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Simple Summary: This study investigated the impact of age and BRAFV600E mutation on papillary thyroid cancer (PTC) recurrence. Among patients with BRAFV600E-positive PTC, those under 35 years of age had a significantly higher risk of recurrence than those over 55 years. However, in BRAFV600E-negative patients, age had no impact on the risk of recurrence. These findings emphasize the importance of considering age and mutation status in tailoring PTC treatment and follow-up. BRAFV600E positivity is associated with increased aggressiveness of papillary thyroid cancer (PTC), and age is an important prognostic factor. However, the association between age and BRAFV600E positivity and the recurrence risk has not been investigated. This study aimed to investigate the impact of age on recurrence between patients with BRAFV600E-positive and -negative PTC. Patients with PTC who underwent initial thyroid surgery between January 2010 and December 2018 at Seoul St. Mary's Hospital (Seoul, Republic of Korea) were retrospectively reviewed. The BRAFV600E-positive (n = 1768) and BRAFV600E-negative groups (n = 428) were divided into two subgroups: younger (<35 years) and older groups (≥55 years). In the BRAFV600E-positive group, the younger group exhibited higher lymphatic and vascular invasion rates, more positive lymph nodes, higher lymph node ratios, and higher recurrence rates than the older group (5.9% vs. 2.1%). Multivariate analysis revealed that age, lymphatic invasion, and N category were significant risk factors in the BRAFV600E-positive group. In the BRAFV600E-positive group, the younger group had a higher recurrence risk than the older group (OR, 2.528; 95% confidence interval, 1.443–4.430; p = 0.001). In the BRAFV600E-negative group, age had no impact on recurrence risk. These results contribute to tailored treatment strategies and informed patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Multifocality is often found in PTC. There are contradicting evidences regarding clinical implications of cancer laterality in multifocal PTC. The current study compared the clinicopathological characteristics and the long-term oncological outcomes of bilateral and unilateral multifocal PTC. Patients with bilateral PTC were more likely to present with aggressive features, including high tumor stage, cervical LN metastasis, gross ETE, and lymphatic and perineural invasion. On the multivariate analysis using Cox regression, gross ETE, perineural invasion, LN metastasis, N1b stage, and RAI therapy were significant risk factors of recurrence. However, bilaterality was not associated with an increased risk of recurrence. In order to reduce selection bias, a subgroup analysis of patients who underwent total thyroidectomy was conducted using propensity score matching. After matching, unilateral multifocality, vascular invasion, and RAI therapy were significant risk factors of recurrence. Patients with unilateral multifocal PTC showed significantly poorer DFS than those with bilateral PTC on the Kaplan-Meier analysis. Papillary thyroid cancer (PTC) is commonly characterized by multifocality, which is associated with aggressive features and a less favorable prognosis. The current study aimed to compare the clinicopathologic characteristics and long-term oncological outcomes of bilateral and unilateral multifocal PTC. The medical records of 1745 patients with multifocal PTC who underwent thyroid surgery at Seoul St. Mary's Hospital were retrospectively reviewed. The clinicopathological characteristics and recurrence rates were compared based on cancer laterality. Further, 357 patients who underwent total thyroidectomy were matched to investigate the recurrence risk and disease-free survival (DFS). Before propensity score matching (PSM), there was no significant difference in the recurrence rate between the bilateral and unilateral multifocal PTC groups. Cancer laterality was not a predictor of DFS based on the Cox regression analyses. However, after PSM, unilateral multifocality was associated with a significantly high risk of recurrence. Similarly, unilateral multifocality was associated with a significantly poor DFS based on the Kaplan–Meier analysis. Compared