BACKGROUND: The current requirement is to establish the preoperative diagnosis accurately as possible and to achieve an adequate extent of surgery. The aim of this study was to define the preoperative clinical and molecular genetic risks of malignancy in indeterminate thyroid nodules (Bethesda III and IV) and to determine their impact on the surgical strategy. METHODS: Prospectively retrospective analysis of 287 patients provided the basis of preoperative laboratory examination, sonographic stratification of malignancy risks and cytological findings. Molecular tests focused on pathogenic variants of genes associated with thyroid oncogenesis in cytologically indeterminate nodules (Bethesda III and IV). The evaluation included clinical risk factors: positive family history, radiation exposure and growth in size and/or number of nodules. RESULTS: Preoperative FNAB detected 52 cytologically indeterminate nodules (28.7%) out of 181 patients. Postoperative histopathological examination revealed malignancy in 12 cases (23.7%) and there was no significant difference between Bethesda III and IV categories (P=0.517). Clinical risk factors for malignancy were found in 32 patients (61.5%) and the presence of at least one of them resulted in a clearly higher incidence of malignancy than their absence (31.3% vs. 10.0%, respectively). Pathogenic variants of genes were detected in 12/49 patients in Bethesda III and IV, and in 4 cases (33.3%) thyroid carcinoma was revealed. The rate of malignancies was substantially higher in patients with pathogenic variants than in those without (33.3% vs. 16.2%, respectively). CONCLUSIONS: Our experience implies that molecular genetic testing is one of several decision factors. We will continue to monitor and enlarge our patient cohort to obtain long-term follow-up data.

• MeSH
• Adult MeSH
• Genetic Testing MeSH
• Middle Aged MeSH
• Humans MeSH
• Thyroid Neoplasms * genetics   MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Biopsy, Fine-Needle MeSH
• Thyroid Nodule * genetics   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Zachování funkčního hrtanu a dosažení dlouhodobé remise je základním postulátem léčby pacientů s maligními nádory hrtanu, a to i pokročilých stadií. Rozvíjeny jsou proto nechirurgické protokoly léčby a hrtan zachovávající chirurgické postupy. Totální laryngektomie je historicky základní výkon laryngeální chirurgie, jehož význam s rozvojem výše uvedených postupů klesá. Přesto jsou stále skupiny nemocných, kteří mohou profitovat z jejího provedení. Rozhodující jsou lokální i celkové charakteristiky tumoru a pacienta. Velikost tumoru, destrukce a nefunkčnost struktur hrtanu, infiltrace štítné chrupavky včetně zevního perichondria případně extralaryngeální propagace jsou faktory, kdy je předpokládaný efekt nechirurgické léčby nedostatečný nebo by vedl k zachování nefunkčního hrtanu. K výkonu také indikujeme pacienty, u nichž pro kontraindikace nemůžeme využít orgán šetřicí protokoly nebo je vysoké riziko komplikací této léčby. Totální laryngektomie má stále své místo v rámci záchranné chirurgie a u specifických malignit, u nichž není efektivní nechirurgická léčba (nejčastěji sarkomy). V této práci je představen náš pohled na indikaci totální laryngektomie v současnosti, který vychází z doporučených postupů a zkušeností s multidisciplinárním klinickým rozhodováním.

Preserving a functional larynx and achieving long-term control is the basic postulate of treating patients with malignant tumors of the larynx, even in advanced stages. Therefore, non-surgical treatment protocols and larynx-preserving surgical procedures are preferred. Total laryngectomy is historically the basic procedure of laryngeal surgery still with the best survival outcomes in advanced laryngeal cancer, but with significantly lower quality of life following surgery. Nevertheless, there are still groups of patients who can benefit from this implementation. Local and overall characteristics are important for the recommendation of treatment. Tumor size, destruction and dysfunction of laryngeal structures, infiltration of the thyroid cartilage including the external perichondrium, or extralaryngeal extent are local factors when the expected effect of non-surgical treatment is insufficient or would only lead to the preservation of a non-functional larynx. We also recommend patients in whom organ-saving protocols are not suitable due to contraindications or there is a high risk of complications. Total laryngectomy still has its place as part of salvage surgery in failure of non-surgical treatment and for specific malignancies for which a non-surgical approach is not effective (most often sarcomas). We present our current view on the indications of total laryngectomy, which is based on international recommendations and our experience with multidisciplinary clinical decision-making.

