-
Annals of Oncology : Official Journal... Jul 1998Medullary thyroid carcinoma (MTC) originates in the thyroid C cells, accounting for 5% to 10% of all thyroid malignancies. Approximately 75% of cases are sporadic.... (Review)
Review
BACKGROUND
Medullary thyroid carcinoma (MTC) originates in the thyroid C cells, accounting for 5% to 10% of all thyroid malignancies. Approximately 75% of cases are sporadic. Significant advances have been made in the molecular biology of MTC, but some aspects of diagnosis and management still remain controversial.
DESIGN
We reviewed relevant articles published in major English-language medical journals. We used the MEDLINE database, selected bibliographies, and articles available in our personal files.
RESULTS
Mutations of the RET proto-oncogene have been identified in the germline DNA of patients with familial MTC syndromes. Genetic testing can identify patients affected by multiple endocrine neoplasia types IIA and IIB and familial MTC, allowing early diagnosis and possible cure. Surgical treatment is total thyroidectomy. Plasma calcitonin measurements are excellent markers for postoperative follow-up. Adjunctive therapy includes radiotherapy and chemotherapy. The overall prognosis is worse than papillary thyroid carcinoma.
CONCLUSIONS
Recent advances in genetic testing allow early diagnosis and treatment of familial MTC syndromes. Despite some advances in treatment, optimal management remains controversial.
Topics: Carcinoma, Medullary; Combined Modality Therapy; Genetic Testing; Humans; Proto-Oncogene Mas; Thyroid Neoplasms; Thyroidectomy
PubMed: 9739433
DOI: 10.1023/a:1008242302749 -
Journal of Internal Medicine Jul 2009The clinical management of patients with persistent or recurrent medullary thyroid carcinoma (MTC) is still under debate, because these patients either have a long-term... (Review)
Review
The clinical management of patients with persistent or recurrent medullary thyroid carcinoma (MTC) is still under debate, because these patients either have a long-term survival, due to an indolent course of the disease, or develop rapidly progressing disease leading to death from distant metastases. At this moment, it cannot be predicted what will happen within most individual cases. Biomarkers, indicators which can be measured objectively, can be helpful in MTC diagnosis, molecular imaging and treatment, and/or identification of MTC progression. Several MTC biomarkers are already implemented in the daily management of MTC patients. More research is being aimed at the improvement of molecular imaging techniques and the development of molecular systemic therapies. Recent discoveries, like the prognostic value of plasma calcitonin and carcino-embryonic antigen doubling-time and the presence of somatic RET mutations in MTC tissue, may be useful tools in clinical decision making in the future. In this review, we provide an overview of different MTC biomarkers and their applications in the clinical management of MTC patients.
Topics: Biomarkers, Tumor; Carcinoma, Medullary; Humans; Medical Oncology; Positron-Emission Tomography; Prognosis; Thyroid Neoplasms
PubMed: 19522831
DOI: 10.1111/j.1365-2796.2009.02106.x -
ESMO Open Jun 2021Medullary thyroid cancer (MTC) represents a rare neuroendocrine neoplasm originating from neoplastic C-cells in the thyroid gland. While localized disease is potentially... (Review)
Review
Medullary thyroid cancer (MTC) represents a rare neuroendocrine neoplasm originating from neoplastic C-cells in the thyroid gland. While localized disease is potentially curable with an optimized surgical approach, the number of relapses is high, and a considerable number of patients present with primary metastatic disease. Multidisciplinary management including standardized surveillance following surgery, but also early involvement of medical oncologists, is therefore important. Several oncogenic pathways are involved in the pathogenesis of MTC including vascular endothelial growth factor receptor, epidermal growth factor receptor, MET, and most importantly RET, and the multi-tyrosine kinase inhibitors vandetanib and cabozantinib have been approved for advanced MTC based on data from phase III studies. As activating RET mutations represent the most important driver, specific RET inhibitors were introduced and suggest high response rates with limited off-target toxicities. The current review provides a practical overview on clinical presentation and management from early to advanced MTC.
