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Abstract Aims In contrast to all prior AJCC/TNM classifications for differentiated thyroid cancer (DTC) the 8th edition does not take minimal extrathyroidal extension (M-ETE) into consideration for local tumor staging. We therefore aimed to retrospectively assess the specific impact of M-ETE on the outcome of M-ETE patients treated in our clinic. Methods DTC patients with M-ETE and a follow-up time of ≥ 5 years were included and matched with an identical number of patients without M-ETE, but with equal histopathological tumor subtype and size. The frequency of initially metastatic disease among groups was compared using Fisher’s exact test, the recurrence rate by virtue of log-rank test. Fisher’s exact test and multivariate analysis were used to account for the presence of confounding risk factors. Results One hundred sixty patients (80 matching pairs) were eligible. With other confounding risk factors being equal, the prevalence of N1-/M1-disease at initial diagnosis was comparable among groups (M-ETE: 42.5 %; no M-ETE: 32.5 %; p = 0.25). No differences with regard to the recurrence rate were shown. However, M-ETE patients were treated with external beam radiation therapy more often (16.3 % vs. 1.3 %; p = 0.004) and received higher median cumulative activities of 131I (10.0 vs. 8.0 GBq; p

ABSTRACT Objective We aimed to evaluate the impact of minimal extrathyroidal extension (mETE) alone on the risk of recurrence of papillary thyroid carcinoma (PTC). The impact of other factors, including multifocality, age, tumor size, and stimulated thyroglobulin (sTg) values was also assessed. Subjects and methods We retrospectively analyzed 1,108 PTC patients from a medical institution, who presented tumors ≤ 4 cm without any adverse characteristics other than mETE. Patients were classified according to their response to initial treatment 12 to 24 months after surgery as proposed by the 2015 American Thyroid Association (ATA) guideline. Statistical analysis was performed using multivariate logistic regression and receiver operating characteristic (ROC) curve. Results In the multivariate logistic regression analysis, mETE did not have an impact on the response to initial treatment (p = 0.44), similar to multifocality, age, and tumor size. Initial Tg value was the only variable associated with a poor response (p < 0.01, odds ratio = 1.303, 95% confidence interval 1.25-1.36). The ROC analysis revealed that Tg was significant (area under curve = 0.8750); the cutoff value of sTg as a predictor of poor response was 10 ng/mL (sensitivity = 72.2%, specificity = 98.5%). Conclusion For low-risk PTC presenting mETE as the only aggressive feature, the initial sTg value is essential to identify patients who may have a poor response after initial treatment and benefit from further treatment. Arch Endocrinol Metab. 2020;64(3):251-6

Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aims of this study were to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p = 0.65), tumor size >2 cm (OR 1.45, p = 0.34), aggressive PTC histology (OR 0.55, p = 0.15), and age at diagnosis (OR 0.90, p = 0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a >2 cm tumor was significantly associated with a worse outcome (OR 5.27 [95% confidence interval], p = 0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and nontreated patients (p = 0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease. [ABSTRACT FROM AUTHOR]

Aims: In contrast to all prior AJCC/TNM classifications for differentiated thyroid cancer (DTC) the 8th edition does not take minimal extrathyroidal extension (M-ETE) into consideration for local tumor staging. We therefore aimed to retrospectively assess the specific impact of M-ETE on the outcome of M-ETE patients treated in our clinic. Methods: DTC patients with M-ETE and a follow-up time of ≥ 5 years were included and matched with an identical number of patients without M-ETE, but with equal histopathological tumor subtype and size. The frequency of initially metastatic disease among groups was compared using Fisher's exact test, the recurrence rate by virtue of log-rank test. Fisher's exact test and multivariate analysis were used to account for the presence of confounding risk factors. Results: One hundred sixty patients (80 matching pairs) were eligible. With other confounding risk factors being equal, the prevalence of N1-/M1-disease at initial diagnosis was comparable among groups (M-ETE: 42.5 %; no M-ETE: 32.5 %; p = 0.25). No differences with regard to the recurrence rate were shown. However, M-ETE patients were treated with external beam radiation therapy more often (16.3 % vs. 1.3 %; p = 0.004) and received higher median cumulative activities of 131I (10.0 vs. 8.0 GBq; p < 0.001). Discussion: Although having played a pivotal role for local tumor staging of DTC for decades M-ETE did not increase the risk for metastases at initial diagnosis and the recurrence rate in our cohort. Patients with M-ETE had undergone intensified treatment, which entails a possible confounding factor that warrants further investigation in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) is a risk factor for tumor recurrence. By TNM Classification (7th edition), differentiated thyroid carcinoma with ETE is designated T3 (minimal invasion), T4a (extended invasion), or T4b (more extensive unresectable invasion), according to the degree of tumor involvement. We subsequently focused our investigation on minimal ETE (MEE), analyzing the clinicopathologic characteristics, recurrence rate, and recurrence-free survival (RFS) in this setting. Methods: A retrospective study was conducted, based on 332 patients undergoing thyroidectomy for PTC between January 2005 and December 2006. Results: The study population was stratified into two groups: PTC with MEE (103/332; 31.0%) and PTC without MEE (229/332; 69.0%). In patients with PTC, MEE correlated with gender, tumor size, multifocality, lymph node (LN) metastasis, underlying Hashimoto's thyroiditis, and the nature of the surgery. However, no significant intergroup differences were evident with respect to age, recurrence rate, and LN metastasis. In multivariate analysis, LN metastasis (odds ratio = 2.273; 95% confidence interval, 1.280–4.037) was recognized as an independent correlate of mETE (p = 0.005). However, recurrence-free survival did not differ significantly between the groups (p = 0.153), even when further stratified by the presence or absence of LN metastasis. Conclusion: In patients with PTC, MEE does not impact RFS. Thus, appropriate surgical intervention and postoperative follow up are mandatory in PTC, regardless of its extent. [Copyright &y& Elsevier]

