Primary Papillary Thyroid Carcinoma Research Articles

BRAF mutation, selected miRNAs and genes expression in primary papillary thyroid carcinomas and local lymph node metastases

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2–1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.

Stimulated Raman Scattering Microscopy Reveals Aberrant Triglyceride Accumulation in Lymphatic Metastasis of Papillary Thyroid Carcinoma.

Lipid metabolic alterations are known to play a crucial role in cancer metastasis. As a key hub in lipid metabolism, intracellular neutral lipid accumulation in lipid droplets (LDs) has become a signature of aggressive human cancers. Nevertheless, it remains unclear whether lipid accumulation displays distinctive features in metastatic lesions compared to the primary ones. Here, we integrated multicolor stimulated Raman scattering (SRS) imaging with confocal Raman spectroscopy on the same platform to quantitatively analyze the amount and composition of LDs in intact human thyroid tissues in situ without any processing or labeling. Inspiringly, we found aberrant accumulation of triglycerides (TGs) in lymphatic metastases but not in normal thyroid, primary papillary thyroid carcinoma (PTC), or normal lymph node. In addition, the unsaturation degree of unsaturated TGs was significantly higher in the lymphatic metastases from patients diagnosed with late-stage (T3/T4) PTC compared to those of patients diagnosed with early-stage (T1/T2) PTC. Furthermore, both public sequencing data analysis and our RNA-seq transcriptomic experiment showed significantly higher expression of alcohol dehydrogenase-1B (ADH1B), which is critical to lipid uptake and transport, in lymphatic metastases relative to the primary ones. In summary, these findings unravel the lipid accumulation as a novel marker and therapeutic target for PTC lymphatic metastasis that has a poor response to the regular radioactive iodine therapy.

Abstract 1762: Characterization of somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma

Abstract Deletion in the long arm of chromosome 22 (22qDEL) is the most prevalent somatic copy number alteration (SCNA) observed in papillary thyroid carcinoma (PTC). Despite its recurrence, the specific characteristics and role of 22qDEL in PTC have not been fully studied. We conducted a pooled analysis of 22qDEL by integrating patient and clinical information and molecular profiles from 1,094 primary PTC tumors across four major published PTC genomic studies: The Cancer Genome Atlas (TCGA) PTC profile study, the National Cancer Institute (NCI) post-Chornobyl PTC study, the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSKCC-IMPACT) PTC cases, and the Seoul National University (SNU) thyroid cancer profile study. The majority of PTC with 22qDEL demonstrated arm-level loss of heterozygosity (86%). Even in PTC cases with partial 22qDEL, we observed a loss across 70% of chromosome 22, encompassing regions 22q12 and 22q13, which harbors known cancer genes (NF2 and CHEK2). More than 90% of 22qDEL co-occurred with established oncogenic drivers of PTC, though a full assessment of PTC drivers was not available for all cases. 22qDEL occurred more frequently with RAS point mutations (50.4%) than other drivers (9.3%). A higher fraction of 22qDEL was clonal in RAS-driven PTCs (78.3%), suggesting 22qDEL occurs early in RAS-driven tumor development. We did not observe any association between 22qDEL and established PTC risk factors such as age, sex, and radiation, nor with clinical features including tumor size, multifocality, and metastasis (p-values>0.22). RNA sequencing gene expression analysis based on 22qDEL status revealed downregulation of most genes residing on chromosome 22q and significant differential expression activity of immune-related genes, further implicating a role of immune dysregulation in PTC. Our study suggests that 22qDEL may not act as a primary driver of PTC but plays an important role as a co-factor of RAS point mutations, which could further drive PTC development. Citation Format: Olivia W. Lee, Danielle Karyadi, Stephen Hartley, Weyin Zhou, Mitchell Machiela, Mykola Tronko, Tetiana Bogdanova, Liudmyla Zurnadzhy, Lindsay Morton, Stephen Chanock. Characterization of somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1762.

Chronic Lymphocytic Thyroiditis with Oncocytic Metaplasia Influences PD-L1 Expression in Papillary Thyroid Carcinoma.