with bilateral PTC, unilateral multifocal PTC was associated with a poor DFS. A comprehensive preoperative examination should be performed to detect multifocality before the initial surgical intervention for optimal treatment. Postoperative short-term follow-up is recommended for unilateral multifocal PTC for recurrence surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: In a retrospective study, researchers analyzed data from 909 patients with papillary thyroid carcinoma (PTC) who underwent thyroidectomy and neck dissection. The aim was to validate the relationship between lymph node ratio (LNR) and recurrence in patients with fewer than six lymph nodes examined after surgery. Over an average follow-up of 127.24 ± 33.6 months, recurrences occurred in 5.1% of the patients. The analysis identified an LNR ≥ 0.29 as an independent prognostic factor for recurrence. This means that patients with an LNR equal to or higher than 0.29 had a higher likelihood of recurrence compared to those with a lower LNR. These findings highlight the importance of considering LNR as a valuable prognostic marker for PTC patients with limited lymph node examination. Incorporating LNR into risk assessment can improve recurrence prediction and help guide treatment strategies. However, further prospective studies are needed to validate these results and determine their clinical implications in managing PTC patients. The American Thyroid Association risk stratification system suggests that having >5 metastatic lymph nodes (LNs) increase the recurrence risk in patients with papillary thyroid carcinoma (PTC). However, little is known about PTC with <5 harvested LNs. This study aimed to stratify patients with low-LN-yield (low-LNY) PTC based on lymph node ratios (LNRs). From 2007 to 2017, 6317 patients who underwent thyroidectomies were diagnosed with PTC at Seoul St. Mary's Hospital, and 909 patients with low LNYs were included in the study. Tumor recurrence was compared based on LNR. The LNR cutoff was determined using a receiver operating characteristic curve. Forty-six patients (5.1%) experienced recurrences over a mean follow-up period of 127.24 ± 33.6 months (range, 5–190 months). The cutoff for the low-LNR (n = 675) and high-LNR (n = 234) groups was 0.29 (AUC = 0.676, 95% CI = 0.591–0.761, p < 0.001). The recurrence rate was significantly higher in the high-LNR group compared to the rate in the low-LNR group (12.4% vs. 2.5%, p < 0.001). Multivariate analysis using Cox regression revealed that tumor size and LNR ≥ 0.29 were independent prognostic factors for recurrence. Therefore, LNR can be utilized to stratify the risk of recurrence in patients with low-LNY PTC. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. However, real-world data of its effectiveness and safety in various clinical situations are lacking. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib with variable clinical situations. Selpercatinib showed good efficacy in all four patients without significant side effects. Despite facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy, although drug safety and durability through long-term use should be further validated. Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib. The first patient was a 63-year-old male with advanced medullary thyroid cancer (MTC) treated with vandetanib. Six months ago, he had an intracranial hemorrhage and swallowing difficulty. He started selpercatinib with percutaneous endoscopic gastrostomy (PEG). For 11 months, a partial response (PR) was observed stably with PEG administration without any more cardiovascular events. The second patient was a 67-year-old female with advanced MTC treated with vandetatib. After selpercatinib treatment, a PR was observed for most metastatic sites, including choroidal metastasis. The third patient was a 32-year-old female with advanced papillary thyroid cancer (PTC) without history of systematic treatment. For six months, a PR was observed at her metastatic site with manageable adverse events. The last patient was a 59-year-old female with advanced PTC treated with lenvatinib. She suffered from a panic disorder and pleural pain due to metastasis during lenvatinib treatment. After selpercatinib treatment, her pain and panic symptoms were improved. Facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy regardless of previous treatment or metastatic site. [ABSTRACT FROM AUTHOR]

