Presence of BRAF V600E in Very Early Stages of Papillary Thyroid Carcinoma

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Abstract
Objective: Extremely small (often 0.5-4 mm) incidental thyroid malignancies (incidental microcarcinomas, IM) might be discovered at histological examination after surgery in patients who were operated on for benign thyroid conditions. Morphologically, these malignancies have virtually always features of differentiated papillary thyroid carcinoma (PTC). Although IM are in general considered of little clinical significance their potential malignant behavior cannot be ignored. BRAF(V600E) mutation has emerged as the most prevalent genetic alteration in PTC. Design: The incidence of BRAF(V600E) was studied in 85 microdissected cases of IM detected in two series of 334 and 398 patients operated on for benign thyroid disease in 2005 and in 2006, respectively. IM ranged in size from 0.5 to 4 mm and all featured cytology consistent with the diagnosis of PTC. Microdissected lesions were also evaluated for galectin-3 expression by immunohistochemistry. Main outcome: BRAF(V600E) was identified in 15 out of 85 (17.6%) IM compared to 45% clinically evident PTCs (n = 91) and 38.3% preoperatively identified microcarcinomas (n 47). Conclusion: These data suggest that it is possible to find BRAF(V600E) in IM despite their extremely small (<1 mm) size. This is not a formal demonstration that IM can evolve into clinical PTC, but on these bases, patients with BRAF(V600E) IM may need to be managed more carefully