Primary pure squamous cell carcinoma of the thyroid: report and histogenic consideration of a case involving a BRAF mutation.

Primary squamous cell carcinoma of the thyroid (SCC-T) is extremely rare. Its clinical presentation is similar to that of anaplastic carcinoma. Metastasis or extension from the head and neck area should be ruled out, as patients with SCC-T have a poorer prognosis than patients who have a thyroid extension from an adjacent tumor. An 87-year-old man presented with a longstanding painless mass in the right thyroid and had experienced 2 months of pain upon swallowing. A right lobectomy was performed with resection of thyroid cartilage, cricoid cartilage, a portion of the first to third tracheal ring and the right neck lymph node. A histological examination revealed pure SCC. The tumor cells showed diffuse immunoreactivity to CK5/6, CK19 and p63. Immunoreactivity to EMA and p53 was focally positive. TTF-1, galectin 3 and thyroglobulin immunoreactivity was restricted to the non-neoplastic thyroid tissue. Both tumor cells and non-neoplastic follicular cells were negative for CD5. The MIB-1 index was 36%. DNA extracted from the tumor identified a BRAF V600E mutation in exon 15 and a BRAF G468A mutation in exon 11, whereas DNA from non-tumorous cells did not contain a mutation. These molecular findings may suggest a direct transformation from papillary carcinoma to SCC-T.

Surgical results of thyroid nodules according to a management guideline based on the BRAF(V600E) mutation status.

CONTEXT: In Korea, where PTC comprises about 90-95% of the reported thyroid cancers, the prevalence of BRAF(V600E) mutation in papillary thyroid carcinoma (PTC) is above 80%. OBJECTIVE: We analyzed the surgical result according to a management guideline based on the BRAF(V600E) mutation status of thyroid nodules. DESIGN: A total of 865 thyroid nodules were prospectively analyzed for their cytology and BRAF(V600E) mutation status by pyrosequencing. For the patients who had a diagnosis of atypical cells of undetermined significance (ACUS), we recommended surgery when there was positivity for BRAF(V600E) mutation or the nodules were clinically suspicious. RESULTS: Among 865 cases, 504, 141, 54, 140, 10, and 16 were diagnosed as benign, ACUS, suspicious for malignancy, malignant, suspicious for follicular neoplasm, and nondiagnostic, respectively. None of the 504 benign, 45 (31.9%) of the 141 ACUS, 46 (85.2%) of the 54 suspicious for malignancy, 129 (92.1%) of the 140 malignant, and one (10%) of the 10 suspicious for follicular neoplasm cases showed BRAF(V600E) mutation. Surgery was recommended to all 45 patients with BRAF(V600E) mutation-positive ACUS nodules; among them, 30 patients underwent surgery, 29 had PTC, and one had nodular hyperplasia. All the patients diagnosed as suspicious for malignancy or malignant were advised to undergo an operation, and they turned out to have PTCs regardless of their BRAF(V600E) mutation status. CONCLUSIONS: We found that performing BRAF(V600E) mutation analysis on the fine-needle aspiration biopsy specimens was of great help to make a therapeutic decision for thyroid nodules when the fine-needle aspiration biopsy results were equivocal.

Clinical and pathological features and the BRAF(V600E) mutation in patients with papillary thyroid carcinoma with and without concurrent Hashimoto thyroiditis.

BACKGROUND: It has been reported that patients with papillary thyroid carcinoma (PTC) have a high incidence of background Hashimoto thyroiditis (HT); however, the linkage of HT to PTC is controversial. Recent studies have shown that the prevalence of activating point mutations in BRAFV600E is much higher (73-86%) in Korea than in Western countries (29-69%), and associated with a poor prognosis in PTC. The purpose of the present study was to investigate the frequency of the BRAFV600E mutation in PTC with and without HT, and to determine clinical and pathological features that were associated with concomitant HT and PTC. METHODS: Fine-needle aspiration slides from 101 patients with surgically confirmed PTC were studied. The DNA was extracted from the atypical cells that were scraped from slides. It was then analyzed for the BRAFV600E mutation by pyrosequencing. In addition, the presence of background HT in surgical specimens and other clinical and pathological features of the patients were characterized. RESULTS: HT was present in 37 (36.6%) of the patients. The BRAFV600E mutation was present in 27 (72.9%) of patients with HT but was present in 61 (95.3%) of patients without HT ( p#0.01). The inverse correlation of concurrent HT with the BRAFV600E mutation was significant for both males and females ( p < 0.01). The presence of background HT was not associated with tumor size, extrathyroidal invasion, lymph node (LN) metastasis, or tumor stage. The patients were younger in the group without background HT (44.1 +/- 13.2 vs. 49.8 +/- 13.9, p 1/40.05). The BRAFV600E mutation was present in 88 (87.1%) of the 101 patients with PTC. The presence of the BRAFV600E mutation was significantly associated with LN metastasis ( p < 0.02; odds ratio, 6.24; 95% confidence interval, 1.51-25.79). CONCLUSION: In Korean patients with PTC, the BRAFV600E mutation is associated with a lower frequency of background HT and a high frequency of LN metastasis.