Papillary Thyroid Carcinoma Lesions Research Articles

Application of color doppler ultrasound and US shear wave elastography with connective tissue growth factor in the risk assessment of papillary thyroid carcinoma

BackgroundThis study aims to investigate the role of shear wave elastography (SWE) and connective tissue growth factor (CTGF) in the assessment of papillary thyroid carcinoma (PTC) prognosis.MethodsCTGF expression was detected with immunohistochemistry. Clinical and pathological data were collected. Parameters of conventional ultrasound combined with SWE were also collected. The relationship among CTGF expression, ultrasound indicators, the elastic modulus and the clinicopathological parameters were analyzed.ResultsUnivariate analysis showed that patients with high risk of PTC were characterized with male, Uygur ethnicity, increased expression of CTGF, convex lesions, calcified, incomplete capsule, intranodular blood flow, rear echo attenuation, cervical lymph node metastasis, lesions larger than 1 cm, psammoma bodies, advanced clinical stage, increased TSH and high value in the shear modulus (P < 0.05). Multivariate analysis demonstrated that the risk factors of high expression of CTGF according to contribution size order were irregular shape, aspect ratio ≥ 1, and increased TSH. The logistic regression model equation was Logit (P) = 1.153 + 1.055 × 1 + 0.926 × 2 + 1.190 × 3 and the Area Under Curve value of the logistic regression was calculated to be 0.850, with a 95% confidence interval of 0.817 to 0.883.ConclusionSWE and CTGF are of great value in the risk assessment of PTC. The degree of fibrosis of PTC is closely related to the prognosis. The hardness of PTC lesions and the expression level of CTGF are correlated with the main indexes of conventional ultrasound differentiating benign or malignant nodules. Irregular shape, aspect ratio ≥ 1, and increased TSH are independent factors of CTGF.

Development and validation of a clinical predictive model for high-volume lymph node metastasis of papillary thyroid carcinoma

The central lymph node metastasis (CLNM) status in the cervical region serves as a pivotal determinant for the extent of surgical intervention and prognosis in papillary thyroid carcinoma (PTC). This paper seeks to devise and validate a predictive model based on clinical parameters for the early anticipation of high-volume CLNM (hv-CLNM, > 5 nodes) in high-risk patients. A retrospective analysis of the pathological and clinical data of patients with PTC who underwent surgical treatment at Medical Centers A and B was conducted. The data from Center A was randomly divided into training and validation sets in an 8:2 ratio, with those from Center B serving as the test set. Multifactor logistic regression was harnessed in the training set to select variables and construct a predictive model. The generalization ability of the model was assessed in the validation and test sets. The model was evaluated through the receiver operating characteristic area under the curve (AUC) to predict the efficiency of hv-CLNM. The goodness of fit of the model was examined via the Brier verification technique. The incidence of hv-CLNM in 5897 PTC patients attained 4.8%. The occurrence rates in males and females were 9.4% (128/1365) and 3.4% (156/4532), respectively. Multifactor logistic regression unraveled male gender (OR = 2.17, p < .001), multifocality (OR = 4.06, p < .001), and lesion size (OR = 1.08 per increase of 1 mm, p < .001) as risk factors, while age emerged as a protective factor (OR = 0.95 per an increase of 1 year, p < .001). The model constructed with four predictive variables within the training set exhibited an AUC of 0.847 ([95%CI] 0.815–0.878). In the validation and test sets, the AUCs were 0.831 (0.783–0.879) and 0.845 (0.789–0.901), respectively, with Brier scores of 0.037, 0.041, and 0.056. Subgroup analysis unveiled AUCs for the prediction model in PTC lesion size groups (≤ 10 mm and > 10 mm) as 0.803 (0.757–0.85) and 0.747 (0.709–0.785), age groups (≤ 31 years and > 31 years) as 0.778 (0.720–0.881) and 0.837 (0.806–0.867), multifocal and solitary cases as 0.803 (0.767–0.838) and 0.809 (0.769–0.849), and Hashimoto’s thyroiditis (HT) and non-HT cases as 0.845 (0.793–0.897) and 0.845 (0.819–0.871). Male gender, multifocality, and larger lesion size are risk factors for hv-CLNM in PTC patients, whereas age serves as a protective factor. The clinical predictive model developed in this research facilitates the early identification of high-risk patients for hv-CLNM, thereby assisting physicians in more efficacious risk stratification management for PTC patients.

