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Nikhil Gupta,
Anil K Dasyam,
Sally E Carty,
Marina N Nikiforova, N Paul Ohori,
Michaele Armstrong,
Linwah Yip,
Shane O Lebeau,
Kelly L McCoy,
Christopher Coyne,
Michael T Stang,
Jonas Johnson,
Robert L Ferris,
R Seethala,
Yuri E Nikiforov,
Steven P Hodak
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ABSTRACT: Introduction:RAS mutations are common in thyroid tumors and confer a high risk of cancer when detected in fine-needle aspiration (FNA) specimens. Specific characteristics of RAS-positive thyroid cancers are not well described.Methods:From April 2007 to April 2009, 921 consecutive patients undergoing FNA were evaluated prospectively with a panel of molecular markers. Ultrasonographic, cytological, histological, and surgical outcomes were retrospectively assessed.Results:Sixty-eight aspirates from 66 patients were positive for RAS mutations including 63 cytologically indeterminate (93%), 3 malignant (4%), and 2 benign (3%) specimens. Cancer was histologically confirmed in 52 of 63 aspirates (83%) including the following: 46 papillary thyroid cancers, 4 follicular thyroid cancers, 1 medullary cancer, and 1 anaplastic cancer. All 46 RAS-positive papillary thyroid cancers, including 1 metastatic cancer, had follicular variant histology papillary thyroid cancer; only 11 tumors demonstrated vascular/capsular invasion and 4 had infiltrative growth. Of 48 patients with differentiated thyroid cancer, lymph node metastasis was uncommon and bilateral cancer was present in 48%. Only 33% of malignant nodules were suspicious by preoperative ultrasonography. At a mean follow-up of 22 months, 31 of 35 differentiated thyroid cancer patients (89%) have no evidence of recurrence, 4 patients (9%) have detectable thyroglobulin, 1 patient has bone metastases, and both patients with medullary and anaplastic cancer have died.Conclusion:Most RAS-positive thyroid cancers have indeterminate cytology, lack suspicious ultrasound features, and are histologically low-grade follicular variant histology papillary thyroid cancer. Lymph node and distant metastases are uncommon but bilateral disease is frequent. Total thyroidectomy should be considered for initial surgical management of most patients with RAS-positive FNA results. The role of prophylactic lymphadenectomy remains unclear.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
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N Paul Ohori,
Rashi Singhal,
Marina N Nikiforova,
Linwah Yip,
Karen E Schoedel,
Christopher Coyne,
Kelly L McCoy,
Shane O Lebeau,
Steven P Hodak,
Sally E Carty,
Yuri E Nikiforov
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ABSTRACT: BACKGROUND: BRAF mutations are highly specific for papillary thyroid carcinoma (PTC) and many cytology specimens with BRAF mutations are expected to demonstrate cytologic features typical of PTC. However, indeterminate thyroid cytology cases are inevitable and understanding the significance of the BRAF mutation within the context of the Bethesda System for Reporting Thyroid Cytopathology would be valuable. METHODS: Thyroid cytology cases submitted for conventional cytomorphologic evaluation and BRAF mutational analyses were selected from the authors' cytopathology files from April 2007 to October 2011. From this group, the diagnostic usefulness of BRAF mutations in indeterminate and malignant cases was assessed and analyses of cytologic and histopathologic features associated with the mutations in this gene were performed. RESULTS: A total of 131 cases with a BRAF mutation were identified. Of these, 119 underwent surgical pathology resection follow-up and demonstrated PTC. Approximately 75% of the cases were cytologically diagnosed as being positive for malignancy and these cases were associated with both the classic and tall cell variants of PTC at the time of resection, a greater likelihood of extrathyroidal extension, and the V600E type of BRAF mutation. In contrast, BRAF-mutated cases with diagnoses of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm/suspicious for follicular neoplasm were found to be more strongly associated with the follicular variant of PTC, a K601E BRAF mutation, and a lower likelihood of extrathyroidal extension. However, a subset of AUS/FLUS cases with the V600E BRAF mutation appeared to represent sampling variability of the classic or tall cell variants of PTC. CONCLUSIONS: Bethesda thyroid diagnoses in the setting of a BRAF mutation reflect differences in PTC subtypes, the nature of cytology specimens, and molecular characteristics. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.
