Diagnosis Of Papillary Thyroid Carcinoma Research Articles

Analysis of risk factors for papillary thyroid carcinoma and the association with thyroid function indicators.

This study aims to analyze the relationship between papillary thyroid carcinoma (PTC) and various factors. The study involved two groups-PTC patients and non-PTC controls. We utilized binary logistic regression and Least Absolute Shrinkage and Selection Operator (Lasso) regression for variable selection and risk factor analysis. Correlation analysis was performed using Spearman's rank correlation. The diagnostic value of thyroid stimulating hormone (TSH) levels for PTC was assessed using Receiver Operating Characteristic (ROC) curves. PTC patients exhibited higher body mass index (BMI) (23.71 vs. 22.66, p<0.05) and TSH levels (3.38 vs. 1.59, p<0.05). Urinary iodine concentration (UIC) was an independent predictor of PTC (OR=1.005, p<0.05). The optimal TSH threshold for PTC diagnosis was 2.4 mIU/L [The Area Under the Curve (AUC)=67.3%, specificity=71.4%, sensitivity=70.1%]. TSH levels positively correlated with BMI (r=0.593, p<0.05) and UIC (r=0.737, p<0.05). UIC may be an independent predictor of PTC, and TSH levels have some diagnostic value for identifying PTC.

MicroRNA Profiling in Papillary Thyroid Cancer.

Genetic alterations are well known to be related to the pathogenesis and prognosis of papillary thyroid carcinoma (PTC). Some miRNA expression dysregulations have previously been described in the context of cancer development including thyroid carcinoma. In our study, we performed original molecular diagnostics on tissue samples related to our own patients. We aimed to identify all dysregulated miRNAs in potential association with PTC development via sequencing much higher numbers of control-matched PTC tissue samples and analyzing a wider variety of miRNA types than previous studies. We analyzed the expression levels of 2656 different human miRNAs in the context of 236 thyroid tissue samples (118 tumor and control pairs) related to anonymized PTC cases. Also, KEGG pathway enrichment analysis and GO framework analysis were used to establish the links between miRNA dysregulation and certain biological processes, pathways of signaling, molecular functions, and cellular components. A total of 30 significant differential miRNA expressions with at least ±1 log2 fold change were found related to PTC including, e.g., miR-551b, miR-146b, miR-221, miR-222, and miR-375, among others, being highly upregulated, as well as miR-873 and miR-204 being downregulated. In addition, we identified miRNA patterns in vast databases (KEGG and GO) closely similar to that of PTC including, e.g., miRNA patterns of prostate cancer, HTLV infection, HIF-1 signaling, cellular responses to growth factor stimulus and organic substance, and negative regulation of gene expression. We also found 352 potential associations between certain miRNA expressions and states of clinicopathological variables. Our findings-supported by the largest case number of original matched-control PTC-miRNA relation research-suggest a distinct miRNA expression profile in PTC that could contribute to a deeper understanding of the underlying molecular mechanisms promoting the pathogenesis of the disease. Moreover, significant miRNA expression deviations and their signaling pathways in PTC presented in our study may serve as potential biomarkers for PTC diagnosis and prognosis or even therapeutic targets in the future.

A Case of Milk Alkali Syndrome: The Forgotten Diagnosis of Generalized Weakness and Altered Consciousness

This case reports outlines a 76-year-old male’s progression from papillary thyroid carcinoma diagnosis to the development of Calcium-Alkali Syndrome (CAS) following thyroidectomy. Initially presenting with thyroid mass, surgery was followed by generalized weakness and altered sensorium, investigations that revealed elevated calcium levels ,metabolic alkalosis and renal impairment . Diagnosis pointed to CAS, likely triggered by prescribed calcium and calcitriol post-surgery. Cessation of supplements and hydration resulted in resolution. While post-thyroidectomy hypocalcemia is anticipated, CAS poses challenges, especially with increasing calcium supplement use. This emphasizes the need for vigilant monitoring of electrolyte imbalances, particularly in regions with limited follow-up practices. Clinicians should balance preventing hypocalcemia without risking hypercalcemia, stressing the importance of timely identification and tailored interventions to prevent CAS complications. This case underscores the significance of recognizing CAS as a potential postoperative complication, urging vigilant monitoring and tailored management in similar clinical settings. J MEDICINE 2024; 25: 184-186

