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Cancer Medicine Jun 2024For medullary thyroid carcinoma (MTC) with no positive findings in the lateral neck before surgery, whether prophylactic lateral neck dissection (LND) is needed remains...
BACKGROUND
For medullary thyroid carcinoma (MTC) with no positive findings in the lateral neck before surgery, whether prophylactic lateral neck dissection (LND) is needed remains controversial. A better way to predict occult metastasis in the lateral neck is needed.
METHODS
From January 2010 to January 2022, patients who were diagnosed with MTC and underwent primary surgery at our hospital were retrospectively reviewed. We collected the patients' baseline characteristics, surgical procedure, and rescored the ultrasound images of the primary lesions using American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Regularized logistic regression, 5-fold cross-validation and decision curve analysis was applied for lateral lymph node metastasis (LLNM) model's development and validation. Then, we tested the predictive ability of the LLNM model for occult LLNM in cN patients.
RESULTS
A total of 218 patients were enrolled. Five baseline characteristics and two TI-RADS features were identified as high-risk factors for LLNM: gender, baseline calcitonin (Ctn), tumor size, multifocality, and central lymph node (CLN) status, as well as TI-RADS margin and level. A LLNM model was developed and showed a good discrimination with 5-fold cross-validation mean area under curve (AUC) = 0.92 ± 0.03 in the test dataset. Among cN patients, our LLNM model achieved an AUC of 0.91 (95% CI, 0.88-0.94) for predicting occult LLNM, which was significantly higher than the AUCs of baseline Ctn (0.83) and CLN status (0.64).
CONCLUSIONS
We developed a LLNM prediction model for MTC using machine learning based on clinical baseline characteristics and TI-RADS. Our model can predict occult LLNM for cN patients more accurately, then benefit the decision of prophylactic LND.
Topics: Humans; Thyroid Neoplasms; Male; Female; Machine Learning; Lymphatic Metastasis; Middle Aged; Carcinoma, Neuroendocrine; Retrospective Studies; Adult; Lymph Nodes; Neck Dissection; Aged; Thyroidectomy
PubMed: 38808852
DOI: 10.1002/cam4.7155 -
Endocrinology, Diabetes & Metabolism... Apr 2024RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented...
SUMMARY
RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented efficacy compared to previous multi-kinase treatments. Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm usually driven by somatic BRAF mutations, resulting in dysregulated MAPK signalling. We describe a 22-year-old woman with metastatic MTC to regional lymph nodes, lung and liver. Tumour tissue harboured a somatic pathogenic RET variant p.(M918T) and selpercatinib was commenced. She experienced sustained clinical, biochemical and radiological responses. Two years later, she developed rapidly progressive apical lung nodules, prompting biopsy. Histopathology demonstrated LCH with a rare BRAF variant p.(V600_K601>D). The lung nodules improved with inhaled corticosteroids. We hypothesize that selective pressure from RET blockade may have activated a downstream somatic BRAF mutation, resulting in pulmonary LCH. We recommend continued vigilance for neoplasms driven by dysregulated downstream MAPK signalling in patients undergoing selective RET inhibition.
LEARNING POINTS
Patients with RET-altered MTC can experience rapid disease improvement and sustained disease stability with selective RET blockade (selpercatinib). LCH is a clonal neoplasm driven by MAPK activation, for which the most common mechanism is BRAF mutation. Both MTC and pulmonary LCH are driven by dysregulated MAPK signalling pathway activation. We hypothesise that the RET-specific inhibitor selpercatinib may have caused the activation of dormant LCH secondary to selective pressure and clonal proliferation.
PubMed: 38804700
DOI: 10.1530/EDM-23-0079 -
Cureus Apr 2024Extramedullary plasmacytomas without evidence of systemic illness make up less than 5% of all plasma cell neoplasms. The incidence of extramedullary plasmacytoma of the...
Extramedullary plasmacytomas without evidence of systemic illness make up less than 5% of all plasma cell neoplasms. The incidence of extramedullary plasmacytoma of the thyroid region is exceedingly rare. This report discusses the case of a 72-year-old male with extramedullary plasmacytoma of the thyroid. The patient underwent a total thyroidectomy for an enlarging right-sided thyroid nodule, and intraoperatively, the plasmacytoma was found to have an extracapsular component with adherence to the regional soft tissue as well as involvement of the right laryngeal nerve and regional lymph nodes. Despite a comprehensive negative workup for multiple myeloma initially, including a bone marrow biopsy and hematologic workup, the disease progressed to multiple myeloma following definitive radiation therapy, as evidenced by the development of hypermetabolic lytic lesions and further pathological examination. The patient's treatment course included systemic chemotherapy and an autologous stem cell transplant, resulting in a favorable treatment response. The progression to multiple myeloma despite established guidelines highlights the need for close observation and the potential for innovative therapeutic strategies to manage this rare entity.
