Malignant Thyroid Tumors Research Articles

Breast cancer and neoplasms of the thyroid gland: a bidirectional two-sample Mendelian randomization study.

With the rising incidence of breast cancer (BC) and neoplasms of the thyroid gland, a potential link between the two has drawn increasing attention. However, the causal relationship remains unclear due to various confounding factors. This study aims to investigate the causality between BC and thyroid tumors using Mendelian Randomization (MR) analysis. We conducted a bidirectional two-sample MR analysis, utilizing breast cancer-associated single nucleotide polymorphisms (SNPs) from the Breast Cancer Association Consortium (BCAC) and thyroid tumor-related SNPs from the FinnGen (https://www.finngen.fi/) database. First, we performed univariable MR (UVMR) to assess the causal relationship between BC and both malignant and benign thyroid tumors, followed by reverse causality analysis. To account for potential confounders, we applied multivariable MR (MVMR). The inverse-variance weighted (IVW) method was primarily used, with secondary analyses performed using the weighted median and MR-Egger regression approaches. UVMR analysis revealed a significant positive causal relationship between BC and malignant thyroid tumors (odds ratio [OR] and 95% confidence interval [CI]: 1.291, 1.143-1.458, P = 3.90×10-5). No causal relationship was found between BC and benign thyroid tumors. The MVMR analysis, adjusting for confounding factors such as smoking, drinking, and body mass index (BMI), confirmed the robustness of the results. This study provides genetic evidence supporting a causal relationship between BC and malignant thyroid tumors. These findings highlight the importance of thyroid cancer screening in BC patients. However, further MR studies or randomized controlled trials (RCTs) are necessary to assess small effects accurately.

Aggressive Types of Malignant Thyroid Neoplasms.

Differentiated thyroid cancer (DTC) includes many subtypes, which demonstrate favorable to aggressive behavior. During the past decades, efforts have been made to describe aggressive thyroid cancers. Within DTC, aggressive variants constitute rare entities with unique histopathological features and compromised survival, as local and distant metastatic disease is frequent. In recent years, the distinct category of poorly differentiated thyroid cancer was introduced in 2004 and the type of differentiated high-grade thyroid carcinoma was recently added in the 2022 WHO classification of thyroid neoplasms. Finally, anaplastic thyroid cancer exhibits a rapid, resistant to therapy, progression and confers the shortest survival. In this review, we will present the characteristics of these thyroid cancer types and also discuss the treatment, management, and follow-up of these difficult cases. Emphasis was given to recent bibliography of the last decade.

8141 A Rare Case of Follicular Adenoma with Osseous Metaplasia and Mature Bone Formation- Is Surveillance Important?

Abstract Disclosure: K. Madani: None. Y. Al-Khazraji: None. D.H. Sacoto: None. G.K. Rai: None. R. Belokovskaya: None. A.A. Franco-Akel, MD: None. Osseous metaplasia and mature bone formation (MBF) are common in malignant thyroid and parathyroid tumors. It is very unusual to have MBF in a benign tumor-like follicular adenoma, as in the case we describe. We found only twelve such cases reported in the literature, and none addressed the cancer risk or need for surveillance for the development of potential malignancy. Thus, further studies are required to investigate the need for surveillance in patients not undergoing excision and in those with remnant thyroid tissue post-removal of the adenoma for recurrence. A 43-year-old female with history of hyperlipidemia and hypothyroidism had an incidental finding of midline neck mass during the evaluation of a left upper extremity lipoma. Ultrasound of the neck showed two nodules in the Left (L) thyroid lobe: a complex nodule measured 2.2 x 1.2 x 2.1 cm and a calcified nodule measuring 1.5 x 0.8 x 0.6 cm. MRI of the neck revealed a 1.9 cm heterogeneously enhancing nodule in the mid to lower pole of the L thyroid lobe. The patient had symptoms suggestive of compression, such as dysphagia, odynophagia, and hoarseness; thus, left hemothyroidectomy was performed. Tissue biopsy was notable for follicular adenoma with osseous metaplasia and mature bone formation. The patient remained clinically and biochemically euthyroid, with only mildly elevated thyrotropin level, and treatment with levothyroxine 25 mcg once daily was initiated. On post-surgical follow-up, there was a lack of data to support close monitoring modality and strategy for the remnant thyroid lobe and neck nodal compartments. We concluded with the patient to follow up in a clinical visit for a physical exam of the neck and to obtain a follow-up sonogram at an interval of six months, in addition to monitoring TSH levels to guide hypothyroidism therapy. Osseous metaplasia has not been established as a premalignant condition, but in certain tissues like the esophagus, metaplasia is a risk factor for malignant conversion, for instance, in Barrett’s esophagus leading to esophageal adenocarcinoma. Moreover, MBF in thyroid tissue has been attributed to the activity of basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2), which are linked with mitogenesis and tumorigenesis. Thus, the question arises if post-excision surveillance is required in patients with a history of osseous metaplasia in remnant thyroid tissue post-lobectomy or partial thyroidectomy. At this point, more epidemiological data on similar cases may help us understand the true risk of this clinical scenario, in order to develop a reasonable approach for surveillance. Presentation: 6/3/2024

