Metastatic Thyroid Research Articles

THE ROLE OF CALCITONIN IN THE PREOPERATIVE STAGE AS THE PREDICTOR OF MEDULLARY THYROID CANCER METASTASES

the aim of the stydy was to analyze the detectability of medullary thyroid metastases in patients at treatment and diagnostic stages, to investigate the applicability of serum calcitonin level as predictor of possible presence of medullary thyroid metastases. The study included data from 148 patients who underwent surgical treatment for the initial diagnosis of medullary thyroid cancer. The age of patients ranged from 12 to 83 years, the mean age was 48,2±1,9 years; the distribution by gender was as follows: men – 34 (23%), women – 114 (77%). Patients were divided into two groups depending on the pathomorphological report: 1 group (100 (67,6%) – patients without metastases), 2 group (48 (32,4%) – patients with locoregional metastases). Among 148 studied patients with medullary thyroid cancer, as a result of the histopathological conclusion, in 48 (32,4%) metastases were detected in regional lymph nodes, among which 10 (6,7%) patients had metastases only in the central collector and 38 (25, 7%) –both in the central and lateral collectors. At the preoperative stage, the level of undiagnosed metastases by ultrasound was 64,58% (31 patients). Subsequently, at the intraoperative stage, during the rapid histological biopsy, the number of undiagnosed metastases decreased to 37,5% (18 patients), and in the postoperative period, according to the results of histopathological examination, the remaining patients were diagnosed with the medullary thyroid cancer metastases. Ultrasound helped to detect metastases in 17 patients, which was 35,42% of all detected metastases. At the stage of intraoperative study, the detection of metastases increased and amounted to 30 (62,5%), and in the postoperative period as a result of histopathological examination metastases were confirmed in 48 patients (100%). Quantitative indicators of both detected and undiagnosed metastases at all stages of treatment and diagnostic search are statistically significant (p<0,01). The detection of metastases in the central lymphatic collector (N1a) at the preoperative stage was 2,08%, this index has doubled (to 4,16%) after intraoperative rapid histological conclusion, and after histopathological conclusion the index has increased more than 10 times (20,84 %). This tendency to grow of metastaseses detection was followed also on lateral collectors: N1b and psilateral were observed at 15 (31,2%) patients at the preoperative stage, their number increased to 23 (47,9%) intraoperatively and to 31 (64,6%) postoperatively; N1b contralateral was observed in 1 (2,1%), 5 (10,4%) and 7 (14,6%), respectively. Such a low percentage of metastases detection at the preoperative stage by ultrasound prompted to CT level study as the predictor of possible metastases. We investigated the preoperative basal blood CT value as a marker of the medullary thyroid cancer metastases presence probability. Due to the small number of the group (n=10) with N1a, the association of CT (cut-off level 137 pg/ml) with the possible presence of metastases was not significant (AUC = 0.594), while in the group with N1b there was a more significant difference. Thus, CT cut-off levels of 358 pg/ml for N1b ipsilateral, and 498 pg/ml for N1b contralateral detection of possible metastases in collectors, with AUC: 0.877 and 0.832, respectively, which justifies the importance of the lateral neck dissection in addition to the mandatory central dissection in order to remov possible medullary thyroid cancer metastases. Thus, ultrasound is insufficiently reliable method of metastases verifying in medullary thyroid cancer (DE = 35.4% at d mts <0.6 cm). In the absence of ultrasound data (or fine needle aspiration (FNA) biopsy results) on the presence of metastases to raise awareness of the disease prevalence, to clarify the prognosis of its development it’s important to use the additional criterion – the calcitonin level. Basal calcitonin level is the reliable predictor of the medullary thyroid cancer metastases. Its cut-off level of 137 pg/ml indicates the possible presence of metastases in the central group (N1a) (AUC=0,594). The CT cut-off level – 358 pg/ml (AUC=0,793) suggests the presence of the medullary thyroid cancer metastases (N1a+N1b). CT cut-off levels – 358 pg/ml for N1b ipsilateral, and 498 pg / ml for N1b contralateral (AUC: 0,877 and 0,832), respectively. The calculated values of the countersensitivity test to detect metastases for different levels of basal CT in the preoperative stage in the clinical setting will help the practitioner in deciding on treatment tactics to determine the extent of surgery in patients diagnosed (or suspected) with the medullary thyroid cancer metastases.