Cancer Cytopathology 08/2012; · 3.33 Impact Factor
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ABSTRACT: Diagnostic thyroidectomy is typically indicated for indeterminate thyroid cytology results. Traditionally, intraoperative pathologic examination (IOPE) helped to guide the extent of initial surgery. Preoperative molecular testing (MT) of fine needle aspiration cytology has emerged as another diagnostic adjunct, is highly specific for thyroid cancer, and can lead to appropriate initial total thyroidectomy. We hypothesized that preoperative MT obviates the need for routine IOPE during lobectomy.
In a retrospective, consecutive cohort study, we compared outcomes of 670 patients undergoing thyroidectomy. Cohort A (January 2005 to December 2006) received surgery without MT, and cohort B (January 2008 to September 2010) had preoperative MT for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations, and cytology assessment by the 2007 modified Bethesda criteria. In both cohorts, IOPE was performed during lobectomy and a positive result prompted total thyroidectomy.
In cohort B, total thyroidectomy was more often the initial surgery (62% vs A 45%; p < 0.001) and a positive MT result was the only factor prompting initial total thyroidectomy in 18 (9%) patients. Among 315 patients who had initial lobectomy, thyroid cancer was infrequently diagnosed by IOPE in both cohorts (A 3.6% vs B 1.7%; p = 0.5). The sensitivity of IOPE in detecting differentiated thyroid cancer ≥1 cm decreased >60% with routine use of MT and the Bethesda criteria (A 18.4% vs B 5.9%). After lobectomy, differentiated thyroid cancer ≥1 cm was equally likely to be diagnosed in both cohorts (p = 0.1), but follicular variant papillary thyroid cancer was more common in cohort B (74% vs 45%; p = 0.02).
Together with the Bethesda cytologic criteria, preoperative MT allows for an increased rate of initial definitive total thyroidectomy and eliminates the need for routine intraoperative pathologic examination during diagnostic lobectomy.
Journal of the American College of Surgeons 07/2012; 215(4):546-54. · 4.55 Impact Factor
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ABSTRACT: This is an unusual case of invasive lobular carcinoma of the breast presenting as an orbital metastasis. A 70 year-old female presented with a gradually worsening blurred vision, periorbital swelling and ascites. The biopsy of the eyelid demonstrated dense fibrosis with neoplastic cells and the diagnosis of carcinoma was made; however, the site of origin of carcinoma was difficult to determine. The histopathologic characteristics of the carcinoma in the orbit and ascites fluid combined with the immunophenotypic features helped determine the primary site of the malignancy. Subsequently, the primary malignancy was identified by examination of the patient's breast.
Internal Medicine 01/2012; 51(12):1635-8. · 0.94 Impact Factor
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ABSTRACT: Nongynecologic (NG) cytology cases usually generate multiple slides. In cases showing overtly malignant or neoplastic cells, the cytotechnologist (CT) may not need to screen all slides. We test the hypothesis that selective screening of a subset of slides by the CT is as effective as "routine screening" of all slides. The selective screening process (SSP) was performed by having the cytotechnologist (CT) screen and mark overtly malignant or neoplastic cells on up to three slides. Cases requiring more slides to be screened were not included in SSP. For each SSP case, the total slide count, number of slides screened, final diagnosis, and cytologic-histologic correlation (CHC) data were collected over 10 months and compared to the data from routinely screened cases. SSP was performed on 191 cases during a 10-month period. An average of 1.9 slides per case was screened by the cytotechnologist using the SSP. The average number of unscreened slides passed to the pathologist was 6.3 per case. On average, SSP resulted in 83.6 min of CT's time saved per day. Quality control by CHC demonstrated no false-positive cases in either the SSP or "routinely screened" groups. The diagnostic accuracy of the specific cytology diagnoses was 98% by SSP and 100% by "routine screening." SSP provides a mechanism for the cytotechnologist to "screen" fewer slides and pass the cases to the pathologist more efficiently without compromising overall patient care.
Diagnostic Cytopathology 10/2011; 39(10):717-22. · 1.16 Impact Factor
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Yuri E Nikiforov, N Paul Ohori,
Steven P Hodak,
Sally E Carty,
Shane O LeBeau,
Robert L Ferris,
Linwah Yip,
Raja R Seethala,
Mitchell E Tublin,
Michael T Stang,
Christopher Coyne,
Jonas T Johnson,
Andrew F Stewart,
Marina N Nikiforova
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ABSTRACT: Thyroid nodules are common in adults, but only a small fraction of them is malignant. Fine-needle aspiration (FNA) cytology provides a definitive diagnosis of benign or malignant disease in many cases, whereas about 25% of nodules are indeterminate, hindering most appropriate management.