Significance of Combined Immuno-histochemical Expression of P63 &amp; CD56 in Papillary and Follicular Thyroid Carcinoma

Background: Thyroid neoplasm is the commonest endocrine neoplasm. More than 80% of thyroid malignancies are papillary thyroid carcinoma (PTC) followed by follicular carcinoma (FC). The diagnosis of papillary thyroid carcinoma is based on characteristic nuclear morphology of a thyroid neoplasm. In contrast, follicular variant of PTC may cause, if the nuclear features of PTC are insufficiently appreciated, severe problems in differentiating from follicular thyroid carcinoma. Several immunohistochemical (IHC) markers such as P63 and CD56 have been recommended to differentiate between this two thyroid malignancies with overlapping histomorphology. Objectives: Our aim was to identify the possible diagnostic role of P63 and CD56 immunoexpression that distinguish PTC, including the follicular variant from follicular thyroid carcinoma. Methods: This cross-sectional descriptive study was conducted in the Department of Pathology, Rajshahi Medical College from March 2020 to February 2022. A total of 44 cases, histologically confirmed as papillary and follicular thyroid carcinoma were included in the study. Immunohistochemistry was done for P63 and CD56 from selected paraffin blocks. Results: Histologically, 39 cases were diagnosed as papillary thyroid carcinoma (27 were classical PTC &amp; 12 were FVPTC) and the rest 5 were follicular thyroid carcinoma. In this study, mean age of the patients was 40.86 ± 6.57 years (SD) and male to female ratio was 1:2.4. P63 showed 74.4% positivity with papillary thyroid carcinoma. Positive immunoreactivity of P63 was highly significant in distinguishing papillary from follicular thyroid carcinoma (P=0.003). Combined P63 positive CD56 negative (P=0.048) and P63 negative CD56 negative immunoexpression (P=0.039) were statistically significant in differentiating papillary from follicular thyroid carcinoma. Conclusion: This study suggested that the use of P63 and CD56 may be helpful in the diagnosis of papillary and follicular thyroid carcinoma along with histopathological examination and their combination may also help in this purpose.

Contrast-enhanced ultrasound (CEUS) characteristics of atypical-enhanced papillary thyroid carcinoma (PTC)

OBJECTIVE: To investigate the diagnostic value of CEUS in atypical-enhanced PTC. METHODS: The clinical data, qualitative and quantitative parameters of CEUS in 177 Iso/hyper-enhanced thyroid nodules with definite pathological results were retrospectively analyzed in the Lanzhou University Second Hospital from June 2019 to January 2021. And the clinical value of CEUS in the diagnosis of atypical-enhanced PTC was assessed using univariate and multivariate analysis. RESULTS: Among the 177 thyroid nodules, 59 were benign and 118 were PTC. There were significant differences in age, enhancement border, ring enhancement, speed of wash in, speed of wash out, enhancement pattern, capsule interruption, time to peak, time to wash out, RT, TPH, and TTP (P &lt; 0.05). Multivariate analysis showed unclear enhancement border and concentric enhancement were independent risk factors for the diagnosis of atypical-enhanced PTC by CEUS. The sensitivity, specificity, PPV, NPV, and accuracy of the model in diagnosing atypical-enhanced PTC were 88.1%, 71.2%, 86.0%, 75.0%, and 82.5%, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.910. CONCLUSION: The diagnosis of atypical-enhanced PTC can be better performed by enhancement characteristics and time intensity curve (TIC) of CEUS, which have a good clinical application value.

Diagnostic value of FNAC combined with BRAFV600E mutation detection in Hashimoto's thyroiditis complicated with papillary thyroid carcinoma.

This study aimed to analyze the effect of preoperative fine needle aspiration cytology (FNAC) combined with BRAFV600E mutation detection as compared to that of fine needle aspiration cytology alone on the diagnostic performance of papillary thyroid carcinoma (PTC) combined with Hashimoto's thyroiditis (HT). Patients with thyroid nodules in Hashimoto's thyroiditis, who underwent fine-needle aspiration cytology examination and BRAFV600E mutation detection in the puncture eluate at the outpatient clinic, were selected. Finally, 122 patients received surgical treatment and were included in the study. We used postoperative pathological results as the gold standard. Accordingly, we compared the sensitivity, specificity and accuracy of preoperative FNAC alone and FNAC combined with BRAFV600E mutation detection in for the diagnosis of PTC combined with HT. For PTC patients with HT, the sensitivity of FNAC diagnosis was 93.69%, the specificity was 90.90% and the accuracy was 93.44%. However, the sensitivity, specificity and accuracy of FNAC combined with BRAFV600E mutation detection were 97.30%, 90.90% and 96.72%, respectively. Therefore, combined detection can improve the sensitivity and accuracy of diagnosis (p<0.05). FNAC combined with eluent BRAFV600E mutation detection can improve the sensitivity and accuracy of diagnosis of PTC in the background of HT.

