Search Results (184)

Background: Thyroid neoplasms exhibit a diverse molecular landscape, and the 2022 WHO classification emphasizes the critical role of molecular profiling in thyroid cancer management; however, comprehensive mutational data from fine-needle aspiration cytology (FNAC) samples using targeted next-generation sequencing (NGS) are still limited, necessitating further investigation to guide clinical practice. Purpose: To characterize the mutational landscape of thyroid neoplasms using targeted NGS of FNAC samples and to assess the clinical implications of molecular profiling. Materials and Methods: This retrospective study included 952 patients with thyroid carcinomaneoplasms who underwent surgery at Sun Yat-sen Memorial Hospital from 2021 to 2023. Preoperative ultrasound, FNAC, and targeted NGS were performed. NGS panels covering 18, 88, and pan-cancer genes were used to analyze FNAC samples. Molecular alterations were correlated with clinical and pathological features. Results: The most frequent mutation was BRAF^V600E (84.45%), followed by RET (6.41%), BRCA1/2 (4.41%) and RAS (4.41%). Patients were categorized into BRAF-like (830 cases), RAS-like (36 cases), high-risk mutations (25 cases), and other mutations (28 cases). High-risk mutations were associated with older age and larger tumor size. BRAF-like tumors had a higher lymph node metastasis rate (58.77%) compared to RAS-like tumors (33.33%). Tumor mutation burden varied significantly among different thyroid neoplasm subtypes. Conclusions: Molecular profiling using targeted NGS of FNAC samples provides valuable insights into the genetic landscape of thyroid neoplasms and has significant clinical implications for diagnosis and personalized treatment strategies. Further validation with paired tumor and plasma samples is warranted. Full article

Background: This study evaluated the association between bilirubin subtypes (total, indirect, and direct bilirubin) and thyroid cancer risk, with a particular focus on stratified analyses using the ALBI (Albumin-Bilirubin) and PALBI (Platelet-Albumin-Bilirubin) indices by sex, smoking and drinking status, and age under 50 years. Methods: Data were obtained from 133,596 participants in the Korean Cancer Prevention Study-II (KCPS-II) cohort. During a mean follow-up period of 13.55 years, 2314 cases of thyroid cancer (ICD-10: C73) were identified. Serum bilirubin levels and ALBI and PALBI indices were analyzed using Cox proportional hazards regression models stratified by age, sex, smoking, and alcohol consumption status to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In women, indirect bilirubin showed the strongest inverse association with thyroid cancer risk. ALBI and PALBI indices based on indirect bilirubin also demonstrated significant associations. A 1 standard deviation (SD) increase in indirect bilirubin was associated with a decreased risk of thyroid cancer (HR: 0.92, 95% CI: 0.84–0.99), and the ALBI index similarly showed an inverse association (HR: 0.92, 95% CI: 0.87–0.99). In contrast, the PALBI index was positively associated with thyroid cancer risk (HR: 1.11, 95% CI: 1.03–1.20). Among women who had never smoked, significant associations were observed for indirect bilirubin (HR: 0.91, 95% CI: 0.83–1.00), ALBI (HR: 0.93, 95% CI: 0.86–1.00), and PALBI (HR: 1.14, 95% CI: 1.05–1.23). In analyses stratified by alcohol consumption, the PALBI index was associated with increased thyroid cancer risk in non-drinkers, former drinkers, and ever drinkers, with respective risk increases of 15%, 18%, and 9%. Conclusions: In women, indirect bilirubin was significantly and inversely associated with thyroid cancer risk, and the ALBI and PALBI indices incorporating indirect bilirubin showed consistent results. These findings suggest that indirect bilirubin may play a critical role in the metabolic pathways underlying thyroid cancer in women. Full article