The objective of the investigation was to study the clinical utility of molecular testing of thyroid FNA samples with indeterminate cytology.
Residual material from 1056 consecutive thyroid FNA samples with indeterminate cytology was used for prospective molecular analysis that included the assessment of cell adequacy by a newly developed PCR assay and testing for a panel of mutations consisted of BRAF V600E, NRAS codon 61, HRAS codon 61, and KRAS codons 12/13 point mutations and RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements.
The collected material was adequate for molecular analysis in 967 samples (92%), which yielded 87 mutations including 19 BRAF, 62 RAS, 1 RET/PTC, and five PAX8/PPARγ. Four hundred seventy-nine patients who contributed 513 samples underwent surgery. In specific categories of indeterminate cytology, i.e. atypia of undetermined significance/follicular lesion of undetermined significance, follicular neoplasm/suspicious for a follicular neoplasm, and suspicious for malignant cells, the detection of any mutation conferred the risk of histologic malignancy of 88, 87, and 95%, respectively. The risk of cancer in mutation-negative nodules was 6, 14, and 28%, respectively. Of 6% of cancers in mutation-negative nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology, only 2.3% were invasive and 0.5% had extrathyroidal extension.
Molecular analysis for a panel of mutations has significant diagnostic value for all categories of indeterminate cytology and can be helpful for more effective clinical management of these patients.
The Journal of clinical endocrinology and metabolism 08/2011; 96(11):3390-7. · 6.50 Impact Factor
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ABSTRACT: Histologic subtyping of non-small cell lung carcinoma (NSCLC) is important because the efficacy of new treatments depends on tumor histologic features. We assessed the diagnostic accuracy of classification of lung adenocarcinoma and squamous cell carcinoma (SCC) on cytologic and biopsy specimens based on cytomorphologic studies alone or in combination with ancillary studies compared with resection specimens. Compared with adenocarcinoma, the diagnosis of SCC was based more often on cytomorphologic studies alone (139/185 [75.1%] vs 107/263 [40.7%]). Significantly increased use of immunohistochemical studies in cytology was noted after introduction of targeted lung carcinoma therapies (22/156 [14.1%] for adenocarcinoma and 5/46 [11%] for SCC from 2000-2004 vs 134/156 [85.9%] for adenocarcinoma and 41/46 [89%] for SCC from 2005-2010). Use of immunohistochemical studies resulted in increased diagnostic accuracy for adenocarcinoma (56% [44/78] from 2000-2004 vs 83.2% [154/185] after 2005) but not for SCC (77% [57/74] before 2004 vs 73.9% [82/111] from 2005-2010). Adenocarcinoma showed high expression of cytokeratin (CK)7 (146/146 [100%]), thyroid transcription factor-1 (131/152 [86.2%]), surfactant A (29/36 [81%]), and periodic acid-Schiff with diastase (69/86 [80%]). All SCCs were positive for CK5/6 and p63. Use of immunohistochemical studies on cytologic cell blocks may improve classification of NSCLC.
American Journal of Clinical Pathology 07/2011; 136(1):81-7. · 2.60 Impact Factor
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ABSTRACT: Detection of thyroid cancer is challenging for several reasons. Although thyroid nodules are common, most are benign. Furthermore, most thyroid cancers are low grade and share pathologic features with benign nodules. Because of these overlapping characteristics and the challenges in performing fine needle aspiration, many cytology cases result in an indeterminate or unsatisfactory diagnosis. This article describes the pathologic features of thyroid nodules, the challenges in obtaining a diagnostic specimen, and the reporting of thyroid lesions using the Bethesda classification system for thyroid cytopathology. The role of molecular and other ancillary studies in refining diagnostic practice is also examined.
