Ja Seong Bae

Incidental thyroid lesions detected by FDG-PET/CT: prevalence and risk of thyroid cancer.

BackgroundIncidentally found thyroid lesions are frequently detected in patients undergoing FDG-PET/CT. The aim of this study was to investigate the prevalence of incidentally found thyroid lesions in patients undergoing FDG-PET/CT and determine the risk for thyroid cancer.MethodsFDG-PET/CT was performed on 3,379 patients for evaluation of suspected or known cancer or cancer screening without any history of thyroid cancer between November 2003 and December 2005. Medical records related to the FDG-PET/CT findings including maximum SUV(SUVmax) and pattern of FDG uptake, US findings, FNA, histopathology received by operation were reviewed retrospectively.ResultsTwo hundred eighty five patients (8.4%) were identified to have FDG uptake on FDG-PET/CT. 99 patients with focal or diffuse FDG uptake underwent further evaluation. The cancer risk of incidentally found thyroid lesions on FDG-PET/CT was 23.2% (22/99) and the cancer risks associated with focal and diffuse FDG uptake were 30.9% and 6.4%. There was a significant difference in the SUVmax between the benign and malignant nodules (3.35 ± 1.69 vs. 6.64 ± 4.12; P < 0.001). There was a significant correlation between the SUVmax and the size of the cancer.ConclusionThe results of this study suggest that incidentally found thyroid lesions by FDG-PET/CT, especially a focal FDG uptake and a high SUV, have a high risk of thyroid malignancy. Further diagnostic work-up is needed in these cases.

p53 as a Specific Prognostic Factor in Triple-negative Breast Cancer

OBJECTIVE A recent suggestion is that the predictive value of a single biomarker may rely on the genetic background on the tumor and that different breast cancer subgroups may have different predictive markers of response to chemotherapy. The prognostic value of p53 in the outcome of adjuvant anthracycline-containing chemotherapy was evaluated according to molecular subclasses defined using the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. METHODS Subjects were patients (n = 135) with invasive ductal carcinoma treated with adjuvant anthracycline-based chemotherapy between 1994 and 2000 in our hospital. Clinico-pathological features were reviewed by retrospective examination of medical records. RESULTS Overall survival rate was not independently predictive by p53 status (P = 0.182). However, in triple-negative cases, there was statistically significant survival difference (P = 0.034) and no statistically significant difference (P = 0.783) in non-triple-negative cases by p53 status. In the Cox proportional hazard analysis, p53 was also strongly predictive for relapse-free survival (P = 0.013) and overall survival (P = 0.049) in triple-negative patients. CONCLUSIONS p53 status could be a specific prognostic factor in triple-negative breast cancer patients treated by adjuvant anthracycline-based regimen. When p53 is positive in triple-negative breast cancer, we could expect poor survival, prompting aggressive or alternative treatment.

Molecular genotyping of follicular variant of papillary thyroid carcinoma correlates with diagnostic category of fine-needle aspiration cytology: values of RAS mutation testing.

BACKGROUND The follicular variant of papillary thyroid carcinoma (FVPTC) presents distinct histologic subtypes and molecular genotyping. The preoperative diagnosis of FVPTC through fine-needle aspiration cytology (FNAC) is challenging. METHODS We reviewed 59 archival thyroid FNAC specimens of surgically confirmed FVPTC according to histologic subtype: encapsulated FVPTC (n = 30) and infiltrative FVPTC (n = 29). Galectin-3 immunostaining and molecular analyses for BRAF and three RAS genes (NRAS, HRAS, and KRAS) were performed. RESULTS FNAC diagnoses of FVPTC included benign (5%), atypia of undetermined significance (19%), follicular neoplasm/suspicious for follicular neoplasm (14%), suspicious for PTC (29%), and PTC (34%). Galectin-3 immunostaining was positive in 50% of FNAC specimens. A BRAF mutation was found only in 14 (24%) tumors with the FNAC diagnosis of PTC or suspicious for PTC: 13 cases with the usual c.1799T>A (p.V600E) mutation and 1 case with a 3 base-pair deletion (c.1799_1801delTGA), resulting in a deletion of lysine at codon 601 and a deletion c.1799_1801delTGA that results in a valine-to-glutamate substitution at codon 600 (p.V600_K601>E) while preserving the reading frame. A BRAF K601E mutation was not found. RAS mutations were observed in 18 (33%) tumors (NRAS, 22%; HRAS, 6%; KRAS, 6%). Mutations of the three RAS genes were detected in codon 61 but not in codons 12 and 13. There was a decreasing trend of RAS mutation rates associated with an increasing risk of malignancy in the FNAC diagnostic categories. The triage efficacy of FNAC to make a recommendation for surgery was 73% for encapsulated tumors and 79% for infiltrative tumors. Addition of galectin-3 or the BRAF test to FNAC showed no significant improvement in the triage efficacy. However, RAS mutations significantly improved the triage efficacy of FNAC. There was no significant difference in the triage efficacy of FNAC, galectin-3 expression, and the prevalence of somatic mutations between encapsulated and infiltrative tumors. CONCLUSION Thyroid FNAC has a low sensitivity for the detection of FVPTC regardless of histologic subtype. Encapsulated FVPTC and infiltrative FVPTC have similar molecular profiles and rates of galectin-3 expression. RAS mutational analysis is more useful than BRAF testing to improve the triage efficacy of FNAC for FVPTC.

