Should Reflexive BRAF Testing Be Performed on Atypical/Borderline Thyroid Nodules?
Jonathan D Marotti, Joel A Lefferts, Vincent A Memoli, Allan C Golding, Gregory J Tsongalis, Vijayalakshmi Padmanabhan. Dartmouth-Hitchcock Medical Center, Lebanon, NH
Background: Diagnosis of classical papillary thyroid carcinoma (PTC) is based on characteristic nuclear features and is usually not a problem. However, follicular lesions with borderline nuclear features of PTC (thyroid tumors of uncertain malignant potential, atypical adenomas) create diagnostic difficulty and clinical uncertainty. Atypical adenomas are diagnosed based on cytologic atypia within otherwise encapsulated, noninvasive lesions that lack sufficient cytological features of encapsulated, noninvasive follicular variants of PTC. Though all variants of PTC share the same nuclear features, thresholds required to recognize them differ among pathologists. This remains subjective with considerable variability in diagnoses. The frequency of BRAF V600E mutations has been shown to range from 12% in follicular variants, to 60% in classical PTCs. Atypical adenomas have not been well studied for the presence of the BRAF gene mutation.
Design: We retrospectively identified and reviewed all thyroid surgical pathology cases that contained “atypical” within the final pathology report during a five-year period (2005-2010). Nodules described as having nuclear atypia insufficient for a diagnosis of thyroid carcinoma were selected. Clinical, pathologic, demographic, and prior FNA information were recorded. Blocks were selected that best represented atypical areas. DNA was extracted from macro-dissected or whole paraffin-embedded sections, and BRAF testing was performed using two allele-specific real-time PCR designed to detect wild-type BRAF and the BRAF V600E mutation.
Results: Twenty cases were identified out of 895 consecutive thyroid specimens (0.02 %). Of these, 16 cases (17 nodules) were available for both histologic review and BRAF testing. Six PTC and 5 multinodular hyperplasia cases were also tested as controls. BRAF mutations were not identified in any of the borderline nodules or in cases of multinodular hyperplasia. Three of six PTC (50%) contained BRAF mutations.
Conclusions: In our population, performing BRAF testing on atypical thyroid nodules with histologic features insufficient for diagnosis of PTC did not yield additional information. Currently, histology remains the gold standard for diagnosis of PTC, and reflexive BRAF testing for borderline cases on thyroidectomy/ lobectomy specimens may be of limited use.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 43, Tuesday Afternoon