Metastatic Thyroid Research Articles

Abstract 1397: Collagen COL26A1 promotes papillary thyroid cancer invasion and metastasis and correlates with poor survival and clinical outcomes

Abstract Papillary thyroid cancer (PTC) is the most common cancer in women under 25 years of age and is increasing in incidence. While PTC is often slow-growing and surgically resectable, recurrence years to decades after initial surgery occurs in ~20% of patients (now only in their 40s/50s), with mortality of 38-69%. The identification of both prognostic biomarkers and actionable therapeutic targets for high-risk PTC at diagnosis is critically important and an unmet need. RNASeq analysis of 45 PTC and matched normal patient tissues from our biobank identified collagen 26A1 (COL26A1) as significantly upregulated in patients with higher risk extrathyroidal extension, lymph node metastasis, and multifocal tumors, compared to those with localized disease. Kaplan Meier survival curves of The Cancer Genome Atlas (TCGA) data confirmed that increased COL26A1 expression significantly decreases survival probability by 25% (p=0.0086). Further analyses of TCGA data indicated that COL26A1 expression significantly correlated with clinical attributes including MACIS score (q=0.001), differentiation score (q=0.025), and tumor stage (q=0.025). Data from our in vitro culture PTC model system indicated that COL26A1 expression was increased 3X in PTC cell line K1, compared to immortalized “normal” thyroid epithelial cells, NThy-ori-3-1. Two CRISPR guides designed to target COL26A1 introduced into K1 resulted in repression of COL26A1 RNA and protein levels by 50% and 70%, respectively. COL26A1 repression decreased critical tumor phenotypes of aggressiveness and metastasis including proliferation (30%), clonogenicity (33%), anchorage-independent growth (37%), cell motility (43%), invasion (30%) and migration (33%). Cell-to-cell adhesion and cell-matrix adhesion also decreased (36% and 25%, respectively). Thus, COL26A1 may have use as a prognostic marker and actionable target for small molecule inhibitors in PTC. Citation Format: Michelle Carnazza, Danielle Quaranto, Nicole DeSouza, Sina Dadafarin, Augustine Moscatello, Jan Geliebter, Raj K. Tiwari. Collagen COL26A1 promotes papillary thyroid cancer invasion and metastasis and correlates with poor survival and clinical outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1397.

Colon Cancer with Thyroid Metastasis – A Case Report

Introduction: Metastasis in the thyroid itself, is unusual, represents 1.5-7.5% of malignant thyroid lesions and the original site of the colon is rare, around 0.1% incidence. The objective is to report the case of a patient diagnosed with colorectal cancer which progressed to thyroid disease. Case Report: It is a 62-year-old male patient who was being followed up at the Cancer Hospital of Londrina due to the resected colon neoplasm, which evolved with disease recurrence for the liver and lung and was controlled with systemic chemotherapy. It evolved with progression to thyroid and it was opted for diagnostic surgical resection. Conclusion: In the case demonstrated, it is a rare presentation of colon cancer metastasis and there is no current literature which would be a better therapeutic approach; surgery or palliative systemic chemotherapy. In this scenario, the importance of reporting cases little described in the literature may help in the decision of future conduct.

Thyroid metastasis from cervical carcinoma

There have been very few reports of thyroid metastasis from cervical carcinoma. This article reports a case of metastasis from cervical carcinoma. A 69-year-old woman with a history of cervical cancer presented to our department with right cervical swelling. She had suffered from paralysis of the left recurrent laryngeal nerve after undergoing left hemithyroidectomy 16 years ago. Computed Tomography (CT) and magnetic resonance imaging scans revealed a right thyroid tumor with bilateral enlargement of the cervical lymph nodes. Fluorodeoxyglucose positron emission tomography/CT imaging revealed high uptake in the right thyroid tumor, cervical lymph nodes, and right iliac bone. Fine-needle aspiration cytology revealed atypical epithelial cells with a high nuclear/cell ratio and hyperchromatic nuclei, which resembled cervical cancer cells. Given the risk of airway obstruction and dysphagia, the patient underwent tracheostomy, right hemithyroidectomy, and neck dissection for preserving the quality of life. Pathological examination revealed normal thyroid tissue with p16-positive atypical epithelial cells, which suggested thyroid metastasis from the cervical cancer. The patient has remained alive without any symptoms for 5 postoperative months.

