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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 -
The Journal of Clinical Endocrinology... Sep 2023Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are...
CONTEXT
Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are often diagnosed incidentally, they pose a management challenge when deciding on further treatment and follow-up.
OBJECTIVE
We report the outcomes of surgically managed sporadic micro-MTC in a specialist endocrine surgery and endocrinology unit and identify associations for recurrence and disease-specific survival in this population.
METHODS
Micro-MTCs were identified from a prospectively maintained surgery database, and slides were reviewed to determine pathological grade. The primary end points were recurrence, time to recurrence and disease-specific survival. Prognostic factors assessed included size, grade, lymph node metastasis (LNM), and postoperative calcitonin.
RESULTS
From 1995 to 2022, 64 patients were diagnosed with micro-MTC with 22 excluded because of hereditary disease. The included patients had a median age of 60 years, tumor size of 4 mm, and 28 (67%) were female. The diagnosis was incidental in 36 (86%) with 4 (10%) being high grade, 5 (12%) having LNM and 9 (21%) having elevated postoperative calcitonin. Over a 6.6-year median follow-up, 5 (12%) developed recurrence and 3 (7%) died of MTC. High grade and LNM were associated with 10-year survival estimates of 75% vs 100% for low grade and no LNM (hazard ratio = 831; P < .01). High grade, LNM, and increased calcitonin were associated with recurrence (P < .01). Tumor size and type of surgery were not statistically significantly associated with recurrence or survival. No patients with low grade micro-MTC and normal postoperative calcitonin developed recurrence.
CONCLUSION
Most sporadic micro-MTCs are detected incidentally and are generally associated with good outcomes. Size is not significantly associated with outcomes. Using grade, LNM, and postoperative calcitonin allows for the identification of patients at risk of recurrence to personalize management.
Topics: Humans; Female; Middle Aged; Male; Calcitonin; Thyroid Neoplasms; Thyroidectomy; Lymph Node Excision; Carcinoma, Medullary; Prognosis; Peptide Hormones; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Retrospective Studies
PubMed: 36964913
DOI: 10.1210/clinem/dgad173 -
BJU International Dec 2017To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS).
OBJECTIVE
To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS).
PATIENTS AND METHODS
RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000-2015 at eight academic institutions in North America and France. The Kaplan-Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS.
RESULTS
In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9-48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months.
CONCLUSIONS
RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.
Topics: Adolescent; Adult; Carcinoma, Medullary; Child; Female; Humans; Kaplan-Meier Estimate; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 27860149
DOI: 10.1111/bju.13705 -
Internal Medicine (Tokyo, Japan) Jan 1999
Review
Topics: Carcinoma, Medullary; Humans; Thyroid Neoplasms
PubMed: 10052732
DOI: 10.2169/internalmedicine.38.3 -
Internal Medicine (Tokyo, Japan) 2011A medullary thyroid carcinoma is a malignant tumor derived from the C-cells of the thyroid. Despite their distinct embryological origin, medullary thyroid carcinomas are... (Review)
Review
A medullary thyroid carcinoma is a malignant tumor derived from the C-cells of the thyroid. Despite their distinct embryological origin, medullary thyroid carcinomas are exceptionally accompanied by a tumor derived from the follicular cells; this is defined as mixed medullary and follicular cell carcinoma. There have been controversies regarding the origin of this rare mixed thyroid carcinoma questioning whether or not a mixed carcinoma originates from a common cancer stem cell. We present a case of mixed medullary and follicular cell carcinoma in which two thyroid carcinomas were found intermingled in the thyroid as well as in the metastatic cervical lymph nodes. We examined the tumor by immunostaining with thyroglobulin, calcitonin, and thyroid transcription factor-1, and also reviewed the literature and discuss the origin of this rare mixed thyroid carcinoma.
Topics: Adenocarcinoma, Follicular; Adult; Calcitonin; Carcinoma, Medullary; Carcinoma, Neuroendocrine; Humans; Immunohistochemistry; Lymphatic Metastasis; Male; Neoplastic Stem Cells; Nuclear Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors
PubMed: 21673468
DOI: 10.2169/internalmedicine.50.4749 -
The Surgical Clinics of North America Oct 2009Medullary thyroid cancer (MTC) accounts for 5% to 10% of all thyroid cancers. The high frequency of familial cases mandates screening and genetic testing. The... (Review)
Review
Medullary thyroid cancer (MTC) accounts for 5% to 10% of all thyroid cancers. The high frequency of familial cases mandates screening and genetic testing. The aggressiveness and age of onset of familial MTC differs depending on the specific genetic mutation, and this should determine the timing and extent of surgery. Sporadic MTC can present at any age, and it is usually associated with a palpable mass and the presence of nodal metastases. Surgery is standard treatment for any patient presenting with resectable MTC. Further studies are needed to investigate the role of radiation therapy in the palliation and local control of postresection and advanced-stage MTC. New systemic therapies for metastatic disease are being investigated. Targeted molecular therapies, based on knowledge of the pathways affected by RET mutations, are being tested in multiple clinical trials.
Topics: Biomarkers, Tumor; Carcinoma, Medullary; Combined Modality Therapy; Diagnosis, Differential; Diagnostic Imaging; Genetic Predisposition to Disease; Genotype; Humans; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Phenotype; Prognosis; Thyroid Neoplasms
PubMed: 19836492
DOI: 10.1016/j.suc.2009.06.021 -
Journal of the National Medical... Jul 2006Renal medullary carcinoma is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle...
