BRAF Mutation Testing in Atypia of Undetermined Significance and Suspicious for Malignant Categories of Thyroid Fine Needle Aspirations in Clinical Practice
Serdar Balci, Nazmiye Dincer, Aylin Kilicyazgan, Cigdem Irkkan, Gulnur Guler. Yildirim Beyazit University, Ankara, Turkey
Background: Genetic analyses of known mutations are helpful in thyroid fine needle aspirations (FNAC) in diagnosing suspicious cases. Herein we report our institution experience of BRAF mutation analyses in FNAC diagnosed as atypia of undetermined significance (AUS/FLUS) and suspicious for malignant/papillary carcinoma (SFM) according to Bethesda classification.
Design: FNACs in our institution are air dried and MGG stained. Cases with AUS/FLUS and SFM categories were further reviewed. After keeping one diagnostic slide for archive, the cases with extra slides with enough cellularity are tested for BRAF mutation. Enough cellularity is defined as a moderately cellular slide with >75% atypical or suspicious cells. BRAF codon 600 (600 GTG>GAG -1799T>A, V600E) mutation was searched by real time PCR (Entrogen BRAF Mutation Analysis Kit, Applied Biosystem Stepone Plus Real Time PCR).
Results: AUS/FLUS group: Fifty of 155 cases diagnosed as AUS/FLUS were included. DNA extraction was successful in 44 of 50 cases DNA. Of 44 cases 2 were positive and 42 were negative. Two BRAF positive cases had thyroidectomy and diagnosed as papillary thyroid carcinoma (PTC). In 4/42 BRAF negative cases, thyroidectomy was performed due to clinical features: 2 were hyperplastic nodules and 2 had PTC. SFM group: Thirteen of 22 cases diagnosed as SFM were included and DNA could be isolated in all of them. Six of 13 cases were positive and 7 of 13 cases were negative. Of 6 BRAF positive cases 4 underwent thyroidectomy and diagnosed as papillary thyroid carcinoma. Of 6 negative cases 1 had thyroidectomy and diagnosed as Hurthle cell carcinoma.
Conclusions: In our series BRAF positivity was 4.5% (2/44) in AUS/FLUS and 46.1% (6/13) in SFM categories. We also found that hypocellularity may be an obstacle in DNA isolation process especially in AUS/FLUS group. Using only BRAF mutation status, there were 3 underpredicted cases whereas no overprediction of malignancy was observed. Since BRAF negativity does not rule out PTC presence; it is necessary to combine Bethesda classification and mutation status with clinical and radiological suspicious features for thyroidectomy decision.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 52, Wednesday Afternoon