Minimal Extrathyroidal Extension Research Articles

“High Risk” Features of Differentiated Thyroid Cancer Are Commonly Found in Autopsy Studies: Implications for the ATA Guidelines

Abstract Background: While the popularity of lobectomy for differentiated thyroid cancer (DTC) has increased since the 2015 American Thyroid Association guidelines, several recent studies reported that “high risk” histological features may be found in up to half of lobectomy specimens, questioning the validity of this approach. In turn, the actual risk associated with some “high risk” features (multifocality, minimal extra-thyroidal extension (ETE), and small lymph node (LN) metastases) has been questioned in recent years. Aim: To assess the prevalence of “high risk” pathological features in occult DTC detected in autopsy studies. Methods: Meta-analysis of autopsy studies of the thyroid gland in subjects without history of thyroid cancer. Studies with DTC lesions and details on histological features were included. Results: Twenty nine studies including 8,750 subjects fulfilled the inclusion criteria, with incidentally discovered DTC in 740 autopsies (prevalence of 8.5%). Age was reported in 17 studies, with a median age of 61 years (range 41-68 years). Multifocality was reported in 27 studies with a calculated event rate of 28.2% (95%CI 23.1% to 33.8%, random effect), with bilateral involvement in 18% (95%CI 12.6%-25/1%). Minimal ETE was reported in five studies, with an event rate of 24.5% (95%CI 9.3% to 50.7%, random effect), and the presence of LN metastases was reported in 13 studies with an event rate of 11% (95%CI 6.1% to 19.1%, random effect). Vascular invasion was reported in seven studies with an event rate of 16% (95%CI 4% to 47%, random effect). Conclusions: “High risk” histological features are common in occult DTC found in autopsy studies, and do not seem to be markers of aggressive disease. These data support a less aggressive therapeutic approach in patients with microscopic “high risk” features which were not detected on pre-operative ultrasound.

Minimal extrathyroid extension in papillary micro carcinoma of the thyroid is an independent risk factor for relapse through lymph node and distant metastases.

Aims: Minimal extrathyroid extension (mETE) is no longer considered in the new 8th edition of the AJCC/UICC staging system. Therefore, papillary thyroid microcarcinoma with mETE previously staged as pT3 will now be staged as pT1a and most likely not receive adjuvant radioiodine therapy. However, it remains unclear if mETE is associated with higher aggressiveness in papillary thyroid microcarcinoma. Therefore, the aim of this study was to investigate if mETE is associated with higher risk of lymph node or distant metastases. Methods: 721 patients with thyroid papillary microcarcinoma presenting at our department for postoperative counseling from 05/1983 to 8/2012 were included in this retrospective analysis (median follow-up time 9.30 years). The impact of mETE on the presence of lymph node metastases at thyroidectomy and relapse through lymph node and distant metastases was assessed by logistic regression and Fine-Gray model analyses. Results: 10.7% (n = 77) of patients had mETE. mETE was an independent risk factor for lymph node metastases at thyroidectomy with an adjusted odds ratio of 4.33 (95%CI: 2.02-9.60, p<0.001) in multivariable analysis. Patients with mETE had significantly more relapses through lymph node (over 5 years: 13.1% vs. 1.25%; P < 0.001) and distant metastases (over 5 years: 7.8% vs. 1.1%; P < 0.001) compared to patients without mETE. mETE was an independent risk factor for relapse through lymph node and distant metastases in multivariable analysis (hazard ratio: 7.78, 95%CI: 2.87-21.16, p< 0.001 and 4.09, 95%CI: 1.25-13.36, P = 0.020). Conclusion: mETE is a statistically significant and independent risk factor for relapse through lymph node and distant metastases in papillary microcarcinoma. Therefore, future studies should evaluate, if patients with mETE and microcarcinoma might benefit from intensified surveillance and therapy.

Factors Influencing Cervical Lymph Node Metastasis in Pediatric Differentiated Thyroid Cancers.