The progress of radiomics in thyroid nodules.

Due to the development of Artificial Intelligence (AI), Machine Learning (ML), and the improvement of medical imaging equipment, radiomics has become a popular research in recent years. Radiomics can obtain various quantitative features from medical images, highlighting the invisible image traits and significantly enhancing the ability of medical imaging identification and prediction. The literature indicates that radiomics has a high potential in identifying and predicting thyroid nodules. So in this article, we explain the development, definition, and workflow of radiomics. And then, we summarize the applications of various imaging techniques in identifying benign and malignant thyroid nodules, predicting invasiveness and metastasis of thyroid lymph nodes, forecasting the prognosis of thyroid malignancies, and some new advances in molecular level and deep learning. The shortcomings of this technique are also summarized, and future development prospects are provided.

Thyroid metastases from colorectal cancer 14 years later: A case report and literature review

Thyroid metastases from colorectal cancer 14 years later: A case report and literature review

Thyroidectomy in dogs with thyroid tumors: Survival analysis in 144 cases (1994-2018).

Few studies have assessed predictors of outcome in dogs with thyroid tumors undergoing thyroidectomy. To estimate the survival and identify prognostic factors in dogs with thyroid tumors treated by thyroidectomy. A total of 144 client-owned dogs with thyroid neoplasia that underwent thyroidectomy. Retrospective study. Data for analysis included hospital attended and year of surgery, signalment, thyroxine concentration, thyroid tumor features (lobe involvement, size, invasiveness, histopathological type), thrombosis, metastasis, additional surgery and therapy, administration of adjuvant chemotherapy. The association of predictors with survival (time from surgery to death) were assessed by calculating cause-specific hazard ratios (HRcs ) and 95% confidence intervals (CI). Causes of death were classified as thyroid-related or because of other cause. Overall median survival time was 802 days (CI95%=723-1015 days); 89 dogs (77.4%) survived >500 days. Metastases were identified at admission in 12 (8.3%) dogs and were associated with higher thyroid cancer-related fatality (HR=5.83, CI95%=1.56-21.78; P= .009). Thrombosis occurred in 40 dogs and was associated with increased risk of death because of other cause (HR=2.73, CI95%=1.18-6.35; P= .019). Nonfollicular carcinoma (HR=4.17, CI95%=1.27-13.69; P= .018) and administration of chemotherapy (HR=3.45, CI95%=1.35-8.82; P= .01) were associated with higher risk of thyroid cancer-relateddeath. Dogs with thyroid tumors undergoing thyroidectomy have a long life expectancy. Despite the rare presence of nonfollicular carcinoma and metastases, thyroidectomy should still be considered in some of these dogs.

Overexpression of the pro-protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling.

Furin belongs to the pro-protein convertases (PCs) family and its aberrant expression has been documented in various types of cancers; however, its role in thyroid cancer remains unclear. We investigated the expression of furin in a large cohort of Middle Eastern papillary thyroid carcinoma (PTC) patient samples and explored its functional role and mechanism in PTC cell lines in vitro and in vivo. Furin overexpression was observed in 44.6% of all PTC cases and was significantly associated with aggressive clinicopathological parameters and poor outcomes. We show that the knockdown of FURIN suppresses tumor growth, proliferation, migration, invasion, spheroid growth, and progression of epithelial-to-mesenchymal transition (EMT) in B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutant cells, whereas its overexpression in BRAF wild-type PTC cell lines reversed the effect. FURIN knockdown in the BRAF mutant cell line led to reduced tumor growth and increased apoptosis. Mechanistically, FURIN knockdown led to MEK/ERK pathway suppression in BRAF mutant cells, although inhibition of MEK did not affect furin expression, which suggests that furin acts through the MEK/ERK pathway. Furthermore, our study revealed the synergistic antitumor effect of furin depletion and anti-MEK inhibitor treatment. Overall, these results indicate that furin is an important prognostic marker in Middle Eastern PTC and that it plays a crucial role in BRAF-associated MAP/ERK pathway activation and tumorigenesis. Furin inhibition could be a potential therapeutic target for aggressive PTC.