Exosomal circular RNA hsa_circ_007293 promotes proliferation, migration, invasion, and epithelial–mesenchymal transition of papillary thyroid carcinoma cells through regulation of the microRNA-653-5p/paired box 6 axis

ABSTRACT Circular RNAs (circRNAs) or exosomes have been reported to exert key regulatory and/or communication functions in human cancer. Nevertheless, current literature on the effects of exosomal circRNAs on tumor invasion and metastasis in thyroid cancer is incomplete. The role of tumor-derived exosomes in driving in vitro papillary thyroid carcinoma (PTC) progression and metastasis requires further investigation. In our study, Exosomes were harvested from PTC patient serum and PTC cell culture medium. Gene expression analysis in PTC cell lines and exosomes was performed with quantitative reverse-transcription polymerase chain reaction. Transwell, wound healing, Western blot assays, and the cell counting kit-8 were applied for functional analysis. Dual-luciferase reporter assay was used to examine the interaction between hsa_circ_007293 (circ007293), microRNA (miR)-653-5p, and paired box 6 (PAX6). Results showed that circ007293 was enriched in exosomes derived from PTC patient serum and cell culture media. Moreover, circ007293 could enter PTC cells through exosomes, and exosomal circ007293 promoted PTC cell epithelial–mesenchymal transition, invasion, migration, and proliferation. circ007293 knockdown reversed the malignant phenotype of PTC cells in vitro. Additionally, circ007293 could competitively bind with miR-653-5p to regulate PAX6 expression. Notably, miR-653-5p overexpression or PAX6 inhibition suppressed the malignant effects of exosomal circ007293. These results evidenced that exosomal circ007293 induced EMT and augmented the invasive and migratory abilities of PTC cells via the miR-653-5p/PAX6 axis, suggesting that it may serve as a promising biomarker for cancer progression.

Squamous cell carcinoma of the uterine cervix metastasising to the thyroid gland: a case report

BackgroundCarcinoma of the uterine cervix (cervical cancer) metastasising to the thyroid gland is a rare phenomenon and only a few cases have been reported. We discuss a patient with cervical cancer presenting with thyroid and cervical lymph node metastasis, exploring the diagnostic difficulty, evaluation and treatment options.Case presentationA previously well 56-year-old female presented with multiple neck lumps for 4 months duration. Examination of the neck revealed multiple firm/hard left cervical lymph nodes with a hard thyroid nodule. There were no abdominal masses however, vaginal examination revealed a hard, unhealthy cervix. Contrast enhanced computed tomography revealed a growth in the uterine cervix with lymph node enlargement in the abdomen, chest and neck along with multiple thyroid nodules. Biopsy of the cervix and cervical lymph node and fine needle aspiration cytology of the thyroid nodules were performed, all revealing a squamous cell carcinoma. Pan-endoscopy performed to rule out any concurrent cancer of the upper aerodigestive tract was negative. The patient was started on palliative therapy, but succumbed to the disease after 6 months.Discussion and conclusionPatients who present with a thyroid nodule along with multiple cervical lymph nodes should be thoroughly assessed for possible metastatic cancers. Metastasis to the thyroid gland indicates a poor prognosis in the background of carcinoma or the uterine cervix. More awareness among the public and primary care providers is necessary regarding freely available screening programmes for early detection of cervical cancer.

