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International Journal of Surgery Case... Jun 2024Intrathyroid thymic carcinoma (ITC) is a malignant epithelial tumor with thymic differentiation within the thyroid gland. Its frequency is up to 0.15 % of all malignant...
INTRODUCTION AND IMPORTANCE
Intrathyroid thymic carcinoma (ITC) is a malignant epithelial tumor with thymic differentiation within the thyroid gland. Its frequency is up to 0.15 % of all malignant thyroid tumors. It is frequently a low-grade tumor. The clinical status is often misleading to other more advanced tumors like cervical lymph node metastasis of nonkeratinizing squamous cell carcinoma, undifferentiated variant, dedifferentiated carcinoma, and medullary carcinoma of the thyroid.
CASE PREPARATION
The patient came to us with the diagnosis of cervical lymph node metastasis of undifferentiated carcinoma. This patient was first diagnosed with cervical lymph node metastasis in the previous hospital. After having an ITC diagnosis, the patient was operated on the rennet of thyroid glands and had a low dose of radio-chemotherapy for recurrent prevention purposes. It is the first case of such a disease diagnosed at our hospital and also the first case reported in Vietnam.
CLINICAL DISCUSSION
ITC is rare and appears similar to all thymic carcinoma variants. The most popular type is squamous carcinoma. Immunohistochemical stains are typical for thymic origin tumors with CD5, CD117 positive. ITC is often negative for monoclonal PAX8 but positive in this case (MRQ-50 clone, Sigma-Aldrich). This finding is an exciting one that should considered.
CONCLUSION
Reporting the case increases the awareness of the disease, especially among Vietnam Doctors and patients.
PubMed: 38762961
DOI: 10.1016/j.ijscr.2024.109762 -
JCO Precision Oncology May 2024Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are...
PURPOSE
Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in oncogene, and lower-frequency alterations are reported in and . Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers.
MATERIALS AND METHODS
Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of novel mutation.
RESULTS
Mutational landscape analysis shows expected mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like , , , and to be altered only in the -negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the -negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation.
CONCLUSION
Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.
Topics: Humans; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Male; Female; Middle Aged; Mutation; Adult; Aged; Young Adult
PubMed: 38754058
DOI: 10.1200/PO.23.00622 -
Endocrine-related Cancer Jul 2024The age-specific development of the three constituent components of multiple endocrine neoplasia type 2 (MEN 2) is incompletely characterized for many of the >30...
The age-specific development of the three constituent components of multiple endocrine neoplasia type 2 (MEN 2) is incompletely characterized for many of the >30 causative rearranged during transfection (RET) mutations, which this genetic association study aimed to specify. Included in the study were 683 carriers of heterogeneous RET germline mutations: 53 carriers with 1 highest-risk mutation (codon 918); 240 carriers with 8 different high-risk mutations (codon 634); 176 carriers with 16 different intermediate-risk mutations (codon 609, 611, 618, 620, or 630); and 214 carriers with 6 different low-risk mutations (codon 768, 790, 804, or 891).There was a strong genotype-specific development of MEN 2 constituent components, with distinct age gradients from C cell disease to node negative medullary thyroid cancer (MTC), from node negative to node positive MTC, from node positive MTC to pheochromocytoma, and from pheochromocytoma to primary hyperparathyroidism. Primary hyperparathyroidism was not observed among the 53 MEN 2B patients who carried highest-risk mutations (age range: 0.5-50 years), of whom no more than 12 (23%) and 3 (6%) carriers were older than age 30 years and 35 years, respectively. The age-specific development of MTC differed significantly between the four RET risk categories, whereas the age-specific development of pheochromocytoma differed significantly only between the two strongest RET risk categories. No significant differences were noted in the development of primary hyperparathyroidism. These findings delineate age-specific disease manifestation corridors for the three constituent components of MEN 2 by RET genotype. These corridors are useful for initial risk assessment and organ-specific surveillance of newly identified RET carriers going forward.
Topics: Humans; Proto-Oncogene Proteins c-ret; Middle Aged; Adult; Multiple Endocrine Neoplasia Type 2a; Adolescent; Male; Female; Thyroid Neoplasms; Young Adult; Pheochromocytoma; Child; Aged; Child, Preschool; Adrenal Gland Neoplasms; Genotype; Infant; Germ-Line Mutation; Carcinoma, Neuroendocrine; Heterozygote; Hyperparathyroidism, Primary; Multiple Endocrine Neoplasia Type 2b; Aged, 80 and over
PubMed: 38753300
DOI: 10.1530/ERC-24-0038 -
Clinical Journal of Gastroenterology May 2024Multiple endocrine neoplasia type 2B is a rare autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, Marfan-like...