Lymph node metastasis is a considerable variable influencing postoperative American Thyroid Association (ATA) risk stratification in pediatric differentiated thyroid cancer (DTC). The primary aim of this study was to ascertain the factors predicting nodal metastasis and describe the outcomes in relation to the ATA risk. Patients 18years or younger operated between December 2005 and December 2019 were analyzed. Demographic, clinicopathological, treatment, and outcome data were recorded. Factors associated with nodal metastasis were assessed by univariate and multivariate regression analysis. Patients were stratified into low-, intermediate-, and high-risk as per the pediatric ATA guidelines. A total of 86 patients (43% male; median [IQR] age, 12 (10-14) years) underwent surgery during the study period. Lymph node metastases were present in 70 (82.4%) patients involving the lateral (8%) and central compartment (4.7%) alone and both (88.6%) compartments. Extrathyroid extension (ETE) was present in 65%; 35%, minimal; and 30%, extensive. On univariate analysis, nodal metastasis was more frequent in male patients, multifocal tumor, lymphovascular invasion, and ETE. On multivariate analysis, only ETE was predictive of nodal disease with an odds ratio of 8. Minimal and extensive ETEs were both significantly associated with lymph node metastases when compared to the absence of ETE. The 5-year disease-free survival was 100%, 95.7%, and 66% in the low-, intermediate-, and high-risk groups respectively (p < 0.0001). Pediatric DTCs have an exceptionally high incidence of lymph node metastasis. ETE is the single most important predictor of nodal disease. The ATA pediatric risk stratification is useful in predicting clinical outcomes.

Obesity and Overweight Are Associated with Minimal Extrathyroidal Extension, Multifocality and Bilaterality of Papillary Thyroid Cancer.

Epidemiological studies have shown a strong association between high body mass index (BMI) and papillary thyroid cancer (PTC). We assessed the clinical and histopathological features of PTC in patients with a higher BMI and compared them to analogous parameters in PTC patients with a normal BMI. We retrospectively analyzed 5021 medical records of patients admitted and surgically treated for thyroid tumors in one center between 2008 and 2018. Finally, we extracted data from 523 adult patients with PTC and stratified patients into two groups according to BMI: Group 1 with BMI < 25 kg/m2 and Group 2 with BMI ≥ 25 kg/m2. Data stratification was performed to estimate the association of overweight and obesity with clinical and histopathological features of PTC in both univariable and multivariable binary logistic regression analyses. Overall, compared to patients with a normal BMI, overweight and obese patients had a greater risk of minimal extrathyroidal extension (minimal ETE), multifocality and bilaterality of PTC (p < 0.001 for all). Analysis did not show that BMI was significantly associated with the more advanced tumor-node-metastasis (TNM) stage (p = 0.894). Obesity and overweight were significantly associated with higher aggressiveness of PTC. When considering various management options for PTC patients, these findings regarding overweight and obesity should be taken into consideration during the decision-making process.

Papillary thyroid microcarcinoma with minimal extrathyroidal extension. Is its course so indolent that it requires a less aggressive treatment?

BackgroundAlthough 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 methodsWe 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. ResultsWe 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). ConclusionsThe 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.

Risk factors of papillary thyroid microcarcinoma that predispose patients to local recurrence.

Currently, less aggressive treatment or even active surveillance of papillary thyroid microcarcinoma (PTMC) is widely accepted and recommended as a therapeutic management option. However, there are some concerns about these approaches. We investigated whether there are any demographic, clinical and ultrasound characteristics of PTMC patients that are easy to obtain and clinically available before surgery to help clinicians make proper therapeutic decisions. We performed a retrospective chart review of 5,021 patients with thyroid tumors surgically treated in one center in 2008-2018. Finally, 182 (3.62%) PTMC patients were selected (158 (86.8%) females and 24 (13.2%) males, mean age 48.8±15.4 years). We analyzed the disease-free survival (DFS) time of the PTMC patients according to demographic and histopathological parameters. Univariate and multivariate logistic regression analyses were used to assess the relationships of demographic, clinical and ultrasound characteristics with aggressive histopathological features. Age ≥55 years, hypoechogenicity, microcalcifications, irregular tumor shape, smooth margins and high vascularity significantly increased the risk for minimal extrathyroidal extension (minETE), lymph node metastasis (LNM), and capsular and vascular invasion (p<0.0001). Multivariate logistic regression analysis demonstrated a statistically significant risk of LNM (OR = 5.98, 95% CI: 2.32-15.38, p = 0.0002) and trends toward significantly higher rates of minETE and capsular and vascular invasion (OR = 2.24, 95% CI: 0.97-5.19, p = 0.056) in patients ≥55 years than in their younger counterparts. The DFS time was significantly shorter in patients ≥55 years (p = 0.015), patients with minETE and capsular and vascular invasion (p = 0.001 for all), patients with tumor size >5 mm (p = 0.021), and patients with LNM (p = 0.002). The absence of microcalcifications, irregular tumor shape, blunt margins, hypoechogenicity and high vascularity in PTMC patients below 55 years and with tumor diameters below 5 mm may allow clinicians to select individuals with a low risk of local recurrence so that they can receive less aggressive management.

