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World Journal of Clinical Cases May 2024Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the proto-oncogene is the only gene implicated in MEN2A...
BACKGROUND
Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the proto-oncogene is the only gene implicated in MEN2A pathogenesis. Once an carrier is detected, family members should be screened to enable early detection of medullary thyroid carcinoma, pheochromocytoma, and hyperparatitity. Among these, medullary thyroid carcinoma is the main factor responsible for patient mortality. Accordingly, delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.
CASE SUMMARY
Herein, we present proto-oncogene mutations, clinical characteristics, and treatment strategies in a family with MEN2A. A family study was conducted on patients diagnosed with MEN2A. DNA was extracted from the peripheral blood of family members, and first-generation exon sequencing of the proto-oncogene was conducted. The mutation was identified in three family members spanning three generations. Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas. A 9-year-old child harboring the gene mutation was diagnosed with medullary thyroid carcinoma. Surgical resection of the tumors was performed. All family members were advised to undergo complete genetic testing related to the mutation, and the corresponding treatments administered based on test results and associated clinical guidelines.
CONCLUSION
Advancements in MEN2A research are important for familial management, assessment of medullary thyroid cancer invasive risk, and deciding surgical timing.
PubMed: 38817239
DOI: 10.12998/wjcc.v12.i15.2627 -
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 -
Current Cancer Drug Targets 2024Medullary thyroid carcinoma (MTC) is a rare but aggressive endocrine malignancy that originates from the parafollicular C cells of the thyroid gland. Enhancer RNAs...
BACKGROUND
Medullary thyroid carcinoma (MTC) is a rare but aggressive endocrine malignancy that originates from the parafollicular C cells of the thyroid gland. Enhancer RNAs (eRNAs) are non-coding RNAs transcribed from enhancer regions, which are critical regulators of tumorigenesis. However, the roles and regulatory mechanisms of eRNAs in MTC remain poorly understood. This study aims to identify key eRNAs regulating the malignant phenotype of MTC and to uncover transcription factors involved in the regulation of key eRNAs.
METHODS
GSE32662 and GSE114068 were used for the identification of differentially expressed genes, eRNAs, enhancers and enhancer-regulated genes in MTC. Metascape and the transcription factor affinity prediction method were used for gene function enrichment and transcription factor prediction, respectively. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to assess the binding of histone H3 lysine 27 acetylation (H3K27ac)-enriched regions to anti- H3K27ac. RIP-qPCR was used to detect the binding between FOXQ1 and LINC00887. CCK8 and Transwell were performed to measure the proliferation and invasion of MTC cells, respectively. Intracellular reactive oxygen species (ROS) levels were quantified using a ROS assay kit.
RESULTS
Four eRNAs (H1FX-AS1, LINC00887, MCM3AP-AS1 and A1BG-AS1) were screened, among which LINC00887 was the key eRNA promoting the proliferation and invasion of MTC cells. A total of 135 genes controlled by LINC00887-regulated enhancers were identified; among them, and were significantly enriched in the "ROS metabolic process" term. As a transcription factor regulating genes enriched in the "ROS metabolic process" term, FOXQ1 could recruit LINC00887. Overexpression of FOXQ1 restored LINC00887 knockdown-induced downregulation of and transcription in MTC cells. Additionally, FOXQ1 overexpression counteracted the inhibitory effects of LINC00887 knockdown on the proliferation and invasion of MTC cells and the promotion of intracellular ROS accumulation induced by LINC00887 knockdown.
CONCLUSION
LINC00887 was identified as a key eRNA promoting the malignant phenotype of MTC cells. The involvement of FOXQ1 was essential for LINC00887 to play a pro-tumorigenic role in MTC. Our findings suggest that the FOXQ1/LINC00887 axis is a potential therapeutic target for MTC.
Topics: Humans; Thyroid Neoplasms; Forkhead Transcription Factors; RNA, Long Noncoding; Carcinoma, Neuroendocrine; Cell Proliferation; Gene Expression Regulation, Neoplastic; Enhancer Elements, Genetic; Disease Progression; Cell Line, Tumor; Cell Movement; Reactive Oxygen Species; Enhancer RNAs
PubMed: 38804344
DOI: 10.2174/0115680096258716231026063704 -
Endocrine, Metabolic & Immune Disorders... May 2024Calcitonin (CT) is a sensitive serum marker of medullary thyroid carcinoma usually detected via immunoassays; however, its levels are easily disturbed by several...
BACKGROUND
Calcitonin (CT) is a sensitive serum marker of medullary thyroid carcinoma usually detected via immunoassays; however, its levels are easily disturbed by several endogenous factors.
OBJECTIVE
The study aimed to discuss a case of suspected interference resulting in aberrant CT values and review previous reports of CT interference.
METHODS
A female patient visited our clinic with a physical ultrasound examination showing a slightly enlarged thyroid gland with small nodules. She had elevated CT levels, inconsistent with the clinical presentation and other findings. We evaluated the results by retesting using the same platform, platform validation, multiplex dilution, Polyethylene Glycol (PEG) precipitation, heterophilic blocking tubes, and RET gene analysis.
