Subtype Of Papillary Thyroid Carcinoma Research Articles

Predicting tall-cell subtype of papillary thyroid carcinomas independently with preoperative multimodal ultrasound.

This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. Forty-six TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, colour Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesions were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. Univariate and multivariate analyses identified that extra-thyroidal extension (odds ratio [OR], 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: P = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm) + 2.957 × (if aspect ratio ≥ 0.91) + 2.819 × (if extra-thyroidal extension). The prediction model had a good discrimination performance for TCPTC: the area under the receiver-operator-characteristic curve, sensitivity, and specificity were 0.928, 0.848, and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923, and 0.926, respectively. Ultrasound has the potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extra-thyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful in predicting TCPTC. Multimodal ultrasound prediction of TCPTC was a supplement to preoperative cytological diagnosis and molecular diagnosis of PTC subtypes.

Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms.

Columnar cell papillary thyroid carcinoma (CC-PTC) is a morphologic subtype of papillary thyroid carcinoma with a variable prognosis. It is characterized by neoplastic thyroid follicular-derived cells with pseudostratified columnar morphology arranged in papillary or follicular structures with supranuclear or subnuclear vacuoles. The molecular profile of this subtype has only recently come under scrutiny, with mixed results. The aim of this study is to further explore the morphologic, immunohistochemical, and genetic profile of CC-PTC, as well as to correlate these features with clinical outcomes. CC-PTC cases were identified from 3 institutions. Immunohistochemistry (ER, CDX2) and molecular testing (DNA and RNA sequencing) were performed. Clinicopathologic parameters and patient outcomes were recorded. Twelve cases (2006-2023) were identified, all in adults (age 45-91). Two presented with disease outside the thyroid gland (neck and mediastinum) and two presented with distant metastasis. Four were high-grade differentiated thyroid carcinomas (necrosis or mitoses), one of which died of disease. Four were noninvasive or minimally invasive, one of which locally recurred. Three patients had lymph node metastases. ER and CDX2 were positive in 73% and 50%, respectively. Pathogenic mutations were found in TERT promoter (n = 3), RAS (n = 2), ATM, NOTCH1, APC, and ESR1, along with cases bearing AGK::BRAF fusion (n = 1), BRAF VE1 expression (n = 1), and NF2 loss (n = 1). This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

Distant metastasis at the time of diagnosis in a young male patient with classical subtype of papillary thyroid carcinoma and graves' disease

Distant metastasis at the time of diagnosis in a young male patient with classical subtype of papillary thyroid carcinoma and graves' disease

Utility of solid area diameter in management of cystic papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) with marked cystic formation (CPTC) is not a subtype of PTC, and its clinical characteristics have not been fully investigated. This study aimed to clarify the clinical and pathological characteristics of CPTC and propose important indicators for its clinical management. Thirty-three CPTC nodules with cystic areas occupying >50% of their volume were examined. Two matched controls (MCs) were prepared, one with tumor diameter matched for whole tumor diameter (WTD) of CPTCs and the other with tumor diameter matched for solid area diameter (SAD) of CPTCs. The mean age of patients with CPTC was 55.2 years significantly older than that in SAD-MCs. Of the CPTCs, 69.7% were classified as highly suspicious by ultrasonography, and the prevalence was lower than that in WTD-MCs (88.9%) and SAD-MCs (91.5%). Total thyroidectomy was performed in 69.7% of CPTC cases, which was significantly less frequent than that in WDT-MCs (91.7%) and similar to that in SAD-MCs (76.1%). Histologically, CPTCs exhibited two characteristic findings: invasion from the solid area into the surrounding normal thyroid tissue and granulation tissue around the cystic wall. The frequencies of the cases with pathological lateral node metastasis, extrathyroidal extension, and Ki-67 labeling index ≥5% in CPTCs were significantly lower than those in WTD-MCs and relatively similar to those in SAD-MCs. In the surgical strategy and prognosis of CPTC, the evaluation of tumor size should be based on SAD rather than on WTD. We advocate measuring not only WTD but also SAD in CPTC.