Renal medullary carcinoma is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, mainly sickle cell trait (SCT). Most patients present with metastatic disease and have a worse prognosis. An African-American male with sickle cell disease (HbSCD) who was diagnosed to have renal medullary carcinoma is presented here. The clinical, histologic and radiologic features of this tumor are described. In the setting of advanced disease, treatment modalities have proved largely unsuccessful. Given the shared demographic, clinical and radiographic features of these patients, awareness and early diagnosis may prove essential in improving survival.
Topics: Adult; Black or African American; Carcinoma, Medullary; Fatal Outcome; Female; Humans; Kidney Neoplasms; Prognosis; Radiography; Sickle Cell Trait
PubMed: 16895289
DOI: No ID Found -
Clinics (Sao Paulo, Brazil) 2012Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine... (Review)
Review
Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine neoplasia type 1 include the so-called "3 P's": parathyroid, pituitary, and pancreatic tumors, including gastroenteroneuroendocrine tumors. Genetic testing can be performed on patients and the potential carriers of the menin gene mutation, but the genotype-phenotype correlation in multiple endocrine neoplasia type 1 is less straightforward than multiple endocrine neoplasia type 2. Most likely, the main advantage of genetic testing in MEN1 is to exclude from further studies those who are negative for the genetic mutation if they belong to a family with a known history of MEN1. In Chile, we started with rearranged during transfection proto-oncogene genetic testing (MEN2) 15 years ago. We carried out a prophylactic total thyroidectomy to prevent medullary thyroid carcinoma in a three-year-old girl who presented with microscopic medullary thyroid carcinoma. More than 90% of the individuals who tested positive using a genetic test achieved a biochemical cure compared with only 27% of patients who receive a clinical diagnosis. Mutations are mainly located in exon 11; the most common is C634W, rather than C634R. Hypertensive crisis was the cause of death in three patients, and extensive distant metastases occurred in nine (including two patients with multiple endocrine neoplasia type 2B) of 14 patients. Earlier recognition of medullary thyroid carcinoma and the other features of the disease, especially pheochromocytoma, will improve the survival rate of patients with multiple endocrine neoplasia.
Topics: Carcinoma, Medullary; Carcinoma, Neuroendocrine; Chile; Female; Genetic Association Studies; Genetic Testing; Humans; Male; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2a; Mutation; Proto-Oncogene Mas; Thyroid Neoplasms; Thyroidectomy
PubMed: 22584699
DOI: 10.6061/clinics/2012(sup01)03 -
Diagnostic and Interventional Imaging May 2013Thyroid nodules are very common, while thyroid cancer is rare and has a very good prognosis. Thyroid nodule ultrasound characterization performed by experienced... (Comparative Study)
Comparative Study Review
Thyroid nodules are very common, while thyroid cancer is rare and has a very good prognosis. Thyroid nodule ultrasound characterization performed by experienced clinicians allows the selection of the tumours to be punctured and guiding fine needle aspiration (FNA). FNA provide cytology information able to differentiate benign tumours from cancer in approximately 80% of cases. However, it remains difficult to identify thyroid cancers with ultrasound imaging, as demonstrated by the very low rate of cancers detected in all of the carried out FNA (approximately 5%). As a majority of thyroid cancers are hard, the stiffness evaluation has become part of nodular characterization. Since 2005, elastography has been used for the evaluation of thyroid nodules; quasi-static elastography was the first technique available and used, at first, an external pressure induced by the probe, which was then replaced by carotid internal excitation allowing improvement in sensitivity. Semi-quantitative analysis allows comparison of tissue elasticities between tissue with elasticity anomalies and normal tissue and provides therefore useful analytic information. Shear wave elastography (SWE) provides a map of the elasticity in a region and allows stiffness quantification of lesions in kilopascals in order to reinforce the predictive value of malignancy. A tumour whose stiffness is greater than 65kPa or for which the stiffness ratio is greater than 3.7 compared to surrounding healthy tissue is highly suspicious. SWE may enable the detection of malignant follicular tumours that currently escape detection by the ultrasound-guided ultrasound/aspiration cytology couple. Lymph node metastasis of papillary thyroid cancer can also be detected by elastography due to its increased stiffness.
Topics: Adenocarcinoma, Follicular; Adenocarcinoma, Papillary; Biopsy, Fine-Needle; Carcinoma, Medullary; Diagnosis, Differential; Elasticity Imaging Techniques; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Lymphatic Metastasis; Sensitivity and Specificity; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography, Interventional
PubMed: 23623210
DOI: 10.1016/j.diii.2013.01.023 -
The Oncologist 2013Medullary thyroid cancer (MTC) typically accounts for 3%-4% of all thyroid cancers. Although the majority of MTCs are sporadic, 20% of cases are hereditary. Hereditary... (Review)
Review
Medullary thyroid cancer (MTC) typically accounts for 3%-4% of all thyroid cancers. Although the majority of MTCs are sporadic, 20% of cases are hereditary. Hereditary MTC can be found in multiple endocrine neoplasia 2A or 2B or as part of familial MTC based on a specific germline mutation in the RET proto-oncogene. This article discusses the current approaches available for the diagnosis, evaluation, and management of patients and their family members with suspected MTC. The disease is predominantly managed surgically and typically requires a total thyroidectomy and lymph node dissection. A review of recent guidelines on the extent and timing of surgical excision is discussed. There are not very many effective systemic treatment options for MTC, but several emerging therapeutic targets have promise.
Topics: Calcitonin; Carcinoma, Medullary; Carcinoma, Neuroendocrine; Germ-Line Mutation; Humans; Lymph Node Excision; Multiple Endocrine Neoplasia Type 2a; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms; Thyroidectomy
PubMed: 24037980
DOI: 10.1634/theoncologist.2013-0053