Topics: Carcinoma, Neuroendocrine; Humans; Neoplasm Recurrence, Local; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 34091261
DOI: 10.1016/j.esmoop.2021.100183 -
Oncology Research 2024This review aimed to describe the inculpation of microRNAs (miRNAs) in thyroid cancer (TC) and its subtypes, mainly medullary thyroid carcinoma (MTC), and to outline... (Review)
Review
This review aimed to describe the inculpation of microRNAs (miRNAs) in thyroid cancer (TC) and its subtypes, mainly medullary thyroid carcinoma (MTC), and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC. Additionally, the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed. This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes, mainly MTC. Additionally, web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described. MiRNAs can perform as oncomiRs or antioncoges, relying on the target mRNAs they regulate. MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases, particularly in cancer. MiRNAs are involved in the modulation of fundamental pathways related to cancer, resembling cell cycle checkpoints and DNA repair pathways. MiRNAs are also rather stable and can reliably be detected in different types of biological materials, rendering them favorable diagnosis and prognosis biomarkers as well. MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets. The contribution of miRNAs in thyroid cancer, particularly MTC, is an active area of research, and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.
Topics: Humans; Thyroid Neoplasms; MicroRNAs; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Prognosis; Computational Biology; Gene Expression Regulation, Neoplastic; Internet; Molecular Targeted Therapy
PubMed: 38827323
DOI: 10.32604/or.2024.049235 -
Seminars in Nuclear Medicine Jul 2023Currently, there is a discrepancy among the available guidelines on the usefulness of nuclear medicine techniques in medullary thyroid cancer (MTC) diagnosis and... (Review)
Review
Currently, there is a discrepancy among the available guidelines on the usefulness of nuclear medicine techniques in medullary thyroid cancer (MTC) diagnosis and treatment. Aim of this review is to provide an update on diagnostic and therapeutic nuclear medicine techniques in this setting. Evidence-based data clearly demonstrates the usefulness of PET/CT with different radiopharmaceuticals in recurrent MTC (in particular when serum calcitonin is higher than 150 pg/mL or calcitonin doubling time is shortened) and F-FDOPA should be the preferred PET radiopharmaceutical. If F-FDOPA PET/CT is negative or unavailable, F-FDG PET/CT or Ga-DOTA-peptides PET/CT could be performed for MTC restaging. There is currently insufficient evidence to recommend PET/CT with several radiopharmaceuticals for MTC staging. Clinical experience on PET/MRI with different radiopharmaceuticals in MTC is still limited. Several investigational nuclear medicine therapeutic options are currently under evaluation in metastatic MTC. More data are needed to evaluate the efficacy, toxicity, and role of these therapeutic options in the management of MTC patients.
Topics: Humans; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Calcitonin; Fluorodeoxyglucose F18; Nuclear Medicine; Neoplasm Recurrence, Local; Carcinoma, Neuroendocrine; Thyroid Neoplasms
PubMed: 36702731
DOI: 10.1053/j.semnuclmed.2023.01.003 -
Scientific Reports Aug 2020To compare the clinicopathological characteristics and survival outcomes of children and adult diagnosed with medullary thyroid carcinoma (MTC). MTC patients were... (Comparative Study)
Comparative Study
To compare the clinicopathological characteristics and survival outcomes of children and adult diagnosed with medullary thyroid carcinoma (MTC). MTC patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 1998 to 2016, followed by stratification into pediatric (< 20 years) or adult (≥ 20 years) groups. In total, 2,197 patients (110 pediatric and 2087 adult) with MTC were identified. Pediatric patients were more likely to have localized stage (70.0% vs. 51.6%), negative regional nodes (48.2% vs. 30.8%) and receive total/subtotal thyroidectomy surgery (97.3% vs. 85.3%). Moreover, CSS and OS rates were significantly higher in pediatric patients (both P < 0.001). Multivariable Cox regression analysis revealed that adult patients were significantly correlated with worse CSS and OS rates [(CSS: HR 11.60, 95% CI 1.62-83.02, P = 0.015); (OS: HR 5.63, 95% CI 2.08-15.25, P = 0.001)]. Further stratified analysis indicated that pediatric group might have significant better CSS and OS for patients with more advanced stage. Patients in the pediatric group were more likely to have earlier stage. Moreover, the prognosis of pediatric MTC patients was significantly better than that in adult patients.
