^
20d
Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms. (PubMed, Head Neck Pathol)
This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.
Journal
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BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • NOTCH1 (Notch 1) • TERT (Telomerase Reverse Transcriptase) • NF2 (Neurofibromin 2) • RAS (Rat Sarcoma Virus) • AGK (Acylglycerol Kinase) • CDX2 (Caudal Type Homeobox 2)
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BRAF V600E • BRAF V600 • ATM mutation • BRAF fusion • AGK-BRAF fusion • TERT mutation
22d
IoN- Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients (clinicaltrials.gov)
P2/3, N=504, Active, not recruiting, University College, London | Trial primary completion date: Dec 2023 --> Dec 2024
Trial primary completion date
25d
A Unique Case of Oncocytic Thyroid Cancer With an NBN Gene Pathogenic Variant (ENDO 2024)
Due to disease progression, lenvatinib was initiated...Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain... The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course.
Clinical
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NRAS (Neuroblastoma RAS viral oncogene homolog) • RAD50 (RAD50 Double Strand Break Repair Protein) • NKX2-1 (NK2 Homeobox 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DAXX (Death-domain associated protein) • PAX8 (Paired box 8) • TG (Thyroglobulin)
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TTF1 negative
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Oncomine™ Comprehensive Assay v3M
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Lenvima (lenvatinib) • zoledronic acid
1m
Molecular Pathology of Thyroid Tumors: Essential Points to Comprehend Regarding the Latest WHO Classification. (PubMed, Biomedicines)
The WHO 5th thus emphasizes the importance of classifying tumors based on both genetic abnormalities and histomorphology. This approach aids in achieving accurate pathological diagnosis and facilitates the early selection of appropriate treatment options, including molecular targeted therapies.
Review • Journal
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BRAF (B-raf proto-oncogene)
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BRAF V600E • BRAF V600
2ms
Trial completion date • Surgery
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RET (Ret Proto-Oncogene)
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sunitinib
3ms
Testing the Combination of Cabozantinib, Nivolumab, and Ipilimumab (CaboNivoIpi) for Advanced Differentiated Thyroid Cancer (clinicaltrials.gov)
P2, N=27, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Sep 2024 | Trial primary completion date: Jan 2024 --> Sep 2024
Trial completion date • Trial primary completion date • Combination therapy • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1)
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PD-L1 expression
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule) • ABP 206 (nivolumab biosimilar)
3ms
Folliculin (FLCN) Alterations in Thyroid Carcinoma: Incidence, Significance and Extraordinary Role as a Driver Gene in an Aggressive Mixed Papillary and Oncocytic Thyroid Carcinoma (USCAP 2024)
FLCN alterations are exceedingly rare in TCa with an incidence of pathogenic changes below 1%. However, FLCN may exceptionally serve as a key driver mutation in TCa, based on our index patient. Identification of FLCN mutations may be clinically important due to possible presence of a germline mutation predisposing to renal tumors and potential responsiveness to immune checkpoint inhibitors.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1) • FLCN (Folliculin) • PAX8 (Paired box 8)
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TP53 mutation • TMB-L • RB1 mutation • TTF1 expression + PD-L1 expression • FLCN mutation • NKX2-1 expression • RB1 mutation + TP53 mutation • TTF1 expression
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MSK-IMPACT
4ms
The Role of 5-Hydroxymethylcytosine as a Potential Epigenetic Biomarker in a Large Series of Thyroid Neoplasms. (PubMed, Endocr Pathol)
However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.
Journal
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HRAS (Harvey rat sarcoma viral oncogene homolog) • TERT (Telomerase Reverse Transcriptase) • RAS (Rat Sarcoma Virus)
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HRAS mutation • TERT mutation • TERT promoter mutation
5ms
Multiple Target Kinase Inhibitor and Anti-Programmed Death-1 Antibody in Patients With Advanced Thyroid Cancer (clinicaltrials.gov)
P2, N=115, Active, not recruiting, Fudan University | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Apr 2023 --> Dec 2023
Trial completion date • Trial primary completion date • Metastases
6ms
Oncocytic Follicular Cell-Derived Thyroid Tumors With Papillary Growth Pattern: A Clinicopathologic Study of 32 Cases. (PubMed, Arch Pathol Lab Med)
Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma.
Journal
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BRAF (B-raf proto-oncogene) • KRT19 (Keratin 19)
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BRAF V600E • BRAF V600 • BRAF wild-type • BRAF V600 wild-type
6ms
Genomic profiling of primary and metastatic thyroid cancers. (PubMed, Endocr Relat Cancer)
The frequency of subclonal mutations in ATCs was significantly higher than in PTCs (43% vs 25%, p#60;0.01) and PDTCs (43% vs 22%, p#60;0.01). Metastatic TCs are enriched in clinically informative genetic alterations such as RET translocations, BRAF hotspot mutations and NF1 biallelic losses that may be explored therapeutically.