Correlations between the average Young's modulus and histopathological characteristics of papillary thyroid carcinoma

Objective: To explore the histopathological factors affecting the stiffness of papillary thyroid carcinoma (PTC). Methods: Ninety-six patients with PTC confirmed by surgery and pathology in Shanxi Bethune Hospital from January 2019 to December 2020 were selected, including 101 nodules. Two-dimensional ultrasound and shear-wave elastography (SWE) were performed before surgery and the average Young's modulus (Emean) of PTC nodules were measured. Histopathological examinations on the nodules were conducted after surgery to decide the lesion size, number of lesions, calcification type, presence or absence of capsular and extracapsular invasion, degree of fibrosis, microvessel density, and number of tumor cells. The correlations between the lesion size, degree of fibrosis, microvessel density, and number of tumor cells and the Emean were analyzed. The Emeans of nodules with different numbers of lesions, presence or absence of capsular and extracapsular invasion, and different pathological calcification types were compared. The multiple linear regression analysis was used to evaluate the histopathological factors influencing the Emean. Results: The ranges of the lesion sizes, degrees of fibrosis, microvascular density, numbers of tumor cells, and the Emeans of the 101 investigated PTC nodules were (1.29±0.95) cm, (30.64±18.37)%, (101.64±30.7) vessels per high power field, (373.52±149.87) cells per high power field, and (36.47±19.62) kPa, respectively. Correlation analysis showed that the lesion size of PTC and the degree of fibrosis were positively correlated with the Emean (r=0.660, P＜0.001; r=0.789, P＜0.001), while the microvessel density was negatively correlated with the Emean (r=-0.198, P=0.047). The Emean of the group with capsular and extracapsular invasion was higher than that of the group without (P=0.014). There were statistical differences in the Emeans among different types of pathological calcification (P＜0.001). The multiple linear regression analysis showed that the lesion size (β=0.325, P＜0.001), degree of fibrosis (β=0.563, P＜0.001), psammoma bodies (β=0.177, P=0.001), stromal calcification (β=0.164, P=0.003), and mixed calcification of both psammoma bodies and stroma (β=0.163, P=0.003) were independent influencing factors for the Emean. The degree of fibrosis had the greatest impact on the Emean. Conclusions: The Emean of PTC lesions was correlated with the histopathological characteristics of PTC. The lesion size, degree of fibrosis, and calcification had significant impact on the Emean, among which the degree of fibrosis had the greatest impact.

Retrospective study of BRAFV600E mutation and CT features of papillary thyroid carcinoma.

This study aimed to examine the correlation between BRAFV600E status and computed tomography (CT) imaging characteristics in papillary thyroid carcinoma (PTC) and determine if suspicious CT imaging features could predict BRAFV600E status. This retrospective study included patients with pathologically confirmed PTC at the Department of Thyroid Surgery of Zhongshan Hospital, Xiamen University, between July 2020 and June 2022. We compared the clinicopathologic factors and CT findings of nodules with and without the mutation, and the multiple logistical regression test was used to determine independent parameters of the BRAFV600E mutation. This study included 381 patients with PTC, among them, BRAFV600E mutation was detected in 314 patients (82.4%). Multivariate logistic regression analysis showed that gender (OR = 0.542, 95% CI [0.296-0.993], P = 0.047) and shape (OR = 0.510, 95% CI [0.275-0.944], P = 0.032) were associated with BRAFV600E mutation. Compared to BRAFV600E mutation-negative, BRAFV600E-positive PTC lesions were more likely to be found in female patients and were characterized by irregular shape. However, the CT imaging finding is not enough to predict BRAFV600E status, but an indication.

