Ultrasound features of medullary thyroid cancer as predictors of biological behavior

Background Medullary thyroid cancer (MTC) has more aggressive behavior and poor prognosis. Ultrasound (US) has facilitated the qualitative diagnosis of thyroid nodules, however, some MTC may be diagnosed as a benign nodule on ultrasound because ultrasound features of malignancy are lacking. The aim of the study was to investigate the association between ultrasound features and biological behavior of MTC. Methods Ultrasound findings and medical records of patients with MTC between Jan 2015 to Jun 2017 were retrospectively reviewed at Tianjin Medical University Cancer Institute and Hospital. MTC were categorized using modified TI-RADS classification, then were classified as “malignant” (m-MTC) or “US-low-suspicious” (l-MTC). We compared the biological behavior between the two groups, and further analyzed the risk factors for the recurrence. Results A total of 78 patients were enrolled, of which 55 m-MTC (70.5%) and 23 l-MTC (29.5%) were identified. The N staging of the m-MTC was significantly higher than that of l-MTC(P = 0.000). The preoperative serum Ct level in m-MTC were significantly higher than that of l-MTC(P = 0.035). Biochemical cure were more frequent in l-MTC than that of m-MTC (P = 0.002). Disease recurrence rates were 19.7% (14 of 71). Disease recurrence was more frequent in m-MTC than that of l-MTC (P = 0.013). Disease recurrence was positively associated with extrathyroid extension (P = 0.047), N staging (P = 0.003), preoperative serum Ct level (P = 0.009) and negatively associated with biochemical cure(P = 0.000). In multivariable Cox regression analysis, extrathyroid extension and biochemical cure were independent risk factors for recurrence of MTC. Conclusions L-MTC has a more indolent character than m-MTC. The extrathyroid extension and biochemical cure were independent risk factors for recurrence of MTC.

Prognostic value and dynamics of antithyroglobulin antibodies for differentiated thyroid carcinoma

Background: The clinical value of antithyroglobulin antibodies (TgAb) as a tumor marker for differentiated thyroid cancer (DTC) is still controversial. Materials & methods: We studied 110 TgAb positive DTC patients who underwent total thyroidectomy and 131I therapies. Multivariate logistic regression was conducted to analyze the association between prognostic factors and disease outcomes. Results & conclusion: Pre-ablation TgAb levels and the changes of TgAb in 6–12 months after the first 131I therapy were risk factors for disease outcome in patients younger than 55, while extrathyroid extension was a risk factor in patients older than 55. The median TgAb half-life was 7.7 months and the median time for TgAb positivity to become negative was 15.8 months. The dynamics of TgAb within the first year after remnant ablation could predict disease outcome for DTC patients.

Diagnostic model incorporating clinicopathological characteristics of Delphian lymph node metastasis risk profiles in papillary thyroid cancer

Background Delphian lymph node (DLN), also known as prelaryngeal node, is the component of central lymph node (Level VI). DLN has been well studied in laryngeal cancer while less in papillary thyroid cancer (PTC). However, increasing attention has been payed to its clinical value in PTC lymph node metastasis. The aim of this study was to assess the clinicopathologic risk factors for DLN metastasis and to calibrate an informative diagnosis model for predicting risk stratification in DLN metastasis. Methods Retrospectively analysis 936 PTC patients who underwent thyroidectomy by a single surgeon, in the department of Head and Neck Surgery of Tianjin Cancer Hospital from 2017 to 2019. Moreover, 250 PTC patients underwent thyroidectomy by another surgeon at Tianjin Cancer Hospital between January 2019 and April 2019 were used as a validation cohort. Univariate analysis and multivariable logistic regression were used to identify clinicopathologic risk factors associated with DLN metastasis. A diagnostic model was generated using logistic regression, and internal validation and external validation were also performed. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC) and calibration plot. A nomogram plot was drawn to predict individual risk based on the diagnosis prediction model. Results In 936 cases, 581 (62.1%) show DLN, and 177 (177/581,30.5%) were verified metastasis. DLN metastasis was significantly associated with gender, age, tumor size, bilateral cancer, multifocality, extrathyroidal extension, lymphovascular invasion and central and lateral neck lymph node metastasis. Multivariate analysis revealed that age, gender, tumor size, extrathyroid extension, lymphovascular invasion and central lymph node metastasis were independent risk factor of DLN metastasis. The nomogram included age, gender, tumor size, extrathyroid extension, lymphovascular invasion and central lymph node metastasis, and all these features had a specificity of 100%. Particularly, tumor size was the best single predictor. The diagnostic model had an area under the curve (AUC) of 0.829 (95% confidence interval, 0.804–0.854). Internal and external validation of nomogram was 0.819 and 0.745, respectively. Conclusions DLN metastasis appears to be an important parameter that predict metastatic disease of the central compartments. To assess DLN metastasis in more precise criterions, has great clinical significance for PTC treatment selection.