Journal • Tumor mutational burden • Metastases
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • BCOR (BCL6 Corepressor)
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BRAF mutation • NF1 mutation
6ms
Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue. (PubMed, J Surg Res)
The CaSR is differentially expressed on parathyroid tissue making it a feasible target for parathyroid imaging. False positives might be anticipated with medullary and Hürthle cell cancers.
Journal
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CASR (Calcium Sensing Receptor)
7ms
Lenvatinib and Pembrolizumab in Differentiated Thyroid Cancers (DTC) (clinicaltrials.gov)
P2, N=57, Completed, Academic and Community Cancer Research United | Active, not recruiting --> Completed
Trial completion
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Keytruda (pembrolizumab) • Lenvima (lenvatinib)
7ms
The Safety and Effectiveness of rhTSH in Radioiodine Treatment for Patients With Differentiated Thyroid Cancer. (clinicaltrials.gov)
P2, N=120, Active, not recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Aug 2023 --> Aug 2024
Trial completion date • Trial primary completion date
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TG (Thyroglobulin)
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recombinant human thyroid stimulating hormone for injection (rhTSH)
8ms
"Copy number alteration" as the sole molecular finding of a Thyroseq test is more commonly seen in Hurthle cell neoplasms. (PubMed, Diagn Cytopathol)
In this study, CNAs were associated with Hurthle cell morphology on thyroid FNA and benign adenomas upon surgical follow-up. Therefore, if the only finding of a positive ThyroSeq v3 GC result is a CNA, conservative management can be considered if clinically indicated.
Retrospective data • Journal
8ms
Safety and efficacy of YBL-006, a novel anti-PD-1 antibody, in advanced solid tumors including G3 NET/NEC: results from a phase 1/2A study (SITC 2023)
Y-biologics Inc would like to thank all the participating patients, dedicated clinical trial investigators and their team members who have helped to bring this novel therapy to the clinic. This research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C1391, Republic of Korea).
P1/2 data • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker • Metastases
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
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TMB-H • MSI-H/dMMR
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Lunit SCOPE IO
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acrixolimab (YBL-006)
8ms
CSPG4-targeted CAR T cells demonstrate potent antitumor activity in an orthotopic murine model of anaplastic thyroid cancer (SITC 2023)
Conclusions Here we demonstrate the preclinical efficacy of a CSPG4-CAR T cell-based immunotherapy for the treatment of ATC. Our findings provide the rationale to design clinical studies for ATC patients not responding to currently available therapies, and patients with BRAF wild type tumors who are not eligible for treatment with the Dabrafenib/Trametinib combination, the only FDA-approved treatment for ATC.
Preclinical • CAR T-Cell Therapy • IO biomarker
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BRAF (B-raf proto-oncogene) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • IL2 (Interleukin 2) • CSPG4 (Chondroitin Sulfate Proteoglycan 4) • GZMA (Granzyme A)
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BRAF wild-type
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Mekinist (trametinib) • Tafinlar (dabrafenib)
8ms
THYROID CANCER IS MORE COMMON AMONG TRANSGENDER FEMALE VETERANS (ATA 2023)
The prevalence of thyroid cancer among transgender female veterans was 0. 341% (95% CI: 0. 223% ‐ 0.
Late-breaking abstract
|
ER (Estrogen receptor)
8ms
A REVIEW OF HURTHLE CELL CARCINOMAS MULTIFARIOUS PRESENTATION: A NEED FOR VIGILANT SURVEILLANCE AND UNMASKING OF DISTANT METASTASES (ATA 2023)
In clinical practice, long term follow up of hurthle cell carcinomas and a need for multidisciplinary team approach is critical for the management of these complex tumors. Our patient continues to receive imaging and biochemical surveillance.
Review • Late-breaking abstract
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TG (Thyroglobulin)
8ms
LOCAL IMMUNE RESPONSE IN THYROID CANCER IS SPECIFIC TO MUTATIONAL BACKGROUND AND HISTOLOGICAL TYPE (ATA 2023)
PD‐L1 expression varies significantly among different histological subtypes of TC highlighting the critical importance of patient selection for PD‐L1 based immunotherapies. Higher levels of suppressive immune markers may underly more aggressive clinical phenotypes in BRAF‐mutated‐TCs.
Late-breaking abstract • IO biomarker
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PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
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PD-L1 expression • BRAF mutation • RAS mutation • CTLA4 expression
9ms
Somatostatin Receptor Type 2 (SSTR2) and Thyroid Stimulating Hormone Receptor (TSHR) Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment. (PubMed, Mod Pathol)
OC patients displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in OA patients. This may be a key relationship that can be utilized to prognosticate and treat OCs.