Thyroid cancer, the most frequently occurring endocrine neoplasm, comprises a heterogeneous group of histological subtypes, spanning from the indolent papillary thyroid carcinoma (PTC) to the rapidly progressive and lethal anaplastic thyroid carcinoma (ATC). Although conventional therapies, such as surgery and radioactive iodine (RAI), are effective for differentiated thyroid cancers, treatment resistance and poor prognosis remain major challenges in advanced and undifferentiated forms. In current times, growing attention has been directed toward the potential of Natural Killer (NK) cells as a promising immunotherapeutic avenue. These innate immune cells are capable of direct cytotoxicity against tumor cells, but their efficiency is frequently compromised by the immunosuppressive tumor microenvironment (TME), which inhibits NK cell activation, infiltration, and persistence. This review explores the dynamic interaction between NK cells and the TME in thyroid cancer, detailing key mechanisms of immune evasion, including the impact of suppressive cytokines, altered chemokine landscapes, and inhibitory ligand expression. We further discuss latest advancements in NK cell-based immunotherapies, including strategies for ex vivo expansion, genetic modification, and combinatorial approaches with checkpoint inhibitors or cytokines. Additionally, emerging modalities, such as NK cell-derived extracellular vesicles, are addressed. By combining mechanistic insights with advancing therapeutic techniques, this review provides a comprehensive perspective on NK cell-based interventions and their future potential in improving outcomes for patients with thyroid cancer. Full article

Thyroid tumors are common in humans and cats, occurring most commonly as benign lesions, whereas thyroid carcinoma is barely detected in both species. Determining the mutational status of MAPK-related genes (BRAF, NRAS, HRAS, and KRAS) and the activation status of MAPK and mTOR pathways is crucial for establishing the diagnosis, treatment, and prognosis of human patients. So far, the role of such players in feline thyroid tumorigenesis remains underexplored. This study aims to elucidate the presence and implications of potential shared molecular mechanisms between human and feline thyroid tumors. Fifteen formalin-fixed paraffin-embedded feline thyroid epithelial tumors (four tumors with atypia and 11 with no atypia) were collected to perform mutational and immunohistochemical analyses. Sanger sequencing targeting human homologous hotspots revealed no mutations in BRAF (human codon 600) or RAS (human codon 61) regions. A KRAS missense mutation (p.Gln232His) was identified in two tumors with no atypia of follicular pattern (2/15, 13%). Regardless of the mutational status, pERK (Thr202/Ty204) was immuno-expressed in 10/11 (91%), pS6 (Ser235/236) in 100%, and pAKT (Ser473) in 8/11 (73%) of the tumors with no atypia. The expression patterns of pERK, pS6, and pAKT and their associations with clinical-pathological features seem to mirror the progression dynamics observed in human thyroid tumorigenesis. pAKT expression was associated with the presence of multiple tumor foci within the same thyroid lobe, suggesting its potential as a marker of aggressiveness in feline thyroid tumors. This study introduces cats as potential animal models for human thyroid tumorigenesis, with further research required to confirm such potential. Full article

Background/Objective: Radiotherapy for leukemia, the most common childhood malignancy, often exposes patients to radiation, increasing the risk of second malignancies, including thyroid cancer. To assess the incidence and survival outcomes of thyroid cancer after childhood acute lymphoblastic leukemia (ALL). Methods: We systematically reviewed articles reporting the incidence of thyroid cancer in childhood leukemia survivors (age at diagnosis < 18 years) published between 2000–2024 in Science Direct, PubMed, Google Scholar, CENTRAL, and EMBASE. The Newcastle Ottawa Scale was utilized to appraise the methodological quality of the included studies. Descriptive statistics and calculations of incidence were performed using Microsoft Excel. Results: The literature search yielded 1265 articles, of which 18 met the inclusion criteria. Data from 135,861 childhood cancer survivors, among whom 102,070 had a confirmed diagnosis of childhood leukemia, including ALL. The crude incidence of secondary malignancies after childhood leukemia was 10.1 per 1000 patients. Among these, 1.5 per 1000 patients developed second thyroid carcinomas. Overall, 14.6% of the second malignancies in childhood leukemia survivors were thyroid carcinomas, mostly of the papillary type. Survival rates after second thyroid cancer were 100% in all 11/18 studies reporting this outcome. Radiotherapy had been used as part of ALL treatments in 17/18 studies. The use of radiotherapy, female sex, and younger age at the diagnosis of primary ALL emerged as important risk factors for thyroid cancer. Conclusions: Thyroid carcinomas account for ~15% of secondary malignancies after childhood leukemia, with radiation remaining a significant risk factor despite its overall reduced use for the treatment of ALL in the last few decades. Importantly, survival rates remain high. Further research is warranted to determine the incidence and outcomes of thyroid cancer in childhood ALL survivors Full article

