Many reports in adults consider that FNA is superior to thyroid ultrasonography (USG) and radionuclide scanning (RS). Only five studies have been published on FNA of childhood thyroid nodules.
AIMS—To investigate the reliability of FNA in the evaluation and management of thyroid nodules, and compare the results of FNA, USG, and RS with regard to final histopathological diagnosis.
METHODS—FNA was performed in 46 children with thyroid nodules after USG and RS examination. We investigated the sensitivity, specificity, accuracy, and positive and negative predictive values of USG, RS, and FNA in their management.
RESULTS—Six patients who had malignant or suspicious cells on FNA examination underwent immediate surgery. The other 40 patients received medical treatment according to their hormonal status. Fifteen of these nodules either disappeared or decreased in number and/or size. Surgery was performed in 25 patients who did not respond to therapy. Statistical analysis revealed sensitivity, specificity, accuracy, and positive and negative predictive values respectively as follows: 60%, 59%, 59%, 15%, and 92% for USG; 30%, 42%, 39%, 12%, and 68% for SC; 100%, 95%, 95%, 67%, and 100% for FNAB.
CONCLUSION—FNAB is as reliable in children as in adults for definitive diagnosis of thyroid nodules. Using this technique avoids unnecessary thyroid surgery in children.



Over the past 3 decades, fine needle aspiration (FNA) has developed as the most accurate and cost-effective initial method for guiding the clinical management of patients with thyroid nodules. Thyroid FNA specimens containing follicular-patterned lesions are the most commonly encountered and include various forms of benign thyroid nodules, follicular carcinomas, and the follicular variant of papillary thyroid carcinoma. Based primarily upon the cytoarchitectural pattern, FNA is used as a screening test for follicular-patterned lesions to identify the majority of patients with benign nodules who can be managed without surgical intervention. The terminology and reporting of thyroid FNA results have been problematic due to significant variation between laboratories, but the recent multidisciplinary NCI Thyroid FNA State of the Science Conference has provided a seven-tiered diagnostic solution. A key element of this approach is the category “atypical cells of undetermined significance” (ACUS) which is used for those aspirates which cannot be easily classified as benign, suspicious, or malignant. Lesions in this category represent approximately 3–6% of thyroid FNAs and have a risk of malignancy intermediate between the “benign” category and the “suspicious for a follicular neoplasm” category. The recommended follow-up for an ACUS diagnosis is clinical correlation and in most cases, repeat FNA sampling.

Background

The aim of this study was to compare the results of palpation-versus ultrasound-guided thyroid fine-needle aspiration (FNA) biopsies.

Findings

Clinical data, cytology and histopathology results were retrospectively analyzed on all patients who underwent thyroid FNA biopsy in our outpatient endocrinology clinic between January 1998 and April 2003. The same investigators performed all thyroid FNAs (ASC) and cytological evaluations (KP). Subjects in the ultrasound-guided group were older, otherwise there were no differences in baseline characteristics (gender, thyroid function, the frequency of multinodular goiter, nodule diameter and nodule location) between groups. Cytology results in nodules aspirated by palpation (n = 202) versus ultrasound guidance (n = 184) were as follows: malignant 2.0% versus 2.7% (p = 0.74), benign 69.8% versus 79.9% (p = 0.02), indeterminate 1.0% versus 4.9% (p = 0.02), inadequate 27.2% versus 12.5% (p < 0.01). Malignant results were compared with Fisher's exact test. Other cytology categories were compared with chi-square test. Eighteen patients from the palpation- and 23 from ultrasound-guided group underwent surgery. In the palpation-guided group, the sensitivity of FNA was 100%, specificity 94%, positive predictive value 67% and negative predictive value 100%. In the ultrasound-guided group, the sensitivity of FNA was 100%, specificity 80%, positive predictive value 73% and negative predictive value 100%.

Conclusion

We demonstrate that ultrasound guidance for thyroid FNA significantly decreases inadequate for evaluation category. We also confirm the high sensitivity and specificity of thyroid FNA biopsy in the diagnosis of thyroid cancer. Where available, we recommend universal application of ultrasound guidance for thyroid FNA biopsy as a standard component of this diagnostic technique.

Purpose

To compare the cytological results of ultrasound-guided fine-needle aspiration (US-FNA) cytology of thyroid nodules to sonographic findings and determine whether US findings are helpful in the interpretation of cytological results.