Radiologic Clinics of North America 05/2011; 49(3):435-51, v-vi. · 2.59 Impact Factor
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ABSTRACT: Recent advances have increased the demand for the accurate diagnosis of pulmonary nonsmall cell carcinoma (NSCLC) rendered by biopsy or cytology. However, precise classification is not possible in all cases. In this study, we investigated the performance characteristics of preresection bronchoscopic and transthoracic procedures for the diagnosis of NSCLC. The pathology files were searched for resected NSCLCs and carcinoid tumors with corresponding preresection cytology and/or biopsy cases. The preresection diagnoses were correlated with the resection diagnosis and the type of bronchoscopic or transthoracic procedure. Among the bronchoscopic procedures, endobronchial/transbronchial biopsy (ETBX) had the highest yield for obtaining a positive (malignant) diagnosis and was the best procedure for obtaining precise classification. For transthoracic procedures, fine-needle aspiration (FNA) and needle core biopsy (NCB) were similar in providing a positive (malignant) diagnosis; however, NCB was better than FNA in obtaining precise classification. From the perspective of the neoplasms, carcinoid tumors yielded a positive (malignant) specimen with accurate classification most often (e.g., 100% by ETBX). This was followed by squamous cell carcinoma and adenocarcinoma. In contrast, precise classification was not possible for adenosquamous carcinoma, large cell carcinoma, and large cell neuroendocrine carcinoma. Bronchoscopic and transthoracic procedures have different performance characteristics. Furthermore, the diagnostic yield is dependent on the histologic type of the neoplasm. While carcinoid tumors are accurately classified in most cases, some other neoplasms are difficult to diagnose and subclassify due to histologic complexity, poor differentiation, or sampling limitations.
Diagnostic Cytopathology 02/2011; 40(8):659-63. · 1.16 Impact Factor
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ABSTRACT: Objective: Of the 6 categories in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has received the most attention. The objectives of this study were to review the use of the AUS/FLUS category in recent studies, to search for likely sources of the variability in its use, and to address possible methods for improvement. Study Design: A PubMed search was performed to retrieve peer-reviewed articles that have comprehensively detailed the incidence and outcome of AUS/FLUS and other BSRTC categories. Related thyroid cytology articles on the BSRTC were also included. Results: Recent series that reported experiences with the BSRTC categories showed that the AUS/FLUS category exhibited a marked variability in incidence (0.7-18%) and malignant outcome (6-48%) in resection specimens. Review of the literature revealed institutional differences in technical aspects, interpretation and application of criteria, analysis of outcome data, and clinicopathologic interactions. Conclusions: A heightened awareness of technical issues, diagnostic borders of AUS/FLUS, and clinical management may aid in diagnostic refinement and help avoid overuse of this category.
Acta cytologica 01/2011; 55(6):492-8. · 0.49 Impact Factor
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ABSTRACT: Autoimmune pancreatitis (AIP) may mimic pancreatic cancer (PC). The detection of DNA mutations in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) material may improve discrimination between AIP and PC and is the context for this study.
In a retrospective study, archived EUS-FNA material from patients with AIP and PC at two centers was analyzed for KRAS mutations and loss-of-heterozygosity analysis involving 18 microsatellite markers. KRAS status and the fractional allelic loss (number of affected microsatellites divided by informative ones) were compared for AIP and PC.
Thirty-two patients with 33 samples were studied. There were 16 patients with AIP (17 samples) and 16 patients with PC. DNA amplification failed in 7 samples. Of 25 patients (26 samples), 14 had AIP (7 male, age 57 ± 17 years; mean ± SD) and 11 had PC (7 male, age 65 ± 14 years; mean ± SD). Cytology results for AIP were inflammatory = 3, inconclusive = 10, suspicious for malignancy = 2 and for PC were malignant = 5, suspicious for malignancy = 4 and inconclusive = 2, respectively. KRAS mutation was detected in none of the AIP cases and 10/11 PC cases (91%, Pearson χ(2) = 22.16, p < 0.001) or 10/16 PC cases (63%) accounting for PC cases with failed DNA amplification. Mean (±SD) fractional allelic loss for the AIP cases (0.16 ± 0.15) was not significantly different from the PC cases (0.26 ± 0.19).
A KRAS mutation in EUS/FNA material from a pancreatic mass is associated with malignancy and may help discriminate from benign conditions such as AIP.
