Guidelines from the Brazilian society of surgical oncology regarding indications and technical aspects of neck dissection in papillary, follicular, and medullary thyroid cancers

ABSTRACT Objective: The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas. Materials and methods: Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians' Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection? Results/conclusion: Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II-V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; "berry node picking" is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.

Risk factors associated with repeat Radioactive Iodine Therapy for differentiated Thyroid Cancer in a tertiary care center in the Philippines: A retrospective cohort study

Introduction@#Thyroid carcinoma remains the most common endocrine malignancy and incidence has increased due to improved diagnosis. Most Differentiated Thyroid Cancers (DTC) are indolent and easily cured with surgery, radioactive iodine (RAI) therapy and TSH suppression. However, persistent and recurrent disease is not uncommon among Filipinos. RAI therapy is being used more frequently even for low risk patients due to this observed aggressiveness of DTC in our population. This study sought to identify factors that are associated with failure of initial RAI for DTC, leading to repeat doses.@*Methods@#This is a single-center, retrospective cohort study conducted in the Nuclear Medicine Department of a tertiary care center in the Philippines, involving 325 patients who underwent RAI from 2006-2016@*Results@#Out of 570 patients who underwent RAI therapy for DTC, only 325 were included. Majority (n=280, 86%) had PTC and the rest had FTC (n=45, 14%). Twenty four percent (n=67) of the PTC group and 31% (n=14) of the FTC had subsequent RAI therapy after initial therapy due to either persistent or recurrent disease, with a mean interval of 21-22 months. Distant metastasis at presentation (M1), uptake in distant tissues on the initial post-therapy whole body scan (WBS) and TNM stage 4 were predictive for repeat RAI for FTC. A negative post-therapy WBS was found to be associated with no need for repeat RAI. On the other hand, the initial RAI dose of 150 mCi or higher was noted to be associated with repetition of RAI for PTC. Other risk factors noted were the presence of lymph nodes and distant metastasis at presentation and loco-regional uptake on the posttherapy WBS. Conversely, a negative post-treatment scan appeared to be protective against repeat RAI, as in FTC. However, multivariate analysis of risk factors showed that only metastasis at presentation (LN or distant) was associated with repeat RAI therapy. @*Conclusion@#The only risk factor associated with failure of initial RAI for patients with PTC and FTC in this study was distant metastasis at presentation. Nodal involvement at presentation was noted to be a significant factor for among those with PTC.

Clinicopathologic Features in Minimally Invasive Follicular Thyroid Cancer Patients with Distant Metastasis / 대한내분비외과학회지

PURPOSE: Although minimally invasive follicular thyroid carcinoma (MIFTC) is considered a thyroid tumor with low malignant potential, some MIFTC can spread, metastasize, and eventually lead to death. This study investigates the risk factors for distant metastasis in MIFTC patients. METHODS: Between 1981 and 2014, the records of 365 consecutive patients who underwent thyroidectomy for MIFTC at Seoul National University Hospital were reviewed. Univariate and multivariate analyses were performed to identify risk factors associated with distant metastasis. RESULTS: Of 351 patients, 10 (2.9%) presented with distant metastasis. Of these, two (0.6%) were found at the time of thyroidectomy, while eight (2.3%) were detected at later exams, over a median of 7.3 years (range, 0.2~30.8). In univariate analysis, lymph node metastasis (P<0.001) was significantly associated with distant metastasis. In multivariate analysis, lymph node metastasis (P<0.001) and locoregional recurrence (P=0.008) were significantly associated with distant metastasis. CONCLUSION: Distant metastasis in MIFTC patients were associated with high-risk clinicopathologic features and more aggressive clinical courses. Further study will be needed to ascertain these results with long-term surveillance.