Background: To define the exact boundary of the intrathyroid and extrathyroid aspects of a gland when determining the extent of cancer invasion, we plan to clarify the definition of sizable vascular structures, which is one of the helpful histologic clues in determining a minimal extrathyroid extension. We hypothesized that arterial wall thicknesses in extrathyroid soft tissue would be significantly different from the arteries in the thyroid parenchyma. Methods: Twenty cases of papillary carcinoma were selected. The numbers and wall thicknesses of the arteries and arterioles in intrathyroid and extrathyroid tissue were evaluated. The absence of nerve tissue in the thyroid gland was confirmed using the S-100 protein immunohistochemical stain. Results: The comparison of the mean thicknesses of the total arteries between the extrathyroid and intrathyroid tissues in the retrospective study (26.88 μm vs. 15.07 μm, respectively) and the prospective study (35.24 μm vs. 16.52 μm, respectively) revealed significant differences (p=0.000). The greatest thickness of the intrathyroid arteries was 67.93 μm. Conclusions: According to our results, the study showed that the extrathyroidal arteries were significantly thicker than the intrathyroidal arteries. We suggest that the sizable blood vessels of extrathyroidal arteries should be greater than 67.93 μm in thickness. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of our retrospective study was to evaluate the impact of minimal extrathyroidal extension on early response rate after (adjuvant) initial radioactive iodine therapy in patients with papillary thyroid cancer (PTC). We found that response rates after radioactive iodine (RAI) therapy in PTC patients were achieved irrespective of minimal extrathyroidal extension (mETE). Nonetheless, the risk of lymph node metastases involvement was significantly higher in the mETE patient group. Background: Extrathyroidal extension of differentiated thyroid cancer is a poor outcome factor but seems to be less significant in minimal extrathyroidal extension (mETE). However, the impact of mETE on response rate after (adjuvant) initial radioactive iodine (RAI) therapy remains unclear. We therefore compared response rates of patients with classical and follicular variants of papillary thyroid cancer (PTC) according to the updated eighth tumor-node-metastasis (TNM) classification to a control group. Methods: 455 patients with T3 (primary tumor > 4 cm) PTC according to the seventh classification who underwent total thyroidectomy followed by RAI therapy were screened. Patients formerly classified as T3 PTC solely due to mETE were reclassified into patients with T1 (primary tumor ≤ 2 cm) or T2 (primary tumor > 2 cm but ≤ 4 cm) +mETE and compared to a control group of T1/T2 −mETE PTC patients. Results: 138/455 patients were reclassified as T1/2 +mETE and compared to 317/455 T1/T2 −mETE control patients. At initial presentation, +mETE patients showed significantly higher rates of cervical lymph node metastases (p-value 0.001). Response rates were comparable in both groups (p-value n.s.). N1a/N1b-stage (Hazard ratio, HR 0.716; 95% CI 0.536–0.956, p-value 0.024) was identified as an independent prognostic factor for lower response rates. Conclusion: Response rates after RAI therapy were comparable in PTC patients irrespective of mETE but with higher rates of lymph node metastases. [ABSTRACT FROM AUTHOR]