Pancreatology 01/2011; 11(5):482-6. · 1.99 Impact Factor
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ABSTRACT: Flow cytometric immunophenotyping (FCI) is recommended in the evaluation of cerebrospinal fluid (CSF) specimens for hematologic neoplasms. This study reviewed FCI of CSF specimens collected for primary diagnosis (n = 77) and follow-up for known malignancy (n = 153). FCI was positive in 11 (4.8%) of 230 specimens: acute myeloid leukemia, 6; precursor B-acute lymphoblastic leukemia, 2; B-cell lymphoma, 2; and T-cell lymphoma, 1. Positive results were obtained in low-cellularity specimens, including 2 with fewer than 100 events in the population of interest. FCI was indeterminate in 19 (8.3%) of 230 specimens, including 3 with only sparse events, 8 with possible artifact (apparent lack of staining, nonspecific or background staining, and aspirated air), and 8 with phenotypic findings considered insufficient for diagnosis. Indeterminate specimens were often limited by low cellularity and lacked normal cell populations to evaluate for appropriate staining. FCI may be of value in low-cellularity CSF specimens, although the results should be interpreted with caution.
American Journal of Clinical Pathology 01/2011; 135(1):22-34. · 2.60 Impact Factor
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ABSTRACT: "Follicular lesion of undetermined significance/atypia of undetermined significance" is a heterogeneous category of cases that cannot be classified into 1 of the other established categories. The use of ancillary molecular studies has not been widely explored for this diagnosis.
All thyroid cytology cases diagnosed as follicular lesion of undetermined significance/atypia of undetermined significance were retrieved from April 2007 to December 2008. During this time period, samples were collected routinely at the time of aspiration for cytologic and molecular studies. Analysis for BRAF and RAS gene mutations and RET/PTC and PAX8/PPARgamma gene rearrangements were performed and correlated with the cytologic features and surgical pathology outcome.
From a total of 513 follicular lesion of undetermined significance/atypia of undetermined significance cases identified, 455 had adequate molecular results. Of these, 117 cases had cytologic-histologic correlation. In this group, 35 (29.9%) cases had a neoplastic outcome and 20 (17.1%) cases from 19 patients were carcinoma. Positive molecular results were found in 12 cases, all of which were papillary carcinoma. There were no false-positive molecular results. In correlating the molecular results with surgical pathology outcome, we found that the cancer probability for follicular lesion of undetermined significance/atypia of undetermined significance cases with molecular alteration was 100%, while the probability for follicular lesion of undetermined significance/atypia of undetermined significance cases without molecular alteration was 7.6% (P < .001).
By cytomorphology alone, follicular lesion of undetermined significance/atypia of undetermined significance specimens represent cases that are intermediate in risk between the benign and "suspicious for follicular neoplasm" categories. Although not all papillary carcinoma cases are detected by molecular testing, a positive molecular test result is very helpful in refining follicular lesion of undetermined significance/atypia of undetermined significance cases into high-risk and low-risk categories.
Cancer Cytopathology 02/2010; 118(1):17-23. · 3.33 Impact Factor
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ABSTRACT: 52-year-old patient presented with palpitation and well tolerated monomorphic ventricular tachycardia. He had normal echocardiogram and coronary angiogram 3 months prior to presentation. Surface EKG revealed regular wide-complex tachycardia with right bundle branch block morphology and right inferior axis. In conjunction with recent negative cardiac evaluation, this suggested idiopathic focal ventricular tachycardia from anterolateral basal left ventricle. CARTO based activation mapping confirmed the presence of VT focus in that area. Radiofrequency ablation at the site of perfect pacemap resulted in a partial suppression of the focus. Echocardiogram was subsequently performed because of progressive dyspnea. It revealed asymmetrical thickening of posterolateral left ventricle, with delayed enhancement on contrast magnetic resonance imaging. Fine needle aspiration of abdominal fat stained with Congo red confirmed the diagnosis of systemic AL amyloidosis due to IgG lambda-light chain deposition. Consequently, the patient underwent placement of implantable defibrillator and hematopoetic stem cell transplantation. He remains in excellent functional status 18 months after presentation.
Indian pacing and electrophysiology journal 01/2010; 10(3):143-7.
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Kenneth E Fasanella,
Alyssa Krasinskas,
Karen E Schoedel,
Eizaburo Sasatomi,
Adam Slivka,
David C Whitcomb,
Michael Sanders,
Laurentia Nodit,
Stephen Raab,
Kevin M McGrath, N Paul Ohori,
Asif Khalid
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ABSTRACT: Preoperative distinction between pancreatic cancer (PC) and extrahepatic cholangiocarcinoma (CC) is desirable due to diverging management options, and to optimize enrollment into neoadjuvant trials.