Sonographic characteristics of diffuse sclerosing variant of papillary thyroid carcinoma with histopathological correlation: a preliminary study

BackgroundDiffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is a rare but high invasive subtype of papillary thyroid carcinoma, which mandates an aggressive clinical strategy. Few studies have focused on the sonographic characteristics of DSVPTC and the role of ultrasound in diagnosis and treatment of this variant remains unknown. This study aimed to identify and understand DSVPTC more accurately under ultrasound in correlation with pathology.MethodsThe ultrasound characteristics and histopathologic sections of 10 lesions in 10 DSVPTC patients who underwent thyroid surgery at our center between 2014 and 2020 were reviewed and compared with 184 lesions in 168 classic variant of papillary thyroid carcinoma (cPTC) patients.Results6 DSVPTC cases (60%) showed the “snowstorm” pattern on sonogram and 4 cases (40%) presented hypoechoic solid nodules only. Vague borders (100.0% vs. 18.5%, P = 0.019) and abundant microcalcifications (66.7% vs. 10.9%, P = 0.037) were more common in DSVPTC nodules than in cPTC nodules, corresponding to the infiltrating boundaries and numerous psammoma bodies under the microscope respectively. Most of the DSVPTC cases had a heterogeneous background (80%) and suspicious metastatic cervical lymph nodes (80%) on sonograms. All DSVPTC cases had histopathological metastatic cervical lymph nodes.ConclusionThe sonographic “snowstorm” pattern indicated DSVPTC with whole-lobe occupation. Hypoechoic solid nodules with vague borders and abundant microcalcifications on sonogram suggested DSVPTC lesion with an ongoing invasion. Regardless of which of the two sonograms was shown, the corresponding DSVPTC lesions were aggressive and required the same attention from the surgeons.

Correlation between genetic alterations and clinicopathological features of papillary thyroid carcinomas.

To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (<45 years). Among the 22 genes tested, the BRAF mutation rates showed a significant difference between the PTC and benign groups. In the subgroup analysis, younger age (odds ratio = 12.512, 95% confidence interval: 3.126-50.087) was an independent risk factor for LNM. In further analyses, BRAF mutation was significantly associated with LNM in the older subgroup (age ≥ 45 years), suggesting that the BRAF mutation test has greater value for determining PTC prognosis in the older age group. Our findings will provide a more comprehensive understanding of the relationship between gene mutations and PTC and may contribute to improved PTC management.

FOXE1 Gene is a Probable Tumor Suppressor Gene with Decreased Expression as Papillary Thyroid Cancers Grow, and is Absent in Anaplastic Thyroid Cancers.

Papillary thyroid carcinoma (PTC), the most prevalent cancer of the thyroid, is more common in women than in men. To uncover the expression profile of FOXE1 gene in PTC tumor etiology. Microarray and RNA sequencing data on PTC in humans were analyzed. Eleven PTC tumor tissue samples and their neighboring normal tissue samples were collected. RT-qPCR was performed. Data normality, ROC construction, and logistic regression analysis were conducted. PTC tumors, normal tissues surrounding tumors, patients of different sexes and ages, metastasizing tumors, and tumor variants were assessed for FOXE1 expression. Eleven PTC tissues were obtained from seven women and four men. Among the PTC subtypes, there were two FV-PTCs, four C-PTCs, one microcarcinoma, and four tissues with an unknown subtype. FOXE1 gene expression was significantly increased in PTC tumors with dimensions less than 10 mm (relative expression = 14.437, p = 0.050). A significant increase in FOXE1 gene expression was observed in the normal tissue adjacent to the tumor, which was less than 10 mm in size, compared to the normal tissue adjacent to the tumor, which was larger than 10 mm (relative expression = 41.760, p = 0.0001). Females diagnosed with PTC showed a significant reduction in FOXE1 mRNA levels compared to their male counterparts (relative expression = 0.081, p = 0.042). In contrast to adjacent normal tissue, there was a significant reduction in FOXE1 gene expression in FV-PTC (relative expression = 0.044 and p = 0.0001). PTC tumors under 10mm had higher FOXE1 gene expression than larger tumors; normal tissue adjacent to smaller tumors also had higher FOXE1 expression. Females with PTC, regardless of their subtype, expressed less FOXE1 mRNA than males. FV-PTC tissues exhibited lower expression of FOXE1 mRNA than their adjacent normal tissues.