• MeSH
• Laryngectomy * history   methods   statistics & numerical data   MeSH
• Larynx, Artificial MeSH
• Larynx surgery   pathology   MeSH
• Organ Sparing Treatments methods   MeSH
• Humans MeSH
• Laryngeal Neoplasms surgery   diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Pacienti se vzácnými nádory, jako jsou nádory štítné žlázy se specifickými mutacemi, donedávna neměli mnoho léčebných perspektiv. Díky precizní medicíně, která nám umožní nalézt konkrétní léčebné cíle, můžeme těmto nemocným nabídnout moderní přípravky a zlepšit tak jejich perspektivu i prodloužit život. Článek se zabývá zvláštní skupinou pacientů s nádory štítné žlázy s fúzí RET a shrnuje možnosti léčby na základě dat z klinických studií. Okrajově jsou zmíněny též tumory štítnice s mutací RET, u nichž jsou používány stejné přípravky.

Until recently, patients with rare tumors, such as thyroid tumors with specific mutations, did not have many treatment alternatives. Thanks to precision medicine, which allows us to find specific treatment goals, we can offer these patients modern preparations and thus improve their perspective and prolong their lives. The article deals with a special group of patients with thyroid tumors with RET fusion and summarizes treatment options based on data from clinical trials. Thyroid tumors with RET mutation are also marginally mentioned, for which the same preparations are used.

• MeSH
• Progression-Free Survival MeSH
• Tyrosine Kinase Inhibitors pharmacology   therapeutic use   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Thyroid Neoplasms * drug therapy   MeSH
• Antineoplastic Protocols MeSH
• Check Tag
• Humans MeSH

OBJECTIVE: Thyroid cancer (TC) is the most common endocrine malignancy, with 90%-95% of the cases representing non-medullary thyroid cancer (NMTC). Familial cases account only for a few of all cases and the underlying genetic causes are still poorly understood. METHODS: We whole-genome sequenced affected and unaffected members of an Italian NMTC family and applied our in-house developed Familial Cancer Variant Prioritization Pipeline (FCVPPv2) which prioritized 12 coding variants. We refined this selection using the VarSome American College of Medical Genetics and Genomics (ACMG) implementation, SNAP2 predictions and further in silico scores. RESULTS: We prioritized 4 possibly pathogenic variants in 4 genes including Ret proto-oncogene (RET), polypeptide N-acetylgalactosaminyltransferase 10 (GALNT10), ubinuclein-1 (UBN1), and prostaglandin I2 receptor (PTGIR). The role of RET point mutations in medullary thyroid carcinoma is well established. Similarly, somatic rearrangements of RET are known in papillary TC, a specific histotype of NMTC. In contrast to RET, no germline variants in PTGIR, GALNT10, or UBN1 have been linked to the development of TC to date. However, alterations in these genes have been shown to affect pathways related to cell proliferation, apoptosis, growth, and differentiation, as well as posttranslational modification and gene regulation. A thorough review of the available literature together with computational evidence supported the interpretation of the 4 shortlisted variants as possibly disease-causing in this family. CONCLUSIONS: Our results implicate the first germline variant in RET in a family with NMTC as well as the first germline variants in PTGIR, GALNT10, and UBN1 in TC.

• MeSH
• Adult MeSH
• Genetic Predisposition to Disease * genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• N-Acetylgalactosaminyltransferases genetics   MeSH
• Thyroid Neoplasms * genetics   MeSH
• Carcinoma, Neuroendocrine * genetics   MeSH
• Polypeptide N-acetylgalactosaminyltransferase MeSH
• Proto-Oncogene Mas MeSH
• Proto-Oncogene Proteins c-ret genetics   MeSH
• Pedigree MeSH
• Whole Genome Sequencing * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Early detection of malignant thyroid nodules is crucial for effective treatment, but traditional diagnostic methods face challenges such as variability in expert opinions and limited integration of advanced imaging techniques. This prospective cohort study investigates a novel multimodal approach, integrating traditional methods with advanced machine learning techniques. We studied 181 patients who underwent fine-needle aspiration (FNA) biopsy, each contributing one nodule, resulting in a total of 181 nodules for our analysis. Data collection included sex, age, and ultrasound imaging, which incorporated elastography. Features extracted from these images included Thyroid Imaging Reporting and Data System (TIRADS) scores, elastography parameters, and radiomic features. The pathological results based on the FNA biopsy, provided by the pathologists, served as our gold standard for nodule classification. Our methodology, termed ELTIRADS, combines these features with interpretable machine learning techniques. Performance evaluation showed that a Support Vector Machine (SVM) classifier using TIRADS, elastography data, and radiomic features achieved high accuracy (0.92), with sensitivity (0.89), specificity (0.94), precision (0.89), and F1 score (0.89). To enhance interpretability, we used hierarchical clustering, shapley additive explanations (SHAP), and partial dependence plots (PDP). This combined approach holds promise for enhancing the accuracy of thyroid nodule malignancy detection, thereby contributing to advancements in personalized and precision medicine in the field of thyroid cancer research.