Thyroid nodules are accidentally found in up to 68% of people undergoing neck ultrasound (US) examination, and fine needle aspiration (FNA) is the current gold standard to discriminate between malignancy and benign lesions. Unfortunately, one-third of FNAs are classified as indeterminate, requiring surgery for definitive diagnosis. This leads to high costs and health risks of unnecessary procedures, since malignancies are observed in less than half of operative specimens. This narrative review aims to describe the most innovative multi-omics approach techniques, including genomics, proteomics, and metabolomics, aimed at making the preoperative evaluation of indeterminate thyroid nodules more accurate. The advantages and disadvantages of the techniques are described in detail, and a SWOT (strengths, weaknesses, opportunities, and threats) analysis of the multi-omic approach is provided. Full article

Background/Objectives: TTF-1 and Napsin A are immunohistochemical markers that are widely used for the diagnosis of lung adenocarcinomas or thyroid carcinomas, as well as the characterization of metastases. However, several publications have reported the aberrant expression of one or both markers in extrathoracic malignancies, including gastrointestinal adenocarcinomas. The goal of our study was to determine the frequency of TTF-1- and Napsin A-positive neoplasms in cohorts consisting of esophageal, gastric and colorectal adenocarcinomas. Methods: Buffered formalin-fixed paraffin-embedded tumor tissues from 854 patients with primary resected gastrointestinal and esophageal carcinomas were placed in tissue microarrays (TMAs) for investigation. Between two and six tumor cores were analyzed for each case. For immunohistochemical staining, we used TTF-1 (SPT24 clone) and Napsin A (IP64 clone). Tumors were considered positive if at least 5% of their tumor cells showed weak nuclear (TTF-1) or cytoplasmic (Napsin A) staining. Results: In total, 16 cases showed positive staining for TTF-1, alongside 7 cases for Napsin A. The greatest proportion of TTF-1- and/or Napsin A-positive tumors was found among esophageal adenocarcinomas (5/125 cases; 4%). Co-expression of TTF-1 and Napsin A was found in five cases, including three esophageal and two gastric adenocarcinomas. In colorectal carcinomas, co-expression of these markers was not detected. Conclusions: TTF-1 and Napsin A are useful immunohistochemical makers for establishing the diagnosis of pulmonary adenocarcinoma. Additionally, knowing that a proportion of gastrointestinal neoplasms express these markers can help to avoid diagnostic misinterpretations. Full article

Background/Objectives: Cowden syndrome (or PTEN hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90–100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. Methods: Next-generation sequencing and Sanger sequencing were used to search for PTEN genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. Results: A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the PTEN pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the PTEN gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. Conclusions: Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS. Full article

Objectives: The current standard of care for endocrine tumors includes a personalized diagnostic and therapeutic approach aimed at the early detection of tumor recurrence after radical surgery. Assessment of tumor-associated biological factors in serum may be useful in patient management. The aim of this study is to determine whether any of the selected growth factors (VEGF, FGF), lectins (Galectin-1, Galectin-3), proteins (Fascin), or TNF-α measured in serum may serve as a potential marker of recurrence. Methods: A total of 68 cases, including 43 patients with disseminated endocrine neoplasm (neuroendocrine tumor (NET) 30 cases, medullary thyroid cancer (MTC) 6 cases, adrenal neoplasm 7 cases) and 25 healthy participants, were included in the analysis. Serum concentrations of TNF-α, Fascin, VEGF, Galectin-1, Galectin-3, and FGF were determined in all cases. The results were compared between groups. Results: A comparison between all patients and controls revealed differences in TNF-α concentrations (2.88 vs. 0.93 (ng/mL), p = 0.008). When comparing the concentrations of the measured factors between the subgroups (classified by tumor type) and the control group, differences were found for TNF-α (p = 0.007) and Fascin (p = 0.035). In the case of Fascin, differences were found for MTC and adrenal neoplasm patients (0.52 vs. 5.28 (ng/mL), p = 0.048), as well as MTC and NET patients (0.52 vs. 5.59 (ng/mL), p = 0.007), while the differences between NET patients and controls were close to significance (5.59 vs. 3.67 (ng/mL), p = 0.076). For TNF-α, significant differences were found between NET patients and controls (2.88 vs. 0.03 (ng/mL), p = 0.005) as well as between MTC patients and controls (2.77 vs. 0.93 (ng/mL), p = 0.004). Conclusions: Serum concentrations of selected proteins and growth factors (Fascin, TNF-α) are significantly higher in those with disseminated endocrine tumors compared to healthy controls. More studies are needed to determine the role of these selected proteins and growth factors in the early detection of NET/MTC recurrence. Full article