Simple Summary: In the 8th edition of the AJCC/UICC TNM staging system, T3b is defined as gross extrathyroidal extension (gETE) invading only the strap muscles from a tumor of any size. However, defining T3b according to tumor size remains controversial. We created new T3b categories according to tumor size (T3b-1, tumor ≤ 2 cm in T3b; T3b-2, 2 cm < tumor ≤ 4 cm in T3b). There was a significant difference only in T3b-2 compared to T2. Novel methods of evaluating the effect of gETE according to tumor size should be considered in further revisions of the AJCC/UICC TNM staging system. The purpose of the present study was to compare the risk of recurrence between T2 and T3b papillary thyroid carcinoma (PTC) and the effect of tumor size on survival in T3b disease. A total of 634 patients with PTC who underwent thyroid surgery at a single center were retrospectively analyzed. Clinicopathological characteristics were compared according to the T category in the TNM staging system, with T3b divided into T3b-1 (tumor size, ≤2 cm) and T3b-2 (tumor size, 2–4 cm). Disease-free survival (DFS) and recurrence risk were compared between T2, T3b, T3b-1, and T3b-2. Tumor size was significantly larger in T2 than in T3b. A significant difference in recurrence was observed between T2 and T3b-2 but not between T2 and T3b-1. T3b-2 was identified as a significant risk factor for PTC recurrence. A significant difference in the DFS curve was observed between T2 and T3b-2. However, no significant differences in survival were observed between T2 and T3b or T3b-1. These results indicate that the prognostic impact of T3b may vary depending on tumor size. Further studies are required to determine the need for T classifications that account for tumor size and gETE invasion of the strap muscles. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recently, the single-port (SP) robotic system was introduced for minimally invasive operative techniques. Thus, this study aimed to validate the safety and feasibility of SP trans-axillary robotic thyroidectomy (SP-TART) through experiences in a single tertiary institution. Materials and Methods: This study retrospectively analyzed 100 consecutive patients who underwent SP-TART from October 2021 to June 2022 in Seoul St. Mary's Hospital in Seoul, Korea. We analyzed the clinicopathological characteristics and perioperative outcomes, including complications. Results: Less than total thyroidectomy (LTT) was performed in 81, total thyroidectomy (TT) in 16, and TT with modified radical neck dissection (mRND) in 3 patients. The mean operation time (min) was 53.3 ± 13.7, 86.3 ± 15.1, and 245.7 ± 36.7 in LTT, TT, and TT with mRND, respectively. The mean postoperative hospital stay was 2.0 ± 0.2, 2.1 ± 0.3, and 3.7 ± 1.5 days, respectively. A total of 84 cases of thyroid cancer were included, and 97.6% of them (82 cases) were papillary carcinoma and the rest were follicular and poorly differentiated carcinomas. Regarding complications, five cases had major complications, including three cases of vocal cord palsy and two cases of transient hypoparathyroidism. Conclusions: SP-TART is safe and feasible with a short operation time and a short length of hospital stay. [ABSTRACT FROM AUTHOR]

The extent of surgery among patients with T2 papillary thyroid carcinoma (PTC) remains controversial. Thus, we herein aimed to evaluate the risk factors for recurrence, particularly based on the extent of surgery, among patients with T2 PTC at a single tertiary institution. We assessed 251 patients who underwent thyroid surgery for T2 PTC from January 2009 to December 2014 at Seoul St. Mary's Hospital (Seoul, Korea). The mean follow-up duration was 100.7 months. Eleven (4.4%) patients had recurrence. The recurrence rates did not significantly differ in terms of the extent of surgery (p = 0.868). Patients with a high lymph node ratio (LNR) had a significantly higher recurrence rate than those with a low LNR (p < 0.001). According to a recurrence pattern analysis, five of six patients in the lobectomy group had recurrence in the ipsilateral lateral compartment. A multivariate analysis revealed that a high LNR was a significant risk factor for recurrence (hazard ratio: 11.025, p = 0.002). Our results suggest that patients without clinical evidence of any lymph node metastases and those with limited lesions in the thyroid gland can undergo lobectomy and LNR can serve as an independent risk factor for predicting recurrence in T2 PTC. [ABSTRACT FROM AUTHOR]

