Multifocal Nonmetastatic Radioactive Iodine Avidity on Whole Body Scan After Thyroidectomy for Thyroid Cancer.

Background/Objective: Non-metastatic radioactive iodine (RAI) uptake can complicate the interpretation of whole-body scan (WBS) for differentiated thyroid carcinoma (DTC) post-thyroidectomy. We present a patient with DTC whose follow-up WBS showed nonmetastatic multifocal avidity in skeletal tissue, an uncommonly reported site of RAI uptake. Case report: A 42-year-old woman underwent a right hemithyroidectomy, followed by completion thyroidectomy and RAI remnant ablation therapy, for a 4.8 cm thyroid tumor consistent with stage pT3aNxMx follicular thyroid cancer. Follow-up WBS showed intense activity in the thyroid bed, right breast, left medial subcortical acetabulum, and several vertebral bodies. Her biochemical and clinical findings were not suggestive of cancer recurrence. Further workup with SPECT/CT and MRI showed no focal vertebral lesions and identified the left femoral lesion as a benign peripheral nerve sheath. Diagnostic mammography and ultrasound showed no evidence of suspicious breast lesions. Neck ultrasound was clear with no suspicious masses or pathologic lymphadenopathy. She remained in remission on continued active surveillance. Discussion: Nonmetastatic RAI uptake on WBS has many causes, including functional sodium-iodide symporter expression in nonthyroidal tissues, radioiodine accumulation in tissues and bodily fluids, and benign tumors. False-positive uptake can decrease the utility of post-treatment WBS in low-risk patients. Careful clinical examination, biochemical and radiologic follow-up, and close active surveillance can help distinguish false-positive uptake from metastatic or recurrent disease. Conclusion: We describe an uncommon case of RAI uptake in skeletal tissues after thyroidectomy for DTC, and we outline the steps taken to rule out underlying metastases.

An update on redifferentiation strategies for radioactive iodine-refractory differentiated thyroid carcinoma.

PURPOSE: Although most patients with differentiated thyroid carcinoma (DTC) have an excellent prognosis, a subset will experience radioactive iodine refractory (RAI-R) disease, associated with recurrence, distant metastases and worse prognosis. In recent years, redifferentiation has emerged as an attractive approach for patients with RAI-R DTC, a strategy to induce iodine uptake in RAI-R DTC tumor cells and ultimately prolong time to initiation of systemic therapy. METHODS: An overview and critical appraisal of the existing literature on redifferentiation will be presented in this review under the lens of the genotype-specific targeted therapy administered with redifferentiation intent. RESULTS/CONCLUSIONS: Due to the significant heterogeneity across studies, it will be key to harmonize research methodology and support future larger, multicenter prospective trials in order to identify the most suitable candidates for this therapeutic strategy.

Dynamic estimates of survival of patients with poorly differentiated thyroid carcinoma: a population-based study.

Background: The real-time prognostic data of patients with poorly differentiated thyroid carcinoma (PDTC) after surviving for several years was unclear. This study aimed to employ a novel method to dynamically estimate survival for PDTC patients. Methods: A total of 913 patients diagnosed with PDTC between 2014 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database, was recruited in our study. Kaplan-Meier method was used to estimate the overall survival (OS). The conditional survival (CS) outcomes of PDTC were analyzed and CS rates were calculated using the formula CS(y/x) = OS(y+x)/OS(x), whereby CS(y/x) denotes the probability of a patient enduring an additional y years subsequent to surviving x years following the diagnosis of PDTC. The least absolute shrinkage and selection operator (LASSO) regression was employed to identify prognostic predicters and multivariate Cox regression was utilized to develop a CS-nomogram. Finally, the performance of this model was evaluated and validated. Results: Kaplan-Meier survival analysis unveiled patient outcomes demonstrating an OS rate of 83%, 75%, and 60% respectively at the end of 3, 5, and 10 years. The novel CS analysis highlighted a progressive enhancement in survival over time, with the 10-year cumulative survival rate progressively augmenting from its initiation of 60% to 66%, 69%, 73%, 77%, 81%, 83%, 88%, 93%, and finally 97% (after surviving for 1-9 years, respectively) each year. And then 11 (11/15) predictors including age at diagnosis, sex, histology type, SEER stage, T stage, N stage, M stage, tumor size, coexistence with other malignancy, radiotherapy and marital status, were selected by LASSO analysis under the condition of lambda.min. Multivariate Cox regression analysis further highlighted the significant impact of all these predictors on the OS of PDTC and we successfully established and validated a novel CS-nomogram for real-time and dynamic survival prediction. Conclusions: This was the first study to analyze the CS pattern and demonstrate a gradual improvement in CS over time in long-term PDTC survivors. We then successfully developed and validated a novel CS-nomogram for individualized, dynamic, and real-time survival forecasting, empowering clinicians to adapt and refine the patient-tailored treatment strategy promptly with consideration of evolving risks.