Benign neoplasms and tumor-like lesions of the tongue are relatively rare entities, encompassing a heterogeneous spectrum of morphological alterations. The recent literature focusing on benign tumors and tumor-like lesions of the tongue is relatively limited, which may lead to a gap in understanding their specific imaging characteristics. Most benign tongue tumors usually appear as submucosal bulges located in the deep portion of the tongue. Both computed tomography (CT) and magnetic resonance imaging (MRI) are essential for the comprehensive diagnostic evaluation of these entities. Cross-sectional imaging plays a pivotal role in narrowing the differential diagnosis and, in selected cases, may suggest a specific histopathological entity. The benign tumors and tumor-like lesions included in this review comprise schwannoma, lipoma, angiomyolipoma, hemangioma, vascular malformations, dermoid cysts, and thyroglossal duct remnants (including cystic formations and ectopic thyroid tissue). Additionally, certain non-neoplastic conditions—such as lingual abscesses, infectious mononucleosis complicated by lingual tonsillitis, and fatty atrophy of the tongue—can mimic neoplastic processes and present as mass-like lesions; these have also been addressed in this pictorial essay. The purpose of this work is to illustrate the key CT and MRI features of the aforementioned benign lingual lesions, with the aim of improving diagnostic confidence and accuracy. Full article

Strumal carcinoid tumors of the ovary are rare neoplasms composed of an intimate mixture of thyroid and carcinoid tissues. Although various theories regarding their histogenesis have been proposed, evidence confirming the origin of the carcinoid component has been lacking. We report a case of a 40-year-old female with an ovarian strumal carcinoid arising in the background of a mature cystic teratoma. Morphological and immunohistochemical findings support the hypothesis that the carcinoid component originates from the thyroid follicular epithelium, undergoing neuroendocrine differentiation. A single-cell growth pattern was also identified, expanding the known histological spectrum of strumal carcinoids. Our case provides additional immunohistochemical support for the histogenetic origin of strumal carcinoids, offering new insights into their pathogenesis. Recognizing these distinct patterns of staining and unusual morphology is critical for accurate diagnosis and differentiation from metastatic disease. Full article

Background: Oncocytic adenomas (OAs) of the thyroid, previously referred to as Hürthle cell adenomas, are uncommon tumors, particularly in pediatric populations, where they represent a minority of thyroid nodules. Due to their rarity and the potential difficulty in distinguishing benign from malignant forms on cytology, these adenomas present unique diagnostic and management challenges. Here, we report a pediatric case of a large OA of the thyroid, managed with surgical resection following inconclusive fine-needle aspiration (FNA) results. Case Presentation: A 13-year-old girl presented with an enlarging thyroid nodule. An ultrasound examination showed a large (26 × 16 mm), solid, isoechoic nodule with a hypoechoic halo. The FNA findings were inconclusive, indicating a follicular neoplasm with oncocytic features, classified as Bethesda IV. The patient underwent a hemithyroidectomy, and a histopathological examination confirmed an encapsulated OA without evidence of capsular or vascular invasion. The postoperative recovery was uneventful, and follow-up assessments showed no recurrence. Conclusions: OAs in pediatric patients are rare and may pose diagnostic challenges. This case highlights the importance of a comprehensive approach, including surgical resection, for definitive diagnoses in cases where FNA results are inconclusive. Further studies are warranted to establish guidelines for the management of oncocytic thyroid neoplasms in pediatric patients, as well as to understand their clinical behavior in this population. Full article