Effects of the Minimal Extrathyroidal Extension on Early Response Rates after (Adjuvant) Initial Radioactive Iodine Therapy in PTC Patients.

Simple SummaryThe 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.

The new T3b category has clinical significance? SEER-based study.

As per the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for differentiated thyroid carcinoma (DTC), minimal extrathyroidal extension (mETE) has been removed. Instead, gross ETE (gETE) invading only strap muscles has been designated as a new T3b category. Our objective was to investigate the impact of the T3b category on survival in order to establish its prognostic value in DTC. In this retrospective study, we included patients who had undergone thyroidectomy between 2004 and 2012. Data from the Surveillance, Epidemiology and End Results (SEER) database were examined. We used the Kaplan-Meier method and log-rank test to analyse overall survival (OS) and cancer-specific survival (CSS). The effect of potential predictors associated with survival were estimated using the Cox regression model. To minimize selection bias, propensity-score matching (PSM) was performed. A total of 63315 patients were included in our study. During the average follow-up duration of nearly 78months, significant differences were observed in cancer-specific survival among patients with no ETE, mETE, gETE invading only strap muscles (T3b) and gETE invading perithyroidal structures other than strap muscles (T4) (P<.05). In univariable and multivariate analysis, both mETE and T3b exhibited significant poorer CSS compared with no ETE. After adjusting for patient features with PSM, it was confirmed that T3b was associated with worse CSS compared with no ETE and mETE. Both mETE and gETE are independent factors for DTC, implying that the new T3b category is worthy of reference for medical workers. Furthermore, mETE was significantly associated with poorer outcome. Our conclusion may provide support for the modification of the TNM staging system in the future.

Influence of Tumor Number on Clinicopathologic Features and Outcomes of Patients With Papillary Thyroid Carcinoma

The purpose of this study was to investigate the significance of tumor number on clinicopathologic factors and outcomes of patients with papillary thyroid carcinoma (PTC). We retrospectively analyzed 667 patients with PTC. We compared clinicopathologic features of patients with a different tumor number. Cox proportional hazards model was used to analyze risk factors of recurrence. In papillary thyroid microcarcinoma (PTMC), the increase in the number of tumor foci was related to a higher risk of minimal extrathyroidal extension (ETE) and lymphovascular invasion (P < .05). Patients with PTMC with four or more foci had a significantly higher risk of central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) than patients with solitary tumors (P < .05). Patients with macro-PTC with four or more foci and with three foci had a higher risk of gross ETE and lymphovascular invasion than patients with solitary tumors (P < .05). The increase in the tumor number was related to a higher risk of CLNM in macro-PTC (P < .05). The number of foci was the independent predictor of recurrence in patients with macro-PTC (P < .05). An increase in the number of tumors was associated with an increased risk of aggressive clinicopathologic features in PTMC and macro-PTC. The number of tumor foci could influence risk of recurrence in macro-PTC.

Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size

Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation. Thyroid surgery cases at a single institution from 2005-2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings. Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology. Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy. ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound.

Prevalence and Risk of Metastatic Thyroid Cancers and Management Outcomes: A National Perspective.

Examine the prevalence and risk of metastasis in thyroid cancers and management outcomes. Retrospective analysis of the National Cancer Database, 2004-2014. The study population included adult (≥ 18 years) patients with thyroid cancer. Analysis included multivariate logistic regression and Cox hazard ratio modeling. A total of 152,979 patients were included. Distant metastasis was reported in 1,867 (1.22%) patients. The distribution of metastatic cases based on pathology and tumor size were as follows in descending order: papillary thyroid carcinoma (PTC) 1 to 4 cm (30.53%), PTC > 4 cm (19.34%), undifferentiated (UTC) > 4 cm (14.14%), PTC < 1 cm (8.46%), follicular thyroid carcinoma (FTC) > 4 cm (7.28%), FTC 1 to 4 cm (5.52%), medullary thyroid cancer (MTC) ≤ 4 cm (3.96%), MTC > 4 cm (3.91%), UTC ≤ 4 cm (3.32%), Hürthle (HCC ) > 4 cm (2.09%), and HCC 1 to 4 cm (1.45%). Significant predictors of distant metastasis, while controlling for tumor pathology and size, included older age, male gender, non-White minorities, presence of multiple comorbidities, minimal, gross extrathyroidal extension (ETE), lymphovascular invasion (LVI), and concomitant central and lateral lymph node metastasis (LNM) (P < .05 each). The risk of distant metastasis in the absence of nodal metastasis, ETE, and LVI was highest for FTC > 4 cm. Although the risk of metastasis in well-differentiated thyroid carcinoma (WDTC) is low, the prevalence of metastatic thyroid cancer is highest in WDTC population because it is the most common type of thyroid cancer. Certain pathological features, including minimal ETE and central LNM, are associated with a higher prevalence of metastatic disease. NA Laryngoscope, 131:237-244, 2021.