Despite the increasing recognition of PD-L1 as predictor of immunotherapeutic response in various malignancies, its role and prognostic significance in thyroid cancer remain underexplored and subject to debate. This study begins to address this gap by comprehensively analyzing PD-L1 expression in papillary thyroid carcinoma (PTC) and investigating its correlation with key clinicopathological variables. We conducted immunohistochemistry (IHC) to assess PD-L1 expression in whole-tissue sections from 121 primary papillary thyroid carcinoma (PTC) cases. We then analyzed the correlations between PD-L1 expression and various clinicopathological variables. PD-L1 expression was detected in 33.1% of papillary thyroid carcinomas (PTCs), predominantly exhibiting weak to moderate intensity. Notably, this study found no significant correlation between PD-L1 expression and various clinicopathological variables. The lack of association with traditional factors such as age, sex, histological subtype, and tumor size suggests the complex and multifaceted nature of PD-L1 regulation in PTC. Multivariate logistic regression analysis identified chronic lymphocytic thyroiditis with oncocytic metaplasia as the sole independent predictor of PD-L1 expression (P = 0.014), underlining the potential influence of the tumor microenvironment on immune checkpoint expression in PTC. Our study underscores the intricate interplay between chronic lymphocytic thyroiditis with oncocytic metaplasia and PD-L1 expression in papillary thyroid carcinoma. The observed link suggests a potential avenue for therapeutic intervention using anti-PD-1/PD-L1 therapies in surgery-refractory PTC. Understanding the dynamics of immune checkpoint regulation in the context of the tumor microenvironment is crucial for devising effective treatment strategies. Future research endeavors should delve deeper into the molecular mechanisms underlying this interaction and explore its implications for patient outcomes. As the field of immunotherapy continues to evolve, our findings contribute valuable insights into the complex immunological landscape of thyroid cancer.

Genomic profiling of primary and metastatic thyroid cancers.

The genetic repertoire of primary thyroid cancers (TCs) is well documented, but there is a considerable lack of molecular profiling in metastatic TCs. Here, we retrieved and analyzed the molecular and clinical features of 475 primary and metastatic TCs subjected to targeted DNA sequencing, from the cBioPortal database. The cohort included primary and metastatic samples from 276 papillary thyroid carcinomas (PTCs), 5 follicular thyroid carcinomas, 22 Hürthle cell carcinomas (HCCs), 127 poorly differentiated thyroid carcinomas (PDTCs), 30 anaplastic thyroid carcinomas (ATCs) and 15 medullary thyroid carcinomas. The ATCs had the highest tumor mutational burden and the HCCs the highest fraction of the genome altered. Compared to primary PTCs, the metastases had a significantly higher frequency of genetic alterations affecting TERT (51% vs 77%, P < 0.001), CDKN2A (2% vs 10%, P < 0.01), RET (2% vs 7%, P < 0.05), CDKN2B (1% vs 6%, P < 0.05) and BCOR (0% vs 4%, P < 0.05). The distant metastases had a significantly lower frequency of BRAF (64% vs 85%, P < 0.01) and a significantly higher frequency of NRAS (13% vs 3%, P < 0.05) hotspot mutations than the lymph node metastases. Metastases from HCCs and PDTCs were found to be enriched for NF1 (29%) and TP53 (18%) biallelic alterations, respectively. The frequency of subclonal mutations in ATCs was significantly higher than in PTCs (43% vs 25%, P < 0.01) and PDTCs (43% vs 22%, P < 0.01). Metastatic TCs are enriched in clinically informative genetic alterations such as RET translocations, BRAF hotspot mutations and NF1 biallelic losses that may be explored therapeutically.

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.

Ultrasound radiomics models based on multimodal imaging feature fusion of papillary thyroid carcinoma for predicting central lymph node metastasis.

This retrospective study aimed to establish ultrasound radiomics models to predict central lymph node metastasis (CLNM) based on preoperative multimodal ultrasound imaging features fusion of primary papillary thyroid carcinoma (PTC). In total, 498 cases of unifocal PTC were randomly divided into two sets which comprised 348 cases (training set) and 150 cases (validition set). In addition, the testing set contained 120 cases of PTC at different times. Post-operative histopathology was the gold standard for CLNM. The following steps were used to build models: the regions of interest were segmented in PTC ultrasound images, multimodal ultrasound image features were then extracted by the deep learning residual neural network with 50-layer network, followed by feature selection and fusion; subsequently, classification was performed using three classical classifiers-adaptive boosting (AB), linear discriminant analysis (LDA), and support vector machine (SVM). The performances of the unimodal models (Unimodal-AB, Unimodal-LDA, and Unimodal-SVM) and the multimodal models (Multimodal-AB, Multimodal-LDA, and Multimodal-SVM) were evaluated and compared. The Multimodal-SVM model achieved the best predictive performance than the other models (P < 0.05). For the Multimodal-SVM model validation and testing sets, the areas under the receiver operating characteristic curves (AUCs) were 0.910 (95% CI, 0.894-0.926) and 0.851 (95% CI, 0.833-0.869), respectively. The AUCs of the Multimodal-SVM model were 0.920 (95% CI, 0.881-0.959) in the cN0 subgroup-1 cases and 0.828 (95% CI, 0.769-0.887) in the cN0 subgroup-2 cases. The ultrasound radiomics model only based on the PTC multimodal ultrasound image have high clinical value in predicting CLNM and can provide a reference for treatment decisions.

Functional loss of tumor suppressor genes detected by loss of heterozygosity, but not driver mutations, predicts aggressive lymph node status in papillary thyroid carcinoma

BackgroundRecognizing aggressive tumor biology is essential to optimizing patient management for papillary thyroid carcinomas (PTC). Aggressive lymph node (ALN) status is one feature that influences decision-making. We evaluated genomic deletions in regions of tumor suppressor genes, detected by loss of heterozygosity (LOH) analysis, to understand causal alterations linked to thyroid cancer aggressiveness and to serve as a molecular diagnostic biomarker for ALN status. MethodsWe analyzed 105 primary PTC enriched for patients with ALN (64% with, 36% without). We also analyzed 39 positive lymph nodes (79% with, 21% without ALN). LOH was determined using a panel of 25 polymorphic microsatellite alleles targeting 10 genomic loci harboring common tumor suppressor genes. Additionally, ThyGeNEXT® and ThyraMIR® assays were performed. ResultsLOH was detected in 43/67 primary PTC from patients with ALN status, compared with only 5/38 primary PTC without ALN (minimal metastatic burden) (P=0.0000003). This is further supported by post hoc analyses of paired primary and metastatic samples. Paired samples from patients with ALN are more likely to harbor LOH, compared to the ALN negative group (P=0.0125). Additionally, 12/31 paired samples from patients with ALN demonstrated additional or different LOH loci in metastatic samples compared to the primary tumor samples. No association was seen between ALN and mutational, translocation, or microRNA data. ConclusionsLOH detected in primary PTC significantly predicts ALN status. Analysis of paired primary and metastatic samples from patients with / without ALN status further supports this relationship. The acquisition of LOH at additional loci is common in lymph nodes from patients with ALN status. Simple summaryA subset of patients with papillary thyroid carcinoma (PTC) will develop recurrent disease. One known predictor of recurrence is the American Thyroid Association category “Aggressive Lymph Node” (ALN) disease, considering metastatic burden. Loss of heterozygosity (LOH) — chromosomal loss in regions of tumor suppressor genes — has yet to be investigated as a possible mechanism driving ALN status in PTC. The ability to predict ALN status prior to surgery can guide the extent of surgery and postoperative treatment options. We found that paired samples from patients with ALN are more likely to harbor LOH, compared to patients without ALN disease. 38% of patients with ALN demonstrated additional or different LOH loci in metastatic samples compared to the primary tumor samples. LOH complements current molecular analysis of thyroid cancer when searching for evidence of aggressive biology.

Second Primary Cancer Among Patients With Papillary Thyroid Carcinoma Following the Chernobyl Disaster