Simple Summary: The lymph node ratio (LNR) is an emerging predictive marker for recurrence in papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the association between LNR and disease-free survival (DFS) in patients with N1b PTC. Unlike that in the lateral or whole neck, LNR in the central compartment (CLNR) was found to have prognostic significance. The high-CLNR group (CLNR ≥ 0.7) had worse DFS and was 4.5 times more likely to experience recurrence in patients with N1b PTC. The lymph node ratio (LNR) indicates the number of metastatic lymph nodes (LNs) to the total number of LNs. The prognostic value of LNR in papillary thyroid carcinoma (PTC) and other solid tumors is known. This study aimed to investigate the relationship between LNR and disease-free survival (DFS) in patients with PTC with lateral LN metastases (N1b PTC). A total of 307 patients with N1b PTC who underwent total thyroidectomy and therapeutic central and lateral LN dissection were retrospectively analyzed. The DFS and recurrence risk in the patients with LNR, central-compartment LNR (CLNR), and lateral-compartment LNR (LLNR) were compared. The mean follow-up duration was 93.6 ± 19.9 months. Eleven (3.6%) patients experienced recurrence. Neither LNR nor LLNR affected the recurrence rate in our analysis (p = 0.058, p = 0.106, respectively). However, there was a significant difference in the recurrence rates between the patients with low and high CLNR (2.1% vs. 8.8%, p = 0.017). In the multivariate analysis, CLNR ≥ 0.7 and perineural invasion were independent predictors of tumor recurrence. High CLNR was associated with an increased risk of recurrence, and was shown to be a significant predictor of prognosis in patients with N1b PTC. [ABSTRACT FROM AUTHOR]

Papillary thyroid microcarcinoma (PTMC) has indolent features and low mortality. Recently, active surveillance (AS) instead of early surgery (ES) has been introduced as one treatment option but economical preference has not been established. The study objective was to systemically review the literature relating to cost-effectiveness of AS compared to ES for PTMC. Keywords were selected through PICO (Population, Intervention, Comparison, and Outcomes) tools. The search was conducted using PubMed, Cochrane, EMBASE, and Elsevier databases. Papers that had irrelevant titles were written in foreign languages, or had no original results were excluded. Out of the 62 papers extracted, five relevant to the subject matter of this study were identified. Three papers made their own decision models and proceeded with cost-effectiveness analysis (CEA), but the remaining two simply compared costs rather than cost-effectiveness. In terms of cost-effectiveness, three papers preferred AS, one preferred ES, and one preferred neither. The major differences in the CEA might arise from variations in each country's medical insurance system, the utility score systems, and decision models used. In subgroup analysis, two papers preferred AS to ES for patients at a younger age at diagnosis in terms of cost-effectiveness as well as tumor biological characteristics. Although AS has been generally more cost-effective than ES in previous publications, younger age at diagnosis could be one factor contributing to preference for ES. The CEA of prospective cohorts based on the decision model and utility score for thyroid cancer should be undertaken to confirm the cost-effectiveness of AS. [ABSTRACT FROM AUTHOR]

