Fine Needle Aspiration Analysis of B-RAF in Thyroid Nodules

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P37-P38
Author(s):  
Brandon G Bentz ◽  
Brian Thomas Miller ◽  
Joseph Holden ◽  
Leslie R Rowe ◽  
Joel Bentz

Objective Fine needle aspiration (FNA) represents the most useful initial diagnostic tool with which to analyze thyroid nodules for carcinoma. A mutation of the B-type RAF kinase (BRAF) represents the most common genetic alteration in sporadic papillary thyroid cancer (PTC), and may signify a more aggressive biological behavior within PTCs. Our objective was to determine if BRAF analysis of FNA cytology may provide clinically useful information in the analysis of thyroid nodules. Methods An IRB-approved retrospective chart review of clinically relevant data for classic PTCs (CPTC), follicular-variant of PTC (FV-PTC), or non-malignant goiter was performed following a blinded pathologic re-review. Both pathologic and cytology samples were analyzed by fluorescent melting curve analysis (FMCA) for the V600E mutation of BRAF, and mutational status was compared with clinical information. Results A 100% concordance was found for BRAF mutation determination between the cytologic and final pathologic malignant and benign tissue samples studied. BRAF mutation was found to be significantly higher in papillary carcinomas when compared to follicular-variant of papillary thyroid carcinomas (55.6% vs. 14.3%, p=0.05), and correlated with cytologic interpretation (p=0.025) and histologic diagnosis (p=0.03). Conclusions FMCA of thyroid nodule FNAs can accurately determine the mutational status of the BRAF gene. Since the presence of BRAF mutation can predict a more aggressive biological behavior, an analysis of BRAF mutational status of initial FNAs may add useful information to the list of risk stratification criteria for PTCs.

2009 ◽  
Vol 140 (5) ◽  
pp. 709-714 ◽  
Author(s):  
Brandon G. Bentz ◽  
Brian T. Miller ◽  
Joseph A. Holden ◽  
Leslie R. Rowe ◽  
Joel S. Bentz

Objective: A mutation of B-type RAF kinase (B-RAF) represents the most common genetic alteration in papillary thyroid cancer (PTC), possibly signifying a more aggressive biology. Fine needle aspiration (FNA) represents the most useful initial diagnostic tool of thyroid nodules. Molecular analysis of the mutation status of B-RAF in thyroid nodule FNAs may provide guidance for treatment planning. Study Design: Cross-sectional study. Subjects and Methods: A retrospective chart review was undertaken for clinically relevant data of papillary thyroid cancer (PTC), follicular variant of PTC (FV-PTC), and nonmalignant goiters. After blinded pathologic review, histologic and cytologic samples were analyzed by LightCycler PCR (LCPCR) with allele-specific fluorescent probe melting curve analysis (FMCA) for the V600E mutation of B-RAF. Results: Of the 45 patient samples analyzed, B-RAF mutation was found to be significantly higher in papillary carcinomas when compared to follicular variant of papillary thyroid carcinomas (55.6% vs 14.3%, P = 0.05). Pathologic B-RAF mutational status significantly correlated with cytologic B-RAF mutational status ( P < 0.0001), cytologic interpretation ( P = 0.012), and histologic diagnosis ( P = 0.011). Conclusions: Determination of B-RAF V600E mutation of thyroid nodule FNAs by LCPCR may be a useful tool to guide treatment planning. These data support investigating the utility of this molecular marker in a prospective manner.


2020 ◽  
Vol 26 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Ngan Betty Lai ◽  
Dave Garg ◽  
Anthony P. Heaney ◽  
Marvin Bergsneider ◽  
Angela M. Leung

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.). Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology. Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 [SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 [SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed). Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly. Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States


Thyroid ◽  
2015 ◽  
Vol 25 (9) ◽  
pp. 987-992 ◽  
Author(s):  
Kyle C. Strickland ◽  
Brooke E. Howitt ◽  
Ellen Marqusee ◽  
Erik K. Alexander ◽  
Edmund S. Cibas ◽  
...  

2010 ◽  
Vol 17 (1-2) ◽  
pp. 35-39
Author(s):  
Svetlana V. MANKOVSKAYA ◽  
Yuri E. DEMIDCHIK ◽  
Shunichi YAMASHITA