7639 A Rare Cause of Lung Adenocarcinoma with Metastasis to the Thyroid

Abstract Disclosure: E. Echevarria-Torres: None. C.G. Yap: None. K.E. Izuora: None. A rare cause of lung adenocarcinoma with metastasis to the thyroid. Metastasis to the thyroid gland from non-thyroid malignancies is rare. When metastasis occurs, presenting symptoms are typically nonspecific, representing a diagnostic challenge. With the goal of raising awareness, we present a case of lung adenocarcinoma with metastasis to the thyroid. An 85-year-old man with a history of hypertension, hyperlipidemia and 60 years smoking history presented to the endocrine clinic for evaluation of subclinical hyperthyroidism. On the physical exam, there was fullness in the right thyroid area which on ultrasound showing a large right thyroid nodule occupying the entire lobe. There was also a solid 4.5 cm x 3.4 cm x 4.6 cm nodule in the mid-anterior left thyroid lobe. Fine needle aspiration cytology of right nodule revealed malignant cells and cell block material positive for TTF-1 (Thyroid Transcription Factor 1) concerning for malignancy. The left thyroid nodule cytology was consistent with benign follicular nodule. Chest CT ordered for surgical planning showed right upper lobe pleural-based lung opacity measuring 3.7 cm x 2.9 cm with supra clavicular lymphadenopathy. Biopsy of lung mass and supra clavicular lymph nodes revealed primary lung adenocarcinoma involving the lymph nodes consistent with stage Iva (cT3NxM1b). The patient was referred to oncology for further management. Discussion: Metastatic lesions to the thyroid gland account for less than 1 % of all malignant thyroid tumors with most cases found on autopsy. This is hypothesized to be due to the rich blood supply and high iodine content of the thyroid gland. Thyroid metastasis usually presents several years after initial diagnosis and treatment of non- thyroid malignancy. Patients can present with enlarging thyroid nodules, neck swelling, dysphagia and, in rare instances, upper airway obstruction. We present a rare case of lung cancer with metastasis into the thyroid. The thyroid nodule initially palpated upon physical exam led to eventual thyroid ultrasound and subsequently to his diagnosis of lung adenocarcinoma after findings of lung nodule which was biopsied and showed primary lung adenocarcinoma. TTF-1 was also positive which is typically expressed by lung adenocarcinomas. Treatment for thyroid metastasis is surgery, along with treatment of primary malignancy. The earlier the diagnosis and treatment the more favorable the prognosis. Radiotherapy and chemotherapy are other means to reduce the recurrence. Thyroid hormone replacement will be warranted post operatively for hypothyroidism. We present this uncommon case to raise awareness about the presentation of thyroid metastasis to enhance timely diagnosis and intervention. Presentation: 6/1/2024