Materials and Methods

Among the thyroid nodules that underwent US-FNA cytology, we included the 819 nodules which had a conclusive diagnosis. Final diagnosis was based on pathology from surgery, repeated FNA cytology or follow-up of more than one year. Cytological results were divided into five groups: benign, indeterminate (follicular or Hurthle cell neoplasm), suspicious for malignancy, malignant, and inadequate. US findings were categorized as benign or suspicious. Cytological results and US categories were analyzed.

Results

Final diagnosis was concluded upon in 819 nodules based on pathology (n=311), repeated FNA cytology (n=204) and follow-up (n=304), of which 634 were benign and 185 were malignant. There were 560 benign nodules, 141 malignant nodules, 49 nodules with inadequate results, 21 with indeterminate results, and 48 that were suspicious for malignancy. The positive and negative predictive values of the US categories were 59.1% and 97.0%, and those of the cytological results were 93.7% and 98.9%. The US categories were significantly correlated with final diagnosis in the benign (p=0.014) and suspicious for malignancy (p<0.001) cytological result groups, but not in the inadequate and indeterminate cytological results groups. The false positive and negative rates of cytological results were 1.9% and 3.2%.

Conclusion

Sonographic findings can be useful when used alongside cytological results, especially in nodules with cytological results that are benign or suspicious for malignancy.

Background

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chornobyl accident (arithmetic mean thyroid dose=0.79 Gray). Subjects are screened by palpation and ultrasound and referred to surgery according to fine needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy following this level of internal exposure to radioiodines is unknown.

Methods

As a result of the first screening cycle (1998-2000), 13,243 individuals were examined, 356 with thyroid nodules were referred for FNA, 288 completed the procedure, 85 were referred to surgery, 82 were operated upon, and pre-operative cytology was available for review in 78. Cytological interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were retrospectively reviewed; and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated.

Results

All 24 cytological interpretations definite for papillary thyroid cancer (PTC) were histopathologically confirmed (PPV=100%) and of 11 suspect for PTC, 10 were confirmed (PPV=90.9%). Ten of 41 FNAs interpreted as either definite or suspect for follicular neoplasm (FN) were confirmed as malignant (PPV=24.4%): 2 follicular thyroid cancers (FTC) and 8 PTCs (all but one of the follicular or mixed subtypes). Depending on whether a cytological interpretation of FN was considered a “positive” or “negative”, sensitivity was 100% or 77.3%, respectively; similarly, specificity was 17.6% or 97.1 %, PPV 61.1% or 97.1% and NPV 100% or 76.7%.

Conclusions

Among children and adolescents exposed to 131I following Chornobyl and evaluated 12 to 14 years later, thyroid cytology has a sensitivity and predictive value similar to that reported in unexposed populations.

Background

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chornobyl accident (arithmetic mean thyroid dose=0.79Gray). Subjects are screened by palpation and ultrasound and referred to surgery according to fine needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy following this level of internal exposure to radioiodines is unknown.

Methods

As a result of the first screening cycle (1998-2000), 13,243 individuals were examined, 356 with thyroid nodules were referred for FNA, 288 completed the procedure, 85 were referred to surgery, 82 were operated upon, and pre-operative cytology was available for review in 78. Cytological interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were retrospectively reviewed; and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated.

Results

All 24 cytological interpretations definite for papillary thyroid cancer (PTC) were histopathologically confirmed (PPV=100%) and of 11 suspect for PTC, 10 were confirmed (PPV=90.9%). Ten of 41 FNAs interpreted as either definite or suspect for follicular neoplasm (FN) were confirmed as malignant (PPV=24.4%): 2 follicular thyroid cancers (FTC) and 8 PTCs (all but one of the follicular or mixed subtypes). Depending on whether a cytological interpretation of FN was considered a “positive” or “negative”, sensitivity was 100% or 77.3%, respectively; similarly, specificity was 17.6% or 97.1 %, PPV 61.1% or 97.1% and NPV 100% or 76.7%.

Conclusions

Among children and adolescents exposed to 131I following Chornobyl and evaluated 12 to 14 years later, thyroid cytology has a sensitivity and predictive value similar to that reported in unexposed populations

Background: A study was undertaken to evaluate the clinical impact of endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) in patients with mediastinal masses suspected of malignancy.