A Case of Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma Mimicking Hashimoto’s Thyroiditis

Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma (DSV-PTC) is a rare and aggressive subtype of Papillary Thyroid Carcinoma (PTC) The prognosis of this variant is as good as classic PTC, but close follow-up is necessary because of frequent tumour recurrence. The authors report a case of a 30-year-old female who presented with a 6-month history of gradually progressive midline neck swelling. Antithyroid antibodies were elevated, and radiology was suggestive of a colloid goitre. Total thyroidectomy was done along with anterior compartment lymph node removal for confirmation. Interestingly, histopathology showed a picture reminiscent of Hashimoto’s Thyroiditis (HT), but the lymph node showed tumour metastasis. Thereafter, additional sections were taken to establish the diagnosis of DSV-PTC in the thyroid. The present case highlights the importance of extensive sampling in histopathology for a suspected case of malignancy, as it can be misdiagnosed as a benign aetiology.

Prediction of classical versus non classical papillary thyroid carcinoma subtypes from cytology of nodules classified according to TIRADS

PurposeOur purposes were: 1) to estimate the prediction performance (PP) of cytology in identifying papillary thyroid carcinoma (PTC) subtypes; 2) to explore how the PTC subtypes distribute among the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories.MethodsNodules were included if both the histology with the PTC subtype report and the cytology report with the possible PTC subtype were available. The PP was calculated by making the proportion of True positives/False positives+false negatives.Results309 cytologically “suspicious for malignancy” and “malignant” thyroid nodules with PTC histology were evaluated. ACR TI-RADS categorization for classical PTC was significantly different from non-classical PTC (p-value 0.02). For the whole cohort the PP of cytologically classical cases was 0.74, while that of cytologically non classical cases was 0.41. ACR TI-RADS categorization was not significantly different for aggressive vs non-aggressive PTC subtypes (p-value 0.1). When considering only aggressive or non-aggressive PTC subtypes, the PP of cytologically classical cases was respectively 0.86 and 0.87, while that of cytologically non classical cases was respectively 0.27 and 0.22. The PP of cytologically classical cases was 0.73 and 0.79, respectively for macroPTCs and microPTCs, while that of cytologically non classical cases was 0.55 and 0.33, respectively for macroPTCs and microPTCs.ConclusionCytology examination reliably performed in predicting classical PTC versus non classical PTC subtypes. ACR TI-RADS categorization was significantly different among classical PTC versus non classical PTC subtypes.

Long-Term Outcomes and Risk Factors of Radiofrequency Ablation for T1N0M0 Papillary Thyroid Carcinoma