Background: Although the incidence of papillary thyroid microcarcinoma (PTMC) has increased in recent decades, the role played by minimal extrathyroidal extension (mETE) in the prognosis of PTMC is still unclear. The aim of this study is to analyze the factors associated with PTMC with mETE and its long-term prognosis., Material and Methods: We conducted a retrospective study on patients with a histological diagnosis of PTMC. We excluded patients who had previously undergone thyroid surgery, those who had other synchronous malignancies, those with an ectopic location of the PTMC, and those lost to follow-up within two years. We compared group 1 (PTMC without extrathyroidal extension) to group 2 (PTMC with mETE) and performed a multivariate analysis., Results: We observed PTMC with mETE in 11.2% (n = 18) of patients. On the multivariate analysis, mETE was associated with an age ≥45 years (OR: 4.383; 95% CI: 1.051-18.283, p = .043), tumor size ≥8 mm (OR: 5.913; 95% CI: 1.795-19.481; p = .003), bilaterality (OR: 4.430; 95% CI: 1.294-15.173; p = .018) and metastatic lymph nodes (OR: 12.588; 95% CI: 2.919-54.280; p = .001). Over the mean follow-up period of 119.8 ± 65 months, one case of recurrence was detected in group 2 (0% vs. 5.6%; p = .112). No patients died of the disease. Disease-free survival was lower in group 2 (124.9 ± 5.6 vs. 97.4 ± 10.3 months; p = .034)., Conclusions: The mETE of PTMC is a factor of worse prognosis associated with the presence of metastatic lymph nodes and a lower rate of disease-free survival., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Purpose: According to American Thyroid Association (ATA) guideline, papillary thyroid cancer (PTC) with minimal extrathyroidal extension (mETE) is classified at "intermediate risk" of persistent/recurrent disease. However, the impact of mETE per se on patients' outcome is not fully understood. The aim of our study was to evaluate the prognostic significance of mETE in patients with PTC not submitted to therapeutic or prophylactic lymph node dissection, according to tumor size and other prognostic factors., Patients and Methods: We retrospectively evaluated a total of 514 PTC patients: 127 (24.7%) had mETE (pT3Nx) and 387 (75.3%) had negative margins (pT1-2Nx). At a median follow-up of 9.1 years, patients were divided in two groups: patients with "good outcome" (no evidence of disease) and patients with "poor outcome" (persistent structural disease or recurrent disease or tumor-related death)., Results: The rate of patients with "poor outcome" was significantly higher in patients with mETE compared with patients with negative margins (11.8 versus 5.1%; OR 2.4576, 95% CI 1.2178-4.9594, p = 0.01). However, mETE was significantly associated with poor outcome only in patients with tumors larger than 1.5 cm., Conclusions: mETE is an unfavorable prognostic factor in tumors larger than 1.5 cm, suggesting that, in the absence of other unfavorable characteristics, smaller tumors with mETE should be classified and managed as "low risk" tumors.

Differentiated thyroid cancer (DTC) with minimal extrathyroidal extension (MEE) is classified as stage III regardless of the tumor size. In this study, we aim to examine the effect of MEE on the overall survival and management of this population. A retrospective cohort study was performed, which utilized the National Cancer Database (NCDB), 2004-2012. The study population included patients, aged ≥ 45 years, who underwent surgery for DTC (pT3N0M0) with MEE compared to that in patients with pT2N0M0. A total of 9556 patients were included. These were divided into four groups, 4410 patients with pT2N0M0 (Group 1: T ≤ 4 cm without MEE), 3274 with pT3N0M0 (Group 2: T ≤ 4 cm with MEE), 447 with pT3N0M0 (Group 3: T > 4 cm with MEE) and 1430 patients with pT3N0M0 without MEE (Group 4: T > 4 cm without MEE). Median follow-up time was 46.7 months (interquartile range: 27.8-72.1). Patients in Group 2 (T ≤ 4 cm with MEE) had no significant worse survival compared to patients in Group 1 (T ≤ 4 cm without MEE) ( P  = 0.85), whereas Groups 3 and 4 (T > 4 cm), both had significantly lower survival ( P  < 0.001) with no difference between the two groups. Total thyroidectomy was associated with improved overall survival compared to that in lobectomy in Group 4 (T > 4 cm without MEE). Radioiodine utilization was associated with improved survival only with tumors larger than 4 cm with or without MEE. In DTC patients aged older than 45 years of age with tumor size less than 4 cm, MEE has no survival significance. Tumor size is an independent prognostic marker regardless of MEE status. Our data support re-evaluation of the current staging system., (© 2017 Society for Endocrinology.)

Background: To define the exact boundary of the intrathyroid and extrathyroid aspects of a gland when determining the extent of cancer invasion, we plan to clarify the definition of sizable vascular structures, which is one of the helpful histologic clues in determining a minimal extrathyroid extension. We hypothesized that arterial wall thicknesses in extrathyroid soft tissue would be significantly different from the arteries in the thyroid parenchyma., Methods: Twenty cases of papillary carcinoma were selected. The numbers and wall thicknesses of the arteries and arterioles in intrathyroid and extrathyroid tissue were evaluated. The absence of nerve tissue in the thyroid gland was confirmed using the S-100 protein immunohistochemical stain., Results: The comparison of the mean thicknesses of the total arteries between the extrathyroid and intrathyroid tissues in the retrospective study (26.88 µm vs. 15.07 µm, respectively) and the prospective study (35.24 µm vs. 16.52 µm, respectively) revealed significant differences (p=0.000). The greatest thickness of the intrathyroid arteries was 67.93 µm., Conclusions: According to our results, the study showed that the extrathyroidal arteries were significantly thicker than the intrathyroidal arteries. We suggest that the sizable blood vessels of extrathyroidal arteries should be greater than 67.93 µm in thickness.