The Definition of Recurrence of Differentiated Thyroid Cancer: A Systematic Review of the Literature.

Background: Recurrence is a key outcome to evaluate the treatment effect of differentiated thyroid carcinoma (DTC). However, no consistent definition of recurrence is available in current literature or international guidelines. Therefore, the primary aim of this systematic review was to delineate the definitions of recurrence of DTC, categorized by total thyroidectomy with radioactive iodine ablation (RAI), total thyroidectomy without RAI and lobectomy, to assess if there is a generally accepted definition among these categories. Methods: This study adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In December 2023, a systematic literature search in MEDLINE and EMBASE was performed for studies reporting on the recurrence of DTC, from January 2018 to December 2023. Studies that did not provide a definition were excluded. Primary outcome was the definition of recurrence of DTC. Secondary outcome was whether studies differentiated between recurrence and persistent disease. Two independent investigators screened the titles and abstracts, followed by full-text assessment and data extraction. The study protocol was registered in PROSPERO, CRD42021291753. Results: In total, 1450 studies were identified. Seventy studies met the inclusion criteria, including 69 retrospective studies and 1 randomised controlled trial (RCT). Median number of patients in the included studies was 438 (range 25-2297). In total, 17 studies (24.3%) reported on lobectomy, 4 studies (5.7%) on total thyroidectomy without RAI, and 49 studies (70.0%) with RAI. All studies defined recurrence using one or a combination of four diagnostic modalities cytology/pathology, imaging studies, thyroglobulin (-antibodies), and a predetermined minimum tumor-free time span. The most common definition of recurrence following lobectomy was cytology/pathology-proven recurrence (47.1% of this subgroup), following total thyroidectomy with RAI was cytology/pathology-proven recurrence and/or anomalies detected on imaging studies (22.4% of this subgroup). No consistent definition was found following total thyroidectomy without RAI. Nine studies (12.9%) differentiated between recurrence and persistent disease. Conclusion: Our main finding is that there is no universally accepted definition for recurrence of DTC in the current studies across any of the treatment categories. The findings of this study will provide the basis for a future, international Delphi-based proposal to establish a universally accepted definition of recurrence of DTC. A uniform definition could facilitate global discussion and enhance the assessment of treatment outcomes regarding recurrence of DTC.

Consider or not consider: the unsolved question on the use of radioactive iodine for differentiated thyroid cancer with low to intermediate risk of recurrence.