PubMed: 38784303
DOI: 10.7759/cureus.58847 -
Cureus Apr 2024The first categorization for renal tumours was made by the WHO in 1981 and included only renal cell carcinoma (RCC). After that, classification was continuously altered... (Review)
Review
The first categorization for renal tumours was made by the WHO in 1981 and included only renal cell carcinoma (RCC). After that, classification was continuously altered over five decades. The WHO 2022 Classification of Urinary and Male Genital Tumours 2022 (5 edition) is molecular-driven and contains major revisions compared to the earlier classification from 2016. This revised edition divided renal tumours into four major broad categories: clear cell renal tumours, papillary renal cell tumours, oncocytic and chromophobe renal tumours, and collecting duct tumours. 'Other renal tumours' and 'molecularly defined renal carcinomas' are two other categories that were also included. Transcription factor binding to IGHM enhancer 3 (TFE3)-rearranged, TFEB-altered, elongin C (ELOC)-mutated (formerly TCEB1)-mutated, fumarate hydratase (FH)-deficient, succinate dehydrogenase (SDH)-deficient, anaplastic lymphoma kinase (ALK)-rearranged, and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient renal cell carcinomas are molecularly defined entities. Eosinophilic vacuolated tumours and low-grade oncocytic tumours are classified as emerging entities. Molecularly characterized renal tumours include those with SMARCB1 deficiencies, TFE3 rearrangements, TFEB alterations, ALK rearrangements, ELOC mutations, etc. Thyroid-like follicular carcinoma, eosinophilic vacuolated tumour, and low-grade oncocytic tumour are a few emerging entities of renal tumours. Improved therapy targets for each kidney tumour can be achieved using immunohistochemistry (IHC) and molecular definition updates. This study aims to highlight new developments in the WHO 2022 categorization of renal tumours with regard to diagnostic, morphological, molecular, IHC, clinical, and prognostic updates.
PubMed: 38765391
DOI: 10.7759/cureus.58470 -
International Journal of Surgery Case... May 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 -
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 -
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 -
Contemporary Clinical Dentistry 2024Multiple endocrine neoplasia (MEN) 2B syndrome is a rare autosomal dominant hereditary condition of neuroendocrine origin characterized by pheochromocytoma, marfanoid...
Multiple endocrine neoplasia (MEN) 2B syndrome is a rare autosomal dominant hereditary condition of neuroendocrine origin characterized by pheochromocytoma, marfanoid habitus, and mucocutaneous neuromas. Multiple mucosal neuromas on the tongue, lips, cheeks, and inner eyelids are often appeared as the earliest signs in most of the undiagnosed cases. Early diagnoses, recognition of phenotype, adequate surgery, and appropriate genetic counseling are very much essential as patients often develop medullary thyroid carcinoma (MTC) and pheochromocytoma. This case report would highlight the oral manifestations of MEN 2B in a 22-year-old female patient with multiple mucosal neuromas and a previous history of thyroidectomy due to MTC.
PubMed: 38707667
DOI: 10.4103/ccd.ccd_215_23 -
Annals of Medicine and Surgery (2012) May 2024Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare autosomal dominant neoplastic syndrome resulting from RET gene mutations, marked by medullary thyroid carcinoma...
INTRODUCTION AND IMPORTANCE
Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare autosomal dominant neoplastic syndrome resulting from RET gene mutations, marked by medullary thyroid carcinoma (MTC) and increased risk of other endocrine tumors. MEN2 includes subtypes MEN2A, MEN2B, and familial MTC. Prophylactic thyroidectomy is recommended for MEN2A due to high MTC risk.
CASE PRESENTATION
A 38-year-old woman with a family history of thyroid cancer presented with headaches, sweating, and palpable breast mass. Exam revealed skin lesions. Lab abnormalities and imaging indicated a large adrenal mass and thyroid nodules. Inconclusive biopsies led to left adrenalectomy, confirming pheochromocytoma. Subsequent total thyroidectomy revealed MTC.
CLINICAL DISCUSSION
This case represents rare MEN2B presentation, featuring MTC, pheochromocytoma, mucosal neuromas, and marfanoid habitus. Genetic testing for RET mutations is crucial with a positive family history. MEN2A individuals undergo prophylactic thyroidectomy due to high MTC risk. Although rare, pheochromocytoma can be an initial MEN2 manifestation, indicated by paroxysmal symptoms. Surgical resection is the treatment.
CONCLUSIONS
The patient's successful adrenalectomy followed by total thyroidectomy confirmed MTC. Thorough evaluation, including inconclusive initial findings, emphasizes imaging, and biopsies. Early detection and appropriate management optimize MEN2 outcomes.
PubMed: 38694328
DOI: 10.1097/MS9.0000000000001867 -
BMJ (Clinical Research Ed.) Apr 2024To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer.
OBJECTIVE
To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer.
DESIGN
Scandinavian cohort study.
SETTING
Denmark, Norway, and Sweden, 2007-21.
PARTICIPANTS
Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment.
MAIN OUTCOME MEASURES
Thyroid cancer identified from nationwide cancer registers. An active-comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting.
RESULTS
The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference -0.13, 95% confidence interval -0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05).
CONCLUSIONS
In this large cohort study using nationwide data from three countries, GLP1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of 3.9 years. In the main analysis comparing GLP1 receptor agonists with DPP4 inhibitors, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk.
Topics: Humans; Thyroid Neoplasms; Glucagon-Like Peptide-1 Receptor; Male; Female; Middle Aged; Dipeptidyl-Peptidase IV Inhibitors; Aged; Denmark; Incidence; Sodium-Glucose Transporter 2 Inhibitors; Cohort Studies; Adult; Sweden; Hypoglycemic Agents; Risk Factors; Diabetes Mellitus, Type 2; Norway; Scandinavian and Nordic Countries; Proportional Hazards Models
PubMed: 38683947
DOI: 10.1136/bmj-2023-078225