The impact of minimal extrathyroidal extension in the recurrence of papillary thyroid cancer patients.

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. 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. 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%). 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.

OR21-01 Pre-Operative Calcitonin Value as a Predictive Factor of Cancer Related Death in Sporadic Medullary Thyroid Carcinoma

Introduction: Medullary thyroid carcinoma (MTC) is a rare tumor, it originates from the C cells producing calcitonin (CT) and can occur as sporadic or associated to germline RET mutation. The initial treatment is represented by total thyroidectomy associated with central compartment lymph nodes dissection and possible extension to the laterocervical compartment. CT is the main marker of follow-up of MTC, conversely its pre-operative role as diagnostic and prognostic factor is still debated. The aim of the present study was to evaluate several predictive factors of cancer related death in a large series of sporadic MTCs. Patients and Methods: We evaluated 537 consecutive patients surgically treated for sporadic MTC, from 2000 to 2019, and followed at the Operative Unit of Endocrinology 1 of the University of Pisa. We evaluated epidemiological, clinical and pathological data and pre and post-operative CT values, and their correlation with cancer related death. Results: At the end of the follow-up (average 75 months), 300/537 (55.9%) pts were cured, 100/537 (18.6%) pts showed biochemical disease, 88/537 (16.4%) pts showed metastatic disease and 49/537 (9.1 %) pts died for the disease. The factors significantly correlated with the cancer related death to the univariate analysis were the male gender, dimension of the primary tumor> 4 cm, the presence of lymph node metastasis to histology (N1) and/or distant metastasis (M1) at the time of diagnosis, multifocality, minimal extrathyroidal extension (mETE), initial staging, pre-operative CT values> 500 pg/ml and post-operative> 20 pg/ml. At multivariate analysis, statistical significance persisted only for pre- and post-operative CT and for the staging. Conclusions: 1) In our study we observed a significant improvement in the outcome and survival in the medium-long term of sporadic CMT patients, compared to the previous studies. 2) A more advanced staging at the time of diagnosis has been confirmed as a negative prognostic factor and it is evident that an early diagnosis is an essential requirement for improving cancer related death. 3) This is the first study that showed, in a large monocentric series of sporadic MTCs, as pre-operative CT represents a prognostic factor associated with cancer related death, as well as the value of post-operative CT.

Minimal and Gross Extrathyroidal Extension in Papillary Thyroid Carcinoma Has an Impact on the Risk of Recurrence and Response to Therapy

Minimal and Gross Extrathyroidal Extension in Papillary Thyroid Carcinoma Has an Impact on the Risk of Recurrence and Response to Therapy

Can Diffusion-Weighted MR Imaging Be Used as a Tool to Predict Extrathyroidal Extension in Papillary Thyroid Carcinoma?

To evaluate whether quantitative diffusion-weighted MR imaging (DWI) with multi-b values can be used as a tool to predict the aggressiveness by using the histological feature of extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC). 238 patients were pathologically confirmed as PTCs underwent preoperative multi-b value DWI (300, 500, and 800 s/mm2) between January 2015 and December 2017. The patients were divided into three groups according to the degree of ETE: without ETE, minimal ETE, and extensive ETE. The apparent diffusion coefficients (ADCs) were evaluated for three different b values (b = 300 s/mm2, b = 500 s/mm2, and b = 800 s/mm2). The ADC values of the groups with and without ETE, minimal and extensive ETE were compared. The diagnostic relevance of the ADC values in terms of predicting ETE was compared using a receiver operating characteristic analysis. Differences between the areas under the curves (AUCs) were compared by using a Delong test. PTCs with ETE had significantly lower ADC300, ADC500 and ADC800 values than PTCs without ETE (p = 0.001, p < 0.001, and p < 0.001, respectively). The AUC of the mean ADC500 value (0.905) was higher than that of the ADC300 and ADC800 values (0.607 and 0.770, respectively) in differentiating ETE from without ETE (p < 0.001). The cut-off value of ADC500 to discriminate PTCs with and without ETE was determined at 1.407 × 10-3 mm2/s, with sensitivity of 80.7%, specificity of 86.7%, and an AUC of 0.905. The ADC value can be demonstrated an effective tool for evaluating the aggressiveness with the histological feature of ETE in PTC. In particular, ADC value at b = 500 s/mm2 showed the best performance for noninvasive preoperative evaluation of ETE.