BACKGROUND: Surgery stands as the cornerstone treatment for differentiated thyroid cancer (DTC). After surgery, radioactive iodine (RAI) administration is primarily recommended for high-risk patients and commonly employed to address residual disease or mitigate the risk of recurrence. However, the optimal application of RAI in cases categorized as low to intermediate risk is still uncertain. This study aims to assess the indication of post-surgical RAI treatment specifically in patients diagnosed with DTC falling within the low to intermediate risk category for recurrent disease. METHODS: retrospective analysis of consecutive patients with DTC falling within the low to intermediate risk category for recurrence and diagnosed between 2009-2015. Patients were categorized into either treated or untreated with RAI. Treatment effect was assessed by the inverse-probability weighted regression adjustment (IPWRA), by balancing the distribution of factors influencing outcome and treatment assignment. RESULTS: after surgery, 328 patients (69.9%) were treated with RAI while 141 (30.1%) were left untreated. Across the entire cohort, 44 individuals (9.4%) displayed biochemical or structural disease after a median time of 17.5 months following diagnosis. Recurrent disease was more prevalent in patients who underwent RAI treatment compared to those untreated (12.5% vs 2.1%, respectively, p < 0.001). Factors independently associated with recurrent disease, identified through multivariate logistic regression analysis, included lymph node metastases (pN1) (OR = 4.07; 95% CI 1.84-8.97), male sex (OR = 2.71; 95% CI 1.31-5.59), tumor size (OR = 1.03; 95% CI 1.00-1.06), and microscopic extrathyroidal extension (OR = 2.36; 95% CI 1.15-4.81). IPWRA analysis revealed that the occurrence of recurrent disease was 9.6% (95% CI = 6.3-12.9) in RAI-treated patients and 15.9% (95% CI = 11.1-20.71) in untreated patients (p = 0.021). As a consequence, if all patients underwent RAI treatment, the estimated risk of recurrence would be reduced by 42% (RR = 0.58; 95% CI = 0.35-0.91, p = 0.018). The greatest benefit was observed in patients with 2 intermediate risk factors. CONCLUSIONS: These results suggest that treatment with RAI in low to intermediate DTC can reduce the risk of recurrence in selected patients. However, definitive answers regarding whether to consider RAI therapy for this category of patients can only be attained through prospective clinical trials. Up to date these results recommend a meticulous assessment of tumor characteristics at diagnosis to guide the decision regarding RAI administration.

MRI features of histological subtypes of thyroid cancer in comparison with CT findings: differentiation between anaplastic, poorly differentiated, and papillary thyroid carcinoma.

PURPOSE: This study aimed to evaluate the MRI features of the main histological subtypes of thyroid cancer and enable differentiation between anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), and papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: This study included 79 patients with histopathologically proven thyroid cancer (14 ATCs, 8 PDTCs, and 57 PTCs) who underwent neck MRI. MRI images were retrospectively reviewed and compared between the three pathologies. RESULTS: The maximum diameter was larger in ATCs and PDTCs than in PTCs (65.2 mm and 38.4 mm vs. 26.0 mm, p < 0.01). The signal intensity ratio of the solid components on T2-weighted images (T2WIs) was higher in ATCs than in PTCs (1.13 vs. 0.89, p < 0.05). The predominant signal intensity of the solid components on T2WI exhibited hyperintensity relative to the spinal cord in ATCs more frequently than in PTCs (71% vs. 30%, p < 0.01), whereas hypointensity was more frequent in PTCs than in ATCs and PDTCs (60% vs. 0% and 13%, p < 0.01). Intratumoral ring-shaped hypointensity on T2WI was more frequent in ATCs than in PDTCs and PTCs (64% vs. 13% and 18%, p < 0.01). An ill-defined margin was more frequent in ATCs and PDTCs than in PTCs (93% and 63% vs. 25%, p < 0.01). Extrathyroidal extension, tracheal invasion, esophageal invasion, vascular invasion, and venous thrombosis were more frequently observed in ATCs than in PTCs (p < 0.05). CONCLUSIONS: MRI could characterize the differences between ATCs, PDTCs, and PTCs.

Pralsetinib as neoadjuvant therapy for RET-Altered differentiated thyroid cancer: Two case reports.

BACKGROUND: 5-10% of thyroid cancers are at locally advanced stage. Neoadjuvant targeted therapy will likely create surgical opportunities for these patients with unresectable or borderline resectable tumors. Pralsetinib, a RET inhibitor, has been approved for advanced or metastatic RET-altered thyroid cancer. However, there is no evidence on the efficacy of pralsetinib as neoadjuvant therapy in locally advanced RET-altered thyroid cancer. CASE REPORT: Two patients with locally advanced pappilary thyroid carcinoma (PTC) were treated with pralsetinib (400 mg daily) to reduce tumor size and increase the chance of R0 resection. Both PTCs, characterized by RET-fusion, underwent successful R0 resection without major surgical complications after 4-months neoadjuvant pralsetinib. CONCLUSION: There is a potential for pralsetinib as a neoadjuvant treatment in PTC with RET-fusion.