Hypoxia Induces Epithelial-Mesenchymal Transition in Follicular Thyroid Cancer: Involvement of Regulation of Twist by Hypoxia Inducible Factor-1alpha

PURPOSE: Although follicular thyroid cancer (FTC) has a relatively fair prognosis, distant metastasis sometimes results in poor prognosis and survival. There is little understanding of the mechanisms contributing to the aggressiveness potential of thyroid cancer. We showed that hypoxia inducible factor-1alpha (HIF-1alpha) induced aggressiveness in FTC cells and identified the underlying mechanism of the HIF-1alpha-induced invasive characteristics. MATERIALS AND METHODS: Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effect of hypoxia on HIF-1alpha, and epithelial-to-mesenchymal transition (EMT) related markers were evaluated by quantitative real-time PCR, Western blot analysis and immunocytochemistry. Invasion and wound healing assay were conducted to identify functional character of EMT. The involvement of HIF-1alpha and Twist in EMT were studied using gene overexpression or silencing. After orthotopic nude mouse model was established using the cells transfected with lentiviral shHIF-1alpha, tissue analysis was done. RESULTS: Hypoxia induces HIF-1alpha expression and EMT, including typical morphologic changes, cadherin shift, and increased vimentin expression. We showed that overexpression of HIF-1alpha via transfection resulted in the aforementioned changes without hypoxia, and repression of HIF-1alpha with RNA interference suppressed hypoxia-induced HIF-1alpha and EMT. Furthermore, we also observed that Twist expression was regulated by HIF-1alpha. These were confirmed in the orthotopic FTC model. CONCLUSION: Hypoxia induced HIF-1alpha, which in turn induced EMT, resulting in the increased capacity for invasion and migration of cells via regulation of the Twist signal pathway in FTC cells. These findings provide insight into a possible therapeutic strategy to prevent invasive and metastatic FTC.

Rare Concurrence of Triple Primary Thyroid Cancer: A Patient of Papillary Carcinoma, Follicular Carcinoma, and Primary Lymphoma of the Thyroid

We report a rare case of co-occurrence of papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC) and primary thyroid lymphoma. A 55-year-old woman presented with a large mass in left lobe of thyroid, biopsy confirmed diffuse large B-cell lymphoma. After 4 cycles of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisolone chemotherapy, positron emission tomography scan revealed markedly decreased in size, but still present. Repeated ultrasonography-guided gun biopsies of 2 lesions indicated Hurthle cell neoplasm. After total thyroidectomy and bilateral central lymph node dissection, residual hypermetabolic lesion of left lobe was determined to be FTC and right lower lesion to be nodular hyperplasia. Besides, a PTC was incidentally detected in left lobe. If there are multiple nodular lesions at diagnosis or there is insufficient response after 1st line chemotherapy for primary thyroid lymphoma, each lesion should be biopsied to confirm its pathological type.

The use of SPECT-CT improves accuracy of post radioiodine therapy imaging and changes the management strategy in a case of advanced follicular thyroid carcinoma

This is a case of follicular thyroid carcinoma with extensive lung, bone and brain metastases. Multi-modality treatments including total thyroidectomy, modified radical neck dissection, cranial radiotherapy and Iodine-131 (RAI) therapy were instituted. Post RAI therapy planar whole body scan showed RAI avid metastases in the skull, cervical spine, bilateral lungs and abdomen. With the use of SPECTCT imaging, rare adrenal metastasis and additional rib metastasis were identified. Besides, management strategy was altered due to detection of non-RAI avid brain and lung metastatic lesions.

Role of adjuvant postoperative external beam radiotherapy for well differentiated thyroid cancer