Preoperative Factors Associated with Extrathyroidal Extension in Papillary Thyroid Cancer

Objective: Extrathyroidal extension may not be accurately recognized during thyroidectomy and can increase the risk of positive margins and even recurrence. This study aimed to investigate the preoperative factors associated with extrathyroidal extension. Methods: We analyzed 887 patients with papillary thyroid cancer (PTC) who underwent surgery in the period of 2005–2017. Binary logistic regression analyses and generalized additive models were used to identify associations. Results: Minimal extrathyroidal extension was present in 233 (26%) patients and advanced extrathyroidal extension was found in 60 (7%) patients. Age, BMI, and tumor size were independent predictors of all or advanced extrathyroidal extension. Among the 493 patients whose BRAF mutation status was available, age (OR = 1.025), BMI (OR = 1.091), tumor size (OR = 1.544), and BRAF V600E mutation (OR = 2.311) were independently associated with extrathyroidal extension. Conclusions: Older age, a greater BMI, a larger tumor size, and presence of the BRAF mutation were predictive of extrathyroidal extension. These factors should be taken into consideration in decision-making before surgery is performed.

Microcarcinoma papilar de tiroides con extensión extratiroidea mínima. ¿Tiene un curso tan indolente para precisar un tratamiento menos intensivo?

BackgroundAlthough 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 methodsWe 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 2years. We compared group 1 (PTMC without extrathyroidal extension) to group 2 (PTMC with mETE) and performed a multivariate analysis. ResultsWe observed PTMC with mETE in 11.2% (n=18) of patients. On the multivariate analysis, mETE was associated with age ≥45 years (OR: 4.383; 95% CI: 1.051-18.283, p = .043), tumor size ≥8mm (OR: 5.913; 95% CL: 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). During a mean follow-up of 119.8±65 months, one 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). ConclusionsThe 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.

Is There a Difference Between Minimal and Gross Extension into the Strap Muscles for the Risk of Recurrence in Papillary Thyroid Carcinomas?

Background: The morbidity of papillary thyroid carcinoma (PTC) is primarily related to locoregional recurrences and distant metastases. The definition of minimal extrathyroidal extension (mETE) has been recently revised. The presence of mETE does not impact mortality and is generally not considered to be a predictor for the risk of recurrence. This study aimed at comparing the risk of recurrence and the response to therapy of PTC with mETE and gross extrathyroidal extension (ETE) into the strap muscles (gETE) with low- and intermediate-risk PTC without ETE (low risk w/o ETE and intermediate risk w/o ETE, respectively) to further characterize the impact of ETE on outcomes. Methods: A total of 596 PTCs were analyzed according to the degree of ETE as well as other predictors of recurrence. Four groups of patients were compared, low risk w/o ETE (n = 251), intermediate risk w/o ETE (n = 89), mETE (n = 191), and gETE (n = 65), to determine the risk of recurrence and the response to treatment. Cox proportional hazards models were used to investigate associations between groups and disease-free survival (DFS). Results: The risk of recurrence was 3% in low risk w/o ETE PTC, 14% in intermediate risk w/o ETE, 14% in mETE, and 25% in gETE. The recurrence risk was increased by the presence of ETE (odds ratio [OR] = 2.86, 95% confidence interval [CI] 1.36-5.85, p = 0.005) and lymph node metastases (OR = 2.44 [95% CI 1.25-4.76], p = 0.009). Patients with low-risk carcinomas w/o ETE experienced longer DFS than those with mETE (hazard ratio = 0.08 [95% CI 0.02-0.28], p < 0.001), but no significant difference was observed between intermediate risk w/o ETE, mETE, and gETE. In terms of the response to therapy, patients with gETE had higher rates of biochemical and/or structural incomplete responses within the first year of treatment (OR = 2.68 [95% CI 1.31-5.45], p = 0.007) and at the final follow-up evaluation (OR = 4.35 [95% CI 1.99-9.51], p < 0.001) compared with those with mETE. An analysis of the subgroups of microcarcinomas without lymph node metastases revealed no significant difference in DFS or the response to therapy between the low risk w/o ETE and mETE PTC groups. Conclusions: The results of this study suggest that both mETE and gETE are independent risk factors for the risk of recurrence in PTC. Although gETE has a more pronounced impact on the recurrence risk and is associated with a worse response to therapy, mETE may not be associated with a low risk of recurrence. This observation suggests that patients with PTC and mETE may, in part, have an intermediate risk of recurrence and need to be followed accordingly.

