Comparison of Immunohistochemistry and Direct Sequencing Methods for Identification of the BRAFV600E Mutation in Papillary Thyroid Carcinoma.

BACKGROUND: BRAFV600E mutation is the most common somatic variant in papillary thyroid carcinoma (PTC) and is associated with aggressive prognostic factors. The conventional detection method for BRAF mutations is polymerase chain reaction followed by Sanger sequencing. Recently, an immunohistochemistry (IHC) method using a BRAFV600E-specific antibody (VE1) has been developed and widely adopted in the clinics; however, there is a lack of evidence regarding the comparability of the IHC and Sanger sequencing methods. METHODS: Our institution began using the BRAFV600E IHC test in January 2013. We retrospectively analyzed 697 samples that were tested using both the IHC and sequencing methods, and evaluated their concordance. RESULTS: BRAF mutation was detected in 90.0% (627/697) of samples using IHC and 83.4% (581/697) of samples using direct sequencing. The diagnostic parameters of IHC compared with Sanger sequencing were as follows: 100% sensitivity (581/581), 60.3% specificity (70/116), 92.7% positive predictive value (581/627), and 100% negative predictive value (70/70). No false negative results were recorded using IHC. The overall concordance rate between the two methods was 93.4% (651/697). Discordant results were found in 46 samples (6.6%), 29 of which were from cases with small tumors (< 6 mm), 8 were from cases with low tumor cellularity, and 9 were specimens yielding low-quality DNA. CONCLUSIONS: IHC using the VE1 antibody is a reliable and highly sensitive method for detecting the BRAFV600E mutation in classic PTC.

Development of a surgical training model for bilateral axillo-breast approach robotic thyroidectomy.

BACKGROUND: Bilateral axillo-breast approach robotic thyroidectomy (BABA RT) is an excellent surgical method, being oncologically safe and with anatomic views similar to those of open surgery. BABA RT, however, requires training and a learning curve for proficiency. We evaluated the educational effectiveness of a surgical training model for BABA RT, comparing objective BABA scores with scores on the da Vinci Skills Simulator (dVSS). METHODS: Medical students, surgical residents, and surgical fellows performed structured tasks with the BABA training model and dVSS under the same conditions. All tasks were videotaped. BABA scores were compared with dVSS scores and with objective evaluation scores (GEARS and OSATS). RESULTS: Eight medical students, ten surgical residents, and eight surgical fellows participated in this study. The educational effect of BABA training improved from one to two (p < 0.001), two to three (p = 0.003), and one to three (p < 0.001) procedures. Statistically significant differences were found when students were compared with residents (p = 0.025) and fellows (p < 0.001) in the BABA training model, and between students and fellows (p = 0.004) in dVSS. BABA scores showed similar distribution patterns in the three groups to GEARS and OSATS scores (p < 0.001 each). CONCLUSIONS: The BABA training model is an excellent educational tool for surgical residents and surgical fellows to learn and practice BABA RT. Assessment by BABA score yielded objective results comparable to those of traditional scoring methodologies.

Upregulation of the ESR1 Gene and ESR Ratio (ESR1/ESR2) is Associated with a Worse Prognosis in Papillary Thyroid Carcinoma: The Impact of the Estrogen Receptor α/ß Expression on Clinical Outcomes in Papillary Thyroid Carcinoma Patients.

BACKGROUND: A gender disparity exists with respect to the incidence of papillary thyroid cancer (PTC), suggesting that sex hormones such as estrogen play a role in PTC development and progression. In this study, we compared estrogen receptor gene expression patterns in PTCs to determine the clinical significance of estrogen gene expression in PTC. METHODS: We analyzed ESR1 and ESR2 messenger RNA expression counts using data from The Cancer Genome Atlas (TCGA). To validate the results of TCGA analysis, we analyzed microarray data (GSE 54958) from the Gene Expression Omnibus. RESULTS: ESR1 gene expression and ESR ratio (ESR1/ESR2) were significantly higher in PTC tissues than in paired normal thyroid tissues (mean 659.427 vs. 264.045 for ESR1, 92.017 vs. 19.064 for ESR ratio). Among female patients, ESR1 expression and ESR ratio were negatively correlated with increased age. ESR1 expression and ESR ratio were higher in patients with classic PTC, lymphovascular invasion, BRAF V600E mutation, and radioiodine therapy. Classification analysis demonstrated that higher ESR1 expression and a higher ESR ratio faced a worse overall survival (hazard ratio 6.348 for ESR1, 4.031 for ESR ratio). Validation microarray analysis demonstrated that ESR1 expression and ESR ratio were higher in tumor tissues, classic PTC, and BRAF V600E. CONCLUSION: Higher ESR1 expression and a higher ESR ratio were associated with aggressive prognostic factors and worse overall survival in female PTC patients. Our results suggest that ESR1 and ESR ratio can be used as prognostic markers to predict female patient survival and have potential as a therapeutic target.

Novel method to save the parathyroid gland during thyroidectomy: Subcapsular saline injection.