Metastatic Clear Cell Renal Carcinoma with Benign Ultrasonographic Findings in the Thyroid Gland

Metastasis to the thyroid gland is rare, and the incidence of thyroid metastasis is from 1.4% to 3% for all thyroid malignancies. The most common metastatic malignancy to the thyroid gland is renal cell carcinoma. Ultrasonography is useful to assess the malignancy risk of thyroid nodules, and the ultrasonographic features of metastatic renal cell carcinoma in the thyroid gland are hypoechoic solid nodules with increased vascularity. Here, we report a case of metastatic clear cell renal carcinoma with benign ultrasonographic features and fine-needle aspiration cytology in the thyroid gland. A 76-year-old woman visited our hospital for surgical management of a growing left thyroid mass. Her history comprised previous left nephrectomy for an unknown reason. Thyroid ultrasonography revealed a well-defined, isoechoic, solid mass. Left thyroidectomy was performed, and the final diagnosis was metastatic clear cell renal carcinoma of the thyroid gland.

MiR-125-5p inhibits thyroid cancer growth and metastasis by suppressing the ERK/PI3K/AKT signal pathway

miR-125-5p inhibits thyroid cancer growth and metastasis by suppressing the ERK/PI3K/AKT signal pathway

Unusual coexistence of late-onset thyroid metastasis from renal cell carcinoma and primary hyperparathyroidism: findings from an 18F-Choline PET/CT and 18F-FDG PET/CT study

Unusual coexistence of late-onset thyroid metastasis from renal cell carcinoma and primary hyperparathyroidism: findings from an 18F-Choline PET/CT and 18F-FDG PET/CT study

Rare Metastasis of Gastric Cancer to the Thyroid Gland: A Case Report and Review of Literature

Background: It is common for patients with gastric cancer to develop distant metastases in the liver, lung, bone, and brain. Although the thyroid also has an abundant blood supply, gastric cancer metastasis to the thyroid is uncommon. Due to the rarity of such metastasis, its clinical features are not well understood. Here, we present the case of a patient with gastric cancer metastasis to the thyroid treated at our hospital.Case Summary: We report the case of a 63-year-old female with a mass in the anterior neck and mild hoarseness for 6 months. The patient underwent proximal subtotal gastrectomy for Siewert III oesophagogastric junction cancer 6 years ago. Subsequently, she received 8 cycles of adjuvant chemotherapy. Her condition was stable until mild hoarseness developed for no apparent reason 6 months prior to presenting at our clinic. Both ultrasonography and computed tomography confirmed a heterogeneous mass in the right lobe of the thyroid gland. Blood thyroid function tests and tumor marker expression levels were normal. Thyroid malignancy was suspected, and the patient underwent a right thyroidectomy. During the surgery, a tumor was found that had invaded the right recurrent laryngeal nerve and trachea. H&E staining and immunohistochemistry results suggested that the cancer cells originated from gastric cancer. The patient was diagnosed with thyroid metastasis of gastric cancer. She refused further treatment and died within 6 months.Conclusion: Metastasis of gastric cancer to the thyroid is rare and is associated with a poor prognosis. Immunohistochemical diagnosis is essential for a conclusive diagnosis. For patients with a history of malignant tumors, the possibility of metastatic thyroid nodules should be ruled out when diagnosing thyroid nodules.

AHNAK2 promotes thyroid carcinoma progression by activating the NF-κB pathway

Thyroid carcinoma metastasis is the main reason for treatment failure; therefore, understanding the regulatory mechanisms of thyroid carcinoma metastasis is critical to treat patients with thyroid carcinoma. The present study aimed to investigate the role of AHNAK Nucleoprotein 2 (AHNAK2) in thyroid carcinoma metastasis. AHNAK2 was found to be upregulated in thyroid carcinoma tissues, especially in metastatic thyroid carcinoma tissues. Patients with high AHNAK2 expression had poor prognosis. AHNAK2 knockdown inhibited thyroid carcinoma migration, invasion, and metastasis. Mechanistic analysis showed that AHNAK2 knockdown reduced thyroid carcinoma progression by inhibiting nuclear factor kappa B (NF-κB) pathway activity. The results identified a novel target to treat metastatic thyroid carcinoma.