The Diagnostic Role of CK19 and CD73 Immunohistochemistry in The Diagnosis of Papillary Thyroid Carcinoma

The Diagnostic Role of CK19 and CD73 Immunohistochemistry in The Diagnosis of Papillary Thyroid Carcinoma

Revisiting the utility of identifying nuclear grooves as unique nuclear changes by an object detector model.

Among other structures, nuclear grooves are vastly found in papillary thyroid carcinoma (PTC). Considering that the application of artificial intelligence in thyroid cytology has potential for diagnostic routine, our goal was to develop a new supervised convolutional neural network capable of identifying nuclear grooves in Diff-Quik stained whole-slide images (WSI) obtained from thyroid fineneedle aspiration. We selected 22 Diff-Quik stained cytological slides with cytological diagnosis of PTC and concordant histological diagnosis. Each of the slides was scanned, forming a WSI. Images that contained the region of interest were obtained, followed by pre-formatting, annotation of the nuclear grooves and data augmentation techniques. The final dataset was divided into training and validation groups in a 7:3 ratio. This is the first artificial intelligence model based on object detection applied to nuclear structures in thyroid cytopathology. A total of 7,255 images were obtained from 22 WSI, totaling 7,242 annotated nuclear grooves. The best model was obtained after it was submitted 15 times with the train dataset (14th epoch), with 67% true positives, 49.8% for sensitivity and 43.1% for predictive positive value. The model was able to develop a structure predictor rule, indicating that the application of an artificial intelligence model based on object detection in the identification of nuclear grooves is feasible. Associated with a reduction in interobserver variability and in time per slide, this demonstrates that nuclear evaluation constitutes one of the possibilities for refining the diagnosis through computational models.

Thyroglobulin Antibodies and Tumor Epitope-Specific Cellular Immunity in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is characterized by T cell infiltration and frequently by the presence of anti-thyroglobulin antibodies (TgAbs). The role of cellular immunity and of TbAbs in this context is a matter of debate. The aim of our study was to correlate the presence of TgAbs, tumor epitope-specific T cells and the clinical outcome of PTC patients. We studied n=183 consecutive patients with a diagnosis of PTC which were treated with total thyroidectomy plus 131I ablation. During a follow-up of in mean 97 months, most of the PTC patients had no signs of tumor relapse (n=157 patients). In contrast, one patient had serum Tg levels above the detection limit and<1 ng/ml, two patients Tg serum levels≥1 ng/ml and<2 ng/ml and n=23 patients had Tg serum levels≥2 ng/ml. Morphological signs of tumor recurrence were seen in 14 patients; all of these patients had serum Tg levels≥2 ng/ml. Importantly, with the exception of one patient, all TgAb positive PTC patients (n=27) had no signs of tumor recurrence as the serum Tg levels were below the assays functional sensitivities. Tetramer analyses revealed a higher number of tumor epitope-specific CD8+T cells in TgAb positive patients compared to TgAb negative PTC patients. In summary, we show that the occurrence of TgAbs may have an impact on the clinical outcome in PTC patients. This might be due to a tumor epitope-specific cellular immunity in PTC patients.

CA19-9 producing locally advanced papillary thyroid carcinoma: a case report.