To our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients following the Chernobyl nuclear accident. To study the risk of second primary cancers in patients with PTC after the Chernobyl disaster. This was a retrospective cohort study conducted in the Republic of Belarus over a 31-year time frame evaluating patients with primary PTC and second malignant tumors. Personal data from the Belarussian Cancer Registry were used in the investigation, and only second primary cancers were included in the analysis. Patients were observed from January 1, 1990, to December 31, 2021, for the establishment of second primary malignant tumors. For analysis, synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). If the patient had more than 2 cancers, they were observed until development of a second tumor and, subsequently, the development of a third tumor. The starting point for calculating the number of person-years was the date of thyroid cancer diagnosis. The end point for calculating the number of person-years was the date of diagnosis of the second primary malignant tumor, the date of death, the date of the last visit of the patient, or December 31, 2021 (the end the of study period). The incidence of a second primary malignant tumor with PTC was calculated for the study groups using standardized incidence ratios. Of the 30 568 patients with a primary PTC included in this study, 2820 (9.2%) developed a second malignant tumor (2204 women and 616 men); the mean (SD) age of all patients at time of the primary cancer was 53.9 (12.6) years and at time of the secondary cancer was 61.5 (11.8) years. Overall, the standardized incidence ratio was statistically significant for all types of cancer (1.25; 95% CI, 1.21-1.30), including solid malignant tumors (1.20; 95% CI, 1.15-1.25) and all leukemias (1.61; 95% CI, 2.17-2.13). Cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall. This cohort study reports the increased incidence of solid secondary tumors in men and women over a 31-year time frame after the Chernobyl disaster. Moreover, there was a statistically significant increased risk of second tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal glands as well as Kaposi sarcoma. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage.

Isolated Papillary Thyroid Carcinoma of the Pyramidal Lobe: A Case Report and Review of Literature.

The pyramidal lobe (PL) represents an embryological remnant of the thyroglossal duct. A solitary focus of papillary thyroid carcinoma (PTC) of the PL of thyroid gland is a rare entity. We present a case of a 33-year-old woman with PTC of the PL with lymph nodal involvement and further discuss the lines of surgical management for primary PTC arising from the PL of thyroid gland.

Clinicopathological features of incidentally detected metastatic thyroid papillary carcinoma in cervical lymph nodes of non-thyroid cancer patients: a retrospective analysis of 31cases

BackgroundThe incidental finding of thyroid inclusions in lymph nodes of neck dissections of non-thyroid cancer patients is an unusual event. It is still controversial for pathologists about whether this represents benign inclusions or metastatic papillary thyroid carcinoma (PTC). This study is to analyze clinicopathological features of such cases in an attempt to explore their clinical implications.MethodsPathological data were searched for incidentally detected PTC of cervical lymph nodes in non-thyroid cancer cases. Clinicopathological characteristics were reevaluated and recorded. BRAF V600E protein expression and sequencing analysis was then performed in cases with sufficient tissues.Results31 patients had an incidental finding of PTC in lymph nodes of patients with non-thyroid cancer. BRAF immunohistochemical staining were performed in 17 metastatic lymph nodes with sufficient tumor tissues, and 6 were positive. BRAF V600E point mutation was detected in 5 of 6 BRAF V600E positive cases. Subsequent imaging examinations of the thyroid showed no nodules or calcifications/benign nodules in 20 patients, and suspected malignant nodules in 5 patients. 12 patients underwent total thyroidectomy or ipsilateral lobectomy, and 6 showed PTC in postoperative pathological examinations. The remaining 19 patients without surgery were kept under active surveillance, and no one had recurrence of PTC.ConclusionIncidentally discovered PTC in lymph nodes has usually interpreted as metastasis from a clinical occult thyroid primary cancer, but primary PTC was not always detected. This suggests it could be double occult lesions. With regards to concurrence with highly malignant tumor, most patients could keep regular surveillance.

Ultrasound radiomics nomogram for predicting large-number cervical lymph node metastasis in papillary thyroid carcinoma.

To evaluate the value of preoperative ultrasound (US) radiomics nomogram of primary papillary thyroid carcinoma (PTC) for predicting large-number cervical lymph node metastasis (CLNM). A retrospective study was conducted to collect the clinical and ultrasonic data of primary PTC. 645 patients were randomly divided into training and testing datasets according to the proportion of 7:3. Minimum redundancy-maximum relevance (mRMR) and least absolution shrinkage and selection operator (LASSO) were used to select features and establish radiomics signature. Multivariate logistic regression was used to establish a US radiomics nomogram containing radiomics signature and selected clinical characteristics. The efficiency of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve, and the clinical application value was assessed by decision curve analysis (DCA). Testing dataset was used to validate the model. TG level, tumor size, aspect ratio, and radiomics signature were significantly correlated with large-number CLNM (all P< 0.05). The ROC curve and calibration curve of the US radiomics nomogram showed good predictive efficiency. In the training dataset, the AUC, accuracy, sensitivity, and specificity were 0.935, 0.897, 0.956, and 0.837, respectively, and in the testing dataset, the AUC, accuracy, sensitivity, and specificity were 0.782, 0.910, 0.533 and 0.943 respectively. DCA showed that the nomogram had some clinical benefits in predicting large-number CLNM. We have developed an easy-to-use and non-invasive US radiomics nomogram for predicting large-number CLNM with PTC, which combines radiomics signature and clinical risk factors. The nomogram has good predictive efficiency and potential clinical application value.