Radiofrequency ablation (RFA) has gained increasing interest as a minimally invasive procedure to treat low-risk papillary thyroid carcinoma (PTC). Considering the indolent nature of this disease, studies in large populations with long follow-up would be invaluable to further substantiate the effectiveness of RFA. To evaluate the long-term (58.5 months) outcomes of patients with T1N0M0 PTC who underwent RFA and investigate risk factors for local tumor progression (LTP). This cohort study included 1613 patients aged 18 years or older with T1N0M0 PTC who underwent ultrasonography-guided RFA between January 2014 and December 2020 at the Chinese People's Liberation Army General Hospital in Beijing, China. Included in the analysis were patients with PTC (confirmed by biopsy) with a maximum diameter of 20 mm or less; no evidence of extrathyroidal extension (capsular disruption or involvement of perithyroidal tissue), lymph node metastasis, or distant metastasis on ultrasonography or computed tomography; and no evidence of an aggressive subtype of PTC on biopsy. Patients with PTC larger than 2 cm, less than 12 months of follow-up, or inadequate follow-up information were excluded. Data were analyzed in April 2023. Long-term progression rate, disease-free survival, and complete tumor disappearance and their associations with patient and tumor characteristics. Disease-free survival was calculated using Kaplan-Meier analysis. Cox proportional hazards regression analyses were performed to assess risk factors for LTP and complete tumor disappearance. The study comprised 1613 patients (mean [SD] age, 43.3 [10.2] years; 1256 women [77.9%]) with 1834 T1N0M0 PTC tumors. During a mean follow-up of 58.5 months (range, 27 to 111 months), LTP was observed in 69 patients (4.3%), including 42 (2.6%) with tumor recurrence and 27 (1.7%) with tumor persistence. Cumulative disease-free survival rates at 1, 3, 5, and 8 years were 98.0%, 96.7%, 96.0%, and 95.7%, respectively. The overall complication rate was 2.0% (32 patients), with 6 (0.4%) major complications. Independent risk factors for LTP included subcapsular tumor location 2 mm or less from the capsule or trachea (hazard ratio [HR], 3.36; 95% CI, 2.02-5.59; P < .001) and multifocal tumors (HR, 2.27; 95% CI, 1.30-3.96; P = .004). Furthermore, 1376 patients (85.3%) showed complete tumor disappearance at follow-up ultrasonographic examination. Factors associated with complete tumor disappearance included age 40 years or less (HR, 0.78; 95% CI, 0.70-0.87; P < .001), stage T1a tumors (HR, 0.37; 95% CI, 0.31-0.45; P < .001), and unifocal tumors (HR, 0.50; 95% CI, 0.42-0.60; P < .001). In this cohort study, ultrasonography-guided RFA for T1N0M0 PTC had excellent long-term outcomes. Patients with unifocal T1N0M0 PTC and subcapsular tumor location more than 2 mm from the capsule or trachea may be the best candidates for RFA.

A Critical Assessment of Diagnostic Criteria for the Tall Cell Subtype of Papillary Thyroid Carcinoma—How Much? How Tall? And When Is It Relevant?

Tall cell papillary thyroid carcinoma (TC-PTC) is considered adverse histology. However, previous studies are confounded by inconsistent criteria and strong associations with other adverse features. It is therefore still unclear if TC-PTC represents an independent prognostic factor in multivariate analysis and, if it does, what criteria should be employed for the diagnosis. We retrospectively reviewed 487 PTCs from our institution (where we have historically avoided the prospective diagnosis of TC-PTC) for both the height of tall cells (that is if the cells were two, or three, times as tall as wide) and the percentage of tall cells. On univariate analysis, there was significantly better disease free survival (DFS) in PTCs with no significant tall cell component (< 30%) compared to PTCs with cells two times tall as wide (p = 0.005). The proportion of tall cells (30–50% and > 50%) was significantly associated with DFS (p = 0.012). In a multivariate model including age, size, vascular space invasion, and lymph node metastasis, the current WHO tall cell criteria, met by 7.8% of PTCs, lacked statistical significance for DFS (p = 0.519). However, in the subset of tumours otherwise similar to the American Thyroid Association (ATA) guidelines low-risk category, WHO TC-PTC demonstrated a highly significant reduction in DFS (p = 0.004). In contrast, in intermediate to high-risk tumours, TC-PTC by WHO criteria lacked statistical significance (p = 0.384). We conclude that it may be simplistic to think of tall cell features as being present or absent, as both the height of the cells (two times versus three times) and the percentage of cells that are tall have different clinical significances in different contexts. Most importantly, the primary clinical significance of TC-PTC is restricted to PTCs that are otherwise low risk by ATA guidelines.

