Thyroid Gland Follicular Carcinoma

Mutation of DICER1 gene is a non-negligible molecular event and it may represent an aggressive subset of FDTCs. DICER1 has RAS-like clinical characteristics and DICER1-mutant tumors exhibit more aggressive clinical behaviors compared with those with BRAFV600E and RET fusions.

P2, N=30, Recruiting, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Trial completion date: Feb 2029 --> Feb 2030 | Trial primary completion date: Feb 2025 --> Feb 2030

P1, N=90, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=2, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=20 --> 2

These cases highlight the critical role of integrating cytological, clinical and histopathological data to navigate the diagnostic complexities of thyroid and salivary gland lesions. A multidisciplinary approach and standardized algorithms are essential for improving diagnostic accuracy and patient outcomes.

P2, N=9, Active, not recruiting, National Cancer Institute (NCI) | N=27 --> 9 | Trial completion date: Oct 2024 --> Dec 2025

These proteins could serve as readily accessible markers in morphologically borderline cases showing RAS mutations. Additionally, our findings may provide insights into the distinct pathogenic pathways through which RAS-mut and RAS-wt NIFTPs arise, highlighting the pivotal role of constitutive RAS-mitogen-activated protein kinase (MAPK) pathway activation in the development and progression of RAS-mut tumors.

P=N/A, N=200, Recruiting, Shanghai 6th People's Hospital | Not yet recruiting --> Recruiting

P=N/A, N=200, Not yet recruiting, Shanghai 6th People's Hospital

Given the germline DICER1 variant, this may also represent the first reported instance of DICER1 syndrome manifesting as HDFCO. Further research into the prognostic factors and optimal treatment of HFDCO is needed.

After 1-year regular follow-up, no significant abnormalities were found in tumor indicators, Tg, thyroid function, neck ultrasound and abdominopelvic enhanced computed tomography (CT). This MSO case with normal Tg and multiple implantation metastasis aimed to discuss its clinical management especially for Tg and 131I and to improve its prognosis.

In this limited case series, two patients were dead at the last follow-up. Whether these findings are consistent within this patient population remains to be addressed as more patient series are published.

The specificity of CD56, CK19, and HBME-1 in diagnosing follicular thyroid carcinoma (FTC) from FA was 84.21%, 85%, and 84.21%, respectively. Our study highlights the diagnostic utility of CD56, CK19, and HBME-1 in thyroid neoplasms incorporating these markers into routine diagnostic panels can significantly enhance the accuracy and reliability of thyroid malignancy assessments.

The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

P2, N=21, Recruiting, City of Hope Medical Center | Initiation date: Nov 2024 --> Jul 2024

The reason why identical mutations in the same miRNA processor gene can lead to such a myriad of thyroid conditions, ranging from benign TFND, to FTCs and PDTCs, remains unclear. This review highlights key features of miRNA regulator gene mutations in thyroid disease and explores their potential roles as drivers or progression events in tumor development.

As the use of PET/CT evolves in oncology, this review explores its application in regard to staging, detection of recurrence, and follow-up in terms of managing DTC while also evaluating potential challenges that may occur in the future. The review also considers emerging radiotracers and the theragnostic potential of PET/CT.

P=N/A, N=12, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Nov 2024 | Trial primary completion date: May 2025 --> Nov 2024

The higher expression of PD-1 and PD-L1 may contribute to tumor progression. Therefore, combinational immunotherapy by these immune checkpoint inhibitors might be a promising strategy for clinical improvement in patients with thyroid cancer, especially those with ATC.

HMBE1 and galectin 3 can be beneficial in distinguishing malignancy from benignity, while CK19, galectin 3, and HMBE1 aid in identifying papillary carcinomas of follicular variant. In the differential diagnosis depending on histological morphology, various panels with automated protocols prove greatly useful.

In summary, the majority of the targeted NIFTPs had "suspicious" Afirma testing results (85 %), TIRADS 4 scores (60 %) and either AUS/FLUS (53.7 %) or FN (31.5 %) FNA results. The sensitivity and specificity of cytology for diagnosing NIFTP were 90 % and 57 %, respectively, with a positive predictive value (PPV) of 16 % and negative predictive value of 98 %.

PD-L1 expression varies across different TC types and histological subtypes and may be modulated by the mutational landscape. PD-L1 expression in ATC is associated with shorter PFS. Follow up studies are warranted to elucidate the molecular mechanism driving the observed differences in immune pathways, potentially paving the way for the development of more effective and personalized immune therapies for patients with aggressive TC.

Despite strong clinical data in humans, there are still major knowledge gaps on the function of TLS in cancer. Herein, we highlight the known biology and clinical impact of TLS, which offer further evidence to harness TLS for improved immunotherapeutics.

It is concluded that AGR2 expression occurs in a broad range of different tumor entities and that AGR2 assessment may serve as a diagnostic aid for the distinction of thyroidal neoplasms and as a prognostic marker in various cancer types.

The detection of BRAF fusions and their many partners was enabled by the Afirma XA exome-enriched RNASeq panel. Although BRAF fusions occurred in only 0.2% of thyroid nodules, they were GSC-Suspicious and lacked typical BRAF/RAS mutations. Interestingly, expression signatures associated with malignancy varied by fusion partner.

P2, N=79, Terminated, Grupo Espanol de Tumores Neuroendocrinos | Trial completion date: Dec 2025 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2025 --> Nov 2024; In compliance with current legislation applicable to Clinical Trials, following the instructions of the Spanish Agency for Medicines and Health Products.

Accurately predicting the malignant pathology of FNs is challenging, and inducing gene panel testing will be helpful for managing FN tumors. Our scoring system would also be useful in estimating the risk of malignancy.

Neoadjuvant use of tyrosine kinase inhibitors seems extremely effective in downstaging surgically unresectable differentiated thyroid cancers to achieve R0 resection while avoiding unnecessary surgical morbidities. A multidisciplinary approach with early genomic profiling to guide personalized neoadjuvant use of tyrosine kinase inhibitors is essential. Prospective studies are urgently needed to define the potential role of neoadjuvant tyrosine kinase inhibitors in advanced thyroid cancer management.

Targeted next-generation sequencing suggested that MYCN and GLI2/3 amplifications and TP53 mutations might be involved in progression of these follicular tumours to BCC. Our study confirms the high prevalence of BFH, representing up to 24% of skin tumours in NBCCS and potentially being BCC precursors.

To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.

While the identification of NIFTP represents a significant advancement in thyroid cancer diagnosis, challenges remain in refining preoperative diagnostic tools and establishing optimal long-term follow-up strategies. The objective of this review is to provide a comprehensive overview of NIFTP, including its histopathological characteristics, molecular profile, clinical presentation, diagnostic criteria, management strategies, and future research directions.

P2, N=30, Recruiting, Massachusetts General Hospital | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Mar 2024 --> Mar 2025

Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin-angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

Our data demonstrate high feasibility of [18F]SiTATE PET/CT in a small cohort of patients with MTC and DTC. The use of [18F]SiTATE may overcome logistical disadvantages of 68Ga-based tracers and facilitate SSTR-targeted PET/CT imaging of thyroid carcinoma.

Since 2016, patients with BRAFK601E-positive nodules receive less aggressive treatment. The risk of recurrence of BRAFK601E-positive tumors without other, high-risk features appears to be low, and lobectomy without radioiodine is likely sufficient treatment for these patients.

P1/2, N=263, Active, not recruiting, Salubris Biotherapeutics Inc | Recruiting --> Active, not recruiting

ThyraMIRv2 platform does not improve indeterminate thyroid nodule malignancy stratification compared to ThyGeNEXT-ThyraMIRv1 multiplatform test version 1. ThyraMIRv2 improves malignant RAS-mutated nodule detection but increases false positives. Future studies encompassing a larger cohort of RAS-mutated with surgical pathology results are warranted to better characterize the performance parameters of this classifier.

67% (95% CI: 35.65-48.84) and 26.79% (95% CI: 19.40-34.33), respectively, and a negative predictive value (NPV) of 95.61% (95% CI: 92.86-97.99) and 94.07% (95% CI: 90.44-97.08) in the training and validation sets, respectively. The model can accurately rule out FTC in low-risk nodules, thereby providing surgeons with a practical tool to determine the necessary extent of surgical intervention for nodules flagged as suspicious by IOFS.

These findings suggest that the symbiotic relationship between these two cell types could represent a therapeutic vulnerability. This review examines the key components and signaling mechanisms involved in the synapses between B cells and Tfh cells, emphasizing their significant role in the pathobiology of AITL and potential as therapeutic targets.

However, they did not affect clinical outcomes, possibly due to short follow-up. Reflex testing for this genetic alteration in miFTCs and miOTCs could be justified regardless of tumor size, though the clinical benefit remains uncertain.

In older adolescents with ITN, the A firma GSC showed excellent performance when de fining a true negative result by histology or clinical follow-up. Our findings indicate that an A firma GSC-B result appears reassuring and may allow for a more conservative management strategy in younger patients with ITN.

miRNA pairwise expression profiling enhances the miRNA algorithmic classifier and mutation status in assessing malignancy risk and allowed for further stratification of both RAS-positive and mutation-negative Bethesda V thyroid nodules.