Application of decision tree algorithms to predict central lymph node metastasis in well-differentiated papillary thyroid carcinoma based on multimodal ultrasound parameters: a retrospective study.

Prophylactic central neck dissection (pCND) in patients with well-differentiated primary papillary thyroid carcinoma (PTC) has become controversial. Several attempts have been made to predict central compartment lymph node metastasis (CLNM) based on clinical and conventional ultrasonic parameters. This study aimed to develop a decision tree (DT) model for predicting the risk of CLNM in patients with PTC based on clinical and preoperative multimodal ultrasound (US) characteristics. A total of 148 PTC nodules confirmed by surgical pathology at Beijing Tiantan Hospital were retrospectively analyzed. All nodules underwent multimodal US examinations preoperatively from January 2020 to September 2021. Correlation analysis of CLNM with clinical characteristics as well as multimodal US parameters of PTC lesions based on gray-scale US, color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), contrast-enhanced ultrasound (CEUS), and shear wave elastography (SWE) technology was carried out. Finally, the chi-squared automatic interaction detector (CHAID) with a 10-fold cross-validation was used to establish DTs for CLNM prediction. The area under the curve was calculated to compare the predictive performance. Univariate analysis indicated that CLNM was positively correlated with thyroglobulin level, maximum size, taller-than-wide, the number of microcalcifications greater than or equal to 5, contact capsule, abnormal cervical lymph node on conventional US, noncentripetal perfusion, delayed clearance, the average shear wave velocity (SWV mean), and the SWV ratio (P<0.05). The multimodal US DT based on taller-than-wide, contact capsule, abnormal cervical lymph node on conventional US, and centripetal enhancement as independent variables showed good discrimination: the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve were 80.0%, 76.7%, 78.4%, and 0.837 [95% confidence interval (CI): 0.771-0.902]. There was a significant difference between the multimodal and conventional US DTs (P=0.009). Our results indicated that the DT based on the preoperative multimodal US characteristics of PTCs has a reasonable predictive ability for CLNM and can be conveniently used for clinical decision-making of individualized treatment in patients with well-differentiated PTC.

Lymph Node Metastases in Papillary Thyroid Carcinoma can be Predicted by a Convolutional Neural Network: a Multi-Institution Study.

The presence of nodal metastases in patients with papillary thyroid carcinoma (PTC) has both staging and treatment implications. However, lymph nodes are often not removed during thyroidectomy. Prior work has demonstrated the capability of artificial intelligence (AI) to predict the presence of nodal metastases in PTC based on the primary tumor histopathology alone. This study aimed to replicate these results with multi-institutional data. Cases of conventional PTC were identified from the records of 2 large academic institutions. Only patients with complete pathology data, including at least 3 sampled lymph nodes, were included in the study. Tumors were designated "positive" if they had at least 5 positive lymph node metastases. First, algorithms were trained separately on each institution's data and tested independently on the other institution's data. Then, the data sets were combined and new algorithms were developed and tested. The primary tumors were randomized into 2 groups, one to train the algorithm and another to test it. A low level of supervision was used to train the algorithm. Board-certified pathologists annotated the slides. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic curves and the Youden J statistic were used for primary analysis. There were 420 cases used in analyses, 45% of which were negative. The best performing single institution algorithm had an area under the curve (AUC) of 0.64 with a sensitivity and specificity of 65% and 61% respectively, when tested on the other institution's data. The best performing combined institution algorithm had an AUC of 0.84 with a sensitivity and specificity of 68% and 91% respectively. A convolutional neural network can produce an accurate and robust algorithm that is capable of predicting nodal metastases from primary PTC histopathology alone even in the setting of multi-institutional data.

Lymph Node Posterior to the Right Recurrent Laryngeal Nerve Metastasis in Right Lobe T1a Papillary Thyroid Carcinoma: A Retrospective Cohort Study.