A single-center retrospective study of patients with PC or CC was undertaken. Four blinded pathologists reviewed all cases and reached a consensus diagnosis (PC or CC). Microdissection-based multiple microsatellite loss analysis and direct sequencing of K-ras oncogene was performed and compared for PC and CC.
Of 33 cases studied (17 males; 16 PC, 17 CC; 10 with primary sclerosing cholangitis), a K-ras mutation was present in 14/16 (87.5%) PC and 1/17 (5.9%) CC cases (p < 0.001), sensitivity and specificity were 87.5 and 94%, respectively. The mean fractional mutational rate was higher in PC (0.51; 95% CI 0.45-0.58) compared to CC (0.34; 95% CI 0.28-0.39, p < 0.001).
The presence of a K-ras mutation in cytology specimens distinguishes PC from CC in this study. and IAP.
Pancreatology 01/2010; 10(4):429-33. · 1.99 Impact Factor
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ABSTRACT: Ultrasound-guided sampling of the thyroid represents a standard diagnostic procedure in the evaluation of thyroid nodules. The two techniques typically used are fine-needle aspiration and fine-needle capillary biopsy. Each has been used with success in various body sites. Recently, a comparison of these two techniques showed no significant difference with regard to specimen adequacy. In this study, the type of technique was correlated with diagnostic accuracy. For each technique, the preoperative cytology diagnosis was compared with the surgical pathology diagnosis in 46 resected thyroid nodules. No false-positive diagnoses were identified. No significant difference in diagnostic accuracy was found on comparison of the two techniques. Therefore, either technique may be used according to the operator's preference.
Diagnostic Cytopathology 12/2008; 36(11):787-9. · 1.16 Impact Factor
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ABSTRACT: Pancreatic endocrine tumors (PETs) are rare (1 per 100,000 population) and are thought to be functioning in up to 85% of cases and are generally less than 2 cm in size. By previous reports, 15% to 50% of PETs are nonfunctioning and are discovered either incidentally or by symptom evaluation from a mass effect. EUS-guided FNA (EUS-FNA) has been shown to accurately diagnose PETs and to localize tumors for surgical resection.
To describe a single-center experience of EUS-FNA diagnosis of PETs and its impact on surgical management.
Retrospective cohort study.
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Patients with PETs diagnosed via EUS-FNA over a 4-year period were identified through the authors' EUS database. Clinical history, laboratory values, diagnostic studies, EUS findings, cytology, pathology, operative records, and surgical pathology records were reviewed.
Impact of definitive preoperative diagnosis of PET on surgical management.
Forty-one patients were diagnosed by EUS-FNA with PET. Thirty-five PETs were nonfunctioning PET; 6 were functioning PET. The mean tumor sizes of functioning and nonfunctioning PETs were 19 mm and 28 mm, respectively. The majority of tumors were located in the pancreatic head. Surgery was performed in 78% of patients; of these, 34% were resected laparoscopipcally.
Retrospective design and selection bias.
In this study, nonfunctioning PETs were more commonly diagnosed compared with functioning PETs. In addition, the PETs were smaller than previously reported, likely because of increasing detection of incidental lesions through widespread use of abdominal imaging.
Gastrointestinal Endoscopy 02/2008; 67(1):44-50. · 4.88 Impact Factor
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ABSTRACT: Both fine-needle aspiration (FNA) and fine-needle capillary (FNC) sampling of palpable thyroid nodules have been advocated. The appropriate technique for biopsy of nonpalpable nodules now sampled under ultrasound guidance has not been assessed. The objective of this study was to determine cytologic adequacy rates of ultrasound-guided FNA and FNC sampling.
Ultrasound-guided fine-needle biopsy was performed on 180 thyroid nodules. Nodules were measured and characterized (mixed cystic-solid or solid) on diagnostic sonography. The technique used for biopsy (FNA versus FNC sampling) alternated sequentially per patient. Four 25-gauge fine-needle samples were obtained from each nodule. The sampling adequacy and cytopathologic diagnoses were recorded. The significance of differences in cytologic adequacy rates between techniques was then assessed with a repeated measures logistic regression model.
