BRAF Mutation in Thyroid FNA Specimens Enhances Predictability of Malignancy in Thyroid Follicular Lesion of Undetermined Significance.
Adebowale J Adeniran, Pei Hui, David C Chhieng, Kevin Schofield, Constantine Theoharis. Yale University School of Medicine, New Haven, CT
Background: The Bethesda 2007 Thyroid cytology classification defines follicular lesion of undetermined significance (FLUS) as a heterogeneous category of cases that are not convincingly benign nor sufficiently atypical for a diagnosis of follicular neoplasm or suspicious for malignancy. In our institution, we refer to these cases as "indeterminate" and they are further subclassified into two: 1) Low cellularity with predominant microfollicular architecture and absence of colloid (INa) and, 2) Nuclear features not characteristic of benign lesions (nuclear atypia) (INb). BRAF mutation occurs in 40-60% of papillary thyroid carcinoma (PTC). Such mutations are associated with a more aggressive phenotype of PTC. In this study, we examined and correlated our "indeterminate" cases with the result of BRAF mutation analysis and surgical pathology outcome.
Design: Thyroid FNA cytology specimens with an "indeterminate" diagnosis and a concurrent BRAF V600E mutation analysis were selected from our files. BRAF mutation analysis was performed by PCR combined with single strand conformation polymorphism gel electrophoresis using the remnant of samples collected for thin-layer processing in each case. Surgical pathology reports were reviewed for the final outcomes in these patients.
Results: Of the 49 indeterminate cases with BRAF mutation analysis, only 25 (51%) had follow-up with surgical intervention (24% of INa and 56% of INb). Ten cases (1 INa and 9 INb) had BRAF V600E mutation, 14 had no mutation while there was insufficient material in 1 case. All the 9 BRAF positive INb cases had a final diagnosis of PTC. In the 9 BRAF negative INb cases, 4 had a final diagnosis of PTC while 5 were benign lesions. The only BRAF positive INa case had a benign diagnosis. Of the 5 BRAF negative INa cases, 4 were benign while one was a follicular variant of PTC.
Conclusions: The sensitivity and specificity of BRAF mutation in detecting PTC in INb FNA specimens were 69% and 100% respectively, while the positive predictive value was 100%. In the INa category, the sensitivity was very low while the specificity and negative predictive value were both 80%. Our limited data supports the stratification of FLUS into two distinct groups and justifies the use of BRAF mutation analysis to predict the risk of malignancy in the two groups. However, a large number of cases may be needed for a more definitive conclusion.
Tuesday, March 1, 2011 11:45 AM
Platform Session: Section F, Tuesday Morning