Predictive value of hematologic parameters and clinicopathological features of poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma.

PURPOSE: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are rare, aggressive thyroid cancers with poor prognosis. At present, there are a limited number of research reports on PDTC and ATC. The study aimed to analysis the predictive value of hematologic parameters and clinicopathological features of PDTC and ATC. METHODS: This study retrospectively analyzed 67 patients at Tianjin Medical University Cancer Hospital from 2007 to 2019. We analyzed the clinicopathological features and survival outcomes of PDTC and ATC. RESULTS: This study showed that positive D-dimer, a high NLR, and a high PLR were more common in death patients. At the end of follow-up, 22 (32.8%) patients were alive at the time of study and 45 (67.2%) patients died from thyroid carcinoma. Disease-related death rates were 93.8% in ATC and 42.9% in the PDTC group. The median overall survival (OS) was 2.5 (0.3-84) months for patients with ATC, and 56 (3-113) months of PDTC patients. Univariate analysis showed that age at diagnosis and surgery were associations with OS in ATC patients, what's more, age at diagnosis, a high NLR, a high PLR, and positive D-dimer were associations with OS in PDTC patients. Multivariate analysis revealed that age at diagnosis was an independent association with OS in ATC patients. CONCLUSIONS: The hematologic parameters and clinicopathological features may provide predictive value of prognosis for patients with PTDC and ATC.

Predictive Factors of Radioactive Iodine Therapy Refractoriness in Patients with Differentiated Thyroid Carcinoma.

Aim Differentiated thyroid carcinoma (DTC) is the most prevalent endocrine malignancy, with radioactive iodine (RAI) therapy being a standard of care. However, RAI refractoriness, occurring in a subset of patients, significantly impacts survival rates. Understanding predictive factors for RAI refractoriness is crucial for optimizing patient management. Methods This retrospective study analyzed data from 90 DTC patients at Ibn Sina University Hospital, Morocco. Patients were categorized into RAI-refractory (RAIR) and non-RAIR groups based on established criteria. Statistical analyses, including univariate and multivariate logistic regression, were performed to identify predictive factors of RAI refractoriness. Results Age at the time of diagnosis ≥ 54 years, primary tumor diameter ≥ 29 mm, and distal/nodal metastasis were independent predictors of RAIR-DTC. Additionally, the oncocytic carcinoma histological subtype significantly increased the risk of refractoriness. These findings were consistent with previous studies and underscored the importance of early detection and risk stratification. Conclusion Recognition of predictive factors for RAI refractoriness, including age, tumor size, distal/nodal metastasis, and histological subtype, facilitates early identification of high-risk patients. This enables timely intervention and personalized treatment strategies, particularly relevant in resource-limited settings. Further prospective studies are warranted to validate these findings and explore additional molecular markers for improved prediction of RAI refractoriness.

Poorly Differentiated Thyroid Carcinoma in a 19-Year-Old Young Female Patient: A Case Report.

Poorly differentiated thyroid carcinoma (PDTC) is a rare type of thyroid carcinoma that develops from follicular epithelial cells. In terms of morphology and prognosis, PDTC falls between well-differentiated thyroid carcinoma (WDTC) and anaplastic thyroid carcinoma (ATC). The spectrum of malignant thyroid tumors originating from follicles ranges from the fatal ATC at one end to the indolent WDTC at the other. We present a case of a 19-year-old female patient complaining of swelling on the right side of the neck. Computed tomography revealed a solid cystic lesion within the right lobe of the thyroid gland. The diagnosis of PDTC was made through histopathological examination. In this case, we evaluated the histological characteristics of the right lobe of the thyroid gland and presented a case report of PDTC in a young female.

Prognostic factors of papillary and follicular carcinomas based on pre-, intra-, and post-operative findings.