• MeSH
• Adult MeSH
• Elasticity Imaging Techniques * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Thyroid Neoplasms diagnostic imaging   classification   pathology   diagnosis   MeSH
• Prospective Studies MeSH
• Radiomics MeSH
• Aged MeSH
• Thyroid Gland diagnostic imaging   pathology   MeSH
• Machine Learning * MeSH
• Support Vector Machine MeSH
• Biopsy, Fine-Needle MeSH
• Thyroid Nodule * diagnostic imaging   pathology   classification   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: patients with type 2 diabetes (T2DM) and obesity are generally known to have increased risk of various types of cancer, though studies addressing associations between T2DM/obesity and thyroid cancer are inconclusive. The aim of our study was to evaluate the risk of thyroid cancer focusing on diabetic patients under conditions of euthyroid status. A retrospective study in 184 patients was performed. Three cohorts were established according to tumor histology: malignant (M), benign (B) and low-risk carcinoma (MB). Fisher's exact test and Kruskal-Wallis one-way ANOVA of ranks were used for statistical analysis. The M (39.1 %), B (57.6 %) and MB (3.3 %) cohorts had comparable age (p=0.4), BMI (p=0.452), glycaemia (p=0.834), Hb1AC (p=0.157) and HOMA-IR (p=0.235). T2DM patients had larger thyroid gland volumes (28.8 vs 17.6 mL;p=0.001) compared to the cohort with normal glucose tolerance. Compared to women, men had more frequently present distal metastases (p=0.017), minimally invasive disease (p=0.027), more advanced staging (p=0.01) and positive pathogenic mutations in the TERT gene (p=0.009);these results were also significant for the diabetic male cohort (p=0.026). Type 2 diabetes and obesity are not risk factors for thyroid cancer, but a subgroup of males seems to have thyroid cancers of poorer prognosis. In general, diabetic patients with insulin resistance and hyperinsulinemia are also prone to have a goiter. KEY WORDS: Thyroid cancer, Type 2 diabetes, Obesity, Thyroid nodule, Insulin resistance.

• MeSH
• Diabetes Mellitus, Type 2 * epidemiology   complications   MeSH
• Adult MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Thyroid Neoplasms * epidemiology   pathology   MeSH
• Obesity * complications   epidemiology   MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

• MeSH
• Cell Nucleus pathology   MeSH
• Adenocarcinoma, Follicular * pathology   epidemiology   diagnosis   MeSH
• Practice Patterns, Physicians' statistics & numerical data   MeSH
• Humans MeSH
• Thyroid Neoplasms * epidemiology   pathology   diagnosis   MeSH
• Thyroid Cancer, Papillary epidemiology   pathology   diagnosis   MeSH
• Carcinoma, Papillary pathology   epidemiology   diagnosis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Asia MeSH
• Europe MeSH
• Oceania MeSH
• North America MeSH

Two benign adenomatous lesions are commonly recognized within the sinonasal tract, namely respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH). We present 10 hitherto unrecognized benign polypoid nasal and sinonasal tumoriform lesions having in average 3.6 cm in largest dimension, which are histogenetically related to SH and REAH. In addition to typical structures of REAH and SH, these lesions contained an additional characteristic and slightly atypical adenomatous component, which we termed atypical sinonasal glands arising in SH (ASGSH). ASGSH often produced deep red colored secretion with peripheral clearing similar to that seen in thyroid follicles. In contrast to SH, ASGSH was endowed by both secretory and myoepithelial layers and had mostly angulated shapes with snout-like protrusions into the lumens. Both layers were formed by an irregular, disorganized, and often incomplete cell lining, which had slightly atypical cytological features without mitoses. In 3 cases, ASGSHs revealed sebaceous differentiation, and in 3 cases the stroma produced a well-differentiated cartilage. Neoplastic nature of ASGSH was supported by finding of various mutations as revealed by next generation sequencing in five cases. In two cases each, we found identical mutations in BRAF gene (Val600Glu), and RET gene (Arg912Trp), respectively and in one case FAT1 gene alteration (Pro1665Leu).

