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Sep 2023 DOI 10.14302/issn.2574-4496.jtc-23-4722
Background Patients with distant metastatic Medullary Thyroid Carcinoma (MTC) have an estimated 40% ten-year survival rate. Gain of function mutations in the REarranged during Transfection or RET gene in MTC can result in an aggressive phenotype resistant to traditional therapy. In this case report, we describe the treatment of an MTC patient with a unique RET kinase deletion mutation. Case presentation Since diagnosis, 21 years ago, this patient has had chronically elevated calcitonin levels (>40,000 pg/mL) that was unable to be controlled by conventual therapy and clinical trials. As result of uncontrolled MTC, metastatic disease was found in the spine, liver, and lungs. Circulating tumor DNA (ctDNA) analysis identified a RET 898-901Del mutation, reported as a variant of unknown significance. The treating physician identified that the deletion was in the activation loop of RET kinase and considered that the mutation was constitutively activating RET kinase. The patient was prescribed Pralsetinib, a small molecule inhibitor targeting the ATP binding site of RET. Pralsetinib treatment achieved a durable response and was able to significantly decrease serum calcitonin levels (<200 pg/mL) and tumor size. Conclusion This RET deletion mutation is a pathogenic mutation with comparable enzymatic activity to the more common RET M918T mutation. The case report highlights the versatility of structural biologic approaches to guide therapeutic decisions.
May 2015 DOI 10.14302/issn.2572-3030.jcgb-14-495
Thyroid carcinomas encompass a wide spectrum ranging from differentiated thyroid carcinoma (DTC) to poorly differentiated (PDC) and anaplastic thyroid carcinoma (ATC). DTC of both follicular (FTC) and papillary (PTC) types can progress to PDC and AC. The aim of our study was to evaluate if there is differential microRNA (miRNA) expression in various tumor subtypes during this progression. The miRNA profile of differentiated carcinomas (Follicular and Papillary) and ATC were compared with that of PDCs either by itself or in a background of differentiated carcinomas and anaplastic carcinomas. Unsupervised hierarchical clustering analysis revealed that FTC and PDC tend to cluster together in the absence of ATC. Interestingly, in cases with presence of all components i.e. FTC, PDC and ATC, the miRNA profile of poorly differentiated component clusters with that of the Anaplastic carcinoma component. miR-494 and miR-125a-5p were found to be differentially regulated in tumors with an anaplastic component and even the well-differentiated component (FTC) of these tumors were found to be aligned with the anaplastic profile. In addition, we also discovered some differentially regulated miRNAs in follicular variant of papillary thyroid carcinoma as compared to follicular thyroid carcinoma (miR-486-5p and miR-31).
Jun 2026 DOI 10.14302/issn.2574-4496.jtc-26-6304
Objective To evaluate the treatment outcomes of patients with Differentiated thyroid cancer (DTC) who underwent total thyroidectomy followed by RAI therapy at the Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC) in Oman. Methods This is a retrospective observational clinical study conducted at SQCCCRC. The study included all patients diagnosed with DTC who were admitted to SQCCCRC between June 2021 and November 2023. A total of 255 patients were identified and met the inclusion criteria for this study. Results The mean age at diagnosis was 39.9 ± 12.4 years (range: 14–79), with 78% of patients being female. The mean BMI was 30.3 ± 6.4 kg/m², with nearly half of the cohort (48.2%) classified as obese (BMI ≥ 30). Most patients had papillary thyroid carcinoma (92.9%), while follicular and Hürthle cell carcinoma accounted for 5.9% and 0.8% of cases, respectively. Based on the American Joint Committee on Cancer (AJCC) staging, 86.3% of the patients were classified as stage I and 3.9% as stage II. Six patients (2.4%) had stage IVB disease. According to American Thyroid Association (ATA) risk stratification the majority were low-risk. Patient age was strongly associated with disease stage. The distribution of metastatic cases varied by region, with the highest proportion observed in Dhofar. Most patients (87.1%) received a single dose of radioactive iodine (RAI), with a median cumulative dose of 3.7 mCi). At six months post-treatment, 70.2% of patients had a TG level < 0.2 ng/mL. Conclusion The outcome of therapy in majority of our patients is favorable with 72% having excellent biochemical response at last follow up. None of the patients with distant metastasis achieved excellent response and a high proportion of them came from the Dhofar governorate, a targeted intervention would be of benefit. Low risk patients require special attention and may need radioactive iodine during follow up, unlike other regions and hence warrant very close follow up and further review to establish the best practice guidelines in our region.
Feb 2019 DOI 10.14302/issn.2574-4496.jtc-19-2657
Image guided ablations might be regarded as a promising effective and safe alternative for treatment of recurrent thyroid cancer in particular in patients with high surgical risk or refusing surgery. Furthermore, image guided ablations seems to represent a promising alternative to surgery or observation for micropapillary thyroid carcinoma, with the aim of providing an effective treatment with minimal invasiveness. Further studies are necessary to confirm the role in this setting
Feb 2016 DOI 10.14302/issn.2574-4496.jtc-15-838
Thyroid transcription factor-1 (TTF-1) is known to play key roles in thyroid organogenesis, in thyroid cell proliferation and in the expression of genes involved in thyroid differentiated function. Many human thyroid cancer cell lines keep producing TTF-1 despite the loss of differentiated gene expression, raising a question about the role of the factor in these cells. In order to investigate this point, we used a chimeric protein acting as a functional antagonist of TTF-1 transcriptional activity that was expressed conditionally in 8505C cells originating from an anaplastic thyroid carcinoma. We observed a growth arrest of 8505C thyroid cancer cells when the endogenous TTF-1 transcriptional activity was inhibited. It correlated with decreased levels of several mRNAs encoding positive effectors of cell proliferation like CDK1 and cyclinB1, and increased levels of various mRNAs encoding negative regulators of cell division like CDKN2B and DUSP6. In conclusion, the persistence of TTF-1 expression observed in the dedifferentiated human thyroid cancer cell line 8505C reflects the need of TTF-1 activity for the proliferation of these tumor cells.
May 2015 DOI 10.14302/issn.2372-6601.jhor-14-382
Background/Aims: Thyroid disorders are a common, worldwide clinical problem in general practice.It presents predominantly as a thyroid nodule. Each thyroid nodule has a risk of cancer. The incidence of thyroid cancer is much more common in Saudi Arabia in comparison to the West. There is a worldwide increase in the incidence of thyroid cancer. The objective of this study is to highlight in details the wide spectrum of histopathologic diagnosis encountered in patient undergoing thyroid surgery in the population of Riyadh region of Saudi Arabia. Patients and Methods: Retrospective review of all thyroid samples for 256 patients whom underwent thyroid surgery at King Khalid University Hospital, King Saud University, Riyadh, during the period between 2000 and 2009. Of those, 171 cases were non neoplastic and 85 neoplastic lesions. Females constitute 80% of non neoplastic lesions and 79% of all thyroid malignancies. The peak incidence of thyroid cancer was in the third decade. Papillary thyroid carcinoma was the most common cancer (71%). Conclusion: Thyroid cancer is a common cancer in Saudi Arabia; it is the second most common cancer in females. The increasing rates of thyroid cancer occur predominantly in women. Papillary thyroid carcinoma accounted for the bulk of this increase. Additional studies are needed to explain the rise in papillary thyroid carcinoma incidence in Saudi Arab as well as throughout the world and to search potential risk factors that are currently unrecognized.