Mst2 Overexpression Inhibits Thyroid Carcinoma Growth and Metastasis by Disrupting Mitochondrial Fitness and Endoplasmic Reticulum Homeostasis.

Although the incidence of thyroid carcinoma has increased over the past several decades, it has an excellent prognosis and overall 5-year survival, with a stable mortality rate, except in cases with advanced stages or rare malignant tumor types. Biomarkers have emerged as effective targets of molecular therapy against thyroid carcinoma due to their rapid and convenient detection; however, there has been little clinical application. Macrophage stimulating 2 (Mst2) is a proapoptotic protein with implications in carcinogenesis and metastasis. We found that Mst2 overexpression-induced endoplasmic reticulum (ER) stress in MDA-T32 thyroid carcinoma cells, accompanied by elevated caspase-12 activity, increased apoptotic rate, and reduced cell viability. In addition, Mst2 overexpression contributed to mitochondrial damage, as evidenced by increased mitochondrial oxidative stress and activated the mitochondrial apoptotic pathway. Inhibition of the JNK pathway abolished these effects. These results show Mst2 to be a novel tumor suppressor that induces mitochondrial dysfunction and ER stress via the JNK pathway. Thus, Mst2 could potentially serve as a biomarker for developing targeted therapy against thyroid carcinoma.

Breast metastasis from medullary thyroid carcinoma: a report of a case

BackgroundMetastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis.Case presentationA 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of 18F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of 18F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month.ConclusionAlthough breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.

Revisiting Combination Chemotherapy as a Single Modality Palliative Therapy for Advanced Anaplastic Thyroid Carcinoma-a Single Institution Experience.

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy with dismal outcome especially in metastatic setting. Consensus for ideal treatment of advanced and metastatic ATC remains elusive. This study aimed to analyze the impact of palliative chemotherapy versus supportive care on overall survival in patients with metastatic anaplastic thyroid carcinoma. Patients diagnosed with ATC between the period January 2018 and December 2019 were prospectively followed. The patients opting for palliative chemotherapy received 3 weekly Paclitaxel (175 mg/m2) and Carboplatin (AUC-5). Out of the 31 patients diagnosed with ATC, clinicopathological profile of 29 patients was analyzed (2 patients who underwent upfront surgical resection with curative intent were excluded), out of which 20 patients were included in the survival analysis. The median age of presentation was 55.8 years with male:female ratio 1.9:1. Seventeen out of the total 29 patients presented with anaplastic transformation in long-standing goiter. Nineteen out of 20 (95%) patients presented with distant metastasis with lungs being the most common site. Nodal metastasis was present in all patients. Invasion of the strap muscles (90%) and trachea (80%) was the most common peri-thyroidal tissue invasion followed by invasion of the esophagus (40%), internal jugular vein (30%), and carotid artery (5%). Twelve out of the 20 patients opted for palliative chemotherapy. Overall, median survival from the time of diagnosis was 2.6 months, with median survival in patients receiving chemotherapy 3.1 months and those opting for supportive care 1.6 months (p=0.004). Out of all the factors analyzed, male sex (HR 6.521, 95% CI 1.143-37.206, p value 0.03) and vascular invasion (HR 0.066, 95% CI 0.009-0.499, p value 0.008) were poor prognostic indicators. Palliative chemotherapy showed increased survival benefit in patients with metastatic ATC. Male sex and vascular invasion were found to be significant factors associated with poor outcomes on Cox regression analysis.

The diagnosis and management of multiple Brown tumours in tertiary hyperparathyroidism in the Jaws

AbstractA 56‐year‐old male patient presented to an emergency dental service with multiple intra‐oral swellings. The intra‐oral swellings were seen radiographically as punched out radiolucencies in the upper right first molar region and the lower left second molar region.The patient had a complex medical history which included a diagnosis of chronic kidney disease (CKD), tertiary hyperparathyroidism and papillary thyroid cancer. Thyroid metastasis and Brown tumours were therefore considered as the differential diagnosis. The radiographic appearance favoured Brown tumours. The tumour in the upper right quadrant was excised with histology confirming Brown tumours. Surgical parathyroidectomy was subsequently performed. There was no further surgical intervention undertaken following the parathyroidectomy and over time, both intra‐oral swellings were found well healed with bony infiltration at both sites.