Genomic and transcriptomic analyses of thyroid cancers identify DICER1 somatic mutations in adult follicular-patterned RAS-like tumors.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Several genomic and transcriptomic studies explored the molecular landscape of follicular cell-derived TCs, and BRAFV600E, RAS mutations, and gene fusions are well-established drivers. DICER1 mutations were described in specific sets of TC patients but represent a rare event in adult TC patients. Here, we report the molecular characterization of 30 retrospective follicular cell-derived thyroid tumors, comprising PTCs (90%) and poorly differentiated TCs (10%), collected at our Institute. We performed DNA whole-exome sequencing using patient-matched control for somatic mutation calling, and targeted RNA-seq for gene fusion detection. Transcriptional profiles established in the same cohort by microarray were investigated using three signaling-related gene signatures derived from The Cancer Genome Atlas (TCGA). The occurrence of BRAFV600E (44%), RAS mutations (13%), and gene fusions (13%) was confirmed in our cohort. In addition, in two patients lacking known drivers, mutations of the DICER1 gene (p.D1709N and p.D1810V) were identified. DICER1 mutations occur in two adult patients with follicular-pattern lesions, and in one of them a second concurrent DICER1 mutation (p.R459*) is also observed. Additional putative drivers include ROS1 gene (p.P2130A mutation), identified in a patient with a rare solid-trabecular subtype of PTC. Transcriptomics indicates that DICER1 tumors are RAS-like, whereas the ROS1-mutated tumor displays a borderline RAS-/BRAF-like subtype. We also provide an overview of DICER1 and ROS1 mutations in thyroid lesions by investigating the COSMIC database. Even though small, our series recapitulates the genetic background of PTC. Furthermore, we identified DICER1 mutations, one of which is previously unreported in thyroid lesions. For these less common alterations and for patients with unknown drivers, we provide signaling information applying TCGA-derived classification.

SAT550 Warthin-like Variant of Papillary Thyroid Carcinoma: An Even Rarer Presentation

Abstract Disclosure: J. Kunadia: None. S. Chablani: None. Introduction: We present a rare case of Warthin-like variant of papillary thyroid carcinoma (WLPTC) with later development of a second primary malignancy. Clinical Case: A 56 year old female with hypertension, hyperlipidemia, ulcerative colitis, asthma, and a strong family history of cancer presented in 2017 for evaluation of an enlarged thyroid gland noted by her primary care provider. Patient was asymptomatic and denied prior thyroid disease and head or neck radiation. Labs demonstrated normal TSH and free T4 levels. TPO antibodies were elevated to 1,155 IU/mL (reference range 0.0 – 5.5 IU/mL). Thyroid US was notable for a diffusely enlarged thyroid gland containing a 1.4 x 0.6 x 1.0 cm solid, hypoechoic nodule without calcifications in the upper pole of the right lobe. Shared decision-making resulted in a plan for continued surveillance. Repeat thyroid US in 2018 demonstrated that this nodule had increased in volume by 56.25%, now measuring 1.4 x 0.75 x 1.25 cm. Fine needle aspiration (FNA) biopsy was performed and positive for papillary thyroid carcinoma (PTC). Patient underwent total thyroidectomy; pathology revealed a 1.2 x 1 x 0.9 cm WLPTC and 0.2 cm papillary thyroid microcarcinoma. There was no evidence of extrathyroidal extension, angioinvasion, or lymph node involvement. Follow-up neck US in 2020 demonstrated a 0.4 cm hypoechoic ovoid structure in the left thyroid bed and an enlarged but morphologically normal-appearing right level II lymph node. Repeat neck US in 2021 showed the appearance of a new 2.8 cm right level II lymph node; FNA was positive for malignancy with negative thyroid transcription factor-1 staining and undetectable thyroglobulin. Patient underwent an excision biopsy of the lymph node, and pathology was consistent with metastatic adenoid cystic carcinoma (ACC). A right submandibular gland lesion detected on subsequent MRI head and neck was resected and confirmed to be the primary source of ACC. Patient was treated with adjuvant radiation therapy with adequate response to therapy. Conclusion: WLPTC is a rare subtype of PTC that accounts for 0.2-1.9% of cases and carries a strong association with Hashimoto’s thyroiditis. It is histologically characterized by papillary architecture, oncocytic changes, nuclear features of PTC, and dense lymphoplasmacytic infiltration of the papillary cores. WLPTC is considered to have a favorable prognosis given its low frequency of lymphovascular invasion and low recurrence risk. This case also highlights the importance of keeping a broad differential when evaluating new findings on neck US in patients with a history of thyroid cancer. Metastases to cervical lymph nodes most commonly occur from head and neck tumors. However, to date, only one other case of PTC with second primary malignancy of salivary ACC has been reported. Presentation Date: Saturday, June 17, 2023