BACKGROUND: Saving the parathyroid gland during thyroidectomy remains challenging. Subcapsular saline injection (SCASI) was developed in February 2015. Its ability to spare the parathyroid gland was assessed. METHODS: All consecutive patients who underwent total thyroidectomy with or without neck lymph node dissection in 2013-2015 were included in this retrospective cohort study. Patients were divided into the SCASI and non-SCASI groups. Serum parathyroid hormone (PTH) levels were measured on day 1 and 6 months after surgery. Transient and permanent hypoparathyroidism were defined as day 1 and 6 month PTH < 10.0 and <15.0 pg/mL, respectively. RESULTS: The groups (both had 98 patients each) did not differ in demographics, tumor size, operation extent, pathology, thyroiditis rate, and incidental parathyroid gland excision rate. Compared with non-SCASI patients, patients who underwent the SCASI method exhibited transient hypoparathyroidism (35.7% vs 19.4%, P < .001) and permanent hypoparathyroidism (4.1% vs 0%, P = .043) significantly less frequently. CONCLUSION: The procedure of SCASI effectively spared the parathyroid gland during thyroidectomy.

Significance of distance between tumor and thyroid capsule as an indicator for central lymph node metastasis in clinically node negative papillary thyroid carcinoma patients.

The aim of this study was to evaluate preoperatively identifiable clinical and ultrasonographic characteristics associated with central lymph node metastasis (CLNM) in clinically node negative papillary thyroid carcinoma (PTC) patients. Records of the patients who underwent thyroidectomy with prophylactic central lymph node dissection due to clinically node negative PTC (size, 1.0-3.0 cm) were reviewed. Of a total of 174 patients, 71 (40.8%) had CLNMs. CLNM was more associated with capsule invasion than capsule non-invasion on ultrasonography (68.4% vs. 37.4%, p = 0.009). In the 155 patients without capsule invasion, a distance from the capsule < 1.9 mm was associated with CLNM in univariable (p = 0.002) and multivariable analysis (p < 0.001). Any PTC patient with a distance from the capsule ≥ 1.9 mm did not have CLNM whereas 40.8% (58/142) of PTC patients with a distance from the capsule < 1.9 mm had CLNM. CLNM was not associated with age, gender, or tumor size on ultrasonography. Distance from capsule ≥ 1.9 mm on preoperative ultrasonography was a significant indicator for not having CLNM in clinically node negative PTC patients. Measuring distance from the capsule on preoperative ultrasonography images could help select patients with PTC who could benefit from prophylactic central lymph node dissection.

A Novel RET D898Y Germline Mutation in a Patient with Pheochromocytoma.

Pheochromocytoma and paraganglioma are tumors of neuroectoderm origin. Up to 40% of patients with these tumors have germline mutations in known susceptibility genes. We report a novel RET germline mutation (exon 15; c.2692G>T (D898Y)) in a pheochromocytoma patient, as well as in her two asymptomatic sons and older sister. A 49-year-old female came to our clinic presenting with a right adrenal gland mass detected during a healthcare examination. Her mother and two sisters had previously undergone thyroidectomy for papillary thyroid carcinomas. The levels of vanillylmandelic acid and other catecholamines were elevated in 24-hour urine, and an imaging study revealed a right adrenal mass. She underwent laparoscopic adrenalectomy and the final pathologic diagnosis was pheochromocytoma. Mutation screening detected a RET p.D898Y mutation, both in the patient and in the patient's two sons and older sister. This is the first description of a RET D898Y mutation in a pheochromocytoma patient and her family. The mutation should be categorized as a variant of unknown significance because no RET gene related disorders were detected in this family. Long term follow-up will be required to determine the clinical significance of the RET D898Y mutation.

Erratum: Addition of funding statement: Clinical characteristics of papillary thyroid carcinoma arising from the pyramidal lobe.

[This corrects the article on p. 123 in vol. 92, PMID: 28289665.].

Clinical characteristics of papillary thyroid carcinoma arising from the pyramidal lobe.

PURPOSE: Papillary thyroid carcinoma (PTC) arising from the pyramidal lobe is rare; therefore, clinicopathologic evaluation is lacking. In addition, the rate of occult malignancy in the pyramidal lobe after thyroid surgery is unclear. This study is to evaluate the clinical characteristics of PTCs that involve the pyramidal lobe. METHODS: The study enrolled 1,107 patients who underwent thyroid surgery for PTC at Seoul National University Hospital from 2006 to 2015. Pyramidal lobe status in pathologic reports was clear in all cases. "Pyramidal lobe-dominant PTC" was defined as single pyramidal lobe cancer or multifocal cancer with larger pyramidal lobe tumor. "Incidental pyramidal lobe PTC" was defined as occult cancer identified after thyroidectomy or as multifocal cancer with smaller pyramidal lobe tumor. RESULTS: Ten patients were included in the pyramidal lobe-dominant PTC group. The mean age was 58 ± 12.5 years, and the mean tumor size was 0.7 ± 0.7 cm. Cervical lymph node metastasis was found in 5 patients (50%). Three patients had microscopic lymphatic invasion, and 7 had advanced American Joint Comitee on Cancer (AJCC) stage disease (5 with stage III and 2 with stage IV). Compared with conventional PTC (n = 1,058), pyramidal lobe-dominant PTC was significantly associated with lymphatic invasion (P = 0.031) and advanced AJCC stage (P = 0.022). The prevalence of incidental pyramidal lobe PTC was 3.56%. CONCLUSION: Pyramidal lobe PTC is relatively small in size; however, the rate of extrathyroidal extension and lymph node metastasis is high. Preoperative evaluation of nodal status is important, and the extent of surgery should be determined in accordance with the preoperative diagnosis.