This study analyzed the incidence and predictors of lymph node posterior to the right recurrent laryngeal nerve metastasis in T1a papillary thyroid carcinoma of the right lobe. This was a retrospective cohort study. Patients were selected from those who had received surgical treatment for primary papillary thyroid carcinoma between January 2019 and December 2020. The association between clinicopathologic variables and lymph node posterior to the right recurrent laryngeal nerve metastasis was assessed using univariate and multivariate analyses. Postoperative complications were also described. Lymph node posterior to the right recurrent laryngeal nerve metastasis was present in 6.0% of the 402 study patients. It was the most likely to occur when there were other lymph node metastases, particularly in the lymph node anterior to the recurrent laryngeal nerve. Independent predictors for lymph node posterior to the right recurrent laryngeal nerve metastasis were a tumor size of ≥5.0mm, a lower pole location, and lymph node anterior to the right recurrent laryngeal nerve metastasis. The rate of persistent vocal cord paralysis was .5%, and no patient developed permanent hypoparathyroidism. Although lymph node posterior to the right recurrent laryngeal nerve metastases of the right lobe T1a papillary thyroid carcinoma is uncommon, the possibility of metastasis should be investigated when there is a positive lymph node anterior to the right recurrent laryngeal nerve in a tumor >5.0mm in size located in the lower pole. Lymph node posterior to the right recurrent laryngeal nerve dissection is recommended for such tumors.

A nomogram based on ultrasound characteristics to predict large-number cervical lymph node metastasis in papillary thyroid carcinoma.

To establish a nomogram for predicting large-number cervical lymph node metastases (LNMs) of primary papillary thyroid carcinoma (PTC) based on ultrasound characteristics. This retrospective study included patients with PTC diagnosed by pathological examination and who underwent surgery between August 2015 and May 2021 at Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo, China). Large-number LNM was defined as >5 lymph nodes with metastases. The patients were propensity score-matched (PSM) for age and sex. A multivariable analysis was used to determine the risk factors for massive LNM. After PSM, the 78 patients with large-number LNM were matched with 312 patients with small-number LNM. Compared with the patients with small-number LNM, those with large-number LNM had larger tumors (13.0 ± 7.7 vs. 6.8 ± 3.8 mm, p < 0.001), and higher frequencies of multifocal nodules (42.3% vs. 22.4%, p < 0.001), taller-than-wide shape (82.1% vs. 56.7%, p < 0.001), calcifications (76.9% vs. 47.4%, p < 0.001), microcalcifications (68.0% vs. 36.5%, p < 0.001), capsule invasion (32.1% vs. 17.6%, p = 0.005), and ultrasound diagnosis of LNM (44.9% vs. 9.3%, p < 0.001). The multivariable analysis showed that nodule size (OR = 1.19, 95%CI: 1.11-1.27, p < 0.001), multifocal disease (OR = 2.50, 95%CI: 1.30-4.80, p = 0.006), taller-than-wide shape (OR = 0.45, 95%CI: 0.22-0.93, p = 0.032), and ultrasound diagnosis of LNM (OR = 5.57, 95%CI: 2.73-11.37, p < 0.001) were independently associated with large-number LNM. A nomogram was built, and the area under the receiver operating characteristics curve was 0.86 (95%CI: 0.81-0.90). A nomogram was successfully built to predict large-number LNM in patients with PTC, based on nodule size, multifocality, taller-than-wide shape, and ultrasound diagnosis of LNM.

Developing and validating a multivariable machine learning model for the preoperative prediction of lateral lymph node metastasis of papillary thyroid cancer

At present, preoperative diagnosis of lateral cervical lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC) mostly depends on the training and expertise of ultrasound doctors. A machine-learning model for predicting LLNM accurately before PTC surgery may help to determine the scope of surgery and reduce unnecessary surgical trauma. The data of patients with primary PTC who underwent thyroidectomy with lateral cervical lymph node surgery at Beijing Tongren Hospital between July 2009 and June 2021 were retrospectively analyzed. All patients had complete ultrasonic examination, clinical data, and definite pathology diagnosis of lymph nodes. LLNM was confirmed by postoperative pathology. The patients were randomly divided into a training set (155 cases) and a test set (98 cases) at a ratio of 6:4. Eleven parameters, including patient demographics, ultrasound results, and tumor-related conditions, were collected, and a prediction model was established using the support vector machine (SVM) algorithm. Several other machine-learning algorithms were also used to establish models for comparison. The accuracy, precision, recall, F1-score, sensitivity, specificity, Cohen's kappa value, and area under the receiver operating characteristic curve (AUC) were used to evaluate model performance. A total of 87 males and 156 females were included in the study, aged 14-80 years. One hundred and four patients of them had LLNM and 139 did not have LLNM. The pandas Python library was used for the statistical analysis, and the Spearman coefficient was used to analyze the correlation between each parameter and the prediction index. The SVM model performed the best among all the models. Its accuracy, precision, recall, F1-score, sensitivity, specificity, Cohen's kappa value, and AUC were 90.8%, 91.0%, 90.8%, 90.8%, 87.5%, 94.0%, 81.6%, and 91.0%, respectively. This model can enable surgeons to improve the accuracy of ultrasonography in predicting LLNM without additional examination, thus avoiding missing positive lateral cervical lymph nodes and reducing the sequelae caused by unnecessary lateral neck dissection.

Primary Papillary Thyroid Carcinoma Arising in a Branchial Cleft Cyst – Navigating a Hidden Malignancy on Histopathology

Primary Papillary Thyroid Carcinoma Arising in a Branchial Cleft Cyst – Navigating a Hidden Malignancy on Histopathology

Efficacy, safety, and controversy of ultrasound-guided radiofrequency ablation in the treatment of T1N0M0 papillary thyroid carcinoma.

To evaluate the safety effect, and controversy on the treatment outcomes of radiofrequency ablation (RFA) for T1N0M0 papillary thyroid carcinoma (PTC). This study is assessed the medical records of 142 patients with primary T1N0M0 PTC tumors after RFA between 2014 and 2022. 4 patients underwent delayed surgery (DS) after RFA and 411 T1N0M0 patients underwent DS were recorded. Outcomes were compared between RFA and DS groups after propensity score matching (PSM). The maximal diameter (MD) and volume (V) increased in months 1 (P < 0.01) and reduced after the 6-month follow-up (all P < 0.01). The disappearance and disease progression rates were 53.5% and 2.1%, respectively. The complication and disease progression rates had no significant difference between RFA and DS (P>0.05). In some cases, the tumors were not fully inactivated after RFA, and the central compartment lymph node (CCLN) were metastasis. The CCLN metastasis rate was 13.4%. MD, V and clustered calcifications were independent risk factors for CCLN metastasis by univariate analysis. RFA is an effective and safe treatment option in selected patients with solitary T1N0M0 PTC. There are the risks of tumor incompletely ablated and CCLN metastasis.

PSAT252 Primary Papillary Thyroid Carcinoma Arising from a Thyroglossal Duct Cyst

Abstract Background Thyroglossal duct cysts (TGDC) are remnants of the thyroglossal duct tract that do not atrophy and disappear, instead undergoing cystic expansion and often presenting as a midline neck mass. Rarely, carcinomas of the thyroglossal duct cyst occur, either arising as a primary carcinoma or as a cystic metastasis from a primary thyroid cancer; the former are particularly rare. These thyroglossal duct cyst carcinomas most commonly present in the adult population. Case Report We present the case of a 32-year-old female without any significant past medical history who presented with a non-tender midline neck mass identified as a thyroglossal duct cyst and completely excised; pathology results were positive for a primary papillary thyroid carcinoma with a tumor measuring 1.3 cm in diameter within the TGDC. Thyroid Ultrasound also showed the presence of two nodules measuring 1.4 cm on the right and 1.2 cm on the left, respectively, with fine needle aspiration (FNA) of both the nodules confirming papillary thyroid carcinoma as well. Lymph node FNA was negative for metastatic carcinoma. The patient underwent a thyroidectomy which definitively confirmed both a classic papillary carcinoma as well as an encapsulated, non-invasive follicular variant. In keeping with the original finding of the patient having a primary thyroglossal duct cyst carcinoma, samples from the thyroidectomy had negative tumor margins, and were also negative for any angioinvasion, lymphatic invasion, or extrathyroidal extension. Conclusion While thyroglossal duct cysts are the most common type of congenital neck cyst, primary carcinomas arising from thyroglossal duct cysts are rare. Masses that occur anywhere along the thyroglossal duct tract should be investigated for malignancy, with additional investigation of the thyroid gland for either a primary or secondary thyroid cancer. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.