Evaluation of Etiology, Clinical Manifestations, Diagnosis, Follow-up, Histopathology and Prognosis Factors in Papillary Thyroid Microcarcinoma: A Systematic Review and Meta-analysis.

The most frequent type of cancer found in the endocrine system is thyroid carcinoma. Among well-differentiated thyroid malignancies, the most commonly occurring type is identified as papillary thyroid carcinoma (PTC), which makes up 70-90% of the cases. A subtype of PTC is papillary thyroid microcarcinoma (PTMC), which includes tumors smaller than 10 mm in diameter. Due to the advancements in diagnostic techniques, the incidence of this type of cancer is on the rise. In this study, we aimed to analyze the factors worsening the PTMC prognosis. In the first step, we searched various databases for the factors affecting this tumor. The relevant articles were collected and different outcomes of this tumor and its associated factors which were studied in more than one article, were classified. Finally, we conducted a meta-analysis of these outcomes and their related factors. In the meta-analysis, a significantly association was found between the following factors: recurrence with gender (P<0.001) lymph node metastasis (LNM) (P= 0.003), and extrathyroidal invasion (P<0.001); lymph node metastasis with extrathyroidal invasion (P<0.001), and multifocality (P<0.001); central lymph node metastasis (CLNM) with gender (P=0.001), tumor size (P<0.001), extracapsular invasion (P<0.001), lateral cervical lymph node metastasis (P<0.001), and extrathyroidal invasion (P<0.001); lymph node metastasis resulted in poor outcomes (P<0.001); and finally tumor size with BRAFV600E mutation (P<0.001). In conclusion, it is essential to note that greater awareness and understanding of this tumor characteristics and special and separate attention to PTMC can significantly improve the society overall health.

Agrin is a novel oncogenic protein in thyroid cancer.

Agrin (AGRN) is a matricellular glycoprotein involved in extracellular signal transduction. AGRN is involved in tumorigenesis and cancer progression; however, the role of AGRN in thyroid cancer (TC) remains unclear. In the present study, using cell lines derived from various subtypes of TC including CGTH, FTC-133 and BcPAP and transcriptomic data from patients with TC, the role of AGRN in TC was analyzed by migration, invasion, viability and proliferation assays as well as Western blot with EMT markers. AGRN expression was significantly increased in thyroid tumors and cell lines derived from various TC subtypes. The highest AGRN expression was found in follicular and papillary thyroid carcinoma subtypes. Immunocytochemistry revealed nuclear AGRN localization in normal (NTHY) and TC cells. Silencing of AGRN decreased viability, proliferation, migration and invasion of TC cell lines by upregulating vimentin and downregulating N-cadherin and E-cadherin. Furthermore, the expression of AGRN was associated with neutrophil infiltration in thyroid tumors. In conclusion, the present results indicated that increased AGRN expression promoted tumorigenic phenotypes of TC cells, while AGRN expression was associated with immune infiltration in thyroid tumors. AGRN may represent a target for future cancer therapy and requires further evaluation.

Solid/trabecular subtype of papillary thyroid carcinoma on cytology with focal differentiated high-grade thyroid carcinoma on histology: a cyto-histologic correlation.

Solid/trabecular subtype of papillary thyroid carcinoma (S/T PTC) is a rare entity that has been shown to have higher tumour recurrence and mortality rates. A definite diagnosis on fine needle aspiration cytology is often not easy. Rather, this entity may be misdiagnosed in cytology due to a lack of widespread features of classic PTC. We present a case of S/T PTC in a 61-year-old female, showing a focus on differentiated high-grade thyroid carcinoma (DHGTC) on histology. We discuss cytological features with the histologic correlation of S/T PTC and briefly discuss the newly introduced entity, DHGTC.