Topics: Adolescent; Adult; Carcinoma, Neuroendocrine; Child; Child, Preschool; Female; Humans; Male; Multivariate Analysis; SEER Program; Survival Analysis; Thyroid Neoplasms; Young Adult
PubMed: 32764626
DOI: 10.1038/s41598-020-70439-7 -
Technology in Cancer Research &... 2022Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy with relatively early lymphatic metastatic spread. The clinical features of MTC remain...
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy with relatively early lymphatic metastatic spread. The clinical features of MTC remain controversial owing to the low incidence rate. This study aimed to analyze the clinical characteristics, prognostic factors, and long-term follow-up of MTC. Medical records of MTC patients treated at our hospital between December 2000 and November 2020 were reviewed retrospectively. Clinicopathologic features of MTC were analyzed using univariate and multivariate analyses. Cumulative survival rates were estimated using the Kaplan-Meier method. In total, 152 patients with MTC were included. The rates of central and lateral lymph node metastases (LNM) were 52.0% and 42.8%, respectively. All patients were followed up with a median follow-up time of 43.5 (17.0-76.3) months. Univariate and multivariate analyses identified two independent factors associated with progressive disease. They were lateral LNM (p < 0.001) and lymph node ratio (LNR) >1/3 (p = 0.009). The 5-, 10-, and 15-year cumulative overall survival (OS) rates of MTC were 88.2%, 83.1%, and 76.2%, respectively. The 5-, 10-, and 15-year cumulative disease-free survival (DFS) rates were 61.8%, 48.6%, and 38.2%, respectively. Patients with stage I, II, and III disease had significantly longer OS and DFS than those with stage IV disease (p < 0.001). MTC is a rare endocrine malignancy and LNM is common. Patients with lateral LNM and LNR >1/3 are more likely to develop progressive disease. The long-term OS rates of MTC are good, but long-term DFS rates are poor.
Topics: Humans; Neoplasm Staging; Prognosis; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy
PubMed: 35188853
DOI: 10.1177/15330338221078435 -
Revue Medicale de Liege Dec 2016The syndrome of Familial Non Medullary Thyroid Carcinoma (FNMTC) includes two or more patients with an isolated non-medullary thyroid cancer (papillary, follicular,... (Review)
Review
The syndrome of Familial Non Medullary Thyroid Carcinoma (FNMTC) includes two or more patients with an isolated non-medullary thyroid cancer (papillary, follicular, anaplastic) within the same family. To diagnose FNMTC, the clinician must exclude a syndromic presentation such as the syndromes of Cowden, Gardner or Werner, and the Carney Complex. Up to now, a hundred families with FNMTC have been genetically studied, including forms with (Ch19p13.2) or without oxyphilia (Ch2q21), in association with a multinodular goiter (Ch14q32), or with a renal cancer (Ch1q21). Several candidate genes of susceptibility have been proposed: SRGAP1, NKX2-1, FOXE1 and HABP2. So far, it is considered that familial cases represent less than 5 % of thyroid cancers. Although rare, these cases represent a unique opportunity to improve our understanding of thyroid cancer. The identification of candidate genes will enrich our knowledge of thyroid cancer pathophysiology. Based on the literature and our experience of the follow-up of eight families with FNMTC, we discuss epidemiological, clinical, pathological and genetic aspects of FNMTC with a view to improve the diagnosis and treatment of this disease.