Fine-needle aspiration and FNC sampling biopsies were performed in 88 and 92 nodules, respectively. Fine-needle aspiration was diagnostic (ie, satisfactory) in 78 (89%) of 88 nodules and nondiagnostic (less than optimal or unsatisfactory) in 10 (11%) of 88 nodules; FNC sampling was diagnostic in 80 (87%) of 92 nodules and nondiagnostic in 12 (13%) of 92 nodules. Fine-needle aspiration sampling was diagnostic in 38 (86%) of 44 solid nodules and 40 (91%) of 44 mixed cystic-solid nodules; FNC sampling was diagnostic in 48 (81%) of 59 solid nodules and 32 (97%) of 33 mixed cystic-solid nodules. These percentages were not significantly different.
Ultrasound-guided FNA and FNC sampling result in comparable diagnostic cytologic adequacy rates. Equivalent diagnostic yields and the technical ease of capillary sampling may prompt adoption of FNC sampling at high-volume endocrine/radiology practices.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 01/2008; 26(12):1697-701. · 1.25 Impact Factor
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ABSTRACT: High false-negative rates for fine needle aspiration biopsy (FNAB) of thyroid nodules greater than 3 cm have prompted recommendations for diagnostic lobectomy. We considered the presence of a greater than 4 cm nodule an independent indication for thyroidectomy regardless of FNAB results.
We reviewed clinical data from 223 patients with thyroid nodules greater than or equal to 4 cm operated on from July 2003 to November 2006. Unifocal micropapillary cancer was considered clinically insignificant.
Clinically significant thyroid cancer was frequent, occurring in 57 of 223 patients (26%). Subgroup analysis showed that 43 of 223 patients (19.3%) had carcinoma within the mass and that 7 of 223 patients (3.1%) had significant carcinoma elsewhere in the resected thyroid. Multifocal micropapillary cancer was found in an additional 7 of 223 patients (3.1%). Preoperative FNAB was read incorrectly as benign in 9 of 71 patients with cancer (13%) (16% including multifocal micropapillary carcinoma). Benign FNAB results failed to identify 24 (34%) follicular lesions (including 7 cancers). In patients with preoperative FNAB results categorized as indeterminate lesions, 17 of 43 patients (40%) had carcinoma of the mass on final pathology.
In thyroid nodules greater than or equal to 4 cm, the incidence of carcinoma is high with a high false-negative rate for preoperative benign cytology. Thyroid nodules greater than or equal to 4 cm should be considered for diagnostic lobectomy regardless of FNAB results.
Surgery 01/2008; 142(6):837-44; discussion 844.e1-3. · 3.10 Impact Factor
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ABSTRACT: Conventional cytologic evaluation of bile duct brushings for neoplasia has high specificity but relatively low sensitivity.
The aim of this pilot study was to examine whether K-ras mutations and loss of heterozygosity for multiple microsatellite markers in bile duct brushings would contribute to the detection of malignancy in cases initially reported as "negative" or "atypical."
Bile duct brushing specimens with a negative or an atypical cytologic result (9 cases) had a benign result on the surgical pathology specimen, and 9 additional negative or atypical cases demonstrated adenocarcinoma on the resected surgical specimen. Cells from representative cytopathology and histology slides were microdissected and analyzed for K-ras mutations and for loss of heterozygosity with a panel of 15 polymorphic markers on chromosomes 1p, 3p, 5q, 9p, 9q, 10q, 17p, and 22q.
Among cytology cases with malignant outcome, loss of heterozygosity or K-ras mutation was detected in 8 (88.8%) of 9 cases. In the corresponding 9 surgical pathology specimens with adenocarcinoma, K-ras mutations and/or allelic losses were detected in all (100%). Loss of heterozygosity or K-ras mutation was not detected in cytology cases that had a benign surgical outcome. The fractional allelic loss of these 9 cytology specimens ranged from 0 to 0.25 (mean, 0.14). This compared with the fractional allelic loss ranging from 0.15 to 0.42 (mean, 0.27) for the corresponding surgical specimens.
This pilot study suggests that low-level fractional allelic loss or K-ras mutation in the negative/atypical cytology samples with malignant outcome is a representation of morphologically subtle molecular alterations.
Archives of pathology & laboratory medicine 02/2007; 131(1):74-80. · 2.58 Impact Factor