PURPOSE: To analyze the outcome of adjuvant postoperative external beam radiotherapy (EBRT) in well-differentiated thyroid cancer (WDTC). MATERIALS AND METHODS: We identified 84 patients treated with EBRT for WDTC from February 1981 to December 2010. Among them, we analyzed 39 patients who received EBRT after initial radical surgery. Twenty-four females and 15 males were included. The median age was 49 years (range, 16 to 72 years). There were 34 papillary thyroid carcinomas and 5 follicular thyroid carcinomas. Most patients showed pathologic T3/T4 stage (54%/26%). Ten patients (25.6%) had gross residual tumors. Five patients (12.8%) had tumor cells at the margin. The median EBRT dose and fraction size were 62.6 Gy and 1.8 to 2.0 Gy, respectively. RESULTS: The median follow-up was 73 months (range, 21 to 372 months). The five-year overall survival (OS) and locoregional recurrence free survival (LRFS) were 97.4% and 86.9%, respectively. Locoregional failures occurred in 5 and all failure sites were the neck node area. In univariate analysis, OS was significantly influenced by invasion of the trachea (p = 0.016) or esophagus (p = 0.006). LRFS was significantly decreased by male (p = 0.020), gross residuum after resection (p = 0.002), close or positive tumor at surgical margin involvement (p = 0.044), and tracheal invasion (p = 0.040). No significant prognostic factor was identified in the multivariate analysis. No patient experienced the Radiation Therapy Oncology Group grade 3 or more toxicity. CONCLUSION: Our locoregional control rate of 87.2% is comparable to historical controls with surgery alone, even though our study had a large proportion of advanced stage. Adjuvant EBRT may an effective and safe treatment option in patients with WDTC.

Application of molecular biomarkers in differential diagnosis of benign and malignant follicular thyroid tumors / 中华内分泌代谢杂志

Twenty-nine thyroid tissue samples were collected from patients with thyroid nodules.The total RNA were extracted,the gene expressions of TFF3,HMGA2,C1orf24,and DDIT3 were detected by RT-PCR.In comparison with normal thyroid tissues,the expression of C1orf24 mRNA was decreased in the follicular thyroid adenoma (FTA) group,but increased in the follicular thyroid carcinomas (FTC) group.The expressions of DDIT3 and HMGA2 mRNA were increased in both FTA and FTC groups,and were even higher in the latter.The expressions of TFF3 mRNA level were decreased in FTA and FTC.The data suggested that molecular markers C1ort24,DDIT3,HMGA2,and TFF3 in thyroid tissue seem to be helpful in the differential diagnosis between follicular adenomas and carcinomas.

Frequency of RAS Mutations and PAX8/PPARgamma Rearrangement in Follicular Thyroid Tumors in Korea

BACKGROUND: Follicular thyroid tumors harbor several genetic alterations such as RAS mutations and PAX8/PPARgamma rearrangement. The aims of our study were to investigate the prevalence of RAS mutations and PAX8/PPARgamma rearrangement in follicular thyroid tumors and to correlate RAS mutations and/or PAX8/PPARgamma rearrangement with clinicopathologic features in Korean patients with follicular thyroid carcinomas. METHODS: RAS mutations were investigated by polymerase chain reaction and DNA sequencing in surgical specimens of 37 follicular thyroid carcinomas (FTCs) and 16 follicular thyroid adenomas (FTAs). PAX8/PPARgamma rearrangement was analyzed by fluorescent in situ hybridization in surgical specimens of 31 FTCs and 13 FTAs. RESULTS: RAS mutations were detected in 30% (11 of 37) of FTCs and 19% (three of 16) of FTAs. Three of 11 FTC patients with RAS mutations died of thyroid cancer, but none of the 26 FTC patients without RAS mutations. PAX8/PPARgamma rearrangement was found in 10% (three of 31) of FTCs, but in none of the 13 FTAs. All three FTC patients with PAX8/PPARgamma rearrangement remained in complete remission during follow-up. There were no FTC patients with both RAS mutations and PAX8/PPARgamma rearrangement. CONCLUSION: The prevalence of RAS mutations in our series of follicular tumors was similar to previous studies. The frequency of PAX8/PPARgamma rearrangements in our group of FTC was lower than previous western reports, but higher than Japanese reports. RAS mutations may be associated with hematogeneous metastasis and poor survival while PAX8/PPARgamma rearrangement may be related to more favorable prognosis in Korean patients with FTCs.