Association of Polygenic Score With Tumor Molecular Subtypes in Papillary Thyroid Carcinoma.

Genome-wide association studies have identified germline variants associated with elevated PTC risk. It is also known that somatic driver mutations contribute to PTC development and as such PTCs can be further categorized into different molecular subtypes based on their somatic alterations. However, it remains unknown whether identified germline variants predictive of PTC risk are associated with specific molecular subtypes. The primary goal of the present study is to determine whether germline genetic risk, as assessed using a polygenic score (PGS) is associated with molecular subtypes of papillary thyroid carcinoma (PTC), defined based on tumor driver mutation status. This study was carried out using data from The Cancer Genome Atlas (TCGA) thyroid cancer study. A previously validated 10-single-nucleotide variation PGS for PTC derived from genome-wide association study hits was calculated to ascertain germline genetic risk. The primary molecular subtypes of interest were defined by tumor driver mutation status (BRAFV600E-mutated vs RAS-mutated vs "other"). We also explored associations between PGS and molecular subtypes defined by messenger RNA (mRNA) expression, microRNA expression, and DNA methylation patterns. Polytomous logistic regression analysis was used to assess the association between PGS and PTC molecular subtype with and without adjustment for clinical variables. Odds ratios (ORs) with their 95% CIs were estimated. A total of 359 patients were included in the study. PGS was significantly associated specific tumor molecular subtypes defined by tumor driver mutation status. Increasing germline risk was associated with having a higher odd of BRAFV600E-mutated PTC compared to PTCs without driver mutations in the "other" category. No significant difference was detected in terms of PGS tumor categorization in the RAS subtype compared to BRAFV600E. In exploratory analyses, PGS was also associated with mRNA-, microRNA-, and DNA methylation-defined molecular subtypes, as defined by the TCGA PTC study. PGS has molecular subtype-specific associations in PTC, which has implications for their use in risk prediction.

Warthin-like papillary thyroid carcinoma: a case report and comprehensive review of the literature.

Papillary Thyroid Carcinoma (PTC) is the most frequent endocrine malignancy with a variety of histological presentations. Warthin-like Papillary Thyroid Carcinoma (WLPTC) is an uncommon neoplasm that is recognized as a distinct subtype of PTC in the WHO classification of thyroid tumors. In this report, we present a novel case of WLPTC in a female patient and provide an in-depth review of the available literature on its clinical, pathological, and therapeutic characteristics. A 27-year-old female patient was referred for neck swelling. Ultrasound showed two suspicious thyroid nodules leading to a thyroidectomy. She was diagnosed with intermediate-risk bifocal foci of classic PTC and WLPTC, arising from a background of chronic lymphocytic thyroiditis (CLT). This pT1b(m) N1b M0 malignancy was treated with adjuvant isotopic ablation and suppressive thyroxine therapy. The 1-year outcomes were favorable. It covered articles published from 1995 to 2022, by searching PubMed and Google Scholar using specific terms. Out of 148 articles reviewed by two authors, 25 relevant articles were selected, including 13 case reports and 12 case series. The study included 150 cases of WLPTC. Data related to clinical presentation, imaging, histological features, management, and outcomes, were extracted. The mean age of diagnosis was 39 years, with a female predominance. The most common clinical presentation was neck swelling. Thyroid autoimmunity was positive in 71.6% of patients. Lymph node metastases were present in 28% of cases, with no reported distant metastases. Overall, the outcomes were favorable. WLPTC shares similar clinical and radiological presentations as classic PTC. The hallmark histological features of WLPTC are papillae lined with oncocytic tumor cells with papillary nuclear changes and lymphoid stroma. WLPTC is almost constantly associated with CLT. The management of WLPTC aligns with that of classic PTC with comparable stage and risk category, often resulting in favorable outcomes.

