Thyroid Rests or Malignancy: Can BRAF Mutation Analysis Help in the Differential Diagnosis?
Anna Best, Cary Chisholm, Daniel Smith, Mae K Lopez, Kimberly Walker, Robert S Beissner, Arundhati Rao. Scott & White Memorial Hospital and Texas A&M Health Science Center College of Medicine, Temple, TX
Background: Thyroid rests can pose diagnostic challenges for status of metastatic disease in papillary thyroid carcinoma (PTC). BRAF V600E mutations are commonly seen in PTC and may indicate aggressive behavior. Mutational status can serve to differentiate metastases from benign rests. To our knowledge, only one case has reported in which a benign-appearing thyroid rest in a cervical lymph node was reclassified as a PTC metastasis by testing for the BRAF V600E mutation. We present the first case series in which BRAF mutation status is investigated in multiple lymph nodes with thyroid rests.
Design: We identified 20 cases of thyroid rests from 1988-2011. 13 were diagnosed as benign and seven were indeterminate as benign versus metastatic. 10/13 benign rests were in patients with PTC; five had other metastases. 3/13 cases were discovered incidentally, not in the context of a known PTC. All seven indeterminate rests were in cases of PTC; four had metastases in other nodes. Five control cases of metastatic PTC in lymph nodes and five primary PTC's without metastases were identified. Cells from areas of interest were laser-captured, amplified using Quiagen's BRAF Pyro Kit and analyzed on the PryoMark Q24 sequencer.
Results: BRAF mutations were not identified in the 20 benign and indeterminate rests, including cases with metastases to lymph nodes. Five of the 10 benign-appearing rests had metastases in other nodes: two had BRAF mutation in the primary and in the metastasis, and three had the mutation in the primary but not in the metastasis. In the other five cases, three had BRAF mutation in the primary and two did not. 4/7 indeterminate cases had metastases in other nodes: two had BRAF mutations in the primary and in the metastases, one had the mutation in the primary only, and one had the mutation in the metastasis only. 3/7 were without metastases and had BRAF mutations in the primary. 4/5 PTC control cases with metastases had the BRAF mutation in the primary only, and one was negative. 4/5 PTC control cases without metastases had BRAF mutation and one did not.