Neuroendocrine neoplasms (NENs) comprise a group of tumours that can develop in various internal organs, but in this review, we will describe only those arising in the lungs, thyroid, and thymus. Pulmonary neuroendocrine neoplasms (pulmonary NENs) account for approximately 25% of all lung cancers. They are classified into four groups of tumours: typical carcinoids (TCs), atypical carcinoids (ACs), small cell lung carcinoma, and large cell lung carcinoma. This review focuses on TC and AC. The treatment consists mainly of radiotherapy, chemotherapy, and surgical resection, but novel drugs like atezolizumab are also utilised. The most common neuroendocrine neoplasm of the thyroid gland is medullary thyroid carcinoma (MTC), which commonly possesses RET protooncogene mutations. MTC is treated by a total thyroidectomy. Recently, tyrosine kinase inhibitors (TKIs) have emerged as an effective treatment option for patients with advanced MTC. Neuroendocrine tumours of the thymus (NETTs) are also being treated with a radical surgery. Full article

Background/Objectives: The 2023 revision of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) simplified the subcategorization of category III into two groups: “AUS-nuclear” and “AUS-other”. The aim of this study was to investigate the risk of malignancy (ROM) of individual BSRTC categories with a particular emphasis on the “AUS-nuclear” and “AUS-other” subcategories and to check whether the low-risk follicular-cell-derived thyroid neoplasm (LRTN) interpretation or EU-TIRADS class of the nodule modify ROM. Methods: The analysis covered the FNA results of 18,225 nodules in 12,470 patients. The rate of malignancy (the upper limit of ROM) was established on the basis of the assessment of 1660 nodules treated surgically in 978 patients. Results: In the broadest variant, with all LRTNs regarded as malignant, the ROM for subsequent categories was as follows: I: 0.4–3.5%, II: 0.1–1.3%, III: 3.8–17.7%, IV: 23.3–27.8%, V: 79.6–90.1%, and VI: 86.3–100.0%. In AUS-nuclear nodules, the ROM was 10.5–28.9%, while in AUS-other nodules, it was 2.2–12.2%. The exclusion of NIFTP or all LRTNs from cancers mainly affected the ROM of AUS-nuclear nodules: 9.4–25.9% or 8.6–23.7%, respectively. EU-TIRADS 5 class increases the ROM in AUS-nuclear nodules to 78.3%, OR: 15.7 and in AUS-other to 40.7%, OR: 6.6. Conclusions: The 2023 BSRTC is a welcome step towards simplification of the way nodules are classified within category III. The AUS-nuclear subcategory is associated with a two-times-higher incidence of malignancy than the AUS-other regardless of LRTN interpretation and EU-TIRADS class of the nodule. The EU-TIRADS 5 class of the nodule is helpful in the identification of category III nodules with a high risk of malignancy. Full article

Thyroid carcinomas are driven by diverse molecular alterations, but the tumor suppressor gene folliculin (FLCN), best known for its role in Birt–Hogg–Dubé (BHD) syndrome, has received limited attention in thyroid tumors. Here, we describe two thyroid tumors with pathogenic FLCN alterations—one germline and one somatic—and analyze the broader prevalence and significance of FLCN in thyroid carcinomas using multiple large sequencing datasets, including ORIEN-AVATAR. Patient 1, with a germline FLCN mutation and a history of BHD syndrome, presented with a well-circumscribed oncocytic adenoma. Molecular testing confirmed biallelic FLCN inactivation, but no additional mutations or aggressive features were observed, and the patient remained disease-free post-thyroidectomy. Patient 2 harbored a somatic FLCN mutation in an oncocytic poorly differentiated thyroid carcinoma, which exhibited extensive angioinvasion, high proliferative activity, and concurrent TP53 and RB1 mutations. The tumor progressed with metastatic disease despite multimodal treatment. Thyroid carcinomas revealed FLCN alterations in 1.1% of cases. Pathogenic mutations were rare but associated with oncocytic morphology, while homozygous deletions occurred more frequently in genomically unstable tumors, including anaplastic thyroid carcinoma. These findings suggest FLCN mutations may act as early oncogenic drivers in oncocytic thyroid neoplasms, while deletions represent secondary events in aggressive tumor evolution. The lack of FLCN coverage in standard thyroid molecular panels likely underestimates its clinical relevance. Including FLCN in genetic testing could improve tumor detection and characterization, particularly in BHD patients who may benefit from routine thyroid screening. Further studies are needed to clarify FLCN’s role in thyroid cancer pathogenesis. Full article