Abstract: Papillary and follicular thyroid carcinomas (PTC and FTC) are prominent malignancies that originate from thyroid follicular cells. PTC is usually diagnosed via preoperative cytology, and large tumor size, clinical node metastasis, and distant metastasis constitute preoperative prognostic factors. Gross extrathyroidal and extranodal tumor extensions have a significant prognostic impact, are evaluated intraoperatively, and are useful for determining the extent of surgery. Aggressive variants, such as tall cell and hobnail variants, a high Ki-67 labeling index (LI), and somatic gene mutations are prognostic factors in postoperative pathological and molecular examinations. In contrast, FTC is generally diagnosed based on postoperative pathology. Large tumor size and M factors have prognostic value; however, the findings of pathological examinations are very important. FTCs are classified as minimally invasive, encapsulated angioinvasive, and widely invasive FTCs. Widely invasive FTC with vascular invasion (VI) and encapsulated angioinvasive FTCs with extensive VI have a poor prognosis, whereas widely invasive FTC without VI has an excellent prognosis, which is similar to that of minimally invasive FTC. This indicates that VI is a considerably more important prognostic marker than capsular invasion. For postoperative follow-up, dynamic markers such as the thyroglobulin-doubling rate (DR), metastatic tumor volume-DR, and change in the neutrophil-to-lymphocyte ratio are important and are useful for evaluating the effectiveness of treatments, such as radioactive iodine therapy and molecular targeted therapy, for recurrent lesions. For clinicians, it is important to accurately evaluate prognostic markers of PTC and FTC in the pre-, intra-operative, and post-operative phases.

Experience in a PHTS Expertise Centre: Yield of Thyroid Ultrasound Surveillance in Children with PTEN Hamartoma Tumor Syndrome.

Objective: Children with PTEN hamartoma tumor syndrome (PHTS) are at increased risk for developing thyroid abnormalities, including differentiated thyroid carcinoma (DTC). The Dutch PHTS guideline recommends ultrasound surveillance starting from age 18. Since the literature describes PHTS patients who developed DTC before age 18, the Dutch PHTS expertise centre has initiated annual ultrasound surveillance starting from age 12. The purpose of this study was to identify the yield of thyroid ultrasound surveillance in children. Methods: A retrospective single centre cohort study was conducted. Pediatric PHTS patients who received thyroid ultrasound surveillance before age 18 between 2016-2023 were included. Patients' medical records have been reviewed. Primary outcomes included prevalence and time to develop thyroid nodules ≥10mm, nodular growth, goiter, thyroiditis and DTC. Descriptive statistics and Kaplan-Meier analyses were performed. Results: Forty-three patients were included. Two patients (5%) were diagnosed with DTC at ages 12 and 17. Both DTCs were identified as minimally invasive follicular carcinoma at stages pT3NxMx and pT1NxMx respectively. A total of 84% were diagnosed with thyroid abnormalities at a median age of 12 years (range 9-18). Most common findings were benign, including nodular disease (74%), goiter (30%) and autoimmune thyroiditis (12%). Nodular growth was observed in 14 patients (33%) resulting in (hemi)thyroidectomy in 7 patients (16%). Conclusion: Thyroid ultrasound surveillance resulted in the detection of DTC in 2/43 PHTS patients before age 18. These findings support the recommendation to initiate thyroid ultrasound surveillance in children at least from age 12, preferably within an expertise centre.

Challenges in treating radioiodine-refractory thyroid cancer: a global perspective with a focus on developing nations in Latin America.