The deubiquitinating enzyme UCHL3 promotes anaplastic thyroid cancer progression and metastasis through Hippo signaling pathway.

Yes-associated protein (YAP) is one of major key effectors of the Hippo pathway and the mechanism supporting abnormal YAP expression in Anaplastic thyroid carcinoma (ATC) remains to be characterized. Here, we identified ubiquitin carboxyl terminal hydrolase L3 (UCHL3) as a bona fide deubiquitylase of YAP in ATC. UCHL3 stabilized YAP in a deubiquitylation activity-dependent manner. UCHL3 depletion significantly decreased ATC progression, stem-like and metastasis, and increased cell sensitivity to chemotherapy. Depletion of UCHL3 decreased the YAP protein level and the expression of YAP/TEAD target genes in ATC. UCHL3 promoter analysis revealed that TEAD4, through which YAP bind to DNA, activated UCHL3 transcription by binding to the promoter of UCHL3. In general, our results demonstrated that UCHL3 plays a pivotal role in stabilizing YAP, which in turn facilitates tumorigenesis in ATC, suggesting that UCHL3 may prove to be a potential target for the treatment of ATC.

Asynchronous thyroid metastases of malignant melanoma: report of a rarity

Thyroid metastasization is a very rare phenomenon with a challenging diagnosis. The incidence is 0.36% in all thyroid malignancies and it is reported it would be up to 2% after surgical specimens’ diagnosis. Thyroid metastasization of a malignant melanoma stands with an incidence of 2% in all thyroid secondarism. We report a 41-years old female with cutaneous malignant melanoma resected four years before the start of compressive symptoms secondary to multinodular goiter. Fine-needle-aspiration showed malignant cells of uncertain origin. A total thyroidectomy was performed. Histopathological examination showed multinodular metastases of malignant melanoma. Thyroid metastasis typically presents as a unifocal thyroid mass or nodule and may occur in the absence of a primary tumor diagnosis, thus leading to a misdiagnosis of thyroid primary tumor. Immunostaining and molecular testing are useful in case of doubt. Although metastases generally indicate disseminated disease, some patients may benefit from aggressive thyroid resection surgery when compared to conservative approaches. Newly-diagnosed thyroid mass in any patient with history of malignancy should raise suspicion for metastasizing. Although the overall prognosis of thyroid metastasis is poor, surgery could be an option in some cases with survival improvement or a palliative role.

Thyroid Metastasis from Lung Adenocarcinoma.

HomeRadiology: Imaging CancerVol. 5, No. 2 PreviousNext Images in CancerThyroid Metastasis from Lung AdenocarcinomaTsz-Kit Chow Tsz-Kit Chow Author AffiliationsFrom the Nuclear Medicine Unit, Department of Radiology, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong.Address correspondence to the author (email: [email protected]).Tsz-Kit Chow Published Online:Feb 10 2023https://doi.org/10.1148/rycan.220154MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In

FN1 Promotes Thyroid Carcinoma Cell Proliferation and Metastasis by Activating the NF-Κb Pathway.