Background: There is an increased use of endoscopic thyroidectomy (ET), including robotic-assisted thyroidectomy (RT), to avoid postoperative scars on the anterior neck. The objective of this study was to compare the surgical and oncologic outcomes between ET and conventional open thyroidectomy (COT) for differentiated thyroid carcinoma (DTC).Methods: We reviewed 4129 patients with DTC who underwent thyroid lobectomy at Seoul St. Mary's Hospital (Seoul, Korea) from January 2009 to December 2014. Patients were categorized according to the type of surgery and statistically compared using propensity score matching analysis.Results: The mean operation time was significantly longer in the ET group than in the OT group (101.2 ± 26.2 min vs. 86.4 ± 27.0 min, p < 0.001). The number of harvested lymph nodes was significantly lower in the ET group than in the OT group (5.5 ± 4.2 vs. 8.3 ± 6.2, p < 0.001). There was no significant difference in the recurrence rate between the two groups (p = 0.879). Kaplan-Meier analysis revealed no significant difference in the disease-free survival after propensity score matching (p = 0.811). The mean follow-up duration was 90.4 ± 21.0 months.Conclusions: Transaxillary ET including RT for DTC is a safe and feasible alternative to COT with a cosmetically desirable outcome. Further studies are required to confirm our results. [ABSTRACT FROM AUTHOR]

Background: Some of patients are suffered from pitch lowering of voice after thyroidectomy. We sought to identify factors predictive of a recovery from lowered pitch voice after thyroid surgery. Methods: We retrospectively reviewed the records of 133 patients who underwent total thyroidectomy to treat papillary carcinoma between January 2012 and February 2013. Of these, we enrolled 78 who exhibited a lower-pitched voice (SFF fall > 12 Hz) at 2 weeks post-operatively than pre-operatively and investigated pitch recovery after 3 months. We subclassified patients into recovery and non-recovery groups and compared videostroboscopic findings, acoustic voice data, and thyroidectomy-related voice questionnaire scores pre-operatively and 2, 8, and 12 weeks post-operatively. Results: Vocal cord asymmetry on videostroboscopic examination at 2 weeks post-operatively (odds ratio 19.056, p = 0.001*) was more frequent in the non-recovery group. In acoustic analysis, mean pre-operative SFF was higher in the non-recovery group than the recovery group (190.9 ± 27.5 and 180.9 ± 24.6 Hz, respectively; p = 0.030*). Also, a reduction in the SFF of > 19.6 Hz, at 2 weeks post-operatively versus pre-operatively, predicted non-recovery of pitch-lowering in patients with reduced SFF within post-operative 3 months, with 72.0% sensitivity and 71.2% specificity. After 6 months of follow-up, no patient who exhibited an SFF fall > 19.6 Hz recovered to within 10 Hz of the pre-operative value. Conclusion: A reduction in the speaking fundamental frequency (SFF) > 19.6 Hz at 2 weeks post-operatively predicted persisting lowering of voice pitch after thyroidectomy among those with lower-pitched voices after surgery. Pre-operative high SFF and post-operative stroboscopic findings including vocal cord asymmetry at 2 weeks post-operatively also predicted persisting lowering of voice pitch for 3 months. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is a heterogeneous tumor with various histological and molecular subtypes. EHD2 is involved in endocytosis and endosomal recycling. This study aimed to investigate the prognostic significance of EHD2 expression in PTC and develop a new model for predicting persistent/recurrent disease after thyroidectomy. Pathologic slides of 512 consecutive patients with PTC ≥ 1 cm were retrospectively reviewed. BRAF mutation analysis and immunohistochemistry for EHD2 were performed. Clinical significance of EHD2 mRNA expression was analyzed in 388 PTC patients using The Cancer Genome Atlas dataset. The presence of dyscohesive cells and psammoma bodies were found have significant association with persistent/recurrent disease (p = 0.049 and p = 0.038, respectively). The best discrimination of disease-free survival was found by dividing patients into three prognostic groups based on the following two risk factors according to the size category: psammoma bodies ≥ 4 and dyscohesive cells (≥ 1% and ≥ 20% in PTCs of < 2.0 cm and ≥ 2.0 cm, respectively). In PTCs of ≥ 2.0 cm, patients with the two risk factors had a hazard ratio of 13.303 (p = 0.005) compared to those without risk factors. High expression level of EHD2 was associated with BRAF V600E (p < 0.001), presence of dyscohesive cells (p = 0.010), and absence of psammoma bodies (p = 0.001). Increased EHD2 mRNA expression level was associated with extrathyroidal extension (p < 0.001), pT3-4 (p < 0.001), lymph node metastasis (p < 0.001), higher risk of recurrence (p < 0.001), and BRAF V600E (p < 0.001). Our prognostic model is useful for predicting persistent/recurrent disease after surgery of PTC. EHD2 mRNA expression could be a novel prognostic marker for PTC patients. [ABSTRACT FROM AUTHOR]

Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC. BRAF mutation was tested with pyrosequencing. Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto’s thyroiditis than classic PTCs (93% versus 36%, resp., P < 0.001) and showed significantly lower rate of BRAF mutation when compared to classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of BRAF mutations was negatively correlated with coexisting Hashimoto’s thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto’s thyroiditis, there were no significant differences in clinicopathologic characteristics or the BRAF mutational rate between the two groups. Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto’s thyroiditis. [ABSTRACT FROM AUTHOR]

Background: BRAF mutation is the most common genetic event in papillary thyroid carcinoma (PTC); however, the prevalence and patterns of the mutation vary worldwide. We investigated the frequency and type of BRAF mutations based on the histologic subtypes in a large cohort of Korean patients with PTC. Methods: A total of 1041 consecutive PTCs were classified according to histologic subtypes. BRAF mutations were examined by denaturing high-performance liquid chromatography and direct sequencing. Rare complex mutations were confirmed by molecular cloning of polymerase chain reaction amplicons and sequencing of the products. Results: BRAF mutations were found in 839 (80.6%) of 1041 patients with PTC. The histologic subtype-specific prevalence of BRAF mutation was as follows: 85.3% (249/292) were classic, 45.8% (11/24) were follicular, 79.9% (576/721) were microcarcinoma, and 75.0% (3/4) were other variants. In addition to the usual c.1799T>A mutation, we identified other four mutation types: c.[1795_1796insA;1770_1795dup26], c.[1742-10T>C;1799T>A] and c.[1796C>G;1799T>A], and c.1799_1800TG>AA, respectively. The former three were novel mutations in thyroid tumors. Within the series of microcarcinoma variants, the BRAF mutation rate was lower in tumors with follicular morphology than those with nonfollicular types (66.7% vs. 80.9%, p=0.0145). Conclusion: Out of 1041 Korean patients with PTC, 0.4% had rare types of BRAF mutation and three new somatic mutations were identified. The BRAF mutation rate was quite low in PTC with follicular morphology regardless of tumor size. However, the prevalence of BRAF mutation in microcarcinoma and follicular variants of PTC is relatively high in Korea and its analysis may be clinically useful for managing the patients. [ABSTRACT FROM AUTHOR]

Patients with papillary thyroid carcinoma (PTC) have excellent survival, but recurrence remains a major problem in the management of PTC. We aimed to determine the prognostic impact of the expression of CD10 and CD15 in patients with PTC. Immunohistochemistry for CD10 and CD15 was performed on the tissue microarrays of 515 patients with PTC. The expression of CD10 and CD15 was detected in 201 (39.0%) and 295 (57.3%) of 515 PTC cases, respectively, but not in the adjacent benign thyroid tissue. Recurrence was inversely correlated with CD15 expression (p = 0.034) but not with CD10 expression. In 467 PTC patients treated with radioiodine remnant ablation, the CD15 expression had an adjusted hazard ratio of 0.500 (p = 0.024) for recurrence-free survival and an adjusted odds ratio of 2.678 (p = 0.015) for predicting long-term excellent therapeutic response. CD10 expression was not associated with clinical outcomes. In the Cancer Genome Atlas dataset, the expression level of FUT4 (CD15) mRNA was higher in the low/intermediate-risk group for recurrence than in the high-risk group and exhibited positive correlation with SLC5A5 (NIS) mRNA expression (p = 0.003). Taken together, CD15 expression was identified as an independent prognostic marker for improved prognosis in PTC patients. [ABSTRACT FROM AUTHOR]

