Medullary thyroid cancer ( MTC ) is a form of thyroid carcinoma derived from parafolicular cells (cell C), which produces the hormone calcitonin. Medullary tumors are the third most common of all thyroid cancers. They make up about 3% of all cases of thyroid cancer.
About 25% of medullary thyroid cancers are genetic in nature, caused by mutations in the proto-oncogen RET. This form is classified as a familial MTC. When MTC happens by itself it is called sporadic MTC. When it coexists with a parathyroid gland tumor and the medullary component of the adrenal gland (pheochromocytoma) it is called multiple endocrine neoplasia type 2 (MEN2). It was first characterized in 1959.
Video Medullary thyroid cancer
Signs and symptoms
The main clinical symptoms of thyroid medullary carcinoma metastasis are diarrhea; sometimes patients will have episodes flushing. Both occur mainly with liver metastasis, and one of the symptoms may be the first manifestation of the disease. The rinsing that occurs in medullary thyroid carcinoma can not be distinguished from those associated with carcinoid syndrome. In MTC, flushing, diarrhea, and itching (pruritus) are all caused by elevated levels of calcitonin gene products (calcitonin or calcitonin-related peptide genes). Alternatively, the rinsing and diarrhea observed in carcinoid syndrome are caused by elevated levels of circulating serotonin.
Medullary thyroid carcinomas can also produce thyroid nodules and enlarged cervical lymph nodes.
The spread sites of medullary thyroid carcinoma include local lymph nodes in the neck, lymph nodes in the middle of the chest (mediastinum), liver, lung, and bone. Spread to other sites such as skin or brain occurs but rarely occurs.
Maps Medullary thyroid cancer
Genetics
Mutations (DNA changes) in the RET proto-oncogene, located on chromosome 10, lead to the expression of a mutated tyrosine kinase receptor protein, called RET (RERangeed during Transfection). RET is involved in growth regulation and cell development and germline mutations responsible for almost all cases of medial or hereditary thyroid carcinoma. Germline mutations are also responsible for the development of hyperparathyroidism and pheochromocytoma. Hereditary medullary thyroid cancer is inherited as an autosomal dominant trait, meaning that each child of the affected parent has a 50% chance of inheriting the mutant RNA proto-oncogene from the affected parent. DNA analysis makes it possible to identify children carrying mutant genes; surgical removal of the thyroid in children carrying a curative mutant gene if the entire thyroid gland is removed at an early age, before there is spread of the tumor. Parathyroid tumors and pheochromocytomas are removed when they cause clinical symptoms. Medullary medullary carcinoma of yediter or multiple endocrine neoplasia (MEN2) accounts for about 25% of all medullary thyroid carcinomas.
Seventy-five percent of medullary thyroid carcinomas occur in individuals without a family history identified and given the term "sporadic". Individuals who develop sporadic medullary thyroid carcinomas tend to be older and have wider disease at the time of initial presentation than those with a family history (screening is likely to begin at an early age in hereditary form). About 25-60% of sporadic medullary thyroid carcinomas have somatic mutations (one that occurs in one "parafollicular" cell) of the proto-oncogen RET. This mutation is considered an initial event, although there may be other causes that have not been identified.
Marker
While elevated serum calcitonin concentrations are harmless, it is useful as a testable marker in the blood.
The second sign, carcinoembryonic antigen (CEA), also produced by medullary thyroid carcinoma, is released into the blood and is useful as a marker of serum or blood tumor. In general, serum CEA measurements are less sensitive than serum calcitonin to detect tumor presence, but have less minute-to-minute variability and are therefore useful as indicators of tumor mass.
Diagnosis
Diagnosis is primarily done through the fine needle aspiration of the thyroid lesion to distinguish it from other types of thyroid lesions. Microscopic examination will show amyloid and parafollicular C cell hyperplasia.
Treatment
Surgery and radiation therapy has become a major treatment for medullary thyroid carcinoma.
Surgery
Total thyroidectomy with bilateral neck dissection is the gold standard for treating medullary thyroid cancer, and is the surest way to achieve cure in patients without distant metastasis or extensive nodal involvement. Due to the extreme degree of difficulty in performing neck dissection without extensive morbidity, it is important for patients to seek care under experienced surgeons at the Center of Excellence that operate on MTC patients at least several times a year. Operating risks include loss of vocal control, irreparable nerve damage, death or second surgery needs to clear up remaining lymph nodes left behind if sentinel node biopsy is positive for cancer spread. Extensive surgery can be effective when conditions are detected early, but the risk of recurrence persists, especially in patients with multiple positive lymph nodes or extracapsular invasion. About half of patients have metastases to the regional lymph nodes at the time of diagnosis.
