Absence of the BRAF mutation in HBME1+ and CK19+ atypical cell clusters in Hashimoto thyroiditis: supportive evidence against preneoplastic change.

An association between Hashimoto thyroiditis and papillary thyroid carcinoma has been postulated for decades. We undertook this study to identify potential precursors of papillary thyroid carcinoma in Hashimoto thyroiditis using a combination of morphologic, immunohistochemical, and molecular techniques. For the study, samples from 59 cases of Hashimoto thyroiditis were stained with antibodies to HBME1 and cytokeratin (CK)19. Tiny HBME1+ and CK19+ atypical cell clusters were identified and analyzed for the BRAF mutation by the colorimetric Mutector assay and allele-specific polymerase chain reaction. HBME1+ and CK19+ atypical cell clusters were identified in 12 (20%) of 59 cases. The minute size (<1 mm) of the clusters and the incomplete nuclear changes precluded a diagnosis of papillary microcarcinoma. The atypical cell clusters from all 12 cases were negative for BRAF. The absence of the BRAF mutation in these atypical cell clusters suggests that they may not be preneoplastic. Caution should be exercised in interpreting positive HBME1 or CK19 staining in Hashimoto thyroiditis.