Is the BRAFV600E mutation useful as a predictor of preoperative risk in papillary thyroid cancer

OBJECTIVE Recent studies have shown that a BRAF(V600E) reflects poor prognosis, mainly in Western countries. However, some clinicians in Japan have suggested that the BRAF(V600E) mutation is not associated with a poor prognosis. Therefore, we investigated a relationship between BRAF(V600E) mutation and clinicopathologic factors. METHODS From September 2008 to December 2009, we performed routine analysis of the BRAF(V600E) mutation using thyroid cancer tissue from 424 patients who underwent thyroidectomy with cervical lymph node dissection. RESULTS The BRAF(V600E) 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 BRAF(V600E) 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 BRAF(V600E) mutation. Multivariate analysis showed that extrathyroidal extension is independently associated with the BRAF(V600E) mutation (relative ratio: 2.466; 95% confidence interval, 1.213-5.011; P < .013). CONCLUSION It is not clear that the BRAF(V600E) mutation is useful for prediction of poor prognosis of PTC.

Comparison of surgical outcomes between endoscopic and robotic thyroidectomy

Gasless transaxillary endoscopic thyroidectomy offers a distinct advantage over the conventional open operation because it leaves no visible neck scar. Indications have expanded with the development of new surgical techniques and instruments. However, because of the two‐dimensional view and the nonflexible instruments, this procedure is not easily amenable for total thyroidectomy. So, robotic surgery has been introduced and offers improved visualization and dexterity. But, it remains unclear whether robotic thyroidectomy offers any potential benefits over endoscopic thyroidectomy. The aim of this present study was to determine whether robotic surgery is superior to endoscopic surgery through a comparison of surgical outcomes.

Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features

Thyroid tumors formerly classified as non-invasive encapsulated follicular variant of papillary thyroid carcinoma were recently renamed ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features’. The current study investigated the frequency of lymph node metastasis and mutational profile of encapsulated follicular variant in the setting of a clinical practice where central neck dissection was the standard of practice. We defined the impact of rigid diagnostic criteria by regrouping such tumors based on the complete absence of papillae or presence of ≤1% papillae. Of a total of 6,269 papillary thyroid carcinomas, 152 tumors fulfilled the criteria for encapsulated follicular variant. The results were stratified according to two different diagnostic cutoff criteria with respect to the extent of papillae. When the cutoff of 1% papillae was used, the rates of lymph node metastasis and BRAFV600E mutation were 3% and 10% in non-invasive tumors and 9% and 4% in invasive tumors, respectively. Despite the lack of invasive growth, one patient with BRAFV600E mutant-tumor displaying predominant follicular growth and subtle papillae developed a bone metastasis. When absence of papillary structure was applied as rigid diagnostic criteria, no BRAFV600E mutation was found in all tumors. However, central lymph node micrometastasis still occurred in 3% of non-invasive tumors. Non-V600E BRAF and RAS mutations were detected in 4% and 47% of non-invasive tumors, respectively. Our findings suggest that non-invasive follicular thyroid neoplasm with papillary-like nuclear features should not be regarded as a benign thyroid neoplasm as it can present with lymph node micrometastasis and should not be diagnosed in the presence of even a single papillary structure. Our findings underscore the original American Thyroid Association recommendation that defined non-invasive encapsulated follicular variants as low risk thyroid cancers. Clinical surveillance similar to low risk differentiated thyroid cancers and capture of this diagnostic category by Cancer Registries should be considered.

Positron Emission Tomography-Computed Tomography in the Detection of Axillary Lymph Node Metastasis in Patients with Early Stage Breast Cancer

OBJECTIVE The status of axillary lymph nodes (ALNs) is the most important prognostic factor in breast cancer. The purpose of this study was to evaluate the clinical usefulness of ALN involvement by means of positron emission tomography-computed tomography (PET-CT) compared with breast sonography and mammography in patients with early breast cancer. METHODS This study involved 108 breast cancer patients with non-palpable ALNs. All patients had PET-CT, breast sonography and mammography imaging before sentinel lymph node (SLN) biopsy. After SLN biopsy, all patients underwent complete ALN dissection. ALNs were evaluated by standard hematoxylin and eosin staining techniques. The findings of PET-CT, breast sonography and mammography imaging of 108 patients were compared with pathologic findings after surgery. Sensitivity, specificity and accuracy of individual diagnostic modalities were compared. Diagnostic accuracy was evaluated applying receiver operating characteristic (ROC) curve areas. RESULTS The sensitivity, specificity and accuracy of PET-CT imaging were 48.5%, 84% and 73.2%, respectively. The sensitivity, specificity and accuracy of breast sonography were 51.5%, 89.3% and 77.8%, respectively. The sensitivity, specificity and accuracy of mammography were 33.3%, 96% and 76.9%, respectively. For involvement of ALNs, PET-CT imaging, breast sonography and mammography had areas under the ROC curve of 0.662, 0.704 and 0.647, respectively. CONCLUSIONS Compared with the combination of breast sonography and mammography, PET-CT was less sensitive and had less accuracy in detecting ALN metastasis. Consequently, PET-CT is not a reliable non-invasive modality for assessing ALN involvement that can replace ALN dissection or SLN biopsy before decisions are made on appropriate systemic interventions.