Methods: From April 1993 to December 1999, 84 patients were referred for EUS-FNA. In all patients CT scanning had shown a lesion of the mediastinum suspected of malignancy located adjacent to the oesophagus. In order to evaluate the clinical impact of EUS-FNA, the history of each patient up to referral for EUS-FNA was reviewed. A board of thoracic specialists was asked to decide the further course of the patient if EUS-FNA had not been available, and this diagnostic strategy was compared with the actual clinical course after EUS-FNA.

Results: For the 79 patients in whom sufficient verification was obtained, EUS-FNA had a sensitivity of 92%, specificity of 100%, PPV of 100%, NPV of 80%, and an accuracy of 94% for cancer of the mediastinum. In 18 of 37 patients (49%) a thoracotomy/thoracoscopy was avoided as a result of EUS-FNA, and in 28 of 41 patients (68%) a mediastinoscopy was avoided. The direct result of the cytological diagnosis obtained by EUS-FNA was that a final diagnosis of small cell lung cancer was made in eight patients resulting in referral for chemotherapy, and in another three patients with benign disease specific treatment could be initiated (sarcoidosis, mediastinal abscess, and leiomyoma of the oesophagus).

Conclusions: EUS-FNA is a safe and sensitive minimally invasive method for evaluating patients with a solid lesion of the mediastinum suspected by CT scanning. EUS-FNA has a significant impact on patient management and should be considered for diagnosing the spread of cancer to the mediastinum in patients with lung cancer considered for surgery, as well as for the primary diagnosis of solid lesions located in the mediastinum adjacent to the oesophagus.

Background

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mediastinal lymphadenopathy has been shown to be a valuable diagnostic tool in high-volume EUS centers (≥50 mediastinal EUS-FNA/endoscopist/year). Our goal was to assess the diagnostic accuracy of EUS-FNA and its impact on clinical management and costs in low-volume EUS centers (<50 mediastinal EUS-FNA/endoscopist/year).

Methods

Consecutive patients referred to two Dutch endoscopy centers in the period 2002–2008 for EUS-FNA of mediastinal lymphadenopathy were reviewed. The gold standard for a cytological diagnosis was histological confirmation or clinical follow-up of more than 6 months with repeat imaging. The impact of EUS-FNA on clinical management was subdivided into a positive impact by providing (1) adequate cytology that influenced the decision to perform surgery or (2) a diagnosis of a benign inflammatory disorder, and a negative impact which was subdivided into (1) false-negative or inconclusive cytology or (2) an adequate cytological diagnosis that did not influence patient management. Costs of an alternative diagnostic work-up without EUS-FNA, as established by an expert panel, were compared to costs of the actual work-up.

Results

In total, 213 patients (71% male, median age = 61 years, range = 23–88 years) underwent EUS-FNA. Sensitivity, specificity, and negative and positive predictive values were 89%, 100%, 80%, and 100%, respectively. EUS-FNA had a positive impact on clinical management in 84% of cases by either influencing the decision to perform surgery (49%) or excluding malignant lymphadenopathy (35%), and a negative impact in 7% of cases because of inadequate (3%) or false-negative (4%) cytology. In 9% of cases, EUS-FNA was performed without an established indication. Two nonfatal perforations occurred (0.9%). Total cost reduction was €100,593, with a mean cost reduction of €472 (SD = €607) per patient.

Conclusions

Mediastinal EUS-FNA can be performed in low-volume EUS centers without compromising diagnostic accuracy. Moreover, EUS-FNA plays an important role in the management of patients with mediastinal lymphadenopathy and reduces total diagnostic costs.