Multiple endocrine neoplasia type 2B is a rare autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, Marfan-like fatigue, a peculiar face with thickening of the lips, mucosal neuromas on the lips and tongue, and gastrointestinal phenomena. Most patients harbor pathological variants of the RET gene. Herein, we present the first case of a 14 year-old boy who experienced small intestinal volvulus along with a megacolon, and he was diagnosed with multiple endocrine neoplasia type 2B. The patient complained of constipation since he was 2 years old and slowly progressive abdominal distension at school age. At 14 years of age, he presented with remarkable megacolon mimicking Hirschsprung's disease and complicated with small intestinal volvulus. The volvulus was successfully repaired, and the particularly dilated transverse colon was resected following a rectal biopsy. Histopathological evaluation of the resected transverse colon revealed to be compatible with ganglioneuromatosis. After emergency surgery, the patient was diagnosed with multiple endocrine neoplasia type 2B with medullary thyroid carcinoma, and a de novo variant of RET was confirmed. Gastroenterologists should consider it when treating patients with constipation, especially those with megacolon. Therefore, timely diagnosis may lead to appropriate treatment of medullary thyroid carcinoma and improve mortality.
PubMed: 38753051
DOI: 10.1007/s12328-024-01979-y -
Small (Weinheim An Der Bergstrasse,... May 2024Misfolding and aggregation of amyloid peptides into β-structure-rich fibrils represent pivotal pathological features in various neurodegenerative diseases, including...
Misfolding and aggregation of amyloid peptides into β-structure-rich fibrils represent pivotal pathological features in various neurodegenerative diseases, including Alzheimer's disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). The development of effective amyloid detectors and inhibitors for probing and preventing amyloid aggregation is crucial for diagnosing and treating debilitating diseases, yet it poses significant challenges. Here, an aggregation-induced emission (AIE) molecule of ROF2 with multifaceted functionalities as an amyloid probe and a screening tool for amyloid inhibitors using different biophysical, cellular, and worm assays, are reported. As an amyloid probe, ROF2 outperformed ThT, demonstrating its superior sensing capability in monitoring, detecting, and distinguishing amyloid aggregates of different sequences (Amyloid-β, human islet amyloid polypeptide, or human calcitonin) and sizes (monomers, oligomers, or fibrils). More importantly, the utilization of ROF2 as a screening molecule to identify and repurpose cardiovascular drugs as amyloid inhibitors is introduced. These drugs exhibit potent amyloid inhibition properties, effectively preventing amyloid aggregation and reducing amyloid-induced cytotoxicity both in cells and nematode. The findings present a novel strategy to discovery AIE-based amyloid probes and to be used to repurpose amyloid inhibitors, expanding diagnostic and therapeutic options for neurodegenerative diseases while addressing vascular congestion and amyloid aggregation risks.
PubMed: 38751069
DOI: 10.1002/smll.202400879 -
ESMO Open May 2024This post-hoc retrospective study describes long-term patient-reported outcomes (PROs) for REarranged during Transfection (RET)-altered non-small-cell lung cancer...
BACKGROUND
This post-hoc retrospective study describes long-term patient-reported outcomes (PROs) for REarranged during Transfection (RET)-altered non-small-cell lung cancer (NSCLC), medullary thyroid cancer (MTC), non-MTC thyroid cancer (TC), and tumor agnostic (TA) patients (Data cut-off: January 2023) from the LIBRETTO-001 trial.
PATIENTS AND METHODS
Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). Patients with MTC also completed a modified version of the Systemic Therapy-Induced Diarrhea Assessment Tool (mSTIDAT). The proportion of patients with improved, stable, or worsened status after baseline was reported. PROs were summarized at 3 years (cycle 37) post-baseline for the NSCLC and MTC cohorts, and at 2 years (cycle 25) post-baseline for the TC and TA cohorts. Time-to-event outcomes (time to first improvement or worsening and duration of improvement) were reported.
RESULTS
The baseline assessment was completed by 200 (63.3%), 209 (70.8%), 50 (76.9%), and 38 (73.1%) patients in the NSCLC, MTC, TC, and TA cohorts, respectively. The total compliance rate was 80%, 82%, 70%, and 85%, respectively. Approximately 75% (NSCLC), 81% (MTC), 75% (TC), and 40% (TA) of patients across all cohorts reported improved or stable QLQ-C30 scores at year 3 (NSCLC and MTC) or year 2 (TC and TA) with continuous selpercatinib use. Across cohorts, the median time to first improvement ranged from 2.0 to 19.4 months, the median duration of improvement ranged from 1.9 to 28.2 months, and the median time to first worsening ranged from 5.6 to 44.2 months. The total compliance rate for the mSTIDAT was 83.7% and the proportion of patients with MTC who reported diarrhea on the mSTIDAT was reduced from 80.8% at baseline to 35.6% at year 3.
CONCLUSIONS
A majority of patients with RET-driven cancers improved or remained stable on most QLQ-C30 domains, demonstrating favorable health-related quality of life as measured by the QLQ-C30 during long-term treatment with selpercatinib.
Topics: Humans; Patient Reported Outcome Measures; Male; Female; Middle Aged; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Thyroid Neoplasms; Pyrazoles; Aged; Quality of Life; Proto-Oncogene Proteins c-ret; Carcinoma, Neuroendocrine; Pyridines; Adult
PubMed: 38749381
DOI: 10.1016/j.esmoop.2024.103444 -
Thyroid : Official Journal of the... May 2024Skip metastases, node metastases in the lateral neck sparing the ipsilateral central neck, challenge the current concept of central-to-lateral lymphatic spread. This...
Skip metastases, node metastases in the lateral neck sparing the ipsilateral central neck, challenge the current concept of central-to-lateral lymphatic spread. This study sought to delineate patterns of central and lateral neck involvement in unilateral papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC). This was a retrospective correlative analysis of nodal patterns in surgical specimens from patients with unilateral PTC or MTC who had undergone thyroidectomy with at least ipsilateral central neck dissection between November 1994 and January 2024 at a tertiary referral center. Included were 833 patients with unilateral PTC and 640 patients with unilateral MTC. Simultaneous presence or absence of node metastases was noted in ipsilateral central and lateral neck compartments in 76.6-78.1% of patients with PTC (both node positive in 27.0-54.7% and both node negative in 23.4-49.6%) and 77.3-80.0% of patients with MTC (both node positive in 26.6-33.2% and both node negative in 44.1-53.4%). Only one ipsilateral neck compartment was node positive in 21.9-23.4% of patients with PTC and 20.0-22.7% of patients with MTC. The ipsilateral central, but not the ipsilateral lateral compartment, was node positive in 8.8-16.9% with PTC and 8.6-8.8% of patients with MTC, whereas the ipsilateral lateral, but not the ipsilateral central compartment, was node positive in 6.5-13.1% with PTC and 11.3-14.1% with MTC. Ipsilateral lateral neck involvement sparing the ipsilateral central neck was 1.5-2 times more frequent in patients with node positive MTC than patients with node positive PTC (24.2-25.2% vs. 12.9-17.1%). Greater numbers of node metastases in the ipsilateral central neck compartment were associated with more frequent involvement of the ipsilateral lateral, contralateral central, and contralateral lateral neck compartments. Thyroid tumor diameter intensified nodal spread without changing nodal spread patterns. These histopathological findings, which need to be interpreted in light of the respective tumor biology, offer an unprecedented glimpse at the metastatic patterns of unilateral PTC and MTC. Customizing neck dissection to the patterns of nodal spread, considering operative status (initial vs. reoperative surgery) and experience with neck dissection, may require more frequent concomitant dissections of ipsilateral central and ipsilateral lateral neck compartments.
PubMed: 38717955
DOI: 10.1089/thy.2024.0076 -
Clinical Nuclear Medicine Jul 2024In adults, 68 Ga-FAP inhibitor ( 68 Ga-FAPI) PET/CT outperforms 68 Ga-radiolabeled somatostatin analog peptides ( 68 Ga PET/CT) and 18 F-FDG PET/CT in detecting thyroid...
In adults, 68 Ga-FAP inhibitor ( 68 Ga-FAPI) PET/CT outperforms 68 Ga-radiolabeled somatostatin analog peptides ( 68 Ga PET/CT) and 18 F-FDG PET/CT in detecting thyroid lesions. This is the case of a 13-year-old boy newly diagnosed with medullary thyroid cancer with high calcitonin level. 68 Ga PET/CT revealed the presence of only a primary thyroid lesion. Proven to be superior in detecting metastasis, 68 Ga-FAPI PET/CT was performed. The results came out negative for primary and potential metastatic lesions. This case sheds shed light on false-negatives reported in 68 Ga-FAPI PET/CT scans in pediatric patients, emphasizing the need for alternate radiotracers when a negative study is met.
Topics: Humans; Male; Adolescent; Thyroid Neoplasms; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Carcinoma, Neuroendocrine; Organometallic Compounds; Octreotide; False Negative Reactions
PubMed: 38717245
DOI: 10.1097/RLU.0000000000005259 -
World Journal of Surgical Oncology May 2024Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time...
BACKGROUND
Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated.
METHODS
A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated.
RESULTS
The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS.
CONCLUSION
Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.
Topics: Humans; Thyroid Neoplasms; Male; Female; Retrospective Studies; Calcitonin; Middle Aged; Carcinoma, Neuroendocrine; Prognosis; Adult; Neoplasm Recurrence, Local; Follow-Up Studies; Thyroidectomy; Aged; Survival Rate; Biomarkers, Tumor; Young Adult; Adolescent; Risk Factors; Time Factors
PubMed: 38711029
DOI: 10.1186/s12957-024-03397-3 -
Timing and Ideal Patient for an Appropriate Search for Somatic Mutation in Medullary Thyroid Cancer.JCO Precision Oncology May 2024RET somatic mutation analysis in sporadic MTC should be guided by postoperative evaluation results.
RET somatic mutation analysis in sporadic MTC should be guided by postoperative evaluation results.
Topics: Humans; Mutation; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms; Time Factors
PubMed: 38709990
DOI: 10.1200/PO.24.00017