Thyroid cancer (THCA) is a common endocrine tumor. This study aims to identify the THCA-related key gene Fibronectin 1 (FN1) by bioinformatics methods and explore its function and regulatory mechanism. Gene Expression Omnibus database (GSE3678, GSE33630, and GSE53157 datasets) was searched for the analysis of differentially expressed genes (DEGs) in THCA tissues v.s. (normal tissues). The enrichment of DEGs was investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways using the DAVID database. Screening the hub gene was performed with the STRING database and Cytoscape software. The expression and survival analyses of these hub genes in THCA were studied with the Gene Expression Profiling Interactive Analysis database. LinkedOmics database was searched for the related signaling pathways regulated by FN1 in THCA. Real-time quantitative reverse transcriptase polymerase chain reaction was adopted to detect the mRNA expression of Fibromodulin, microfibril-associated protein 4, Osteoglycin, and FN1. The cell viability, growth, migration and aggressiveness were examined by Cell counting kit-8, 5-Ethynyl-2 '- deoxyuridine assay, scratch assay, and Transwell assay. The expression levels of NF-κB signaling pathway-related proteins (p-IκB-α, p-IKK-β, NF-κB p65) were detected by Western blot. FN1 mRNA was up-regulated in THCA tissues and cell lines (MDA-T85 and MDA-T41). The high expression of FN1 is relevant to larger tumor diameters and lymph node metastasis in sufferers with THCA. Functional experiments showed that overexpression of FN1 in the MDA-T85 cell line promoted growth, migration and aggressiveness; knockdown of FN1 in MDA-T41 cells inhibited these malignant behaviors. In mechanism, FN1 promoted the expression levels of proteins related with NF-κB signaling pathway and activated NF-κB signaling pathway. FN1 is up-regulated in THCA and facilitates cell growth, migration and invasion by activating the NF-κB signaling pathway. FN1 will be a promising biomarker of THCA and may become a molecular target for THCA treatment.

A Case of Thyroid Gland Metastasis in a Patient with Squamous Cell Lung Cancer

A Case of Thyroid Gland Metastasis in a Patient with Squamous Cell Lung Cancer

Thyroid metastasis presenting as backache and lower limb weakness without any primary tumor - a case report

Background: Differentiated thyroid cancer is the commonest endocrine malignancy. Mortality in the presence of distant metastasis can increase dramatically. Bony metastasis often leads to increased morbidity and mortality. We report a case of a 60-year-old male who had metastatic spread of follicular cancer of the thyroid, without any identifiable primary. Case Presentation: A 60-year-old male presented with backache and weakness of lower limbs due to the collapse of the 11th thoracic vertebra. He underwent laminectomy and internal fixation. The histopathology revealed that it was the metastatic spread of follicular cancer of the thyroid. The histopathology revealed no malignancy in the thyroidectomy specimen. Subsequent administration of radioactive iodine showed a fall in thyroglobulin from 6,000 to 203 ng/ml. Conclusion: In cases of metastasis from an unknown primary, follicular thyroid cancer should be included in the differential diagnosis. Treatment after thyroidectomy can lead to good results.

Clinical characteristics and risk factors of central lymph node and thyroid metastasis in patients with hypopharyngeal carcinoma

ObjectiveOur study sought to analyze the clinical characteristics and risk factors of central lymph node and thyroid metastasis in patients with hypopharyngeal carcinoma. MethodsThe current study included a total of 152 patients who suffered from hypopharyngeal cancer in our hospital from January 2019 to December 2020. Univariate/multivariate Logistic regression analyses were applied to analyze the risk factors of both central lymph nodes and thyroid metastasis in patients with hypopharyngeal cancer. ResultsSignificant differences were found in tobacco use, drinking history, PS score, site of tumor, pT and pN stage, pathological stage, differentiation degree, postoperative calcium ion level and postoperative FT3 level between the thyroid metastasis group and the non-thyroid metastasis group, and between the central lymph node metastasis group and the non-central lymph node metastasis group (P < 0.05). The multivariate logistic regression analysis showed that the risk factors of thyroid metastasis in patients with hypopharyngeal cancer were pathological stage and differentiation degree. ConclusionsPatients with hypopharyngeal cancer complicated by thyroid metastasis or central lymph node metastasis may be associated with tobacco use, drinking history, PS score, site of tumor, pT and pN stage, pathological stage, differentiation degree, postoperative calcium ion level, and postoperative FT3 level. Moreover, the risk factors responsible for central lymph node and thyroid metastasis in hypopharyngeal cancer patients were thought related to pathological stage and differentiation degree.