Radiofrequency Ablation to Treat Loco-Regional Recurrence of Well-Differentiated Thyroid Carcinoma

Objective To evaluate the efficacy of radiofrequency ablation (RFA) in the treatment of loco-regional, recurrent, and well-differentiated thyroid carcinoma. Materials and Methods Thirty-five recurrent well-differentiated thyroid carcinomas (RTC) in 32 patients were treated with RFA, between March 2008 and October 2011. RTCs were detected by regular follow-up ultrasound and confirmed by biopsy. All patients had fewer than 3 RTCs in the neck and were at high surgical risk or refused to undergo repeated surgery. Average number of RFA sessions were 1.3 (range 1-3). Post-RFA biopsy and ultrasound were performed. The mean follow-up period was 30 months. Pre- and post-RFA serum thyroglobulin values were evaluated. Results Thirty-one patients with 33 RTCs were treated with RFA only, whereas 1 patient with 2 RTCs was treated with RFA followed by surgery. At the last follow-up ultrasound, 31 (94%) of the 33 RTCs treated with RFA alone completely disappeared and the remaining 2 (6%) RTCs showed decreased volume. The largest diameter and volume of the 33 RTCs were markedly decreased by 93.2% (from 8.1 ± 3.4 mm to 0.6 ± 1.8 mm, p < 0.001) and 96.4% (from 173.9 ± 198.7 mm3 to 6.2 ± 27.9 mm3, p < 0.001), respectively. Twenty of the 21 RTCs evaluated with post-RFA biopsies (95%) were negative for malignancy. One (5%) showed remaining tumor that was removed surgically. The serum thyroglobulin was decreased in 19 of 26 patients (73%). Voice change developed immediately after RFA in 6 patients (19%) and was spontaneously recovered in 5 patients (83%). Conclusion Radiofrequency ablation can be effective in treating loco-regional, recurrent, and well-differentiated thyroid carcinoma in patients at high surgical risk.

Performing Contralateral Central Lymph Node Dissection in Papillary Thyroid Carcinoma: A Decision Approach

BACKGROUND Substantial controversy exists over the role of prophylactic neck dissection for patients with papillary thyroid carcinoma (PTC). We hypothesized that a therapeutic strategy of performing a routine intraoperative frozen section of the ipsilateral central lymph node (CLN) after elective ipsilateral CLN dissection (CLND) for all unilateral PTC and then performing a contralateral CLND if the frozen section is positive for malignancy would reduce morbidity compared to a therapeutic strategy of routine bilateral CLND. METHODS In a group of 419 patients with PTC undergoing thyroidectomy during study the period, the 203 patients who had unilateral PTC and no evidence of adenopathy on ultrasonography were prospectively enrolled in our nonrandomized study that was performed between March 2009 and February 2010. Patients underwent a total thyroidectomy if tumor size was over 1 cm or extrathyroidal was detected on ultrasonography. Patients underwent a subtotal or near-total thyroidectomy if tumor size was <1 cm and additional benign tumor existed on contralateral lobe. There were 25 patients who had a unilateral CLND with a subtotal or near-total thyroidectomy, and 178 patients who underwent a unilateral or bilateral CLND with a total thyroidectomy. RESULTS There was no difference in the rate of major complications between unilateral CLND group and bilateral CLND group. The rate of transient hypocalcemia was 31.8% in the unilateral CLND group and 45.7% in the bilateral CLND group (p = 0.084). The rate of voice change was 7.6% in the unilateral CLND group 4.3% in the bilateral CLND group (p = 0.438). The ratio of malignant to all nodes retrieved was 0.5/7.88 in the unilateral CLND group and 5.13/17.20 in the bilateral CLND group. There was 78.3% sensitivity and 100% specificity for frozen biopsy of ipsilateral CLN to predict contralateral CLN metastasis. A positive ipsilateral CLN frozen biopsy was significantly associated with contralateral CLN metastasis (p < 0.001), as was younger age (p = 0.002) and existence of extrathyroidal extension (p = 0.031), each on univariate analysis. CONCLUSIONS In patients with unilateral PTC, routine ipsilateral CLND with intraoperative reading of the frozen section can be employed to assess the risk of contralateral CLN metastasis. This information should be of value in deciding whether to perform contralateral CLND or not.

Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>C mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>C mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma. Graphical Abstract