M2‑like tumour‑associated macrophage‑secreted IGF promotes thyroid cancer stemness and metastasis by activating the PI3K/AKT/mTOR pathway.

M2-like tumour-associated macrophages (TAMs) have been demonstrated to promote the growth of anaplastic thyroid carcinoma (ATC). However, the underlying mechanism of M2-like TAMs in ATC remains unclear. Thus, in the present study, the role and mechanism of M2-like TAMs in ATC were investigated. M2-like TAMs were induced by treatment with PMA, plus IL-4 and IL-13, and identified by flow cytometry. Transwell and sphere formation assays were applied to assess the invasion and stemness of ATC cells. The expression levels of insulin-like growth factor (IGF)-1 and IGF-2 were examined by ELISA and reverse transcription-quantitative PCR. Proteins related to the epithelial-mesenchymal transition (EMT), stemness and the PI3K/AKT/mTOR pathway were examined via western blotting. Immunohistochemistry (IHC) was used to detect the expression of the M2-like TAM markers CD68 and CD206 in ATC tissues and thyroid adenoma tissues. It was found that treatment with PMA plus IL-4 and IL-13 successfully induced M2-like TAMs. Following co-culture with M2-like TAMs, the invasive ability and stemness of ATC cells were significantly increased. The expression levels of the EMT-related markers N-cadherin and Vimentin, the stemness-related markers Oct4, Sox2 and CD133, and the insulin receptor (IR)-A/IGF1 receptor (IGF1R) were markedly upregulated, whereas E-cadherin expression was significantly decreased. In addition, the production of IGF-1 and IGF-2 was significantly increased. Of note, exogenous IGF-1/IGF-2 promoted the invasion and stemness of C643 cells, whereas blocking IGF-1 and IGF-2 inhibited metastasis and stemness by repressing IR-A/IGF-1R-mediated PI3K/AKT/mTOR signalling in the co-culture system. IHC results showed that the expression of CD68 and CD206 was obviously increased in ATC tissues. To conclude, M2-like TAMs accelerated the metastasis and increased the stemness of ATC cells, and the underlying mechanism may be related to the section of IGF by M2-like TAMs, which activates the IR-A/IGF1R-mediated PI3K/AKT/mTOR signalling pathway.

Abstract #1002416: Delayed Diagnosis of Metastatic Follicular Thyroid Cancer in a Patient with Multiple Benign Fine Needle Aspirations

Abstract #1002416: Delayed Diagnosis of Metastatic Follicular Thyroid Cancer in a Patient with Multiple Benign Fine Needle Aspirations

A pooled analysis of response to selective RET inhibitors among patients with medullary thyroid cancer with M918T versus non-M918T RET mutations.

