A Case of Multifocal Papillary Thyroid Carcinoma Consisting of One Encapsulated Follicular Variant with BRAF K601E Mutation and Three Conventional Types with BRAF V600E Mutation
A 44-year-old female was referred from a local clinic for a papillary carcinoma of the thyroid that was diagnosed by fine needle aspiration. The patient did not have a past history of neck radiation or a family history of thyroid cancer. Thyroid ultrasonography revealed a spiculated, hypoechoic solid nodule measuring 0.8 cm in diameter with a capsular invasion at the left paraisthmic area of the thyroid. The ultrasonography also revealed three smooth, oval, and slightly hypoechoic solid nodules measuring 2.3 cm, 1.3 cm, and 0.8 cm in diameter at the right upper, middle, and lower lobes, respectively. The lymph nodes at the central and lateral neck were not significantly enlarged. Total thyroidectomy with central node dissection was performed.\nThe specimen consisted of a reddish brown total thyroidectomy tissue. The right thyroid gland measured 4.5×2.3×2.0 cm, and the left thyroid gland measured 4.5×2.3×1.7 cm. Both glands weighed 20 g in total. On the serial cut sections of the right thyroid, there were two ill-defined grayish white solid masses measuring 1.2×0.9×0.6 cm and 2.1×1.9×1.5 cm at the upper and lower poles, respectively. At the right mid pole, there also was a well-defined tan, yellow, solid mass measuring 1.3×1.1×0.8 cm. On the serial cut sections of the left lobe, there was an ill-defined grayish white nodule measuring 0.8×0.6×0.5 cm at the paraisthmic area.\nHistological examination revealed three conventional PTCs in the right upper and lower poles and also in the left paraisthmic area. All the conventional PTCs revealed an infiltrative growth pattern with typical histological features. The mass at the right mid pole was characterized by total encapsulation without papilla formation or psammoma bodies and corresponded to the encapsulated variant of FVPTC. Characteristic nuclear features, particularly nuclear enlargement, chromatin clearing and irregular nuclear contours were present. Nuclear grooves were present, but not frequently. Deeply eosinophilic colloid with peripheral scalloping was also present (). Three perithyroidal lymph nodes were involved by conventional PTC.\nImmunohistochemical staining was performed on the 5-µm-thick sectioned slides obtained from the formalin-fixed, paraffin embedded tissue using an autoimmunostainer (Ventana, Tucson, AZ, USA) with monoclonal mouse anti-cytokeratin 19 (CK19) antibody (clone A53-B/A2.26, NeoMarkers, Fremont, CA, USA) and polyclonal rabbit anti-galectin-3 antibody (Zymed, San Francisco, CA, USA). The tumor cells of the conventional PTC exhibited a strong, diffusely positive immunoreactivity to CK19 (1:1,500) and galectin 3 (1:100), whereas the tumor cells of the follicular variant revealed no reactivity to galectin 3, and showed only focal and weak staining to CK19 ().\nThe tumor cells were micro-dissected from both the conventional and follicular variant areas of the hematoxylin and eosin stained 10 µm-thick sections of the formalin-fixed, paraffin embedded tissue. The genomic DNA was extracted using the extraction buffer solution (50 mM Tris buffer, pH 8.3; 1 mM EDTA, pH 8.0; 5% Tween 20 and 100 µg/mL proteinase K). Mutations of V600E (T1799A) and K601E (A1801G) in exon 15 of the BRAF gene and the codons 12, 13, and 61 of the KRAS and NRAS genes were evaluated by the pyrosequencing method. The DNA extracted from the FVPTC foci revealed a BRAF K601E (A1801G) mutation. The conventional PTCs revealed BRAF V600E (T1799A) mutations in all 3 tumors (). Neither the conventional nor follicular variant revealed KRAS or NRAS mutations.