8728 Radiofrequency Thermal Ablation in Thyroid Microcarcinomas: Experience of the Brazilian Group with 143 Cases

Abstract Disclosure: L.G. Amato: None. P.H. Carani: None. L.D. Volpi: None. A. Rahal: None. E.M. Volpi: None. Introduction: Thyroid nodules are quite prevalent worldwide, with papillary thyroid carcinoma (PTC) being the most common histological subtype of thyroid malignant neoplasm, accounting for approximately 85% of thyroid cancers. When this carcinoma is less than 10 mm in its longest axis, it is defined as papillary thyroid microcarcinomas (mPTCs) which has had an increasing proportion of thyroid cancers and with a disease-specific survival of patients having this diagnosis more than 99% after 10 years of follow-up. Most guidelines concerning thyroid cancer care recommend a lobectomy as the first-line treatment strategy for low-risk unifocal mPTC but often results in aggressive overtreatment. Thyroid surgery comes with significant costs and morbidity rates caused by iatrogenic hypothyroidism and recurrent laryngeal nerve damage, resulting in poor quality of life, justifying the growing search for minimally invasive and effective methods in the treatment of mPTC and in this context Radiofrequency thermal ablation (RFA), a minimally invasive treatment that preserves thyroid function have been proposed for patients with low-risk mPTC. Clinical case: From April 2018 to January 2024, 143 patients with mPTC, were submitted to RFA and patient's follow-up were dated 1, 3, 6, 12 and 18 months after the procedure. During the follow-up we observed 3 (2%), complications, 1 case of permanent paralysis unilateral vocal cord, 1 Horner Syndromes and 1 case of transient paralysis, with total reversal. In all cases there was a reduction in the volume of the node after 6 months of the procedure. Conclusion: The reported incidence rate of postoperative hypothyroidism in patients underwent hemithyroidectomy is 10.9-48.8%, therefore, risks of complications with radioablation in our series were lower than those previously described during hemithyroidectomy. Radiofrequency thermal ablation (RFA) is a minimally invasive treatment that preserves thyroid function with a lower incidence of complications compared to thyroidectomy or lobectomy, and and should be considered the selection procedure for low-risk thyroid microcarcinomas. Presentation: 6/3/2024

Overexpression of NR1D1 portends disease recurrence in thyroid cancer.

Dysregulation of circadian rhythms has been linked to cancer susceptibility. Thyroid cancer cells demonstrate altered circadian oscillations in endogenous clock transcripts. Our previous research identified NR1D1, a component of the circadian clock, as one of the recurrence-associated genes in papillary thyroid cancer. The objective of this study was to investigate the expression pattern of NR1D1 in thyroid cancer and explore its prognostic and translational implications. We assessed NR1D1 expression using immunohistochemical analysis and examined its correlation with clinicopathological parameters. In vitro and in vivo experiments were performed to elucidate the oncogenic roles of NR1D1 and potential mechanisms. Nuclear NR1D1 expression was present in thyroid follicular epithelial-derived cancers, whereas normal thyroid tissue and benign nodular goiter showed no detectable NR1D1 immunoreactivity. Patients with high expression of NR1D1 had more advanced disease stages, extrathyroidal extension, lymphovascular invasion, and shorter recurrence-free survival compared to those with low levels of NR1D1. Through gain- and loss-of-function studies, we demonstrated that NR1D1 modulation affected the growth of organoids, resistance to anoikis, and the invasive and migratory capacity of thyroid cancer cells. The invasion-promoting effect of NR1D1 was regulated by the β-catenin/ZEB1 axis. Moreover, the overexpression of NR1D1 accelerated xenograft growth and lung metastasis in vivo. NR1D1 is overexpressed in malignant thyroid tumors and has prognostic significance. Our findings suggest therapeutic potential in targeting NR1D1 for thyroid cancer.