A machine learning-based approach to predicting the malignant and metastasis of thyroid cancer.

Thyroid Cancer (TC) is the most common malignant disease of endocrine system, and its incidence rate is increasing year by year. Early diagnosis, management of malignant nodules and scientific treatment are crucial for TC prognosis. The first aim is the construction of a classification model for TC based on risk factors. The second aim is the construction of a prediction model for metastasis based on risk factors. We retrospectively collected approximately 70 preoperative demographic and laboratory test indices from 1735 TC patients. Machine learning pipelines including linear regression model ridge, Logistic Regression (LR) and eXtreme Gradient Boosting (XGBoost) were used to select the best model for predicting deterioration and metastasis of TC. A comprehensive comparative analysis with the prediction model using only thyroid imaging reporting and data system (TI-RADS). The XGBoost model achieved the best performance in the final thyroid nodule diagnosis (AUC: 0.84) and metastasis (AUC: 0.72-0.77) predictions. Its AUCs for predicting Grade 4 TC deterioration and metastasis reached 0.84 and 0.97, respectively, while none of the AUCs for Only TI-RADS reached 0.70. Based on multivariate analysis and feature selection, age, obesity, prothrombin time, fibrinogen, and HBeAb were common significant risk factors for tumor progression and metastasis. Monocyte, D-dimer, T3, FT3, and albumin were common protective factors. Tumor size (11.14 ± 7.14mm) is the most important indicator of metastasis formation. In addition, GGT, glucose, platelet volume distribution width, and neutrophil percentage also contributed to the development of metastases. The abnormal levels of blood lipid and uric acid were closely related to the deterioration of tumor. The dual role of mean erythrocytic hemoglobin concentration in TC needs to be verified in a larger patient cohort. We have established a free online tool (http://www.cancer-thyroid.com/) that is available to all clinicians for the prognosis of patients at high risk of TC. It is feasible to use XGBoost algorithm, combined with preoperative laboratory test indexes and demographic characteristics to predict tumor progression and metastasis in patients with TC, and its performance is better than that of Only using TI-RADS. The web tools we developed can help physicians with less clinical experience to choose the appropriate clinical decision or secondary confirmation of diagnosis results.

Metástasis tiroidea como forma de presentación de carcinoma renal de células claras

Resumen El carcinoma renal de células claras es el subtipo histológico más frecuente de los tumores renales, con gran capacidad de provocar metástasis a distancia, siendo el origen más frecuente de metástasis en la glándula tiroidea. Normalmente, las metástasis a este nivel se diagnostican de forma tardía, puesto que la mayoría son de pequeño tamaño y no provocan síntomas, pudiendo ser confundidas al inicio por nódulos benignos. El diagnóstico definitivo se realiza mediante estudio histológico. En cuanto al tratamiento, la cirugía suele ser de elección, salvo en casos diseminados. Se presenta el caso de una paciente mujer de 61 años intervenida de nefrectomía y suprarrenalectomía izquierda por carcinoma renal de células claras tras hallazgo incidental posthemitiroidectomia izquierda por nódulo Bethesda III con AP definitiva de metástasis tiroidea de origen renal.