CA19-9 is a tumor marker for gastrointestinal and biliary-pancreatic adenocarcinomas; however, its association with thyroid cancer is unknown. Here, we report a case of CA19-9 producing locally advanced papillary thyroid carcinoma (PTC). A 66-year-old woman who was identified with a thyroid tumor after a close examination of an elevated serum CA19-9 level, which was detected at health screening, was referred to our hospital. Ultrasonography revealed a 34 × 31mm hypoechoic lesion in the lower pole of the left thyroid lobe. Computed tomography revealed a solid thyroid tumor with tracheal invasion without any distant metastases. Bronchoscopy revealed tumor exposure into the tracheal lumen on the left side of the trachea. Fine-needle aspiration cytology led to a diagnosis of papillary thyroid carcinoma (PTC). The patient underwent a total thyroidectomy, tracheal sleeve resection with end-to-end anastomosis, and lymph node dissection in the left cervical and superior mediastinal regions (D3c) with a reversed T-shaped upper sternotomy down to the third intercostal level. Histopathological analysis confirmed the diagnosis of PTC with tracheal invasion and no lymph node metastases (pT4a Ex2 N0). Immunohistochemical staining showed the expression of CA19-9 in cancer cells. Postoperatively, the serum CA19-9 level of the patient decreased to within the normal range. Some PTCs produce CA19-9, although less frequently. When elevated serum CA19-9 levels are observed, PTC should be included in the differential diagnosis for further investigation.

Papillae, psammoma bodies, and/or many nuclear pseudoinclusions are helpful criteria but should not be required for a definitive cytologic diagnosis of papillary thyroid carcinoma: An institutional experience of 207 cases with surgical follow up.

Noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP) was introduced in 2016 replacing noninvasive follicular variant of papillary thyroid carcinoma, with recommendations to label them "noncancer." To avoid reducing risk of malignancy (ROM) and overdiagnosing NIFTP as malignant, some authors required restricted cytologic criteria (RC) for a definitive diagnosis of papillary thyroid carcinoma (PTC), including papillae, psammoma bodies. or≥3 nuclear pseudoinclusions. Since then, NIFTP criteria have been revised, biologic behavior better understood, and incidence reported to be much lower than initially anticipated. This study examines the impact of RC on PTC cytologic diagnoses, ROM, and detection of clinically significant carcinomas (CSC). A total of 207 thyroid FNAs originally diagnosed as PTC and suspicious for PTC (SPTC) with surgical follow-up were evaluated. RC were retrospectively applied to cases as a requirement for diagnosing PTC, and cases that did not meet RC were reclassified as SPTC. ROMs and diagnostic accuracies of pre- and post-RC diagnoses were correlated with followup CSC. RC were met in 118/142 (83%) and 20/65 (31%) of cases originally diagnosed as PTC and SPTC, respectively. Post-RC, 29% (19/65) of CSC originally diagnosed as SPTC were upgraded to PTC, and 17% (24/142) of CSC originally diagnosed as PTC were downgraded to SPTC. No NIFTPs were diagnosed as malignant. RC should not be required for a definitive diagnosis of PTC when other nuclear features of PTC are diffuse and overt. Applying RC, however, helps the pathologist arrive at a more definitive diagnosis of PTC in suspicious cases.

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas.

The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients. This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2-ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated. All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.

Diagnostic Efficiency of ACR-TIRADS Score for Differentiating Benign and Malignant Thyroid Nodules of Various Pathological Types.

BACKGROUND Thyroid nodule prevalence reaches 65% in the general population. Hence, appropriate ultrasonic examination is key in disease monitoring and management. We investigated the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) score for diagnosis of benign and malignant thyroid nodules and pathological types. MATERIAL AND METHODS A retrospective study was conducted. According to ultrasound images, ultrasonic characteristics of benign and malignant thyroid nodules and different pathological types were analyzed using ACR-TIRADS score, and diagnostic value was determined. AUCs were compared for tumor diagnosis and differentiation. RESULTS Overall, 1675 thyroid nodules from 1614 patients were included. AUC value of papillary thyroid carcinoma (PTC) diagnosed with ACR-TIRADS was highest (0.955 [95% CI=0.946-0.965]), while that of follicular thyroid carcinoma (FTC) was lowest (0.877 [95% CI=0.843-0.912]). FTC had the highest sensitivity (95.1%) and lowest specificity (64.8%). When the cut-off value was 5.5 points, accuracy of diagnosing PTC and anaplastic thyroid carcinoma (ATC) was highest, 80.5% and 78.7% respectively. Comparison of the multi-index prediction model constructed by multivariable logistic regression analysis and prediction model constructed by ACR-TIRADS score showed, when evaluating PTC and ATC, the multi-index model was better: AUCs of PTC were 0.966 vs 0.955, and AUCs of ATC were 0.982 vs 0.952, respectively, (P<0.05). CONCLUSIONS ACR-TIRADS score-based ultrasound examination of thyroid nodules aids diagnosis of benign and malignant thyroid nodules. TIRADS criteria favor diagnosis of PTC (and ATC) over FTC. ACR-TIRADS score can help clinicians diagnose thyroid nodules quickly and earlier, exhibits good clinical value, and can prevent missed diagnoses.

Diagnostic and prognostic utility of TROP-2, SLP-2, and CXCL12 expression in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most frequent thyroid malignancy. Histopathological examination is widely accepted as the gold standard test for the diagnosis of PTC. However, the histopathological examination sometimes can't differentiate PTC from other thyroid diseases. Differentiating PTC from other thyroid diseases is essential for a therapeutic approach and prognosis. The current study was performed to investigate the utility of TROP-2, SPL-2, and CXCL12 mRNA and protein expression in discriminating PTC from other thyroid diseases that mimic PTC. The current study was performed on 75 cases of surgically resected thyroid glands. The cases were distributed in two groups: the PTC group and the non-PTC group. The PTC group consisted of 35 cases (25 patients of the classic PTC variant and 10 patients of the PTC follicular variant). The non-PTC group consisted of 40 cases (10 cases were multinodular goiter, 5 cases were Graves' disease, 5 cases were Hashimoto thyroiditis, 15 patients were follicular adenoma (FA) and 5 cases were follicular carcinoma). TROP-2, SPL-2, and CXCL12 mRNA expression were estimated by qRT-PCR, and protein expression was estimated by immunohistochemistry. There were upregulated TROP-2, SPL-2, and CXCL12 mRNA and protein expressions in PTC compared to non-PTC (P< 0.001, for each). There was a statistically significant upregulation in the mRNA expression of the three genes among PTC cases with larger tumor sizes (P< 0.001, for each), those with tumor stages III and IV (P= 0.008, 0.002 and < 0.001 respectively), and those with LN metastasis (P< 0.001, for each). Moreover, there was a statistically significant upregulation in CXCL-12 gene expression among PTC cases with extra-thyroid extension (P< 0.001). mRNA expression of TROP-2, SPL-2, and CXCL12 among PTC cases increased in larger tumor size, tumor stages III and IV, and LN metastasis. Moreover, there was an increase in CXCL-12 gene expression among PTC cases with extra-thyroid extension. Thus, TROP-2, SPL-2, and CXCL12 expressions could be possible diagnostic and prognostic markers in PTC.

The impact of intraoperative neural monitoring during papillary thyroid cancer surgery on completeness of thyroidectomy and thyroglobulin response: a propensity-score matched study

Background Intraoperative neural monitoring (IONM) has been utilized for a variety of thyroid pathologies, including papillary thyroid carcinoma (PTC). Remnant thyroid tissue following total thyroidectomy (TT) in patients with PTC is associated with increased recurrence. The aim of this study is to investigate whether the use of IONM in PTC surgery has an impact on the completeness of thyroidectomy. Methods Retrospectively, patients with preoperative diagnosis of PTC, who underwent TT in a tertiary center were reviewed. They were grouped based on the IONM usage, and 1:1 propensity-score match was performed. Primary outcome was the completeness of thyroidectomy, determined by measuring postoperative stimulated thyroglobulin levels (sTg). Results Among 274 clinically node-negative PTC patients who underwent TT and ipsilateral prophylactic central lymph-node dissection, a total of 170 patients (85:85) were matched. Postoperative sTg levels were significantly lower in the IONM group (1 ng/dL vs. 0.4 ng/dL; p < 0.01) with higher percentage of the patients with sTg levels <1 ng/ml (50.6% vs. 69.4%; p = 0.01). More patients in the no-IONM group received RAI ablation with significantly higher doses (mean mci: 120 vs. 102; p = 0.02). Conclusion The use of IONM during thyroidectomy provides improvement in the completeness of thyroidectomy and reduction in postoperative sTg levels which can be used as a guide by clinicians to avoid RAI ablation in selected PTC patients and to adjust low ablative doses in patients who are scheduled for remnant ablation.

Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma

Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.

Application of Ultrasound Shear Wave Elastography Combined With BRAFV600E Mutation for the Diagnosis of Papillary Thyroid Carcinoma.

This prospective study aimed to investigate the combination of shear wave elastography (SWE) and BRAFV600E mutation testing for the diagnosis of papillary thyroid carcinoma (PTC). One hundred thyroid nodules with an American College of Radiology thyroid imaging reporting and data system classification of 4 or 5 were subjected to SWE measurement, BRAFV600E genotyping, fine-needle aspiration, and surgery. Nonparametric statistical tests were used to compare the differences in the elastic parameters and BRAF genotypes between benign and malignant thyroid nodules of PTC, and receiver operating characteristic curve analysis was conducted to compare the diagnostic efficacy. In addition, the correlations between elastic parameters and BRAFV600E mutation in PTC were analyzed using binary logistic regression. The SWE, BRAFV600E, and their combination exhibited sensitivities of 72.9%, 81.3%, and 85.4%, respectively, and specificities of 66.7%, 90.3%, and 86.5%, respectively, in the diagnosis of PTC ( P < 0.05). The SWE, BRAFV600E, and their combination exhibited sensitivities of 50.0%, 24.1% and 56.3%, respectively, and specificities of 89.7%, 87.5% and 82.8%, respectively, in the diagnosis of central cervical lymph node metastasis ( P < 0.05). The combined use of SWE and BRAFV600E detection had the largest area under the curve, indicating that this combination is more effective in diagnosing PTC and lymph node metastasis in the central region than either method alone. Furthermore, Emax was positively associated with the BRAFV600E genotype. In conclusion, the combination of SWE and BRAFV600E genotype detection can improve the diagnostic efficacy for PTC. Emax can predict the BRAFV600E mutation status.

A Misleading Case of NTRK-Rearranged Papillary Thyroid Carcinoma.

Herein, we present a misleading case of advanced papillary thyroid carcinoma with lung, node, and pleural metastases, initially diagnosed as metastatic lung adenocarcinoma with papillary features, based on the histological and immunohistochemical analysis of a pleural biopsy. Between August 2019 and August 2020, the patient received 2 ineffective lines of systemic therapy, including a first line of chemotherapy with cisplatin and pemetrexed, and a second line of immunotherapy with atezolizumab. Comprehensive genomic profiling by next-generation sequencing on the archival pleural biopsy revealed an NTRK1-TMP3 fusion and comutation of the TERT promoter, commonly found in papillary thyroid carcinoma. After palliative partial thyroidectomy that confirmed the diagnosis of papillary thyroid carcinoma, in February 2021, the patient was enrolled in the STARTRK-2 GO40782 basket trial and received entrectinib, an oral pan-TRK inhibitor specifically targeting NTRK-rearranged tumors. After initially experiencing drug-related grade 2 anorexia, dysgeusia, and neurotoxicity and grade 3 asthenia, the dose was reduced, and an excellent and durable objective response was observed.

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.

Significance of LINC02082 and LOC105369812 in differentiating papillary thyroid cancer from benign nodules.

To explore the significance of LINC02082 and LOC105369812 in the differential diagnosis of papillary thyroid carcinoma (PTC) and benign nodules. Cancer tissues and benign nodules from 8 patients were sequenced and constructed using high-throughput sequencing. Differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) with significant differences were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the mRNAs co-expressed by DEmRNAs and DElncRNAs. LncRNAs with significant differences, good consistency, and enrichment in the PI3K-AKt signaling pathway were selected as candidate lncRNAs, and the target lncRNAs were screened by correlation analysis. Target lncRNAs and co-expressed mRNAs enriched in the PI3K-AKt signaling pathway and microRNAs (miRNAs) interacting with each other were used to construct a competing endogenous RNA (ceRNA) network. Finally, the PTC-related gene set (GSE33630) was downloaded from the GEO database and the expression of the genes obtained by sequencing was compared. Differential expression was verified using quantitative real-time PCR (qRT-PCR). Finally, the receiver operating characteristic (ROC) curve was used to evaluate the value of the target lncRNAs in diagnosis, when used alone or in combination. A total of 1113 differential RNAs (DE RNAs) were identified, of which 338 were DElncRNAs and 775 were DEmRNAs. Three lncRNAs enriched in the PI3K-AKt signaling pathway, LINC02082, LOC105369812, and LOC105375170, were used as candidate lncRNAs. After correlation analysis with known biomarkers, LINC02082 and LOC105369812 were selected as the target lncRNAs. The qRT-PCR results showed that the target lncRNAs were significantly different among the 3 tissues. The ROC curve showed that LOC105369812 could be used to differentiate PTC from benign thyroid nodules, whereas LINC02082 and its combination had lower predictive value. LOC105369812 is valuable for differentiating benign from malignant thyroid nodules, whereas LINC02082 has lower diagnostic value.