High Expression of Interleukin-12A and Its Association with the Clinicopathology and Prognosis of Differentiated Thyroid Cancer

Background: The inflammatory microenvironment is closely related to the occurrence and development of cancer. Members of the interleukin-12 (IL-12) cytokine family play synergistic or antagonistic roles in the tumor microenvironment, in the form of classic heterodimers or newly discovered monomers or homodimers. Objective: The purpose of this study was to investigate the association between IL-12A and the clinicopathology and prognosis of differentiated thyroid cancer (DTC). Methods: A total of 101 pathologically confirmed DTC patients were included in this study. Immunohistochemistry was performed to assess IL-12A expression in DTC and corresponding paracancerous tissues. The associations of IL-12A with clinicopathology and prognosis were evaluated. Results: IL-12A was expressed in both normal thyroid tissues and DTC, but its expression level was significantly higher in DTC than in normal thyroid tissues (p < 0.001). IL-12A was positively correlated with tumor size (p = 0.027), risk stratification (p = 0.020), and TNM (Tumor-Node-Metastasis) stage (p = 0.024), but not with age, sex, pathological type, multifocality, extrathyroid extension, lymph node metastasis, and distant metastasis (all p > 0.05). Lymphocytic thyroiditis was found in 26/101 patients (25.7%), which was negatively associated with IL-12A expression (p = 0.018). Multivariate logistic regression analysis showed that risk stratification was the significant independent predictor of IL-12A expression. The rate of disease persistence or recurrence (P&amp;R) was 13/101 (12.9%), and a positive relationship was found between IL-12A expression and P&amp;R (p = 0.020). Disease-free survival was affected by factors such as tumor size, extrathyroid extension, tumor stage (T stage), and IL-12A expression, with p values of 0.006, 0.048, 0.002, and 0.012, respectively. Multivariate Cox proportional-hazards analysis showed that tumor size ≥2 cm (hazard ratio [HR] = 4.041 [95% CI: 1.144–14.274], p = 0.031) and high IL-12A expression (HR = 4.027 [95% CI 1.014–15.994], p = 0.049) were independent predictors of prognosis of DTC patients. Conclusions: IL-12A is highly expressed in DTC and is associated with disease aggressiveness. In addition, IL-12A is an independent predictor of the outcome of DTC.

Prognostic Value of Extranodal Tumor Extension in Papillary Thyroid Carcinoma: Proposal for Upstaging of Cases with Extranodal Tumor Extension

Background Recently, we have created a revised version of the eighth edition of the tumor–node–metastasis classification for papillary thyroid carcinomas (PTCs) by subdividing the T4a (T4a1 [moderate] and T4a2 [significant]) and N (N1 [N ≤ 3 cm] and N2 [N > 3 cm]) classifications. This re-staging better stratified patient outcomes. In this study, we investigated the prognostic significance of extranodal tumor extension (LNEx) in PTC. Methods Five thousand six hundred and eighty-three patients with PTC surgically treated in Kuma Hospital were enrolled. We evaluated LNEx based on intraoperative findings. Results One hundred and twenty-seven patients (2%) displayed LNEx. In contrast to what we observed for extrathyroid extension, the prognostic value of LNEx did not change based on the organ that had been invaded, and we therefore analyzed LNEx patients as a single group. In patients aged 55 or older, LNEx independently affected patients’ prognoses, as did T4a2 and N2. The cancer-specific survival (CSS) of patients in Stage I but having LNEx demonstrated the similar prognosis to patients in Stage II. Further, in the subset analysis for Stage II patients aged 55 or older, LNEx had a significant prognostic value for CSS in both the univariate and multivariate analyses, as did N2. The CSS of Stage II patients aged 55 or older with LNEx did not differ from that of Stage III patients. Conclusions It is appropriate that, similar to T4a2 or N2 patients, LNEx-positive patients younger than 55 years in Stage I and those aged 55 or older in Stage II are re-staged to II and III, respectively.

Active Surveillance as First-Line Management of Papillary Microcarcinoma

Papillary thyroid microcarcinoma (PMC) is defined as papillary thyroid carcinoma ≤10 mm. Active surveillance of PMC without high-risk features, such as clinical node metastasis, distant metastasis, and clinical evidence of significant extrathyroid extension, was initiated in two Japanese hospitals in the mid-1990s. This strategy was incorporated into guidelines in Japan in 2010 and in the United States in 2015. In studies conducted by the two hospitals, most PMCs grew very slowly or did not grow, and none of the patients during active surveillance showed distant metastasis or died of thyroid carcinoma. Furthermore, none of the patients who underwent surgery after progression signs were detected showed significant recurrence. Therefore, we conclude that active surveillance should be the first line in management of low-risk PMC, because it is safer and less costly than immediate surgery. Active surveillance helps in avoiding adverse events of surgery and is an economical strategy.