Preoperative detection of cervical lymph node metastasis in papillary thyroid carcinoma (PTC) is crucial for determining the surgical strategy to prevent locoregional recurrence of the disease. We identified the cytological predictors of lymph node metastasis in 222 consecutive patients with PTC using fine-needle aspiration cytology (FNAC) of the thyroid. Cervical lymph node metastases occurred in 99 (44.6%) of 222 PTC patients. Lymph node metastasis was significantly associated with tumor multifocality (p = 0.003), and high cellularity (p = 0.021), atypical histiocytoid cells (p < 0.001), and multinucleated giant cells (p < 0.001) in thyroid FNAC. The BRAF V600E mutation was marginally associated with lymph node metastasis (p = 0.054). Multivariate analysis revealed that atypical histiocytoid cells (odds ratio = 2.717; p = 0.001) and multinucleated giant cells (odds ratio = 3.070; p = 0.031) were independent predictors of lymph node metastasis in patients with PTC. In a subgroup analysis of 164 patients with microcarcinomas, atypical histiocytoid cells (odds ratio = 2.761; p = 0.005) was an independent predictor of lymph node metastasis. Cytological detection of atypical histiocytoid cells and multinucleated giant cells on thyroid FNAC can be used to preoperatively predict cervical lymph node metastasis in patients with PTC. [ABSTRACT FROM AUTHOR]

Abstract: The BRAFV600E mutation has been reported to occur in 30% to 80% of papillary thyroid carcinomas (PTCs). Although direct sequencing is the method most commonly used to identify mutations, this technique is not sensitive enough to accurately detect low level mutation. To determine the optimal diagnostic method for detecting the BRAFV600E mutation in PTC, we compared the diagnostic efficacy of four representative detection methods in formalin-fixed paraffin-embedded thyroid tissues obtained from 40 patients diagnosed with PTC. To detect the BRAFV600E mutation, we amplified exon 15 of the BRAF gene and performed mutational analysis with direct sequencing, denaturing high-performance liquid chromatography (DHPLC), pyrosequencing and colorimetric assay. The BRAF mutation was detected in 33 cases (82.5%) by DHPLC, 23 cases (57.5%) by direct sequencing, 22 cases (55.0%) by pyrosequencing, and 37 cases (92.5%) by colorimetric assay. The sensitivity, negative predictive value and accuracy of DHPLC were 100%. The specificity and positive predictive values for DHPLC, direct sequencing and pyrosequencing were 100%, and for colorimetric assay they were 14.3% and 83.8%, respectively. The kappa value for DHPLC was a perfect 1.0, which was superior to the other methods. In conclusion, DHPLC is a sensitive, specific and accurate method for detecting the BRAFV600E mutation, especially low level mutation, in PTC. [Copyright &y& Elsevier]

Abstract: Objective: Recent studies have shown that a BRAFV600E reflects poor prognosis, mainly in Western countries. However, some clinicians in Japan have suggested that the BRAFV600E mutation is not associated with a poor prognosis. Therefore, we investigated a relationship between BRAFV600E mutation and clinicopathologic factors. Methods: From September 2008 to December 2009, we performed routine analysis of the BRAFV600E mutation using thyroid cancer tissue from 424 patients who underwent thyroidectomy with cervical lymph node dissection. Results: The BRAFV600E mutation was found in 335 of 424 cases (79%) and was higher in classic papillary thyroid carcinoma (PTC) (79.7%) than in the follicular variant of PTC (62.5%) (P = .019). On univariate analysis, the BRAFV600E mutation was associated with extrathyroidal extension (P = .009) and variants of PTC (P = .019), but a high-risk Metastasis, Patient Age, Completeness of resection, local Invasion and Tumor Size (MACIS) score (≥ 6) (P = .146) and lymph node metastasis (P = .628) were not significantly associated with the BRAFV600E mutation. Multivariate analysis showed that extrathyroidal extension is independently associated with the BRAFV600E mutation (relative ratio: 2.466; 95% confidence interval, 1.213–5.011; P < .013). Conclusion: It is not clear that the BRAFV600E mutation is useful for prediction of poor prognosis of PTC. [Copyright &y& Elsevier]