A rare but very serious disease: Tumors metastasizing to the thyroid in the light of cases

IntroductionMetastasis to the thyroid gland is a rare condition that can pose diagnostic difficulties. The purpose of the present study was to provide an overview of non-thyroid tumors metastasizing to the thyroid based on our institutional experience. Material and methodThe data of the study were obtained by using the pathology database investigating patients diagnosed with tumor metastasis to° the thyroid between 2013 and 2022 at Firat University Hospital and reviewing their medical files. ResultsAs a result of histochemical and immunohistochemical examinations of the thyroid, seven patients were diagnosed with tumor metastasis. Of the seven patients, 3 (42.85%) were female and 4 (57.14%) were male. The median age at which thyroid metastases were detected was 60.71 (52−80). The most common metastatic thyroid tumors of primary origin were kidney (28.5%), lung (28.5%), head and neck malignancies (28.5%) and unknown primary tumors (14.5%). The median time from diagnosis of primary tumor to diagnosis of thyroid metastasis was 26 months (12−36). The longest survival was determined in clear cell renal cell carcinoma, and the shortest survival was determined in lung cancer. ConclusionThyroidal metastases are rare; however, they must be suspected in patients with a previous history of non-thyroid malignancy and a thyroid nodule. The prognosis is quite poor and the overall survival of the patient depends on the type and location of the primary tumor. The most common primary tumors metastasizing to the thyroid are kidney, lung, and head and neck malignancies, and surgery/chemotherapy may be beneficial.

Thyroid metastasis of prostate cancer as a rare entity detected by 68Ga-PSMA PET/CT

Extremely rare cases of thyroid metastasis from prostate cancer (PC) have been reported in the literature. This patient demonstrated an unusual thyroid metastasis from PC detected by 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET/CT and confirmed with histopathologically. Three months after treatment, a 68Ga-PSMA scan to assess treatment response showed partial regression of skeletal metastases and complete regression of soft tissue metastases, including PC, nodal metastases, and thyroid gland.

Anaesthetic Management of Total Thyroidectomy in a Patient with Spinal Cord Compression due to Metastatic Follicular Thyroid Carcinoma

Vascular invasion is characteristic for follicular carcinoma of the thyroid and distant metastasis is common. Spinal cord compression due to metastases of differentiated thyroid carcinoma as the initial presentation is an extremely rare condition. We report a case of asymptomatic metastatic thyroid cancer which presented with spinal cord compression. This patient with metastasized follicular carcinoma of the thyroid to the spinal cord and narrowing of the airway posed many challenges to the anesthetist.

Relationship between pretracheal and/or prelaryngeal lymph node metastasis and paratracheal and lateral lymph node metastasis of papillary thyroid carcinoma: A meta-analysis

ObjectiveWe conducted a meta-analysis to study the relationship between pretracheal and/or prelaryngeal lymph node metastasis and paratracheal and lateral lymph node metastasis in papillary thyroid carcinoma.MethodA systematic literature search was conducted using PubMed, Embase, and the Cochrane Library electronic databases for studies published up to February 2022. The reference lists of retrieved articles were also reviewed. Two authors independently assessed the methodological quality and extracted the data. A random-effects model was used to calculate the overall pooled relative risk. Publication bias in these studies was evaluated using Egger’s test and Begg’s test.ResultsTwenty-five independent studies involving 10,525 patients were included in the meta-analysis. The pooled relative risk for ipsilateral and contralateral paratracheal lymph node metastasis was 3.01 (95% confidence interval [CI]: 1.66, 5.45) and 5.68 (95% CI: 2.50, 12.88), respectively, in patients with pretracheal lymph node metastasis. Among patients with prelaryngeal lymph node metastasis, the pooled relative risk for ipsilateral paratracheal and/or pretracheal contralateral paratracheal, and lateral lymph node metastasis was 2.02 (95% CI: 1.90, 2.14), 2.22 (95% CI: 1.34, 3.67), and 3.85 (95% CI: 2.89, 5.14), respectively.ConclusionPretracheal lymph node metastasis and prelaryngeal lymph node metastasis were significantly associated with an increased likelihood of both ipsilateral lymph node metastasis and contralateral paratracheal lymph node metastasis in papillary thyroid carcinoma. Prelaryngeal lymph node metastasis was positively correlated with the incidence of lateral lymph node metastasis.