Evaluation of GARP immunohistochemical expression in papillary thyroid carcinoma

BackgroundGlycoprotein A repetitions predominant (GARP) is a novel transmembrane protein highly expressed on the surface of regulatory T cells (Tregs), which are a subset of immunosuppressive T lymphocytes that play a major role in inhibiting the antitumor immune response. Many studies documented increased GARP expression in various tumors, which is related to a poorer prognosis, and only one single paper investigated its expression in thyroid tumors.AimTo evaluate the immunohistochemical expression of GARP in differentiated thyroid carcinomas and their tumor-infiltrating lymphocytes (TILs) in comparison to its expression in other benign and low-risk lesions.MethodsSixty-nine cases of different thyroid lesions were subgrouped into 37 cases of malignant thyroid neoplasms, 25 cases of benign thyroid lesions, and 7 cases of low-risk neoplasms collected from the Pathology Department Laboratories of Ain Shams University Hospitals during the period from January 2017 to December 2021 and stained immunohistochemically for GARP. Immunohistochemical (IHC) results were evaluated in thyroid epithelial cells and TILs. The expression of GARP was correlated with the different clinicopathological parameters.ResultsGARP expression discloses a significant statistical difference between the three studied groups (P < 0.001). High GARP expression was detected in 89.19% of the malignant cases and in 28.57% of low-risk neoplasms, while all benign lesions exhibited low GARP expression. High GARP expression of TILs was detected in 60% of the malignant cases. Synchronous high GARP expression in tumor tissue and in the surrounding TILs was detected in 63.16% of the malignant cases, yet these results did not reach statistical significance.ConclusionGARP is a marker of Tregs, whose high expression is increased in malignant over benign and low-risk lesions. It might be a potential novel target for anticancer immunotherapy.

Management of Giant Thyroid Tumors in Patients with Multiple Comorbidities in a Tertiary Head and Neck Surgery Center.

Background/Objectives: The thyroid gland can represent the seat of development for giant tumors exceeding 10 cm in diameter. A retrospective analysis on 21 cases of giant thyroid tumors with comorbidities, operated in the ENT Department of the Bucharest University Emergency Hospital has been conducted. Methods: Giant benign tumors accounted for 28.57% of the cases studied and reached gigantic volumes in an average time interval of 3 years, with an average resection piece weight of 318 g. Malignant tumors accounted for 71.43%, with an average duration of evolution of 7 years, with an average resection piece weight of 581 g. Results: Dysphagia was present in all patients, dyspnea in 47.61% and dysphonia in 38.09% of cases. Total thyroidectomy is the gold standard in giant thyroid tumors, associated with radical neck dissection, extended to groups VI and VII in malignant tumors. In 10 of 11 cases of giant malignant thyroid tumors (90.90%), without anaplastic thyroid carcinoma, the survival at 5 years after multimodal oncologic treatment was favorable. Anticoagulant treatment increased the risk of postoperative reversible recurrent laryngeal nerve lesion. Conclusions: The management of giant thyroid tumors in patients with multiple comorbidities needs a multidisciplinary team including endocrinologist, radiologist, anesthesiologist, pathologist, ENT surgeon, thoracic surgeon, oncologist and radiotherapist.

The Genomic Landscape of Benign and Malignant Thyroid Tumors from Individuals Carrying Germline PTEN Variants Is Distinct from Sporadic Thyroid Cancers.

Exome sequencing reveals the distinct mutational landscape of PTEN hamartoma tumor syndrome-associated thyroid cancers from sporadic counterparts, providing insights into tumor progression and behavior that could help improve diagnosis, surveillance, and treatment.

Development of Melanoma and Other Nonkeratinocyte Skin Cancers After Thyroid Cancer Radiation

This cohort study evaluates the association between thyroid malignant neoplasms and melanoma and other nonkeratinocyte skin cancers.

Serum microRNA-146a-5p and microRNA-221-3p as potential clinical biomarkers for papillary thyroid carcinoma