• MeSH
• Adenoma pathology   genetics   MeSH
• Adult MeSH
• Hamartoma * pathology   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• Nose Neoplasms pathology   genetics   MeSH
• Paranasal Sinus Neoplasms pathology   genetics   MeSH
• Respiratory Mucosa pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: Papillary thyroid carcinoma (PTC) frequently harbors the BRAF V600E mutation. Recent research suggests that aggressive behavior in BRAF V600E+ PTC may be due to an undetected mutation in the TERT gene. This study aims to observe the clinicopathological features of BRAF V600+ PTC and correlate them with surgical treatment complications. METHODS: A retrospective analysis was conducted on the BRAF V600E+ PTC cohort from July 2019 to January 2023. The histopathological features and surgical treatment (total thyroidectomy - group A, total thyroidectomy + central block neck dissection - group B) complications were correlated. Patients with TERT and TP53 mutation were excluded. Next-generation sequencing and real-time PCR were used for genetic analysis. RESULTS: Out of 121 PTCs, 65 cases showed BRAF V600E mutation with the following features: intracapsular spread (13.8%), extracapsular spread (27.7%), extrathyroidal spread (15.4%), multifocality (26.2%), angioinvasion (12.3%), and local metastasis (27.7%). The incidence of surgical complications in group A/B was: reversible recurrent laryngeal nerve (RLN) paresis 3.7/7.1%, RLN paresis permanent 0/2.4%, paresthesia 6.8/23.8%, hypocalcemia 36.4/61.9% on day 1 and 27.3/33.3% on day 3, and bleeding 2.3/9.5%. There was no significant difference in clinicopathological features between the BRAF V600E+ and BRAF V600E- PTC groups. Group B had a significantly higher incidence of hypoacalcaemia on postoperative day 1 (p = 0.047). CONCLUSION: The BRAF V600E mutation will certainly remain important in the preoperative diagnosis of PTC. The more radical surgical procedures currently recommended may be abandoned in the future, particularly elective CLND, which has a higher risk of postoperative complications.

• MeSH
• Adult MeSH
• Neck Dissection adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation * MeSH
• Tumor Suppressor Protein p53 * genetics   MeSH
• Thyroid Neoplasms * genetics   surgery   pathology   MeSH
• Thyroid Cancer, Papillary * genetics   surgery   pathology   MeSH
• Postoperative Complications epidemiology   etiology   MeSH
• Proto-Oncogene Proteins B-raf * genetics   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Telomerase * genetics   MeSH
• Thyroidectomy * adverse effects   methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Differentiated thyroid carcinoma is the most common endocrinological malignancy with an increasing incidence over the last 30 years, with women being more frequently affected. In indicated cases, total thyroidectomy followed by adjuvant radioiodine administration is performed, despite current trends towards less aggressive treatment. We would like to investigate the possible adverse effects of radioiodine (RAI) on ovarian function using a simple serum biomarker. Anti-Müllerian hormone (AMH) appears to be the best endocrine marker for assessing physiological age-related oocyte loss for healthy women. The aim of our ongoing prospective study is to determine serum AMH to estimate ovarian reserve for premenopausal women treated with RAI. Over the course of one year, 33 serum samples from women with thyroid cancer and 3 serum samples from healthy women were examined. AMH levels were compared before radioiodine treatment and at regular intervals after treatment. Mean of the AMH level was 5.4 ng/ml (n=33) prior to RAI. The average level of AMH decreased to 1.8 ng/ml in 4-6 months after treatment. In 22.2 % of patients AMH dropped to 0 ng/ml from a non-zero value. Thereafter, we observed an increase in AMH, the average value was 2.7 ng/ml in 8-12 months. We demonstrated a significant decrease in AMH shortly after radioiodine treatment and a subsequent trend of increase at one year after treatment. Consequently, predicting the adverse effects of radioiodine by assessing a serum biomarker could help to select an appropriate treatment strategy for young women planning pregnancy.

• MeSH
• Anti-Mullerian Hormone * blood   MeSH
• Biomarkers blood   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Thyroid Neoplasms * radiotherapy   blood   surgery   MeSH
• Ovarian Reserve radiation effects   MeSH
• Predictive Value of Tests MeSH
• Premenopause * blood   MeSH
• Primary Ovarian Insufficiency blood   etiology   diagnosis   MeSH
• Prospective Studies MeSH
• Iodine Radioisotopes * therapeutic use   adverse effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH