European Thyroid Journal最新文献

Background: Papillary thyroid carcinoma (PTC) has an excellent prognosis, yet recurrence remains a clinical concern. Patients at intermediate risk may benefit from additional prognostic markers. We aimed to evaluate whether tumor desmoplasia predicts recurrence in intermediate-risk PTC patients and to assess its prognostic clinical utility.

Methods: We conducted a retrospective study with follow-up of at least 36 months at a high-volume tertiary endocrine center. We included 121 patients with intermediate-risk PTC who achieved an excellent or indeterminate response to initial therapy at 12 months. Tumor desmoplasia was assessed on hematoxylin-eosin-stained thyroid sections by two pathologists. Desmoplasia was graded on a semi-quantitative 4-point scale based on the proportion of tumor area occupied by fibrotic stromal tissue. Patients were followed for the occurrence of biochemical or structural recurrence, which was defined as the primary study endpoint.

Results: Desmoplasia was significantly associated with recurrence (odds ratio = 2.99; 95% CI: 1.51-6.34; P < 0.01). Receiver operating characteristic analysis identified grade 2 as the optimal cut-off for predicting recurrence. Notably, the negative predictive value reached 95% in patients with absent or mild desmoplasia. Kaplan-Meier analysis confirmed a significant difference in recurrence-free survival between patients with mild versus severe desmoplasia (hazard ratio = 3.00; 95% CI: 1.45-6.24; P = 0.003).

Conclusion: Desmoplasia is an independent predictor of recurrence in intermediate-risk PTC. Patients with minimal or no desmoplasia have an extremely low risk of recurrence. These findings support the potential role of desmoplasia as a prognostic feature in risk stratification and personalized management of intermediate-risk PTC.

Thyroid cancer is the most prevalent endocrine malignancy. Distinct genetic alterations drive the development and progression of thyroid tumors of follicular cells with remarkable genotype-phenotype correlation. In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations. Progression of thyroid tumors to advanced and less-differentiated carcinomas requires additional oncogenic alterations, including TP53 and TERT promoter mutation, and aberrant PI3K-PTEN-AKT signaling. Understanding the genetic landscape of thyroid carcinoma of follicular cells is essential to optimize clinical management and to identify molecular targets to treat cases with aggressive disease refractory to standard radioactive iodine therapy. What follows is a comprehensive and updated outline of the main somatic genetic and molecular alterations in thyroid carcinoma of follicular cells.

Background: Observational studies in adults suggest that incidental PTC (iPTC) and non-incidental PTC (niPTC) are distinct entities. We examine the incidence of iPTC in pediatric patients undergoing thyroidectomy for benign conditions and compare clinical and histopathologic findings, and outcomes, of iPTC with those of niPTC.

Methods: A retrospective chart review was conducted at the Children's Hospital of Philadelphia between August 2010 and February 2023 to identify pediatric patients who underwent thyroidectomy and were diagnosed with pT1a PTC.

Results: iPTC was identified in 23 of 453 (5.1%) patients undergoing thyroidectomy for benign conditions. Within a cohort of 66 patients diagnosed with pT1a PTC, 23 (34.8%) were classified as iPTC and 43 (65.2%) were classified as niPTC. Compared to niPTC, iPTC had a significantly smaller median greatest dimension (iPTC: 3 mm, niPTC: 7 mm, P < 0.001), a lower rate of lymphatic invasion (iPTC: 0%, niPTC: 60.5%, P < 0.001), and AJCC N1 disease (iPTC: 0%, niPTC: 55.8%, P < 0.001). Most iPTC (22 out of 23 (95.7%)) were classified as ATA pediatric low-risk, while six out of 43 (14.0%) niPTC were categorized as intermediate/high-risk. Patients with iPTC and niPTC were followed for a median of 3.3 and 5.7 years, respectively. There was no evidence of persistent or recurrent disease in any patient with iPTC during this time frame.

Conclusions: iPTC may be found in 5.1% of pediatric patients undergoing thyroidectomy for benign conditions. Similar to adults, iPTC in pediatric patients appears to be indolent with a minimal risk for invasive features and a low risk for persistent or recurrent disease. In contrast to iPTC, niPTC exhibits the potential for invasive behavior and should be regarded as a distinct entity.

Background: Persistent Graves' disease (GD) after total thyroidectomy is sporadic and may be explained by incomplete total thyroidectomy, GD in ectopic thyroid tissue (ETT) or struma ovarii.

Methods: We present a novel case of ectopic GD in a giant paracardiac mass, including an in-depth histologic exam. We searched the PubMed database on GD in ETT.

Results: A 34-year-old woman presented with severe thyrotoxicosis, 4 months after total thyroidectomy, and 6 weeks after cessation of levothyroxine substitution. Persistently high thyrotropin receptor antibodies (TSH-R-Ab) (27 IU/L, normal: <1.5 IU/L) and thyroglobulin >5,000 μg/L (normal: <77 μg/L) suggested GD in ETT. A 99mTc-pertechnetate SPECT/CT scan showed uptake in a paracardiac mass. After surgical removal of the 13 cm paracardiac mass, euthyroidism was achieved. Histology was typically remarkable for a Graves' pattern in the ETT, as opposed to a nodular pattern in the eutopic thyroid. The additional scoping review encompasses 29 reported ETT cases, of which only 11 were in the mediastinum. Graves' eye disease was present in 11/29 subjects.

Conclusion: This is the first report showing a markedly different histology between the thyroid and the ectopic tissue. Persistent systemic severe GD post-thyroidectomy led to the detection of a giant paracardiac ectopic thyroid. GD in ETT is rare and presents a diagnostic challenge.

Objectives: In thyroid cancer with marked laryngotracheal invasion, life-threatening airway stenosis necessitates urgent procedures such as extensive curative surgery, tracheostomy, stenting, or laser bronchoscopy. These interventions are invasive and may significantly compromise quality of life. In anaplastic thyroid cancer (ATC), the delay during genetic testing turnaround time before initiating targeted therapy poses an additional therapeutic challenge. This study aimed to assess lenvatinib (LEN) as an initial and bridging treatment to rapidly alleviate airway stenosis and avoid emergency invasive interventions.

Methods: This retrospective study analyzed 14 patients with remarkable laryngotracheal invasion among 69 thyroid cancer patients treated with multikinase inhibitor(s). All 14 patients received LEN as first-line or post-paclitaxel treatment. Response was assessed by CT imaging per RECIST 1.1, with particular attention to changes in tumor size and airway diameter. Symptom improvement and adverse events, such as fistula formation, were also recorded.

Results: Of the 14 patients, 13 showed tumor reduction and airway improvement on initial CT post-LEN induction. Median response rate was 28.4%, with airway diameter improving by 15.9% on the initial CT. Airway symptoms resolved in a median of 3 days. One patient developed a tumor-tracheal fistula, managed with LEN dose adjustment. LEN was also successfully used as a bridging therapy before BRAF-targeted treatment in ATC cases.

Conclusions: Initial LEN therapy rapidly alleviates airway stenosis in advanced thyroid cancer with laryngotracheal invasion, offering a non-invasive alternative to emergency procedures under careful monitoring for fistula formation. LEN is especially valuable as a bridging therapy during the genetic testing period in ATC.

Background: Nuclear protein in testis (NUT) carcinomas are aggressive, poorly or undifferentiated cancers, generally arising from midline structures. This subtype of squamous cell carcinoma is rare and has a poor prognosis. NUT cancers are defined by NUTM1 fusions. Rearrangements of the NUTM1 gene have rarely been described in primary thyroid cancer and are mainly reported in patients ≤45 years old. NSD3::NUTM1 translocation is the most common NUTM1 fusion transcript reported in thyroid cancer. As they are very infrequent, NUTM1 fusions are not routinely sought in poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC).

Case presentation: We report two PDTC patients >65 years old with locally advanced disease and 18FDG-avid distant metastases. NSD3::NUTM1 translocation was evidenced in both patients by RNA sequencing using the next-generation sequencing panel of our institution.

Conclusion: We suggest including the search for NUTM1 fusions in the RNA sequencing panel for advanced and refractory thyroid cancers.

Objective: Thyrotoxic periodic paralysis (TPP) is a rare but potentially lethal complication of thyrotoxicosis. Absence of large cohorts limits the conduct of epidemiology studies. We aimed to establish a population-based registry of thyrotoxicosis and TPP in Hong Kong and evaluate their trend.

Methods: We developed algorithms to identify thyrotoxicosis and TPP cases from a representative electronic medical database in Hong Kong. Of the potential cases (thyrotoxicosis:83,184; TPP:999), we reviewed clinical notes and laboratory test records of 200 randomly selected cases. Population-based registries of thyrotoxicosis and TPP were subsequently established. Their standardized incidence rate, TPP-associated hospitalization rate, length of stay (LOS), and trends from 2002 to 2021 were evaluated.

Results: Positive predictive values for thyrotoxicosis and TPP were 0.86-0.97, respectively, enabling establishment of population-based cohorts of incident thyrotoxicosis (n = 77,856) and TPP (n = 994). Age- and sex-standardized incidence rate (per 100,000 person-years) of thyrotoxicosis increased from 41.31 in 2002 to 69.51 in 2021 (average annual percentage change: 4.77%), with a similar trend observed in both sexes. TPP patients were predominantly male (93.66%). In 2002 and 2021, the age-standardized incidence rate (per 100,000 person-years) of TPP in males was 1.43 and 1.18, respectively, while that in females was 0.11 and 0.13, without a significant trend observed. TPP-associated hospitalization rate (90.91-100%) and median LOS (2-3 days) were steady across the two decades.

Conclusion: This is the first study establishing a TPP cohort based on validated clinical data from an electronic medical database. It is important to keep monitoring the increasing incidence rate of thyrotoxicosis.

Graves' orbitopathy (GO) is characterized by orbital inflammatory infiltration, expansion of orbital tissues due to de novo adipogenesis and over-production of hydrophilic glycosaminoglycans, as well as myofibroblastic differentiation resulting in tissue fibrosis. Thyrotropin receptor antibody (TSH-R-Ab) is the major stimulus, which activates thyrotropin receptor (TSH-R)/insulin-like growth factor-1 receptor (IGF-1R) and its downstream signalling in orbital fibroblasts (OF). Clinical evaluation of TSH-R-Ab, the specific biomarker of Graves' disease (GD) and the associated orbitopathy, provides important clinical information concerning diagnosis, disease monitoring and prognosis of GO. TSH-R/IGF-1R crosstalk represents the principal mechanism of activation of OF, the key effector cells in GO. T cells and monocytes/macrophages predominate in the inflammatory infiltrates and B-T cell co-stimulation results in mutual activation. Mast cell-derived products also activate OF. In the presence of various pro-inflammatory molecules, activated OF and lymphocytes perpetuate orbital inflammation and mediate tissue remodelling. Enhanced oxidative stress drives various pathological processes in GO and many antioxidant agents have shown inhibitory effects on OF. Highly differential gene and protein expression exists between GO and normal subjects, as well as between active/severe and inactive/mild GO, providing important insights into the disease mechanisms. The lack of confirmed genetic susceptibility to GO development suggests that epigenetic mechanisms (e.g. DNA methylation and microRNAs) may play a role in regulating gene and protein expression, and hence disease phenotypes. The gut microbiome differs significantly between GO patients and healthy individuals. Modifying gut microbiota in GO animal models improves GO. Emerging evidence indicates that hypercholesterolaemia is associated with increased risk of developing GO, while statin use is a protective factor.