PURPOSE: This article aims to comprehensively analyze the unique challenges in managing patients with metastatic Differentiated Thyroid Cancer (DTC) that develop radioiodine-refractory disease, especially in developing countries in Latin America. We discuss key contentious aspects of their treatment, such as the optimal timing for initiating systemic therapy, the choice of first-line medications, the appropriate timing for requesting molecular interrogation, and the challenges associated with accessing these drugs and molecular panels. METHODS: To illustrate these challenges and enhance understanding, we present five real clinical cases from the authors' experiences. RESULTS: Patients with Differentiated Thyroid Cancer (DTC) generally have an excellent prognosis, with an overall 10-year survival rate exceeding 97%. However, approximately 5% of DTC patients, especially those with distant metastases, may develop radioiodine-refractory disease, reducing survival rates. Access to medications remains difficult and time-consuming, particularly for patients within the public healthcare system. Urgent discussions on drug pricing involving all stakeholders are imperative. To break free from complacency, stakeholders must prioritize patient well-being by advocating for evidence-based drug pricing, increased participation in clinical trials, and streamlined regulatory processes. CONCLUSION: Beyond the recognized need for prospective randomized clinical trials to determine the optimal first-line drug and the timing of molecular testing, this type of manuscript plays a pivotal role in stimulating discussions and disseminating comprehensive knowledge about the challenges associated with treating and monitoring patients with radioiodine-refractory thyroid carcinoma, especially in developing countries.

Defining angioinvasion and lymphatic invasion in papillary thyroid carcinoma: morphological criteria, utility of D2-40/CD31/ERG immunohistochemistry and correlation with clinicopathological characteristics.

AIMS: While CAP and ICCR protocols mandate the separation of angioinvasion (AI) and lymphatic invasion (LI) in thyroid carcinoma, distinction between them can be difficult. Because the presence of AI is used to stratify patients with papillary thyroid carcinoma (PTC), there is a need to accurately diagnose AI and LI. METHODS AND RESULTS: AI and LI were evaluated in 162 cases of PTC (n = 155) and high-grade differentiated thyroid carcinoma, papillary phenotype (HGDTCp, n = seven) using haematoxylin and eosin (H&E), D2-40 and CD31/ERG. In encapsulated carcinomas, vascular invasion (VI) was only of AI nature. Infiltrative carcinomas showed LI (46 of 131, 35%) and AI (19 of 131, 16%). The frequency of nodal metastasis (NM) and large volume of NM was 93 and 85%, respectively, in tumours with LI, and 39 and 26%, respectively, in those without LI. Luminal red blood cells and smooth muscle in the wall of large-calibre vessels were not reliable criteria to exclude LI and were seen in 23 and 6% of LI, respectively. LI was an independent predictor for NM, whereas AI is an independent predictor for distant metastasis at presentation in PTC/HGDTCp. CONCLUSION: VI in encapsulated carcinomas, including follicular variant PTC, is only of AI nature, confirming the position of this variant as a close entity to follicular carcinoma rather than classic PTC, whereas infiltrative PTC/HGDTCp may have LI or, less frequently, AI. As no morphological features reliably distinguish LI from AI, D2-40 and CD31/ERG immunostains should be considered for separating AI from LI when dealing with vascular invasion in an infiltrative PTC.

The Effect of 131I Therapy on the Eradication of Helicobacter pylori in Patients with Thyroid Disorders: A Preliminary Study.

The leading cause of gastritis and its complications is Helicobacter pylori Radioactive iodine (131I) accumulates significantly in the stomach after consumption. On this basis, we decided to determine whether different doses of 131I in the stomach would be effective in eradicating the infection. Methods: All patients with hyperthyroidism or differentiated thyroid carcinoma who were referred for 131I treatment were invited to the study. A stool antigen test was conducted before consumption of 131I (0.15-5.5 GBq) and was repeated 2 mo later to detect H. pylori infection. Results: H. pylori positivity was found in 51.8% (14/27) of the patients. At 2 mo after treatment, 13 of the 14 patients with differentiated thyroid carcinoma or hyperthyroidism who had been identified as positive for H. pylori stool antigen before 131I administration were still positive, representing a nonsignificant eradication rate of 7.1%. Conclusion: Administration of 131I to patients with H. pylori did not show potential to eliminate the infection.

The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review.

BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) has an intermediate prognosis between indolent well-differentiated thyroid carcinoma (TC) and anaplastic carcinoma. Herein, we present a case report with a PDTC component, along with a systematic review of the literature. CASE REPORT: We report a case of a 45-year-old man diagnosed with a PDTC component, along with hobnail and tall-cell variant features positive for BRAFV600E mutation, after a total thyroidectomy and neck dissection. Radioactive iodine (RAI)-131 therapy was applied, but an early recurrence led to complementary surgeries. The anti-Tg rise, the presence of new lymph nodes, and the negative whole-bodyradioiodine scan were suggestive of a radioiodine-resistant tumor. Lenvatinib, sorafenib, dabrafenib/trametinib, cabozantinib and radiotherapy were all administered, controlling the tumor for a period of time before the patient ultimately died post-COVID infection. Systematic Review: We searched PubMed, Scopus, and WebofScience to identify studies reporting clinicopathological characteristics, molecular marker expression, and management of non-anaplastic TC with any proportion of PDTC in adult patients. Of the 2007 records retrieved, 82were included in our review (PROSPERO-ID545847). CONCLUSIONS: Our case, together with the systematic review, imply that a combination of molecular-targetedtreatments may be safe and effective in patients with RAI-resistantBRAF-mutated advanced PDTC when surgery has failed to control tumor progression.

Unusual Metastatic Sites and Radioiodine Uptake in Patients of Differentiated Thyroid Carcinoma with Atypical Clinical Presentations: Utilization of 131 I-Whole-Body Scintigraphy with Regional SPECT/CT.

Differentiated thyroid carcinoma (DTC) usually is slow growing and carries a good prognosis. It most commonly tends to spread locally to regional lymph nodes in 20 to 60% of patients. The presence of distant metastasis impacts overall survival and prognosis. The lungs, bones, and the brain are typically involved in distant sites with less common metastatic sites that include the liver, kidney, skeletal muscle, adrenal glands, bladder, and skin. These unusual sites are rare and pose a diagnostic challenge and impact clinical decision-making to a great extent. The radioiodine 131 I whole-body scintigraphy with single-photon emission computed tomography/computed tomography can provide a thorough investigation of unusual sites of uptake leading to diagnosis of these metastases. We present a case series of DTC showing unusual sites of metastasis and/or radioiodine uptake in urinary bladder, in the third metacarpal bone of left hand and lastly in the forearm at postoperative hypertrophic scar area.

Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells.

Introduction: The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3), specifying the variant proline (P64) to histidine (H64), is known to affect the protein's functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC). Materials and methods: To deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome. Results: Firstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization. Conclusion: Our study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies.

Development and validation of a lung metastases-predicting nomogram for intermediate- to high-risk differentiated thyroid carcinoma patients.

Aim: This research aimed to construct a clinical model for forecasting the likelihood of lung metastases in differentiated thyroid carcinoma (DTC) with intermediate- to high-risk.Methods: In this study, 375 DTC patients at intermediate to high risk were included. They were randomly divided into a training set (70%) and a validation set (30%). A nomogram was created using the training group and then validated in the validation set using calibration, decision curve analysis (DCA) and receiver operating characteristic (ROC) curve.Results: The calibration curves demonstrated excellent consistency between the predicted and the actual probability. ROC analysis showed that the area under the curve in the training cohort was 0.865 and 0.845 in the validation cohort. Also, the DCA curve indicated that this nomogram had good clinical utility.Conclusion: A user-friendly nomogram was constructed to predict the lung metastases probability with a high net benefit.

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Management of Poorly Differentiated Thyroid Cancer and Differentiated High-Grade Thyroid Carcinoma.

Thyroid carcinoma of follicular cell origin exists on a histopathologic and clinical spectrum. The authors focus on the category of tumors that fall between the very favorable well-differentiated thyroid carcinomas and the very unfavorable anaplastic thyroid carcinomas. These intermediately aggressive tumors include poorly differentiated thyroid carcinoma and the newly defined differentiated high-grade thyroid carcinoma. Both diagnoses require certain histopathologic requirements be met in order to accurately identify these tumors post-operatively. Management remains primarily surgical though adjunctive treatments such as molecular targeted therapies (eg, tyrosine kinase inhibitors) and differentiation therapy (to restore tumor response to radioactive iodine) are also becoming available.