RESULTS
Retesting CT using the same platform confirmed the high value obtained. However, serial dilution of the sample produced nonlinear results, suggesting some interference. While PEG precipitation did not significantly reduce the CT level, incubating the sample in HBTs normalized the CT value, indicating interference from heterophilic antibodies. Gene sequencing revealed no RET mutations.
CONCLUSION
In cases where elevated CT levels are inconsistent with clinical presentations and other findings, the laboratory technicians should communicate with clinicians, analyze the reasons for the inconsistent results, and use different methods to verify the results. Accurate testing provides realistic and reliable data for doctors and patients and helps to avoid unnecessary procedures.
PubMed: 38798210
DOI: 10.2174/0118715303287794240519191720 -
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 -
Zhonghua Yi Xue Za Zhi May 2024To analyze the clinical characteristics and prognosis of medullary thyroid microcarcinoma (MTMC). A case series studies. The clinical data of patients with medullary...
To analyze the clinical characteristics and prognosis of medullary thyroid microcarcinoma (MTMC). A case series studies. The clinical data of patients with medullary thyroid carcinoma (MTC) diagnosed by postoperative pathology and with complete follow-up data who were initially treated in Tianjin Medical University Cancer Hospital from January 2013 to December 2019 were retrospectively analyzed. There were a total of 170 cases, including 70 males and 100 females, aged (49.7±12.3) years old. Among them, there were 61 patients with MTMC. They were divided into group A (with a maximum tumor idameter of ≤0.5 cm, =13) and group B (with a maximum tumor diameter >0.5~≤1.0 cm, =48) based on whether the maximum diameter of the tumor was >0.5 cm. Analysis was conducted on their pathological results and prognosis. Among the MTC, MTMC accounted for 26.4% (61/231) with 26 males and 35 females aged [,]51.0 (41.0, 59.0) years. Among the MTMC patients, 57.4% (35/61) were in stage Ⅰ, 16.4% (10/61) were in stage Ⅲ, and 26.2% (16/61) were in stage Ⅳ. For MTMC with a maximum diameter of≤0.5 cm and a maximum diameter of >0.5-≤1.0 cm, there was no statistically significant difference between the two groups in terms of gender, age, mixed cancer, invasion of glandular lobes, multifocal, central lymph node metastasis, lateral neck lymph node metastasis rate and other pathological characteristics(both >0.05). In terms of prognosis, the recurrence free survival time of MTMC patients was 83.1 (68.0, 97.0) months. Among them, structural tumor recurrence occurred in 5 patients (8.2%) after surgery, and 1 patient (1.6%) died. The expected 5-year and 10-year survival rates were 93.4% and 89.0%, respectively. There was no statistically significant difference in recurrence free survival time among MTMC patients, MTC patients with a maximum diameter of >1.0-≤2.0 cm, and MTC patients with a maximum diameter of >2.0 cm (all >0.05). MTMC has strong invasiveness, and although the prognosis of most MTMCs is relatively good, the risk of long-term recurrence and death is still high.
Topics: Humans; Male; Female; Thyroid Neoplasms; Middle Aged; Prognosis; Retrospective Studies; Carcinoma, Neuroendocrine; Lymphatic Metastasis; Adult; Neoplasm Recurrence, Local
PubMed: 38782750
DOI: 10.3760/cma.j.cn112137-20231225-01476 -
Zhonghua Yi Xue Za Zhi May 2024Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from the parafollicular cells (C cells) of the thyroid gland, classified as sporadic and...
Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from the parafollicular cells (C cells) of the thyroid gland, classified as sporadic and hereditary. Calcitonin (Ctn) secreted by the C cells is a specific serological marker for MTC, which is of great value in diagnosis, treatment and postoperative management of MTC. The effect of chemoradiotherapy and I therapy on MTC is limited, with surgery being the primary therapy. Given the aggressive nature and relatively poor prognosis of MTC, the reasonable surgical extent is crucial for improving cure rate and prognosis of patients. However, there are still some controversies regarding the extent of surgery for MTC. This article elaborates on the research progress and controversies of serum Ctn levels in assisting the evaluation of the extent of surgery for MTC.
Topics: Humans; Thyroid Neoplasms; Calcitonin; Carcinoma, Neuroendocrine; Prognosis; Carcinoma, Medullary
PubMed: 38782745
DOI: 10.3760/cma.j.cn112137-20231110-01059 -
The Laryngoscope May 2024Medullary thyroid carcinoma (MTC) comprises less than 5% of thyroid cancers but is responsible for over 10% of deaths related to thyroid cancer. Regional lymph node...
Medullary thyroid carcinoma (MTC) comprises less than 5% of thyroid cancers but is responsible for over 10% of deaths related to thyroid cancer. Regional lymph node metastasis is common and associated with mortality, thus total thyroidectomy with central compartment lymph node dissection is the standard surgical treatment for MTC. In this best practice submission, we aim to review the existing literature and determine whether calcitonin levels can serve as a reliable method for risk-stratifying MTC without overt lymph node involvement.
PubMed: 38771083
DOI: 10.1002/lary.31516 -
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