6078 Background: Medullary thyroid cancer (MTC) accounts for 1 to 2% of thyroid cancers in the United States; RET alterations occur in >95% of hereditary and 50% of sporadic forms. Up to 80% of patients with sporadic MTC have somatic M918T RET mutations, which is associated with poor prognosis (1). The tyrosine kinase inhibitors (TKIs) cabozantinib and vandetanib are approved to treat patients with MTC regardless of RET status; however, retrospective analyses have suggested that there may be greater benefit in patients with M918T mutations (1,2). Newly approved therapies selpercatinib and pralsetinib, developed for patients with RET mutations, have demonstrated higher response rates than previous first line therapies. In this analysis, we examine the differences in overall response rate (ORR) between patients with MTC with RET M918T non- RET M918T mutations. Methods: An analysis of ORR in patients with MTC with RET M918T mutations with non-M918T mutations was conducted using the efficacy populations used to support the approvals of pralsetinib and selpercatinib using the following groups: Patients who received prior cabozantinib or vandetanib (referred to as “previously treated”). Patients with no prior cabozantinib or vandetanib (“TKI naïve”). All patients regardless of prior therapy. Results: Exploratory analysis of ORR of pooled population of Selpercatinib and Pralsetinib in patients with MTC with RET M918T mutations and non-M918T mutations. 1 Prior vandetanib or cabozantinib. 2 No prior vandetanib or cabozantinib. Two groups of patients were analyzed ( RET M918T mutation and RET non-M918T mutation), with subgroups with respect to prior treatment. Among all patients regardless of prior therapy, the ORR was similar between M918T non-M918T groups. Among previously treated patients, the ORR was lower in the M918T group vs. the non-M918T group, while in the TKI naïve group the ORR was higher in the M918T groups vs the non-M918T group although the 95% CIs overlap in both comparisons. Conclusions: There were no major differences in ORR among mutational subtypes in patients with MTC treated with RET inhibitors, regardless of prior therapy. ORR was similar between patients with M918T and non-M918T mutations. Additional experience in ongoing clinical studies may provide additional data regarding responses across specific mutation types.

CircPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling

BackgroundMedullary thyroid cancer (MTC) represents 13.4 % of all thyroid cancers-related deaths. The treatments for MTC are very limited especially for patients with distal metastasis. Therefore, it is critical to understand the mechanisms of MTC to pursue novel therapeutic avenues. Here, we studied the function of circPVT1/miR-455-5p in MTC.MethodsHuman MTC tissues and cell lines were used. qRT-PCR and Western blotting were employed to measure expression levels of miR-455-5p, circPVT1, CXCL12, and epithelial mesenchymal transformation (EMT)-related proteins. Colony formation assay, flow cytometry, transwell assay, and scratch wound healing assay were used to assess the abilities of cell proliferation, apoptosis, migration and invasion, respectively. Dual luciferase assay and RNA immunoprecipitation were employed to validate interactions of circPVT1/miR-455-5p and miR-455-5p/CXCL12. Nude mouse xenograft model was used to evaluate the effects of shcircPVT1 and miR-455-5p mimics on tumor growth and metastasis in vivo.ResultsmiR-455-5p was reduced in MTC tissues and cells while circPVT1 was elevated. Their levels were correlated with prognosis of MTC. Overexpression of miR-455-5p or sh-circPVT1 suppressed EMT and MTC cell proliferation, migration and invasion. miR-455-5p targeted CXCL12 while circPVT1 sponged miR-455-5p. Knockdown of CXCL12 or CXCL12/CXCR4 signaling inhibitor reversed the effects of circPVT1 overexpression or miR-455-5p inhibitor on EMT and MTC cell proliferation, migration and invasion. Knockdown of circPVT1 or miR-455-5p overexpression repressed MTC tumor growth and lung metastasis in vivo.ConclusionsmiR-455-5p suppresses MTC growth and metastasis by targeting CXCL12/CXCR4 signaling pathway while circPVT1 promotes MTC by sponging miR-455-5p. Our study sheds light on the mechanisms of MTC growth and metastasis.

Generation of Adult Stem Cell Derived Organoid Cultures From Thyroid Follicular Cells