Clinical value of Cyclin D1 and P21 in the differential diagnosis of papillary thyroid carcinoma

BackgroundWith the continuous discovery of new borderline thyroid lesions and benign and malignant “gray areas”, coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear.MethodsIn our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied.ResultsAmong 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher.ConclusionsThe results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.

Collision tumor of a papillary and follicular thyroid carcinoma: a case report

BackgroundPapillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are common differentiated thyroid cancers, but the detection of a collision tumor is an extremely rare event. Case presentationThe patient was a 69-year-old Japanese female with multiple cervical lymph node swellings and a thyroid tumor. Preoperative fine needle aspiration cytology of the enlarged lymph node revealed a cytological diagnosis of papillary thyroid carcinoma (PTC). A total thyroidectomy, right cervical dissection and paratracheal dissection were performed. Histopathological and immunohistochemical analyses of resected specimens revealed a collision tumor of PTC and FTC. Multiple metastases of papillary carcinoma were found in the dissected lymph nodes. In the PTC lesion, IHC for BRAF (V600E) was positive but negative for the FTC lesion. Genetic analyses further revealed a TERT promoter C228T mutation in PTC and a NRAS codon 61 mutation in FTC. The patient died of recurrent cancer 8 months after surgery.ConclusionsA case of a collision tumor of PTC and FTC is very rare, and even fewer cases have been subjected to genetic scrutiny. The present case was successfully diagnosed by pathological examination using immunohistochemical and genetic analyses. The TERT promoter mutation in the PTC lesion was consistent with the aggressive behavior of the cancer.

Preoperative prediction of extrathyroidal extension: radiomics signature based on multimodal ultrasound to papillary thyroid carcinoma

BackgroundThere is a recognized need for additional approaches to improve the accuracy of extrathyroidal extension (ETE) diagnosis in papillary thyroid carcinoma (PTC) before surgery. Up to now, multimodal ultrasound has been widely applied in disease diagnosis. We investigated the value of radiomic features extracted from multimodal ultrasound in the preoperative prediction of ETE.MethodsWe retrospectively pathologically confirmed PTC lesions in 235 patients from January 2019 to April 2022 in our hospital, including 45 ETE lesions and 205 non-ETE lesions. MaZda software was employed to obtain radiomics parameters in multimodal sonography. The most valuable radiomics features were selected by the Fisher coefficient, mutual information, probability of classification error and average correlation coefficient methods (F + MI + PA) in combination with the least absolute shrinkage and selection operator (LASSO) method. Finally, the multimodal model was developed by incorporating the clinical records and radiomics features through fivefold cross-validation with a linear support vector machine algorithm. The predictive performance was evaluated by sensitivity, specificity, accuracy, F1 scores and the area under the receiver operating characteristic curve (AUC) in the training and test sets.ResultsA total of 5972 radiomics features were extracted from multimodal sonography, and the 13 most valuable radiomics features were selected from the training set using the F + MI + PA method combined with LASSO regression. The multimodal prediction model yielded AUCs of 0.911 (95% CI 0.866–0.957) and 0.716 (95% CI 0.522–0.910) in the cross-validation and test sets, respectively. The multimodal model and radiomics model showed good discrimination between ETE and non-ETE lesions.ConclusionRadiomics features based on multimodal ultrasonography could play a promising role in detecting ETE before surgery.

MiR-204-5p-targeted AP1S2 is necessary for papillary thyroid carcinoma

MiR-204-5p, as a tumour suppressor, has been found in several cancers. However, whether miR-204-5p is involved in papillary thyroid carcinoma (PTC) has not yet been investigated. In this study, we identified miR-204-5p as a down-regulated miRNA in PTC tissues, unveiling that the levels of miR-204-5p in serum of patients with PTC were linked to PTC risk, and that the expression in patients concomitant with both PTC and benign lesions was much lower than that in patients only with PTC. Furthermore, we documented that miR-204-5p inhibited proliferation, migration, invasion, and cell cycle progression and triggered apoptosis of PTC cells via cell biology experiments. Finally, we identified that AP1S2 was a target of miR-204-5p using RNA-seq, iTRAQ, and bioinformatics prediction. Overall, miR-204-5p functions as a suppressor for PTC pathogenesis via the miR-204-5p/AP1S2 axis.

Ultrasound-based radiomics XGBoost model to assess the risk of central cervical lymph node metastasis in patients with papillary thyroid carcinoma: Individual application of SHAP.

ObjectivesA radiomics-based explainable eXtreme Gradient Boosting (XGBoost) model was developed to predict central cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC), including positive and negative effects.MethodsA total of 587 PTC patients admitted at Binzhou Medical University Hospital from 2017 to 2021 were analyzed retrospectively. The patients were randomized into the training and test cohorts with an 8:2 ratio. Radiomics features were extracted from ultrasound images of the primary PTC lesions. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator regression were used to select CCLNM positively-related features and radiomics scores were constructed. Clinical features, ultrasound features, and radiomics score were screened out by the Boruta algorithm, and the XGBoost model was constructed from these characteristics. SHapley Additive exPlanations (SHAP) was used for individualized and visualized interpretation. SHAP addressed the cognitive opacity of machine learning models.ResultsEleven radiomics features were used to calculate the radiomics score. Five critical elements were used to build the XGBoost model: capsular invasion, radiomics score, diameter, age, and calcification. The area under the curve was 91.53% and 90.88% in the training and test cohorts, respectively. SHAP plots showed the influence of each parameter on the XGBoost model, including positive (i.e., capsular invasion, radiomics score, diameter, and calcification) and negative (i.e., age) impacts. The XGBoost model outperformed the radiologist, increasing the AUC by 44%.ConclusionsThe radiomics-based XGBoost model predicted CCLNM in PTC patients. Visual interpretation using SHAP made the model an effective tool for preoperative guidance of clinical procedures, including positive and negative impacts.

Diagnostic utility of CK19 and galectin-3 in differentiating papillary thyroid carcinoma from nonneoplastic lesions of thyroid.

Thyroid neoplasm is one of the most common endocrine neoplasms. The diagnosis and the distinction between malignant and benign neoplasms can be difficult, but it has clinical, therapeutic, and prognostic significance. Hence, it is necessary to make precise diagnosis by using biomarkers. This is a laboratory observational study considering histologically diagnosed cases of papillary thyroid carcinoma (PTC) and nonneoplastic thyroid lesions. Immunohistochemistry (IHC) staining was done on tissue sections of all cases for CK19 and galectin-3 using appropriate positive and negative controls. The expression of immunomarkers was evaluated by a semi-quantitative method as negative, weak positive, moderate positive, and strong positive. The data were entered in Microsoft Excel sheet and were analyzed using SPSS 22 version software. A total of 52 cases were considered for the study, of which 26 cases each were PTC and nonneoplastic lesions of thyroid. Among the 26 PTC cases, 6 were classical variant of PTC (CVPTC) and 20 were follicular variant of papillary thyroid carcinoma (FVPTC). Among 26 nonneoplastic cases, 13 each were nodular hyperplasia cases and lymphocytic thyroiditis. There was a statistically significant (P < 0.01) association of CK19 and galectin-3 expression between CVPTC and FVPTC. There was no statistically significant association (P = 0.271) of CK19 expression between PTC and nonneoplastic cases. There was a statistically significant association (P = 0.003) of galectin-3 expression between PTC and nonneoplastic cases. Galectin-3 expression can be used to differentiate PTC from nonneoplastic lesions of thyroid in ambiguous cases. Galectin-3 and CK19 expression can be used to classify PTC into CVPTC and FVPTC.

Combined Application of Fine-Needle Aspiration Cytology with BRAFV600E Mutation Screening in the Detection of Different Grades of Papillary Thyroid Carcinoma

The present study aimed to evaluate the application of fine-needle aspiration cytology (FNAC) of the thyroid coupled with the screening of serine/threonine-protein kinase B-Raf (BRAF) gene mutation in the detection of papillary thyroid carcinoma (PTC). From October 2016 to June 2019, 1244, liquid-based specimens originated from the patients diagnosed with PTC and benign lesions were collected from the Pathology Department of First Central Hospital of Baoding. BRAFV600E mutation was screened in all the liquid-based specimens using quantitative fluorescence polymerase chain reaction. Combined with the pathological results after surgery, the results of FNAC alone and FNAC combined with BRAFV600E screening results in PTC of different grades were compared and analyzed. Of the 1244 cases, there were 818 cases with definite cytological diagnosis and 426 cases with uncertain diagnoses. Combined with BRAFV600E screening, 36 out of 90 cases with atypical cells and 150 out of 223 suspected PTC were diagnosed as PTC. In conclusion, coupled with BRAFV600E mutation screening, the pre-operative detection rate of PTC can be increased in patients with atypical cells and suspected PTC which cannot be confirmed by pre-operative FNAC.

Surgical management of papillary thyroid carcinoma

Background: Papillary thyroid carcinoma (PTC) is the most prevailing thyroid cancer but remains of a favorable prognosis. Thyroidectomy with excision of all positive cervical nodes remains the cornerstone of the management PTC. The role for prophylactic central neck dissection (PCND) remains controversial. Methods: A prospective non randomised open label study of 20 PTC patients, 8 of them underwent total thyroidectomy with PCND and 12 underwent total thyroidectomy with modified radical neck dissection type III in El Zahraa hospital, Azhar university, and Damanhour oncology center, Egypt starting from September 2019 to August 2021. The incidence of central lymph node metastasis in N0 cases underwent PCND were reported, the relationship between lymph node metastasis with lympho-vascular permeation and capsular invasion, were analysed and sensitivity of fine needle aspiration cytology in diagnosis of PTC was reported.Results: Occult central lymph node metastasis was observed in 62.5% of PTC lesions. The FNAC showed a sensitivity of 85%. Lympho-vascular permeation and capsular invasion showed a sensitivity of 94.12% and 58.82%, respectively for lymph nodes metastasis. Thyroiditis is detected in 50% of cases with PTC. Postoperative ablative dose of radioactive iodine 131 (RAI-131) ranged from 80 to 100 millicurie.Conclusions: R0 resection is mandatory to cure PTC. PCND remains a debatable issue, that needs a large multicentre study with large sample of patients with long term follow up to ascertain the efficacy of PCND in reducing rate of local recurrence, morbidity and mortality.

The potential diagnostic value of TROP-2 expression in papillary thyroid carcinoma, benign thyroid lesions, and borderline thyroid lesions: immunohistochemical study

Background The diagnosis of the papillary thyroid carcinoma (PTC) depends on characteristic histopathological features. However, there may be cases with inconsistent features, necessitating the use of immunohistochemical markers. Aim To investigate the value of TROP-2 expression in the diagnosis of PTC and its differentiation from benign thyroid lesions and to evaluate its expression in the newly introduced WHO borderline thyroid lesions. Patients and methods The immunohistochemical expression of TROP-2 was analyzed in 55 selected cases of surgically removed thyroid lesions, which included PTC (30), benign thyroid lesions (16), and borderline thyroid lesions (nine), namely, noninvasive follicular tumor with papillary nuclear features and well-differentiated tumors of uncertain malignant potential. Results TROP-2 positivity and combined score were significantly higher in PTC than in benign thyroid nodules with TROP-2 positivity, showing 86.7% sensitivity and 93.8% specificity. TROP-2 positivity disclosed significant differences between follicular variant papillary thyroid carcinoma (FVPTC) and benign follicular patterned nodules (BFPN), with sensitivity and specificity of 70 and 80%, respectively, and between borderline lesions and BFPN, with sensitivity and specificity of 55.6 and 73.6%, respectively. TROP-2 combined score cutoff points of more than or equal to 3, more than or equal to 2, and more than or equal to 2 can significantly differentiate total PTC versus benign lesions, FVPTC versus BFPN, and borderline lesions versus BFPN, respectively, with specificity mounting to 100%, whereas no significant difference was found between FVPTC and borderline lesions with respect to TROP-2 positivity and combined score. Conclusion TROP-2 is a potential valuable marker that can aid in diagnosis of PTC and differentiating it from its benign mimics with high sensitivity and specificity. The immunohistochemical profile of borderline thyroid lesions (well-differentiated tumors of uncertain malignant potential and noninvasive follicular tumor with papillary nuclear features) for TROP-2 suggests the possibility of their malignant precursor nature. Hence, close strict follow-up for borderline cases may be advisable.