The influence of extrathyroidal extension in development of metastasis in papillary thyroid cancer

Background: Papillary thyroid cancer (PTC) course and outcome very much depend on prognosis factors. One of the most significant factors is extrathyroidal extension (ETE), which can be local or extensive. In the view of some authors, tumor grow beyond the thyroid capsule is associated with high risk locoregional and distant metastasis, which increase disease recurrence and reduce survival. Some others do not see influence of minimal ETE on disease prognosis, so we need more trials to clarify the role of ETE in PTC.&#x0D; Aims: To evaluate the ETE role in development of metastasis in PTC patients.&#x0D; Materials and methods: The study includes 233 patients with PTC who receive treatment in RSCRR. 185 patients had clinical N0 stage, 48 patients were with verified N1a1b. All patients with cN0 underwent thyroidectomy with central neck dissection, patients with N1 thyroidectomy combined with different neck dissections, also superior mediastinal lymphadenectomy if required. Within combination treatment the radioiodine therapy was carried out. The histology evaluated thyroid capsule involvement and lymph node metastasis. Data processing was carried out in a Microsoft Access database, a one-factor dispersion analysis was used for the analysis of the quantitative signs, and a -square criterion was used for qualitative ones. Multifactor analysis was done in SPSS20 program.&#x0D; Results: Thyroid capsule extension was detected in 111 cases (47.6%), from which 92 were microscopic. 122 patients did not have ETE. The frequency of lymph node metastasis with or without ETE was 62.2% and35.8% respectively, which is significantly more often (р = 0.000, 2 = 21.342). In microscopic and macroscopic extension regional metastasis were 56.5% and 94.7%, distant metastasis 1.1 and 21% respectively. Statistically significant, the ETE was more prevalent in non-encapsulated tumor cases (р = 0.000, 2=15.122), and if the tumor size was more than 1cm (р = 0.026, 2 = 7.293). Only 41% of patients with cN0 had ETE, and patients with N1 72.9%, which is statistically significant (р = 0.000, 2 = 14.235).&#x0D; Conclusion: ETE is a predictor of PTC metastasis. The presence of ETE requires the necessity to apply the more aggressive treatment of PTC including thyroidectomy with central neck dissection and radioiodine therapy. Gross ETE significantly increases the risk of regional together with distant metastasis.

Prognostic value of tumor size and minimal extrathyroidal extension in papillary thyroid carcinoma

BackgroundTumour size and extrathyroidal extension (ETE) may impact papillary thyroid carcinoma (PTC) outcomes. We therefore examined the prognostic value of tumour size and ETE for predicting posttreatment recurrence in PTC patients. MethodsA total of 2,902 patients who underwent thyroidectomy for previously untreated T1–T3 PTC (7th edition American Joint Committee on Cancer) at our tertiary referral center were included. Univariate and multivariate Cox proportional hazard regression analyses were used to determine significant factors predictive of posttreatment recurrence-free survival (RFS). ResultsIn univariate analysis, tumour factors (including tumour size, multifocality, ETE, and lymphovascular invasion), nodal factors (including positive lymph node number, lymph node ratio, and extranodal extension), and MACIS (metastases, age, completeness of resection, invasion, and size) scores were significantly associated with RFS outcomes (P < 0.001). In multivariate analysis, tumour size >4 cm (P < 0.001) and multifocality (P = 0.038) were the independent factors of RFS. Nodal factors and MACIS scores were also independent factors of RFS. ConclusionTumour size impacts RFS after thyroidectomy in T1–T3 PTC patients.