Impact of Minimal Extrathyroid Extension in Differentiated Thyroid Cancer: Systematic Review and Meta-Analysis

Background Minimal extrathyroid extension (mETE) in patients with differentiated thyroid cancer (DTC) was defined as an intermediate risk feature in the 2015 American Thyroid Association guidelines. However, controversy persists as several studies suggested mETE has little effect on disease outcome. Objective To assess the impact of mETE on DTC patients' outcome. Methods Meta-analysis of controlled trials comparing patients with DTC with and without mETE. Data Extraction and Synthesis Thirteen retrospective studies including 23,816 patients were included, with a median follow-up of 86 months. mETE in patients without lymph node involvement (N0 disease) was associated with increased risk of recurrence [seven studies: odds ratio (OR), 1.73; 95% confidence interval (CI), 1.03 to 2.92]. The absolute risk of recurrence was 2.2% in patients without extension and 3.5% in patients with mETE (P = 0.04). In studies including patients with and without lymph node involvement (N1/N0 disease), mETE resulted in a significantly higher risk of recurrence (eight studies: OR, 1.82; 95% CI, 1.14 to 2.91). The absolute risk of recurrence was 6.2% in patients without extension and 7% in patients with mETE (P = 0.01). In patients with micropapillary carcinoma (&lt;1 cm), the impact of mETE was nonsignificant (OR, 2.40; 95% CI, 0.95 to 6.03). mETE had no impact on disease-related mortality (eight studies: OR, 0.5; 95% CI, 0.11 to 2.21). Conclusion mETE increases risk of recurrence in patients with DTC; however, the absolute increase in risk is small, and in patients with N0 disease the risk is within the low-risk of recurrence category at 3.5%. mETE has no impact on disease-related mortality and should not change tumor stage.

Mutación BRAF V600E en pacientes con cáncer de tiroides. Fundación Clínica Valle del Lili: una serie de casos

Objetivo: Describir las características clínicas y los hallazgos histopatológicos de los pacientes con diagnóstico de cáncer de tiroides y estudio de la mutación del Gen BRAF V600E.Métodos: Estudio descriptivo, retrospectivo, con información obtenida de las historias clínicas de los pacientes con diagnóstico de cáncer de tiroides atendidos durante 2014 y 2105 en la Fundación Clínica Valle del Lili con estudio para la mutación del gen BRAF V600E.Resultados: De los 344 pacientes con diagnóstico de cáncer de tiroides durante los años 2014 y 2015, se les realizó estudio de la mutación BRAF V600E a 24. La edad promedio fue de 47 años, con predominio en mujeres (87,5%), fueron positivos para la mutación 66% de los pacientes. En relación a las características histopatológicas, el 95,8% de los casos correspondían a cáncer papilar de tiroides, la mayoría de la variedad clásica. Los pacientes con la mutación BRAF V600E tenían mayor extensión extratiroidea, invasión linfática, invasión vascular y compromiso ganglionar, pero no se encontró relación con respecto a tamaño tumoral, multicentralidad, bilateralidad, tiroiditis de Hashimoto o presencia de metástasis.Conclusión: Este es el primer estudio en Colombia, que describe las características clínicas e histopatológicas de los pacientes con cáncer de tiroides en relación a la presencia de la mutacion del Gen BRAF.Abstract Objective: To describe the clinical and histopathological findings of patients diagnosed with thyroid cancer and BRAF V600E gene mutation study. Methods: A descriptive, retrospective study, with information obtained from the medical records of patients diagnosed with thyroid cancer seen during 2014 and 2105 in the Fundacion Clínica Valle del Lili with analysis of the BRAF V600E gene mutation. Results: Of the 344 patients diagnosed with thyroid cancer during the years 2014 and 2015, underwent study of the BRAF V600E to 24. The average age was 47 years, with prevalence in women (87.5%) were positive for mutation 66% of patients. Regarding the histopathologic features, 95.8% of the cases werepapillary thyroid cancer, most classic variety. Patients with BRAF V600E mutation were more extrathyroid extension, lymphatic invasion, vascular invasion and nodal involvement, but no relationship was found with respect to tumor size, multicentrality, bilateralism, Hashimoto’s thyroiditis or presence of metastasis. Conclusion: This is the first study in Colombia, describing the clinical and histopathologic of patients with thyroid cancer in relation to the presence of the BRAF gene mutation characteristics.-