Clinicopathologic features and BRAF^V600E mutation analysis in cutaneous metastases from well-differentiated thyroid carcinomas

BACKGROUND. Cutaneous metastases from well-differentiated thyroid carcinomas are rare and are usually identified in patients with widely disseminated disease. Occasionally, thyroid carcinomas can present as cutaneous metastases for which the primary site needs to be determined. Papillary thyroid carcinomas (PTCs) commonly have BRAF^V600E mutation. A series of 16 cutaneous metastases were analyzed from well-differentiated thyroid carcinomas to learn more about the clinicopathologic features and BRAF^V600E mutation status. METHODS. Eleven cases of PTC and 5 of follicular thyroid carcinoma (FTC) metastatic to the skin were evaluated. All cutaneous metastases were studied histologically and with thyroglobulin and thyroid transcription factor immunostains. All tumor samples were analyzed for mutations at nucleotide 1799 in exon 15 of the BRAF gene. RESULTS. Two patients with FTC presented with cutaneous metastases. Fourteen of 16 patients died of disease and 2 were alive with disease at follow-up. The histologic features of the cutaneous metastases were generally characteristic of the primary tumor; however, 2 of the 11 PTC metastases demonstrated cytoplasmic clearing not typical of classic PTC. BRAF^V600E mutation (T1799A) was detected in 5 of 11 cases of PTC and in none of the 5 FTCs. CONCLUSIONS. Cutaneous metastases from PTC may show prominent clear cell change requiring differentiation from clear cell hidradenoma, clear cell dermatofibroma, malignant melanoma with prominent clear cell change, and cutaneous metastasis from renal cell carcinoma. BRAF ^V600E mutation is identified in a subset of cutaneous metastases from PTC. Cutaneous metastases from PTC and FTC are associated with a very poor prognosis.