BRAF mutation in solid cell nest hyperplasia associated with papillary thyroid carcinoma. A precursor lesion?

We describe a case of solid cell nest hyperplasia associated with papillary thyroid carcinoma in a 48-year-old man with goiter. The entire gland was examined; in 1 section, the cells of 1 solid cell nest were in close contact with a follicular variant of papillary microcarcinoma. A second follicular variant of papillary microcarcinoma, 1 follicular adenoma, hyperplastic nodules, and some lymphoid aggregates were also found. Scattered p63-positive cells were found in the second papillary microcarcinoma. After microdissection, the same BRAF(V600E) mutation was found both in a pool of 5 solid cell nests and in the adjacent papillary microcarcinoma. BRAF(V600E) mutation and the previously unreported BRAF(G593D) mutation along with p.G606G silent change were found in the second papillary microcarcinoma, but no mutations were detected in the follicular adenoma or in the 2 other pools of solid cell nests screened for BRAF gene mutations. These findings support a histogenetic link between the main cells of solid cell nests and papillary thyroid carcinoma, and suggest solid cell nest hyperplasia as a precursor lesion of papillary thyroid carcinoma.