Abstract Purpose Papillary thyroid carcinoma (PTC) is the most common malignant thyroid neoplasm, accounting for approximately 85% of all follicular cell-derived thyroid nodules. This study aimed to assess the diagnostic potential of circulating microRNA-146a-5p and microRNA-221-3p as biomarkers for PTC and their usefulness in monitoring disease progression during patient follow-up. Methods An observational study was conducted on two cohorts of PTC patients and healthy controls (HCs) using digital PCR. We collected patients’ clinical, biochemical, and imaging data during the post-surgery surveillance. We analyzed the levels of circulating miRNAs in serum samples of patients before surgery and during the follow-up, including those with indeterminate/biochemical incomplete response (IndR/BIR) and residual thyroid tissues (Thy Residue). Results Both miR-146a-5p and miR-221-3p were confirmed as effective biomarkers for PTC diagnosis. They enabled differentiation between pre-surgery PTC patients and HCs with an area under the curve (AUC) of 92% and 87.3%, respectively, using a threshold level of 768,545 copies/uL for miR-146a-5p and 389,331 copies/uL for miR-221-3p. It was found that miRNA fold change levels, rather than absolute levels, can be useful during patient follow-up. In particular, we found that a fold change of 2 for miR-146a-5p and 2.2 for miR-221-3p can identify a progressive disease, regardless of the presence of TgAbs or remnant thyroid. Conclusion MiRNA-146a-5p and miRNA-221-3p, particularly the former, could be valuable diagnostic biomarkers for PTCs. They also seem to be effective in monitoring disease progression during patient follow-up by evaluating their fold change, even when thyroglobulin is uninformative.

Utilization of recurrent laryngeal nerve monitoring during thyroid surgery in china: a point prevalence survey (2015-2023).

The survey aimed to elucidate the complete range of national practices, including all technical and non-technical aspects, as well as surgical stratification and maturation, of the use of intraoperative neuromonitoring (IONM) during thyroid surgery in China. Six national questionnaires, developed by the Chinese Neural Monitoring Study Group (CNMSG) between 2015 and 2023, were used to collect and analyze data regarding the clinical application, education, and scientific research related to IONM in Chinese medical institutions. Among the surveyed hospitals, 45% reported an average annual surgical volume exceeding 3,000 cases, with 82.5% performing more than 80% of the surgeries for malignant thyroid tumors. Additionally, 97.5% of the hospitals reported a<3% incidence of postoperative hoarseness with IONM. Statistical analysis from 2011 to 2015 found that the incidence of postoperative hoarseness decreased by 30% in 2013 compared with 2011, when the technology was introduced. Preoperative and postoperative laryngoscopies were routinely performed by 82.5% and 15% of the hospitals, respectively. For 65% of the hospitals, the publication of the Chinese edition of neuromonitoring guidelines in 2013 prompted the utilization of IONM technology. An average annual number of IONM applications exceeding 500 cases (18.5% the average volume) was reported by 80% of the hospitals, while 62.5% reported a cumulative number of applications greater than 5,000 cases (47.1% the average cumulative volume). Regarding technical parameters, 75% of the hospitals reported an intraoperative V1 amplitude of >500µV, and 70% reported an intraoperative loss of signal (LOS) rate of<3%. 92.5% of the surveyed hospitals believed that IONM could help identify dissociated nerves, and 95% of the surveyed hospitals believed that IONM could reduce nerve damage. However, 72.5% of the respondents thought that cost was the main limitation. Furthermore, 67.5% of the hospitals reported that half of their thyroid surgical team members were trained in IONM, with 17.5% reporting that all team members were trained. Areas for reinforced training included IONM research methods and directions (72.5%), and analysis and treatment of abnormal EMG signals (72.5%). Research projects related to IONM were conducted by 42.5% of the hospitals, while 52.5% had published papers on neuromonitoring. IONM was independently and incrementally associated with the annual surgical volume. This survey emphasized the importance of national collaboration and/or a registry for the uptake, consolidation, and development of CNMSG consensus.

Thyroid differentiation score (TDS) can differentiate between malignant and benign thyroid neoplasms

Thyroid differentiation score (TDS) can differentiate between malignant and benign thyroid neoplasms

High-Performance Metabolic Profiling of High-Risk Thyroid Nodules by ZrMOF Hybrids.