Topics: Carcinoma, Papillary; Chromosome Aberrations; Forkhead Transcription Factors; Genetic Predisposition to Disease; Genetic Testing; Humans; Molecular Diagnostic Techniques; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 28387096
DOI: No ID Found -
Sante (Montrouge, France) 2007Various studies of medullary thyroid carcinoma have found its apoptosis rate to be very low. Tumor growth is usually progressive but in some cases, rapid progression and... (Review)
Review
Various studies of medullary thyroid carcinoma have found its apoptosis rate to be very low. Tumor growth is usually progressive but in some cases, rapid progression and high proliferation are seen. Some mutations of the RET proto-oncogene are thought to have a direct or indirect effect on this clinical process. Five characteristics are significantly associated with poor survival: tumor necrosis, squamous histology, age older than 45 years, oxyphilic tumor cells together with a lack of intermediary cytoplasm cells, and finally, less than 50% of tumor cells immunoreactive to calcitonin. Although recent studies have identified the gene involved in this cancer, its molecular pathogenesis has not yet been elucidated. Medullary thyroid carcinoma is rare, but practitioners must be familiar with it because it presents specific therapeutic and diagnostic problems. Sensitive and specific direct genetic diagnosis of the principal mutation of the RET proto-oncongene is possible in patients with familial thyroid carcinoma or multiple endocrine neoplasia type 2. Screening is based on the immunoradiometric assay of calcitonin levels before and after pentagastrin stimulation in different populations: healthy subjects, persons with family members who have medullary thyroid carcinoma, patients with thyroid nodules or autoimmune chronic thyroiditis. Recently a somatic mutation on RET codon 918 was reported in patients with medullary thyroid carcinoma and those with C cell hyperplasia and multiple endocrine neoplasia together. This finding suggests that this particular mutation may play a role in tumorigenesis. Compared with patients with endocrine neoplasia syndromes type 2A and 2B, these patients appeared to have a syndrome clinically overlapping these, and its genetic basis may be distinct from them. Family members of patients with medullary thyroid carcinoma must be screened for this inherited disease. The mutations associated with medullary thyroid carcinoma and parathyroid tumors together appear to be closely related to the centromeric region of chromosome 10. At three months of age, Wag/Rij rats show hypersecretion under secretagogues and C cell hyperplasia; both signs are described as "pretumoral" in humans. A battery of markers are useful even though the gene for multiple endocrine neoplasia type 2 gene has recently been thought to be located in the pericentromeric region of chromosome 10 in white Europeans.
Topics: Animals; Carcinoma, Medullary; Chromosomes, Human, Pair 10; Disease Models, Animal; Humans; Middle Aged; Multiple Endocrine Neoplasia Type 2a; Mutation; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Rats; Rats, Wistar; Thyroid Neoplasms
PubMed: 17897902
DOI: No ID Found -
Endocrine, Metabolic & Immune Disorders... 2019Medullary thyroid cancer (MTC) accounts for 5% of all thyroid cancers and occurs either sporadically or in a hereditary pattern. Routine calcitonin (CT) measurement is... (Review)
Review
BACKGROUND
Medullary thyroid cancer (MTC) accounts for 5% of all thyroid cancers and occurs either sporadically or in a hereditary pattern. Routine calcitonin (CT) measurement is suggested for MTC screening in patients with nodular thyroid disease.
PATIENT FINDINGS
A 45 years-old woman incidentally discovered, with neck ultrasound, the presence of thyroid micronodules. Fine-needle aspiration (FNA) on thyroid prevailing nodule did not demonstrate cellular atypia. During follow-up, FNA was repeated on the previously analyzed nodule suspicious for Hürthle cell nodule suspicious for follicular neoplasm and on another hypoechoic right nodule which showed cellular atypia. CT was <2 pg/ml (normal values <18.2 pg/ml), anti-thyroid antibodies were positive and the patient showed a normal thyroid function. The patient also was diagnosed with primary hyperparathyroidism with an enlarged parathyroid gland behind the right thyroid lobe. Therefore, she underwent total thyroidectomy and a selective parathyroidectomy was performed. Histology showed an encapsulated microMTC (pT1aNxMx) associated with diffuse C-cell hyperplasia and lymphocytic thyroiditis. The neoplasm was positive for calcitonin and chromogranin A and negative for thyroglobulin. A right parathyroid adenoma was also diagnosed. One month after surgery basal and stimulated CT were <2 ng/ml. Genetic analysis did not reveal mutation of RET proto-oncogene. Twelve months after surgery, neck ultrasonography, chest and abdomen computed tomography did not demonstrated residual/recurrent disease with undetectable serum CT.
CONCLUSION
In the literature, few MTC cases with normal serum CT have been reported. Although MTC without elevated plasma CT is extremely rare, normal or low CT levels, do not entirely exclude this diagnosis.
Topics: Biopsy, Fine-Needle; Carcinoma, Neuroendocrine; Diagnosis, Differential; Female; Humans; Incidental Findings; Middle Aged; Proto-Oncogene Mas; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule; Thyroidectomy
PubMed: 30574858
DOI: 10.2174/1871530319666181220165350