Role of Immunohistochemistry in Diagnosis of Papillary Thyroid Carcinoma: The Use of Ck19, CD56, P63 and CD117

Objective: Papillary thyroid carcinoma (PTC) is the most frequent histologic type of all thyroid malignancies. The presence of characteristic nuclear changes focally in a thyroid lesion may cause diagnostic dilemma. Immunohistochemistry may be helpful in the diagnosis of PTC yet not conclusive. The aim of this study is to test the applicability immunohistochemical markers; CK19, P63, CD56 and CD117 in distinguishing PTC from other follicular thyroid.&#x0D; Methods: Fifty nine cases of unequivocal diagnosis were selected to be rolled in our study; 24 papillary carcinoma cases and 35 cases representing other follicular throid lesions. Immunohistological studies include CK19, P63, CD56 and CD117. Subsequent statistical analysis of immunohistochemical data in relation to diagnosis was performed.&#x0D; Results: The diagnosis of PTC was significantly associated with Strong diffuse Ck19 expression, P63 expression and negative CD56 in relation to studied non PTC follicular thyroid lesions. On the other hand, CD117 was negative in most of the studied thyroid lesions with no significant difference between PTC and other lesions. CK19 was the most sensitive marker (91.2%) and P63 was the most specific one (87.5%), with better specificity in combining markers. Expression of CK19 and lost CD56 provided 97.1% sensitivity and 91.2% diagnostic accuracy in differentiating PTC from other studied lesions.&#x0D; Conclusions: Immunohistochemical markers, Ck19, P63 and CD56 are helpful in diagnosis of PTC and their combination can further improve diagnostic accuracy. CD117 is of no value in the diagnosis of studied cases.

Simultaneous Hodgkin lymphoma and BRAF V600E -positive papillary thyroid carcinoma

Rationale:Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. However, the simultaneous occurrence of PTC and Hodgkin Lymphoma (HL) was rarely reported.Patient concerns:We present a case of simultaneous BRAFV600E-positive PTC and HL in a 17-year-old female.Diagnosis:She was referred to our clinic with a painless lump in her left neck. A highly suspicious thyroid nodule and multiple enlarged lymph nodes in the neck were found by ultrasonography examination. The suspicious nodule was diagnosed as PTC by fine needle aspiration cytology.Interventions:A total thyroidectomy with bilateral lymph node dissection was performed and the microscopic examination revealed a 2-cm PTC with BRAFV600E mutation and HL (mixed cellularity) in the bilateral lymph nodes. PTC was postoperatively considered as T1bN0M0. Levothyroxine (125 μg/d) was administered to the patient for thyrotropin suppression therapy. Then the patient was referred to the Department of Hematology to receive 4 cycles of ABVD followed by 30 Gy involved-site radiotherapy and radioactive iodine (RAI) therapy for thyroid cancer.Outcomes:After two cycles of ABVD, multiple enlarged lymph nodes showed a significant response to the chemotherapy in the patient.Lessons:Simultaneous HL and BRAFV600E-positive PTC is extremely rare. Biopsy of the suspicious lymph nodes should be performed to confirm malignancy metastasizing from PTC or other lesions. Similarly, in HL patients with suspicious thyroid nodule, ultrasound-guided fine needle aspiration of thyroid nodule should be performed to exclude thyroid malignancy.