Thyroid nodules (TNs) have emerged as the most prevalent endocrine disorder in China. Fine-needle aspiration (FNA) remains the standard diagnostic method for assessing TN malignancy, although a majority of FNA results indicate benign conditions. Balancing diagnostic accuracy while mitigating overdiagnosis in patients with benign nodules poses a significant clinical challenge. Precise, noninvasive, and high-throughput screening methods for high-risk TN diagnosis are highly desired but remain less explored. Developing such approaches can improve the accuracy of noninvasive methods like ultrasound imaging and reduce overdiagnosis of benign nodule patients caused by invasive procedures. Herein, we investigate the application of gold-doped zirconium-based metal-organic framework (ZrMOF/Au) nanostructures for metabolic profiling of thyroid diseases. This approach enables the efficient extraction of urine metabolite fingerprints with high throughput, low background noise, and reproducibility. Utilizing partial least-squares discriminant analysis and four machine learning models, including neural network (NN), random forest (RF), logistic regression (LR), and support vector machine (SVM), we achieved an enhanced diagnostic accuracy (98.6%) for discriminating thyroid cancer (TC) from low-risk TNs by using a diagnostic panel. Through the analysis of metabolic differences, potential pathway changes between benign nodule and malignancy are identified. This work explores the potential of rapid thyroid disease screening using the ZrMOF/Au-assisted LDI-MS platform, providing a potential method for noninvasive screening of thyroid malignant tumors. Integrating this approach with imaging technologies such as ultrasound can enhance the reliability of noninvasive diagnostic methods for malignant tumor screening, helping to prevent unnecessary invasive procedures and reducing the risk of overdiagnosis and overtreatment in patients with benign nodules.

Ki-67 Labelling Index as a Predictor of Invasive Features in Thyroid Cancer: Retrospective Analysis and Implications.

Ki-67 immunostaining is commonly used in neuroendocrine tumors to estimate the proliferative index and for grading. This study investigates its association with the invasiveness of follicular-derived thyroid carcinomas (TCs). A retrospective analysis of patients with TC at three McGill University teaching hospitals between January 2018 and November 2023 was conducted. The inclusion criteria included patients with malignant thyroid tumors and accessible Ki-67 LI data from final pathology specimens. The data collected included patient demographics, Ki-67 LI values, and different invasiveness attributes, such as molecular mutations, the histological subtype, lymphovascular invasion (LVI), extrathyroidal extension (ETE), and positive lymph nodes (LNs). In total, 212 patients met the inclusion criteria, of which 80.7% were females and 19.3% were males. The Ki-67 LI ranged from 1% to 30%, with the majority of the cases within the range of 1-15%. A significant association was observed between higher Ki-67 LI and high-risk histological subtypes of thyroid carcinoma (p < 0.001). Similarly, Ki-67 LI was significantly associated with LVI and positive LN metastasis (p < 0.001 and p = 0.036, respectively). However, no significant association was found between the Ki-67 LI and gene mutations or ETE (p = 0.133 and p = 0.190, respectively). Using percentiles to establish a cutoff, patients with a Ki-67 LI higher than 6.7 showed a higher likelihood of being associated with invasive features. Elevated Ki-67 LI can serve as an indicator of aggressiveness in follicular-derived TC, especially when associated with distinct histological subtypes, LVI and positive LNs.

Effects of disease recurrence on the prognosis of treatment of patients with malignant tumors of the thyroid gland depending on their dissemination and morphological differentiation