Demographic and socioeconomic factors of patients with nonencapsulated sclerosing carcinoma: An NCDB analysis.

e18103 Background: Nonencapsulated sclerosing carcinoma (NSC) is a rare and aggressive variant of papillary thyroid carcinoma (PTC) that accounts for 0.7-6.6% of its cases. It is associated with greater rates of vascular invasion, metastasis, and relapse compared to classic PTC. With prompt initiation of aggressive treatment including radical surgery, lymph node resection, and possible radioiodine treatment, NSC has a 10-year survival rate of 93%. Given the importance of proper diagnosis and selection of aggressive treatments, data regarding its epidemiology could further improve patient outcomes. The demographics of NSC patients were analyzed using the National Cancer Database (NCBD). Methods: Data from NCDB was queried and patients with a confirmed diagnosis of NSC between 2004 and 2020 were identified for a retrospective cohort analysis (N = 1,130). Yearly diagnosis rates were analyzed using regression analysis. Factors including patient age, sex, race, insurance status, urban/rural residence, surgical treatment approach, treatment facility type, and 90-day mortality were identified and evaluated via descriptive statistics. Results: The NCDB contained a total of 1,130 patients with a confirmed diagnosis of NSC from 2004 – 2020. The incidence rate of new diagnoses remained stable over this time (R2 = 0.0). Women were much more likely to be diagnosed (78.5%) compared to men (21.5%) with an average age at diagnosis of 44.0 years (SD = 18.7, range = 6 – 90 years). Most patients were White (86.0%), lived in metropolitan areas with a greater than 1 million population (56.5%), and were privately insured (68.9%). The vast majority of patients were treated surgically (99.9%). A complete thyroidectomy was the most common surgical approach (89.3%), more so than subtotal thyroidectomy or lobectomy. For the patients with valid data, the most common treatment facility type was an academic/research program (42.6%) followed by comprehensive community cancer programs (33.8%). Most patients survived at least ninety days after their primary surgery (98.2%) and were still alive at the date of last contact (88.4%). Conclusions: NSC is an aggressive subtype of PTC, but it generally has a good prognosis with initiation of aggressive treatment. The findings of this research corroborated previous studies showing that NSC is much more common in females than males, is most commonly treated with complete thyroidectomy, and has high 90-day survival rates. In examining the demographic features of this patient population, it was found that the majority of patients were White, lived in large metropolitan areas, and were privately insured. This may suggest that a relative ease of access to healthcare aided in their diagnosis. Future research should focus on understanding how demographic and socioeconomic factors may contribute to the timing of diagnosis, chosen treatments, and overall mortality rates of patients with NSC.

RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients.

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The RET gene rearrangements CCDC6::RET and NCOA4::RET are the most common RET gene rearrangements in PTC patients. Different RET::PTC rearrangements are associated with different PTC phenotypes. Methods: Eighty-three formalin-fixed paraffin-embedded (FFPE) PTC samples were examined. The prevalence and expression levels of CCDC6::RET and NCOA4::RET were determined using semi-quantitative polymerase chain reaction (qRT-PCR). The association of these rearrangements with clinicopathological data was investigated. Results: The presence of CCDC6::RET rearrangement was significantly associated with the classic subtype and absence of angio/lymphatic invasion (p < 0.05). While NCOA4::RET was associated with the tall-cell subtype, and presence of angio/lymphatic invasion and lymph node metastasis (p < 0.05). Multivariate analysis demonstrated that an absence of extrathyroidal extension and extranodal extension were independent predictive factors for CCDC6::RET, whereas the tall-cell subtype, large tumor size, angioinvasion, lymphatic invasion and perineural invasion were independent predictive factors for NCOA4::RET (p < 0.05). However, the mRNA expression level of CCDC6::RET and of NCOA4::RET were not significantly associated with clinicopathological data. Conclusion: CCDC6::RET was correlated with an innocent PTC subtype and characteristics, but NCOA4::RET correlated with an aggressive phenotype of PTC. Therefore, these RET rearrangements strongly associated with clinicopathological phenotypes and can be used as predictive markers in PTC patients.