The European Community of Endocrine Surgeons has published recommendations to manage this condition in the carrier genes. Operation times depend on the type of mutation. For those who are in the highest risk group, surgery is recommended in the first year of life. In lower risk cases, surgery may be delayed until the age of ten, the exact time depends on mutations and other factors.
Radiation
External beam radiotherapy is recommended when there is a high risk of regional recurrence, even after optimal surgical treatment. In this study, patients treated with external beam radiation were compared with the control group. The control of the disease with radiation is far superior in the group receiving radiation. The study authors [14] wrote: "In 40 high-risk patients (residual microscopic disease, extraglandular invasion, or lymph node involvement), the local/regional relapse rate was 86% at 10 years with postoperative external beam radiation (25 patients ), and 52% for those without postoperative external radiation (p = 0.049).To optimize local/regional tumor control, we therefore continue to suggest external beam radiation in patients at high risk of local/regional relapse. "
Unlike other differentiated thyroid carcinomas, there is no role for the treatment of radioiodine in medullary disease.
Protein kinase inhibitor
Clinical trials of protein kinase inhibitors, which block the abnormal protein kinase involved in the development and growth of medullary cancer cells, show clear evidence of response in 10-30% of patients. In most respondents there is less than 30% reduction in tumor mass, but the response has been long-lasting; a stable response for more than 3 years. The main side effects of this class of drugs include hypertension, nausea, diarrhea, some heart electrical abnormalities, and thrombotic episodes or bleeding.
Vandetanib, the caprelsa trade name, is the first drug (April 2011) approved by the US Food and Drug Administration (FDA) for the treatment of terminal (metastatic) medullary thyroid cancer in adult patients not eligible for surgery.
Cabozantinib, the trade name Cometriq, was granted marketing approval (November 2012) by the US FDA for this indication. Cabozantinib which is a potential inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo-controlled trial. This was shown to improve overall survival for 5 months for the treated group vs placebo, which was not statistically significant. However, cabozantinib is highly effective in patients with RET M918T mutations, prolonging overall survival by about 2 years, doubling survival vs untreated patients (4 years vs. 2 years). Treatment with cabozantinib does require a lot of dose reduction to reduce side effects. It has been suggested that an experimental 140 mg dose is excessive, especially in patients with lower body mass. Ongoing trials have been scheduled to identify a more optimal dosing regime. Activity has been observed, in practice at the rate of 1.2, mg/kg.
Prognosis
Depending on the source, the 5-year survival rate for medullary thyroid cancer is 80%, 83% or 86%, and the 10-year survival rate is 75%.
With the entire stage of cancer becoming stage I to IV, the survival rate of 5 years is 100% in stage I, 98% in stage II, 81% in stage III and 28% in stage IV. MTC prognosis is worse than follicular and papillary thyroid cancer when it has spread (spread) outside the thyroid gland.
The prognostic value for measuring the concentrations of calcitonin and carcinoembryonic antigen (CEA) in blood was studied in 65 MTC patients who had abnormal calcitonin levels after surgery (total thyroidectomy and lymph node dissection). The prognosis correlates with the rate at which the postoperative calcitonin concentration doubles, called calcitonin doubling time (CDT), rather than the absolute pre- or post-operative level of calcitonin:
- CDT less than 6 months: 3 patients from 12 (25%) survived 5 years. 1 patient out of 12 (8%) survived 10 years. All died within 6 months to 13.3 years.
- CDT between 6 months and 2 years: 11 patients out of 12 (92%) survived 5 years. 3 patients from 8 (37%) survived 10 years. 4 patients from 12 (25%) survived until the end of the study.
- CDT for more than 2 years: 41 patients from 41 (100%) were alive at the end of the study. These included 1 patients whose calcitonin was stable, and 11 patients had decreased levels of calcitonin.
Calcitonin doubling time is a better predictor of MTC survival than CEA but after these two tests it is recommended.
References
Source of the article : Wikipedia
0 Comments