In recent years, the number of disseminated malignant tumors of the thyroid gland is growing rapidly, most often with medium or low histological differentiation, which worsens prognosis for patients’ recovery. The most important prognostic factors are the degree of primary tumor dissemination and morphological differentiation of the tumor. Taking into account the great impact of recurrences or prolongation of the disease on the prognosis of treatment, the authors investigated these indicators, and separately the survival in cases when they occur, depending on the degree of tumors’ dissemination and morphological differentiation. Objective — to study the rates of recurrence or prolongation of the disease, as well as their effects on the prognosis of treatment in patients with malignant thyroid tumors, depending on the spread of the primary tumor and the degree of its morphological differentiation. Materials and methods. The study involved 2.300 patients with malignant thyroid tumors after treatment, the rates of recurrence (prolongation) of the disease and survival depending on the occurrence of recurrence (prolongation) were investigated in comparison with the general sample in groups according to the degree of spread of the primary tumor T1—3a, T3b, T4a, and T4b and the degree of morphological differentiation of tumors (high, medium and low). Results. The increase in the percentage of relapses or prolongations of the disease in patients with disseminated thyroid malignant tumors after complex treatment depended on the degree of spread of the primary tumor and the degree of morphological differentiation of the tumor, which significantly worsened the prognosis for patient survival. The difference in survival rates among patients with relapse or prolongation of the disease in comparison with the general group (sample) increased with an increase in the spread of the primary tumor and a decrease in the degree of morphological differentiation of the tumors. Mortality rates at disease recurrences, regardless of their treatment, gradually increased, both with an increase in the spread of the primary tumor, and with a decrease in the degree of morphological differentiation of the tumor, and the worst indicator (0%) of survival was in the T4b group with tumors of low differentiation. Conclusions. The onset of relapse (prolongation) of the disease is a factor that significantly worsens the prognosis of patients, especially with widespread primary tumors of medium and low morphological differentiation. The main factors are the degree of spread of the primary tumor and the degree of morphological differentiation of the tumor.

Aspectos anatomopatológicos de um tumor misto maligno de tireoide com múltiplas metástases em cão

Thyroid tumors are uncommon. Malignant mixed tumor, or carcinosarcoma, is a rare, malignant, infiltrative, and metastatic neoplasm. This paper aims to report a case of a metastatic malignant mixed thyroid tumor in a 10-year-old mixed-breed female dog. The patient presented respiratory symptoms and had an unfavorable evolution of the clinical scenario. It was euthanized and submitted to necroscopic examination, which led to subsequent histopathological and immunohistochemical (IHC) evaluation. The macroscopic evaluation revealed neoformations in the thyroid, lung, heart, kidneys, and abdominal skeletal muscles. Microscopically, the thyroid presented mixed neoplastic cellularity as well as mesenchymal and epithelial cells. Metastases of the mesenchymal component were observed in the kidneys, heart, and musculature, while there was an invasion of neoplastic epithelial cells in the lung. On the IHC, there was positive staining for thyroglobulin, TTF-1, and vimentin. The histopathological and IHC findings indicated a metastatic malignant mixed thyroid neoplasm.

Disease types and pathogenic mechanisms induced by PM2.5 in five human systems: An analysis using omics and human disease databases

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.

RAS-Mutant Follicular Thyroid Tumors: A Continuous Challenge for Pathologists.

The classification of thyroid nodules, particularly those with a follicular growth pattern, has significantly evolved. These tumors, enriched with RAS or RAS-like mutations, remain challenging for pathologists due to variables such as nuclear atypia, invasion, mitotic activity, and tumor necrosis. This review addresses the histological correlates of benign, low-risk, and malignant RAS-mutant thyroid tumors, as well as some difficult-to-classify follicular nodules with worrisome features. One prototypical RAS-mutant nodule is non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The assessment of nuclear characteristics in encapsulated/well-demarcated non-invasive RAS-mutant follicular-patterned tumors helps distinguish between follicular thyroid adenoma (FTA) and NIFTP. Despite this straightforward concept, questions about the degree of nuclear atypia necessary for the diagnosis of NIFTP are common in clinical practice. The nomenclature of follicular nodules lacking clear invasive features with increased mitotic activity, tumor necrosis, and/or high-risk mutations (e.g., TERT promoter or TP53) remains debated. Invasion, particularly angioinvasion, is the current hallmark of malignancy in RAS-mutant follicular-patterned neoplasms, with follicular thyroid carcinoma (FTC) as the model. Assessing the tumor interface is critical, though full capsule evaluation can be challenging. Multiple levels and NRASQ61R-specific immunohistochemistry can aid in identifying invasion. Controversies around vascular invasion persist, with ancillary stains like CD31, ERG, and CD61 aiding in its evaluation. Moreover, the review highlights that invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC) is closely associated with FTC, suggesting the need for better nomenclature. The concept of "high-grade" differentiated carcinomas, applicable to FTC or IEFVPTC with necrosis and/or high mitotic activity, is also discussed.

Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience.

Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.