Ultrasound radimoics nomogram for predicting lymph node metastasis in papillary thyroid carcinoma

Objective To establish an ultrasound (US) radimoics nomogram for predicting central neck lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC). Method A training cohort of 300 patients and validation cohort of 143 patients were established from January to December 2017. US radiomics score was built by using radiomics to analyze ultrasound image of PTC lesion. A nomogram was established by logistic regression from selection of gender, age, thyroglobulin (TG), thyroglobulin antibodies (TGAB), thyroid peroxidase antibody (TPOAB), US radiomics score and US report LNM status. C-index was calculated to evaluate discrimination of this nomogram. Also, calibration curve was drawn to evaluate calibration of it. Results The positive rates of LNM in two cohorts were 29.7% and 34.6%, respectively. In this study, 23 predictive US radiomics features (26:1) were screened out from 609 cases in the training set, which were nonzero coefficients in the LASSO logistic regression model. US radiomics score yield a C-index of 0.802 (95% CI, 0.791 to 0.815) in training cohort and 0.809 (95% CI, 0.801 to 0.816). Through binary logistic regression, indexes were filtered as age, TPOAB, US radiomics score and US report LNM status. The area under curve, accuracy, sensitivity and specificity of this nomogram was 0.801, 0.812, 0.628 and 0861, respectively, from validation cohort. The C-index was 0.811 (95% CI, 0.804 to 0.818). Conclusion US radiomics nomogram can predict LNM in PTC effectively.

A Nomogram Based on the Characteristics of Metastatic Lymph Nodes to Predict Papillary Thyroid Carcinoma Recurrence.

The extent of metastatic lymph node (LN) invasion was not considered in the postoperative stratification of the recurrence risk of papillary thyroid carcinoma (PTC) in the 2015 American Thyroid Association (ATA) guidelines, and the recommended risk stratification cannot be applied to individuals. A nomogram based on these risk factors was developed based on the risk factors to predict individual recurrence risk. Data from 1788 PTC patients at the West China Hospital and 306 cases from the Shang Jin Nan Fu Hospital between August 2013 and July 2015 were included in this study. The 1788 cases were randomized into two groups-the training set (896 cases) and the testing set (896 cases)-and 306 cases were used as the external evaluation set. Univariate and multivariate analyses identified the following independent prognostic factors associated with recurrence in the three independent sets and the combined set (p < 0.01): LN invasion in the capsule or organ, more than five metastatic LNs, and a largest metastatic LN diameter >3 cm. Importantly, PTC patients showed significantly different recurrence rates depending on the extent of LN invasion in the three sets and in the combined set (p < 0.001). The nomogram was developed based on the risk factors in the training set and was validated in the independent testing and validation sets. The largest LN metastasis diameter, number of metastatic LNs, and the extent of extranodal invasion had significant prognostic value for predicting the risk of recurrence. Based on the characteristics of the thyroidal PTC lesion and metastatic LNs, the nomogram showed good prediction of recurrence in individual PTC patients.

Discriminatory miRNAs for the Management of Papillary Thyroid Carcinoma and Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features.

Papillary thyroid carcinoma (PTC) variants have several overlapping clinical and pathological features. The World Health Organization recently published a new classification of thyroid tumors containing significant revisions. Encapsulated papillary thyroid carcinoma (EPTC) has been recognized as a distinctive variant of PTC. The noninvasive encapsulated follicular variant of PTC has been reclassified as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Different neoplasms are associated with different outcomes and require different clinical management. The objective of this study was to explore the miRNA expression patterns specific for classic PTC (cPTC), EPTC, follicular variant of PTC, and NIFTP in order to identify biomarkers of diagnostic and prognostic utility aiming for better clinical decisions. The expression of 84 miRNAs was determined by quantitative real-time polymerase chain reaction in 113 thyroid tissues of PTC (classic, encapsulated, and follicular), NIFTP, and hyperplasia lesions. Expression of the same miRNAs was tested in pre- and postoperative whole-blood samples. Several miRNAs were differentially expressed in the different groups. Expression profile of miRNAs in the tissue was similarly reflected in the circulation. Receiver operating characteristic curve analysis showed that miR-7-5p, miR-222-3p, and miR-146b-5p can discriminate between the different groups with high sensitivity and specificity. Downregulation of miR-144-3p, miR-15a-5p, miR-20a-5p, miR-32-5p miR-142-5p, miR-143-3p, and miR-20b-5p is associated with aggressive behavior in cPTC. Circulating miR-146b-5p, miR-222-3p, miR-155-5p, and miR-378a-3p are potential diagnostic and follow up biomarkers for PTC. Downregulation of miR-7-5p discriminates NIFTP from hyperplasia. Upregulation of miR-222-3p discriminates follicular variant of PTC from NIFTP. High levels of miR-146b-5p distinctively characterize cPTC. These miRNAs are useful biomarkers in the diagnosis of PTC and NIFTP, and help to avoid unnecessary thyroidectomy and improve clinical management.

Contrast-enhanced ultrasonography features of papillary thyroid carcinoma for predicting cervical lymph node metastasis.

The present study was performed to evaluate the predictive value of contrast-enhanced ultrasonography (CEUS) for the risk of cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC). Between May 2014 and November 2016, 42 patients who received surgery for suspicious PTCs were enrolled in the present study. Each individual underwent CEUS with conventional ultrasound (US), preoperative US-guided fine needle aspiration and personalized surgery. Subsequently, the microvascular density (MVD) of all surgical specimens was measured. According to the results of surgical histopathology, individuals were divided into two groups: LNM+ (PTCs with LNM), and LNM− (PTCs without LNM). Clinicopathological characteristics, CEUS enhancement patterns, perfusion parameters and measurements of MVD were compared. The correlation between quantitative variables and LNM was analyzed using Spearman's correlation analysis. Compared with that in the LNM− group, patients in the LNM+ group were younger (P<0.05) and had a larger mean tumor size (P<0.05). The incidence ratio of patients who were ≤45 years old (P<0.05), tumors >10 mm in size (P<0.05) and capsular infiltration (P<0.05) were statistically higher in the LNM+ group. Following the use of a novel classification system, the ratio of PTCs with early partial hyper-enhancement was identified to be significantly higher in the LNM+ group (P<0.01). The mean intensity, intensity increase velocity, MVD ratio and mean intensity ratio of intratumoral/peripheral thyroid parenchyma (MIR) were statistically higher in the LNM+ group compared with that in the LNM− group (all P<0.05). MIR was identified to be positive correlated with LNM (P<0.05). A MIR value of 0.86 was the optimal threshold of LNM in PTCs. In conclusion, LNM may rely on the local rich blood supply of PTC lesions. Partial hyper-enhancements of CEUS and higher values of MIR may suggest a high risk for LNM in PTC.

Clinicopathological significance of loss of p27kip1 expression in papillary thyroid carcinoma.

A meta-analysis was done to investigate the clinicopathological significance of the loss of p27kip1 expression in papillary thyroid carcinoma (PTC). The meta-analysis involving 17 studies included 1,652 PTC and 328 benign cases. The rate of p27kip1 expression loss in PTC and benign lesions, and the correlations between p27kip1 expression loss and clinicopathological characteristics of PTC were determined. The estimated rate of p27kip1 expression loss was 0.557 (95% confidence interval [CI] 0.443-0.665) and 0.139 (95% CI 0.062-0.283) in PTC and benign lesions, respectively. In subgroup analysis, the rates of p27kip1 expression loss were 0.683, 0.393, and 0.414 in the classical variant, follicular variant, and papillary thyroid microcarcinoma, respectively. Loss of p27kip1 expression was significantly correlated with lymph node metastasis and distant metastasis (odds ratio 3.559, 95% CI 1.146-11.056 and 4.735, 95% CI 1.322-16.960, respectively). Extrathyroidal extension was correlated with loss of p27kip1 expression, but not in a statistically significant way (p = 0.051). There were no significant correlations between loss of p27kip1 expression and sex, tumor size, BRAFV600E mutation, and tumor multifocality. Loss of p27kip1 expression is frequently found in PTC compared with benign lesions and normal thyroid tissue. When present in PTC, it is correlated with aggressive tumor behavior.