Journal
|
SSTR (Somatostatin Receptor) • SSTR2 (Somatostatin Receptor 2)
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SSTR2 expression • SSTR2 positive
9ms
A Study of Avutometinib and Defactinib in People With Thyroid Cancer (clinicaltrials.gov)
P2, N=30, Recruiting, Memorial Sloan Kettering Cancer Center
New P2 trial
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • NF1 (Neurofibromin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • ALK rearrangement • BRAF V600K • NF1 mutation • RAS mutation • RET mutation • RET rearrangement
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avutometinib (VS-6766) • defactinib (VS-6063)
10ms
5hmC Immunohistochemistry: A Predictor of TERT Promoter Mutational Status in Follicular Thyroid Carcinoma? (PubMed, J Histochem Cytochem)
The sensitivity and specificity for 5hmC immunohistochemistry (IHC) to detect mutated cases were 10% and 100% (RM236) and 20% and 89% (4D9). Therefore, 5hmC IHC is not a sensitive marker for detecting TERT promoter mutations in follicular thyroid tumors.
Journal
|
TERT (Telomerase Reverse Transcriptase)
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TERT mutation • TERT promoter mutation
10ms
Mitochondrial-encoded complex I impairment induces a targetable dependency on aerobic fermentation in Hurthle cell carcinoma of the thyroid. (PubMed, Cancer Discov)
We demonstrate in cultured cells and a PDX model that small molecule inhibitors of lactate dehydrogenase selectively induce an ATP crisis and cell death in HTC. This work demonstrates that complex I loss exposes fermentation as a therapeutic target in HTC and has implications for other tumors bearing mutations that irreversibly damage mitochondrial respiration.
Journal
10ms
Effectors enabling adaptation to mitochondrial complex I loss in Hurthle cell carcinoma. (PubMed, Cancer Discov)
Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity.
Journal
|
GPX4 (Glutathione Peroxidase 4)
10ms
Characterizing the Immune Microenvironment and Neoantigen Landscape of Hürthle Cell Carcinoma to Identify Potential Immunologic Vulnerabilities. (PubMed, Cancer Res Commun)
The authors found the immune microenvironment in HCC to be depleted. This immunosuppression is associated with a global LOH from haploidization and uniparental disomy, resulting in whole chromosome losses across the genome.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
|
PD-L1 expression
10ms
A clinically applicable molecular classification of oncocytic cell thyroid nodules. (PubMed, Endocr Relat Cancer)
CNA patterns were different between the histopathological subgroups (p<0.001). By applying the structured interpretation and considerations provided by the current study, CNA-LOH analysis using an NGS panel that is feasible for daily practice may be of great added value to the widespread application of molecular diagnostics in the diagnosis and risk stratification of OCN.
Journal
11ms
A Study to Evaluate the Safety and Efficacy of Lenvatinib in Participants With Refractory Differentiated Thyroid Cancer (clinicaltrials.gov)
P4, N=50, Active, not recruiting, Eisai Pharmaceuticals India Pvt. Ltd | Trial completion date: Dec 2022 --> May 2024 | Trial primary completion date: Dec 2022 --> May 2024
Trial completion date • Trial primary completion date • Metastases
|
Lenvima (lenvatinib)
11ms
Evaluation of 177Lu-DOTA-EB-FAPI in Patients With Metastatic Radioactive Iodine Refractory Thyroid Cancer (clinicaltrials.gov)
P1, N=20, Recruiting, The First Affiliated Hospital of Xiamen University | Phase classification: P2 --> P1
Phase classification • Metastases
|
FAP (Fibroblast activation protein, alpha)
|
177Lu-DOTA-EB-FAPI
11ms
Pituitary Metastases From Differentiated Thyroid Cancers: A Systematic Review. (PubMed, World J Oncol)
Larger studies are needed to examine the relationship between age and survival in PM from DTC. Also, more observational data are required to determine the predictors of survival and compare the efficacy of the different treatment modalities in patients with PM from DTC.
Review • Journal
11ms
A Case Report For Hurthle Cell Neoplasm Suspicious For Carcinoma (ENDO 2023)
Despite being rare, Hurthle cell carcinoma still affects several patients every year. It is usually diagnosed when patients present clinically with thyroid nodules or incidental findings on imaging of the neck, like in this case. It is characterized by the presence of Hurthle cells in histology.
Clinical • Late-breaking abstract
12ms
Clinico-cytopathological subcategorization in thyroid nodules of atypia of undetermined significance/follicular lesion of undetermined significance using the TIRADS and Bethesda classifications. (PubMed, Front Endocrinol (Lausanne))
ACR TI-RADS helps evaluate malignancy only in the Hürthle cell AUS/FLUS subcategory of AUS/FLUS. Besides, cytopathological reporting based on the suggested AUS/FLUS subclassification could help clinicians take appropriate measures to manage thyroid nodules.
Journal
12ms
High Grade Differentiated Follicular Cell-Derived Thyroid Carcinoma Versus Poorly Differentiated Thyroid Carcinoma: A Clinicopathologic Analysis of 41 Cases. (PubMed, Endocr Pathol)
PDTC presents at a slightly younger age, with large tumors, often in a background of multifocal tumors, with tumor necrosis nearly always seen, a median Ki-67 labeling index of 6.9%, with 29% of patients developing metastatic disease. Separation between groups is meaningful as early metastatic disease is relatively common, but mitotic counts/labeling indices are not different between the groups nor able to potentially risk stratify development of metastatic disease.
Journal
1year
Hurthle cell carcinoma: a rare variant of thyroid malignancy - a case report. (PubMed, Ann Med Surg (Lond))
Pain, rapid growth, or significant compressive symptoms are suggestive of an invasive one. This case highlights on rarity of disease, presentation, and availability of treatment modality.
Journal
1year
Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis. (PubMed, Cancers (Basel))
They presented quantitative levels and distribution patterns that were different for each tumor and differed from those of a benign thyroid pathology, goiter (BG). Therefore, the reported methodology can be beneficial when the microscopist must differentiate between HC, AC, MC, and BG.
Journal
|
HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1) • HSPD1 (Heat Shock Protein Family D (Hsp60) Member 1)
1year
PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer (clinicaltrials.gov)
P2, N=19, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 19
Enrollment closed • Enrollment change • Combination therapy
|
BRAF V600E • BRAF V600 • BRAF V600K • BRAF V600D
|
Mekinist (trametinib) • Tafinlar (dabrafenib) • spartalizumab (PDR001)
1year
An Unusual Case of Papillary Thyroid Carcinoma With Biallelic MEN1 Variants In a Patient With MEN1 (ENDO 2023)
PTC in MEN1 has been rarely reported in the literature [1]. However, per our knowledge, this is the first report of a PTC with second-hit in the MEN1 gene. Somatic MEN1 pathogenic variants have been reported in occasional cases of thyroid oncocytic tumors and NRAS is more frequently associated with follicular or oncocytic thyroid tumors.
Clinical
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NRAS (Neuroblastoma RAS viral oncogene homolog) • MEN1 (Menin 1)
|
NRAS Q61K • NRAS Q61 • TERT 124C>T
|
TruSight Oncology 500 Assay
1year
Concomitant Metastatic Hurthle Cell Carcinoma and Rectal Cancer, Challenges in Diagnosis and Management (ENDO 2023)
He underwent 6 cycles of palliative chemotherapy with carboplatin and Taxol for carcinoma of unknown origin...He received suppressive dose levothyroxine...For rectal cancer, he received radiation therapy and capecitabine.Our case is interesting for several reasons...Combination therapy with Lenvatinib and Pembrolizumab is currently under trial for aggressive thyroid malignancy...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*
PD(L)-1 Biomarker • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • NCAM1 (Neural cell adhesion molecule 1) • NKX2-1 (NK2 Homeobox 1) • SDC1 (Syndecan 1) • NTRK (Neurotrophic receptor tyrosine kinase) • PAX8 (Paired box 8) • TG (Thyroglobulin)
|
PD-L1 negative • TMB-L • ATM positive • PAX8 positive • NTRK fusion
|
Keytruda (pembrolizumab) • carboplatin • paclitaxel • Lenvima (lenvatinib) • capecitabine
1year
Metastatic Oncocytic (formerly Hürthle Cell) Thyroid Carcinoma in a Patient With Birt-Hogg-Dubé Syndrome (ENDO 2023)
Thyroid tumors have been occasionally reported in BHD. While most of them are papillary or follicular tumors, only one case of OTC in BHD has been previously reported in the literature [1]. This report underscores the importance of screening for thyroid neoplasms in patients with BHD.
Clinical • Metastases
|
TP53 (Tumor protein P53) • FLCN (Folliculin) • DAXX (Death-domain associated protein) • TG (Thyroglobulin)
|
TP53 R248Q • FLCN mutation
1year
Large (>4 cm) Intrathyroidal Encapsulated Well-Differentiated Follicular Cell-Derived Carcinoma Without Vascular Invasion May Have Negligible Risk of Recurrence Even When Treated with Lobectomy Alone. (PubMed, Thyroid)
Large intrathyroidal encapsulated well-differentiated thyroid carcinoma without vascular invasion follow an extremely indolent clinical course with negligible risk of recurrence. Lobectomy alone without RAI may be the appropriate treatment strategy for this selected group of patients.
Journal