Abstract The thyroid is essential for maintaining systemic homeostasis by regulating thyroid hormone concentrations in the bloodstream. Due to the limited number of representative model systems, there is limited understanding of fundamental thyroid biology as well as thyroid carcinogenesis. To fill the caveats in the understanding of thyroid cell biology, we aimed to develop an adult stem cell-derived three-dimensional (3D) organoid culture system using murine and human thyroid follicular cells (TFCs). We have succeeded to grow such an organoid culture system that harbours the complete machinery of hormone production visualised by the presence of colloid in the lumen and essential transporters and enzymes in a polarised cell layer. Both the established murine as human thyroid organoids express canonical thyroid markers PAX8 and NKX2.1/TTF1. Moreover, the thyroid hormone precursor thyroglobulin is expressed in both cultures to similar levels as in tissue. Extensive characterisation furthermore identifies known and new biological insights in TFC subclassification, subcellular organisation and hormone production using state-of-the art techniques like single cell RNA sequencing, transmission electron microscopy and genome editing. These 3D in vitro cultures allow for a variety of thyroid-related studies including the progression of wild type cells towards cancer. Additionally, due to the success of generating patient-specific tumour organoids of primary differentiated thyroid carcinoma and metastasis, insights in drug resistance and metastases can be identified. In short, this newly developed organoid culture of murine and human wild type TFCs as well as tumour tissue opens up an extensive area of research that will help understand the drivers for growth and development of thyroid (cancer) cells and enable studies upon drug responsiveness.

Thyroid metastasis from lung carcinoid detected by 68Ga-DOTATOC PET/CT

Thyroid metastasis from lung carcinoid detected by 68Ga-DOTATOC PET/CT

Dual-source dual-energy thin-section CT combined with small field of view technique for small lymph node in thyroid cancer: a retrospective diagnostic study.

To evaluate the diagnostic performance of quantitative spectral parameters derived from dual-source dual-energy CT at small field of view (FOV) for small lymph node metastasis in thyroid cancer. This was a retrospective diagnostic study. From 2016 to 2019, 280 patients with thyroid disease underwent thin-section dual-source dual-energy thyroid CT and thyroid surgery. The data of patients with lymph nodes having a short diameter of 2-6 mm was analyzed. The quantitative dual-energy CT parameters of targeted lymph nodes were measured, and all parameters between metastatic and non-metastatic lymph nodes were compared. These parameters were then fitted to univariable and multivariable binary logistic regression models. The diagnostic role of spectral parameters was analyzed by receiver operating characteristic (ROC) curves and compared with the McNemar test. Small FOV CT images and a mathematical model were used to judge the status of lymph nodes respectively, and then compared with the golden criterion-pathological diagnosis. The cut-off value of the model was 0.4419, with a sensitivity of 90.2% and a specificity of 92.7%. Of the 216 lymph nodes investigated in this study, 52.3% and 23.6% had a short diameter of 2-3 and 4 mm, respectively. Multiple quantitative CT parameters were significantly different between benign and malignant lymph nodes, and binary regression analysis was performed. The mathematical model was: p=ey/(1+ ey), y=-23.119+0.033× precontrast electron cloud density +0.076× arterial phase normalized iodine concentration +2.156× arterial phase normalized effective atomic number -0.540× venous phase slope of the spectral Hounsfield unit curve +1.676× venous phase iodine concentration. This parameter model had an AUC of 92%, with good discrimination and consistency, and the diagnostic accuracy was 90.3%. The diagnostic accuracy of the CT image model was 43.1%, and for lymph nodes with a short-diameter of 2-3 mm, the diagnostic accuracy was 22.1%. The parameter model showed higher diagnostic accuracy than the CT image model for diagnosing small lymph node metastasis in thyroid cancer, and quantitative dual-energy CT parameters were very useful for small lymph nodes that were difficult to be diagnosed only on conventional CT images. This study is retrospectively registered, and we have registered a prospective study (Registration number: ChiCTR2000035195; http://www.chictr.org.cn).

Recurrent follicular thyroid carcinoma presenting as a cutaneous lesion. An unusual case of pigmented skin lesion.

Follicular thyroid carcinoma most commonly metastasises to the lungs, liver, and non-cranial bones. Where skin metastases have occurred, this has been in the context of diffuse metastatic disease, and most commonly occur in the scalp. Cutaneous deposits in the neck have been described in papillary thyroid carcinoma, but we believe this to be the first description of cancer recurrence presenting as cutaneous metastatic follicular thyroid carcinoma. A pigmented skin lesion in a patient with a history of thyroid cancer could represent a metastasis and should be treated with suspicion.