AIMS: To evaluate the correlation of fine needle aspiration (FNA) cytology and frozen section biopsy in the diagnosis of thyroid nodules. METHODS: The medical records of 662 patients who underwent FNA cytology of the thyroid and thyroid surgery were analysed. Frozen section biopsies were taken from 586 of the 662 patients. The diagnostic correlations of FNA cytology, frozen section, and both FNA cytology and frozen section with definitive histological assessment were evaluated. RESULTS: Among the 662 patients who received FNA cytology, there were 356 cases (53.8%) diagnosed as benign, 114 cases (17.2%) as malignant, 148 cases (22.4%) as indeterminate, and 44 cases (6.6%) as unsatisfactory. The positive predictive value for the detection of malignancy by FNA cytology was 92.1% and the negative predictive value was 95.2%. The incidence of malignancy in the indeterminate cytological diagnosis was 23%. The diagnosis from frozen sections was benign in 445 cases (75.9%), malignant in 134 cases (22.9%), and deferred in 7 cases (1.2%). By frozen section, the positive and negative predictive values were 97% and 95.5%, respectively. Diagnostic accuracy up to 98% was achieved when FNA cytology and frozen section diagnoses were in agreement. No false positives were observed when FNA cytology and frozen sections were both positive for malignancy. When FNA cytology and frozen section diagnoses were discordant, frozen section showed a higher accuracy (78.9%) than FNA cytology (21.1%). In the face of an indeterminate or unsatisfactory cytological diagnosis, the diagnostic accuracy of frozen sections reached 92.6%. CONCLUSIONS: The results confirm that FNA cytology is a useful tool in the initial evaluation of thyroid nodules. Intraoperative frozen section is a valuable procedure to confirm the cytological diagnosis and identify malignancy in patients with indeterminate or unsatisfactory cytological diagnosis. With reliance on frozen sections as an intraoperative guide of thyroid surgery, the possibility of unnecessary extensive surgery and the need for the second operation are considerably lower.

Ruling out malignancy in thyroid nodules historically depended on thyroid resection and histopathological evaluation until fine needle aspiration (FNA) biopsy was introduced into the United States in the 1970's. Thyroid FNA biopsy identified a majority of thyroid nodules as benign, obviating the need for surgery in over half of the patients. However, 15%-30% of thyroid FNAs have indeterminate cytology that still requires operation, even though most of these operated nodules prove to be benign post-operatively. In order to predict which cytologically indeterminate thyroid nodules are benign and to potentially avoid surgery on these nodules, a recently described commercially available Gene Expression Classifier (GEC) test (Afirma®, Veracyte, Inc., South San Francisco, CA) has been developed that can be run on the FNA sample. This paper reviews the published literature and technology assessments/guidelines by independent parties and professional groups regarding the clinical utility as well as the analytic and clinical validity of the Afirma GEC.

Background

Thyroid fine-needle aspiration (FNA) biopsy is indeterminate or suspicious in up to 30% of cases and these patients are commonly subjected to at least a diagnostic hemithyroidectomy. If malignant on histology, a completion thyroidectomy is usually performed, which may be associated with higher morbidity. To determine the clinical utility of genetic testing in thyroid FNA biopsy, we conducted a prospective clinical trial.

Methods

Four hundred seventeen patients with 455 thyroid nodules were enrolled and had genetic testing for common somatic mutations (BRAF, NRAS, KRAS) and gene rearrangements (RET/PTC1, RET/PTC3, RAS, TRK1) by PCR and direct sequencing and by nested PCR, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of genetic testing in thyroid FNA biopsy were determined based on the histologic diagnosis.

Results

One hundred twenty-five of 455 thyroid nodule FNA biopsies were indeterminate or suspicious on cytologic examination. Overall, 50 mutations were identified (23 BRAF, 4 RET/PTC1, 2 RET/PTC3, 21 NRAS) in the thyroid FNA biopsies. There were significantly more mutations detected in malignant thyroid nodules than in benign (P = 0.0001). For thyroid FNA biopsies that were indeterminate or suspicious, genetic testing had a sensitivity of 12%, specificity of 98%, PPV of 38%, and NPV of 65%.

Conclusions

Genetic testing for somatic mutations in thyroid FNA biopsy samples is feasible and identifies a subset of malignant thyroid neoplasms that are indeterminate or suspicious on FNA biopsy. Genetic testing for common somatic genetic alterations thus could allow for more definitive initial thyroidectomy in those with positive results.

Introduction of endoscopic ultrasound (EUS) to medical practice has brought a huge change in diagnostic algorithm of many gastrointestinal diseases. Addition of EUS-guided fine needle aspiration (FNA) upgraded diagnostic power of EUS. In this focused review series, value of EUS-FNA in the diagnosis of various diseases and tips for getting the best results with EUS-FNA are described by four invited authors including myself. First, Dr. Jeong Seop Moon discussed about EUS-FNA in submucosal lesion. He also touched on basic techniques and needles of EUS-FNA in his article. Next, I focused on additional value of EUS-FNA in the staging of hollow viscus cancer to optimize the treatment strategy. World's well-known endosonographer, Dr. Robert H. Hawes kindly presented his profound thoughts on EUS-FNA in pancreatic cystic lesions. Dr. Jayapal Ramesh and Dr. Shyam Varadarajulu shared their valuable tips for getting the best results when using EUS-FNA. Nobody doubts now EUS-FNA is an indispensable procedure in gastrointestinal endoscopy. Therefore, this focused review series will provide the readers with the concentrated knowledge of "What should we know about EUS-FNA."

THIS ARTICLE DESCRIBES CONTEMPORARY UNDERSTANDING of fine-needle aspiration (FNA) biopsy of the thyroid gland, with particular reference to its triage role in the investigation of thyroid nodules. A team approach involving the pathologist and the clinician is crucial for its success. A nonsuction technique with a 25- or 27-gauge needle is recommended. Performance of FNA biopsy by physicians with faulty technique and interpretation of FNA specimens by pathologists without proper training are detrimental to patient outcome. These problems may lead to a high failure rate, which in turn might discourage use of FNA biopsy and could lead to use of other diagnostic methods that are more expensive or are associated with greater morbidity (or both). The size of the nodule may be important in determining the need for surgery in some patients. Decisions regarding surgery that are based on the size of the nodule and the specific cytologic features are discussed. A standardized terminology for reporting is proposed.

We review the utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), a rapid, safe, cost-effective, and accurate diagnostic modality for evaluating pancreatic tumors. EUS-FNA is currently used for the diagnosis and staging of pancreatic tumors. The sensitivity of EUS-FNA for pancreatic malignancy ranges from 75% to 94%, and its specificity approaches 100% in most studies. However, EUS-FNA has some limitations in the diagnosis of well-differentiated or early-stage cancers. Recent evidence suggests that molecular biological analysis using specimens obtained by EUS-FNA improves diagnostic sensitivity and specificity, especially in borderline cytological cases. It was also reported that additional information regarding patient response to chemotherapy, surgical resectability, time to metastasis, and overall survival was acquired from the genetic analysis of specimens obtained by EUS-FNA. Other studies have revealed that the analysis of KRAS, MUC, p53, p16, S100P, SMAD4, and microRNAs is helpful in making the diagnosis of pancreatic carcinoma. In this paper, we describe the present state of genetic diagnostic techniques for use with EUS-FNA samples in pancreatic diseases. We also discuss the role of molecular biological analyses for the diagnosis of pancreatic carcinoma.

Background

A large amount of information has been collected on the molecular tumorigenesis of thyroid cancer. A low expression of c-KIT gene has been reported during the transformation of normal thyroid epithelium to papillary carcinoma suggesting a possible role of the gene in the differentiation of thyroid tissue rather than in the proliferation. The initial presentation of thyroid carcinoma is through a nodule and the best way nowadays to evaluate it is by fine-needle aspiration (FNA). However many thyroid FNAs are not definitively benign or malignant, yielding an indeterminate or suspicious diagnosis which ranges from 10 to 25% of FNAs. BRAF mutational analysis is commonly used to assess the malignancy of thyroid nodules but unfortunately it still leaves indeterminate diagnoses. The development of molecular initial diagnostic tests for evaluating a thyroid nodule is needed in order to define optimal surgical approach for patients with uncertain diagnosis pre- and intra-operatively.

Methods

In this study we extracted RNA from 82 FNA smears, 46 malignant and 36 benign at the histology, in order to evaluate by quantitative Real Time PCR the expression levels of c-KIT gene.

Results

We have found a highly preferential decrease rather than increase in transcript of c-KIT in malignant thyroid lesions compared to the benign ones. To explore the diagnostic utility of c-KIT expression in thyroid nodules, its expression values were divided in four arbitrarily defined classes, with class I characterized by the complete silencing of the gene. Class I and IV represented the two most informative groups, with 100% of the samples found malignant or benign respectively. The molecular analysis was proven by ROC (receiver operating characteristic) analysis to be highly specific and sensitive improving the cytological diagnostic accuracy of 15%.

Conclusion

We propose the use of BRAF test (after uncertain cytological diagnosis) to assess the malignancy of thyroid nodules at first, then the use of the c-KIT expression to ultimately assess the diagnosis of the nodules that otherwise would remain suspicious. The c-KIT expression-based classification is highly accurate and may provide a tool to overcome the difficulties in today's preoperative diagnosis of thyroid suspicious malignancies.

Thyroid nodules in children are uncommon but often present an increased risk of malignancy in comparison to their adult counterpart. Multiple diagnostic modalities are frequently employed to characterize these nodules including ultrasound, radionuclide scans, fine needle aspiration (FNA), thyroid function tests, and evaluation of patient demographics. We chose to evaluate if any of these modalities influence treatment or signify a tendency for a nodule to represent a malignant lesion. A retrospective review of patients <21 years of age who underwent partial or total thyroidectomy from 2004 to 2009 was performed (IRB no. 4695). Other than an FNA indicating a malignancy, there does not appear to be any value to extensive preoperative imaging, nor can patient risk be stratified based upon age. We conclude that there is minimal utility in an extensive preoperative workup in a child with a thyroid nodule.

Background:

In the recent years, the advances in digital methods in pathology have resulted in the use of telecytology in the immediate assessment of fine needle aspiration (FNA) specimens. However, there is a need for organ-based and body site-specific studies on the use of telecytology for the immediate assessment of FNA to evaluate its pitfalls and limitations. We present our experience with the use of telecytology for on-site evaluation of ultrasound-guided FNA (USG-FNA) of axillary lymph nodes in a remote breast care center.

Materials and Methods:

Real-time images of Diff-Quik-stained cytology smears were obtained with an Olympus digital camera attached to an Olympus CX41 microscope and transmitted via ethernet by a cytotechnologist to a pathologist who rendered preliminary diagnosis while communicating with the on-site cytotechnologist over the Vocera system. The accuracy of the preliminary diagnosis was compared with the final diagnosis, retrospectively.

Results:

A total of 39 female patients (mean age: 50.5 years) seen at the breast care center underwent USG-FNA of 44 axillary nodes. Preliminary diagnoses of benign, suspicious/malignant, and unsatisfactory were 41, 52, and 7%, respectively. Only one of the 23 cases that were initially interpreted as benign was reclassified as suspicious on final cytologic diagnosis. Seventeen of 18 suspicious/malignant cases on initial cytology corresponded with a malignant diagnosis on final cytology. One suspicious case was reclassified as benign on final cytologic diagnosis. All unsatisfactory cases remained inadequate for final cytologic interpretation. The presence of additional material in the cell block and interpretative error were the main reasons for discrepancy, accounting for the two discrepant cases.

Conclusions:

This retrospective study demonstrates that the on-site telecytology evaluation of USG-FNA of axillary lymph nodes in patients at a remote breast care center was highly accurate compared with the final cytologic evaluation. It allows pathologists to use their time more efficiently and makes on-site evaluation at a remote site possible.

Background

At present only few studies directly compare the diagnostic yield of endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) and transcervical video-assisted mediastinoscopy (TM) for mediastinal lymph node staging in patients with NSCLC. If and when EBUS-FNA may replace TM as Gold Standard remains controversial.

Methods

From April 2008 to December 2009, 36 patients with mediastinal lymphadenopathy underwent simultaneous EBUS-FNA/ TM at our institution. Among them were 26 patients with confirmed or suspected NSCLC.

Results

A total of 133 samples were obtained by EBUS-FNA and 157 samples by TM. EBUS-FNA achieved significantly less conclusive, but more indeterminate pathological results in comparison to TM (78.7% vs. 98.6%, p < 0.001; 14.9% vs. 1.4%, p = 0.007). Less paratracheal nodes were sampled by EBUS-FNA (right: 46.2% vs. 88.5%, p = 0.003; left: 23.1% vs. 65.4%, p = 0.005), while sampling rates in the subcarinal localisation were comparable (96.2% vs. 80.8%, p = NS). Among patients with confirmed NSCLC and conclusive EBUS-FNA/ TM findings (n = 18), the prevalence of N2/N3 disease was 66.7% (n = 12) according to TM findings. Diverging nodal stages were found in five patients (27.8%). Three patients who were N2 negative in EBUS-FNA were upstaged to N2 or N3 by TM, two patients with N2 status in EBUS-FNA were upstaged to N3 by TM.

Conclusions

Compared to TM, EBUS-FNA had a lower diagnostic yield and resulted in systematic mediastinal nodal understaging. At this point we suggest corroborating negative EBUS-FNA results by transcervical mediastinoscopy.

PURPOSE: To evaluate the risk of pneumothorax during CT-guided fine-needle aspiration (FNA) of lung nodules with single needle and coaxial needle techniques and to assess the effect on diagnostic accuracy of immediate cytological examination of lung FNA samples. MATERIALS AND METHODS: This prospective study analysed 53 patients undergoing transthoracic FNA biopsy of lung. 36 cases were performed by a radiologist using a coaxial technique, with 17 cases performed by a radiologist using a direct single-needle method. Effect of technique on occurrence of pneumothorax was recorded. FNA samples from all the patients in the study were examined immediately on-site by a cytologist or MLSO to determine whether sufficient aspirate had been obtained. Provisional diagnosis at immediate examination was compared to final diagnosis following full pathological evaluation. RESULTS: Coaxial and non-coaxial groups were comparable for age and gender. Number of pleural passes was significantly lower in coaxial group (P < 0.01). Pneumothorax occurred in six (17%) of the 36 patients biopsied by coaxial technique, compared to four (24%) of the 17 patients by non-coaxial method (P = 0.55). Chest tube placement was required in four patients (11%) in the coaxial group, and two patients (12%) in the non-coaxial group (P = 0.85). A provisional cytological diagnosis was recorded for 74% of the patients in the study. 83% of the provisional reports were accurate on comparison with full pathology report. Specimen size was sufficient in 81% of cases. CONCLUSIONS: The use of coaxial technique for CT-guided lung FNA biopsy reduced the number of pleural passes but did not significantly reduce the occurrence of pneumothorax. Immediate cytological examination of FNA specimens provided an accurate provisional diagnosis in the majority of cases, and should be routinely employed.

Images

Background

We evaluated the usefulness of follow-up BRAFV600E mutation analysis using ultrasonography-guided fine-needle aspiration (US-FNA) in diagnosis of thyroid nodules showing negative BRAFV600E mutation on prior analysis.

Methodology/Principal Finding

A total of 49 patients (men: 6, women: 43, mean age: 50.4 years) with 49 thyroid nodules were included. Patients had undergone initial and follow-up US-FNA and subsequent BRAFV600E mutation analysis from US-FNA aspirates. All patients had negative results on initial BRAFV600E mutation analysis. Clinicopathologic findings, US assessment, and BRAFV600E mutation results were analyzed according to the final pathology. Of the 49 nodules, 12 (24.5%) were malignant and 37 (75.5%) were benign. Seven (58.3%) of the 12 malignant nodules were positive for BRAFV600E mutation on follow-up, all showing suspicious US features. Initial US-FNA cytology of the 7 nodules were non-diagnostic (n = 2), benign (n = 2), or atypia (n = 3), while follow-up were benign (n = 1), indeterminate (n = 1), suspicious for malignancy (n = 4), and malignancy (n = 1).

Conclusions/Significance

Follow-up BRAFV600E mutation analysis may be helpful in the diagnosis of selected thyroid nodules negative for BRAFV600E mutation on initial analysis, which are assessed as suspicious malignant on US, diagnosed as non-diagnostic, benign or atypia on follow-up US-FNA.

Purpose

Preoperative axillary lymph node ultrasound (US) and fine-needle aspiration (FNA) biopsy can identify a proportion of node-positive patients and avoid sentinel lymph node (SLN) surgery and direct surgical treatment. We compared the costs with preoperative US/FNA to without US/FNA (standard of care) for invasive breast cancer.

Methods

Using decision-analytic software we constructed a model to assess the costs associated with the two preoperative strategies. Diagnostic test sensitivities and specificities were obtained from literature review. Costs were derived from Medicare payment rates and actual resource utilization. Base-case results were fully probabilistic to capture parameter uncertainty in economic results.

Results

Base-case results estimate total mean costs per patient of $10,947 (“$” indicates US dollars throughout) with the US/FNA strategy and $10,983 with standard of care, an incremental cost savings of $36, on average, per patient [95% confidence interval (CI) of cost difference: −$248 to $179]. Most (63%) of the simulations resulted in cost saving with axillary US/FNA. One-way sensitivity analyses suggest that results are sensitive to assumed diagnostic and surgical costs and selected diagnostic test parameters. US/FNA approach was similar in costs or cost saving relative to the standard of care for all tumor stages.

Conclusions

The additional cost of performing axillary US with possible FNA in every patient is balanced, on average, by the savings from avoiding SLN in cases where metastasis can be documented preoperatively. Routine use of preoperative axillary US with FNA to guide surgical planning can decrease the overall cost of patient care for invasive breast cancer.

A submucosal lesion, more appropriately a subepithelial lesion, is hard to diagnose. Endoscopic ultrasonography is good to differentiate the nature of submucosal lesion. For definite diagnosis, tissue acquisition from submucosal lesion is necessary, and many methods have been introduced for this purpose mainly by endoscopic ultrasonography, such as endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), EUS-guided Trucut Biopsy (TCB), and EUS-guided fine needle biopsy (FNB). For EUS-FNA, adequate processing of specimen is important, and for proper diagnosis of EUS-FNA specimen, both cytologic and histologic examinations, including immunohistochemical stains, are important. All gastrointestinal stromal tumors have some degree of malignant potential, so there have been a lot of efforts and methods to increase diagnostic yields of submucosal lesion. We herein review the current hot topics on EUS-FNA for submucosal tumor, such as needles, on-site cytopathologists, immunohistochemical stains, EUS-TCB, EUS-FNB, Ki-67 labelling index, DOG1, and combining EUS-FNA and EUS-TCB.

Background

Fine needle aspiration (FNA), although very reliable for cytologically benign and malignant thyroid nodules, has much lower predictive value in the case of suspicious or indeterminate nodules. We aimed to identify clinical predictors of malignancy in the subset of patients with suspicious FNA cytology.

Methods

We reviewed the electronic medical records of 462 patients who had FNA of thyroid nodules at our institution with a suspicious cytological diagnosis, and underwent surgery at Mayo Clinic between January 2004 and September 2008. Demographic data including age, gender, history of exposure to radiation and use of thyroid hormone was collected. The presence of single versus multiple nodules by ultrasonography, nodule size, and serum thyroid-stimulating harmone (TSH) level before thyroid surgery were recorded. Analysis of the latter was limited to patients not taking thyroid hormone or antithyroid drugs at the time of FNA.

Results

Of the 462 patients, 327 had lesions suspicious for follicular neoplasm (S-FN) or Hürthle cell neoplasm (S-HCN), 125 had cytology suspicious for papillary carcinoma (S-PC) and 10 had a variety of other suspicious lesions (medullary cancer, lymphoma and atypical). Malignancy rate for suspicious neoplastic lesions (FN+HCN) was ∼15%, whereas malignancy rate for lesions S-PC was 77%. Neither age, serum TSH level, or history of radiation exposure were associated with increased malignancy risk. The presence of multiple nodules (41.1% vs. 26.4%, p=0.0014) or smaller nodule size (2.6±1.8 cm vs. 2.9±1.6 cm, p=0.008) was associated with higher malignancy risk. In patients with cytology suspicious for neoplasm (FN, HCN) malignancy risk was higher in those receiving thyroid hormone therapy than in nonthyroid hormone users (37.7% vs. 16.5%, p=0.0004; odds ratio: 3.1), although serum TSH values did not differ significantly between thyroid hormone users and nonusers.

Conclusion

In patients with cytologically suspicious thyroid nodules, the presence of multiple nodules or smaller nodule size was associated with increased risk of malignancy. In addition, our study demonstrates for the first time, an increased risk of malignancy in patients with nodules suspicious for neoplasm who are taking thyroid hormone therapy. The reason for this association is unknown.

Background

The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated “suspicious or indeterminate”, but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology.

Methods

Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology.

Results

Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of≥0.95 (80% sensitivity; 100% specificity) and≥0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively.

Conclusions

Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.

The role of hepatic fine-needle aspiration (FNA) biopsy has evolved. Advances in imaging modalities have obviated the need for tissue confirmation in most hepatocellular carcinomas (HCCs). There is risk of needle-tract seeding. Increasingly, small nodules are being detected on ultrasound surveillance of high-risk patients. Diagnostic challenges associated with cirrhosis include distinction of benign hepatocellular nodules, namely, large regenerative nodules and dysplastic nodules, from reactive hepatocytes; and distinction of well-differentiated HCCs from benign hepatocellular nodules. This paper will discuss (i) controversies regarding preoperative/pretransplantation FNA diagnosis of HCC, (ii) update of biological evolution, nomenclature, and histopathologic criteria for diagnosis of precancerous nodules and small HCCs, and (iii) algorithmic approach to FNA diagnosis of hepatocellular nodules. Optimal results depend on dedicated radiologist-cytopathologist team, on-site cytology service; combined cytohistologic approach, immunohistochemistry, and clinicopathologic correlation. Hepatic FNA is likely to be incorporated as a point of care as we move towards personalized medicine.