Background. The diagnostic efficacy of the molecular analysis that included determination of papillary thyroid carcinoma (PTC) marker gene expression levels and BRAF mutation in fine-needle aspiration biopsy material was evaluated in a prospective study of patients with thyroid nodules. Materials and methods. Totally, 36 patients (29 females and 7 males) with thyroid nodules were included in the study. The mRNA expression of genes (SFTPB and TFF3) was estimated in relation to a housekeeping gene level (KPNA4) by means of duplex RT-PCR followed by the band intensity measurement. Detection of BRAF mutation was performed by PCR followed by direct sequencing. Results. In 25/32 (78.1%) cases, results of the molecular test were in agreement with the cytological diagnosis (7/7 PTC and 18/25 non-PTC) further confirmed by histological examination of tissues surgically removed from all seven PTC patients and 10 individuals with benign nodules. In 7/32 patients (21.9%) there was a discrepancy between cytological findings and molecular results, which revealed a benign nodule and a PTC-like pattern, respectively. Upon a repeated examination of five of these patients about one year later, three were cytologically diagnosed with PTC (all patients had been operated on), and the diagnosis of the other two patients remained unchanged. Conclusions. The results have demonstrated that the molecular analysis of FNAB material is an informative means of the preoperative diagnosis of thyroid nodules as it allows identification of patients with suspected PTC before other diagnostically significant changes take place. Keywords: papillary thyroid carcinoma, fine-needle aspiration biopsy, preoperative diagnosis, molecular test


2001 ◽  
Vol 125 (4) ◽  
pp. 484-488 ◽  
Author(s):  
Mojghan Amrikachi ◽  
Ibrahim Ramzy ◽  
Sheldon Rubenfeld ◽  
Thomas M. Wheeler

Abstract Context.—Fine-needle aspiration has become an accepted and cost-effective procedure for rapid diagnosis of thyroid lesions. The routine use of fine-needle aspiration has reduced the rate of unnecessary surgery for thyroid nodules. Objectives.—To determine the accuracy of fine-needle aspiration biopsy diagnosis and to discuss the possible pitfalls. Design, Setting, and Participants.—Reports of 6226 fine-needle aspiration biopsies of the thyroid performed during a period of 16 years (1982–1998) were reviewed. Computerized reports of the fine-needle aspiration biopsies were sent to the physicians who performed the procedures, and clinical follow-up information regarding the patients was requested. Twenty-four clinicians participated in the study. Histologic diagnoses were available for 354 cases. The cytopathologic diagnoses were correlated with the histologic findings or clinical outcomes. Results.—The cytologic diagnoses were as follows: 210 (3.4%) malignant, 450 (7.2%) suspicious, 3731 (60%) benign, and 1845 (29.5%) unsatisfactory. Most of the cases with negative or unsatisfactory aspirates were followed clinically or by repeat fine-needle aspiration. We identified 11 false-negative and 7 false-positive diagnoses. For aspirates considered sufficient for diagnosis, the sensitivity and specificity levels were 93% and 96%, respectively. Conclusions.—Fine-needle aspiration of the thyroid gland is highly accurate and has a low rate of false-negative and false-positive diagnoses. The major diagnostic problems are caused by diagnosis using a marginally adequate specimen, diagnosis of malignancy based on just 1 or 2 atypical cytologic features, or overlapping cytologic features of follicular neoplasm with those of follicular variant of papillary carcinoma.


2004 ◽  
Vol 89 (6) ◽  
pp. 2867-2872 ◽  
Author(s):  
Mingzhao Xing ◽  
Ralph P. Tufano ◽  
Anthony P. Tufaro ◽  
Shehzad Basaria ◽  
Marge Ewertz ◽  
...  

Abstract Numerous biomolecular markers have been studied to improve the accuracy of fine needle aspiration biopsy (FNAB) in the diagnostic and prognostic evaluation of thyroid tumors, but none of them has yet become clinically useful. The recently discovered BRAF mutation, which occurs specifically in papillary thyroid cancers (PTC) with a high prevalence and is associated with poor clinicopathological outcomes, has the potential to be a useful diagnostic and prognostic marker for PTC. In the present study, we investigated whether detection of BRAF mutation on FNAB specimens was technically possible and could be used as an adjunct diagnostic tool with routine FNAB. Evaluation of a new colorimetric mutation detection method demonstrated 100% sensitivity and 100% specificity in comparison with conventional DNA sequencing as the “gold standard” in a large pool of DNA samples from various primary thyroid tumor specimens and cell lines. We found this novel technique even more sensitive in detecting BRAF mutation on FNAB specimens than conventional sequencing. In a series of 48 patients undergoing thyroidectomy, mostly for thyroid cancer or for suspicion of cancer, we performed preoperative FNAB and, using the colorimetric mutation detection method, identified BRAF mutation on the cytological specimens. Prospective analysis showed that 50% of the nodules that proved to be PTC on surgical histopathology were correctly diagnosed by BRAF mutation analysis on FNAB specimens; there were no false positive findings. Thus, we have demonstrated the usefulness of BRAF mutation detection on FNAB specimens that can help diagnose and identify those PTC patients who may need more aggressive surgical treatment and vigilant clinical monitoring.


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