Medullary thyroid cancer is a tumor originating from the C cells of the thyroid gland. 5-10% of all thyroid cancers are medullary thyroid cancers. Approximately 75% of these cancer types occur randomly, while 25% show familial development.
Medullary thyroid cancers with familial development are divided into 3 groups among themselves:
- Familial isolated medullary thyroid cancer
- MEN 2A family medullary thyroid cancer (MCT, mixed pheochromocytoma, primary hyperparathyroidism)
- MEN 2B family medullary thyroid cancer (MCT, pheochromocytoma, multiple mucosal neuromas and rarely primary hyperparathyroidism)
Medullary thyroid cancer usually develops as a thyroid nodule in the middle and upper regions of the lobes located symmetrically on both sides of the thyroid gland. Random (sporadic) ones are typically unilateral. Familial ones can hold both sides.
Medullary thyroid cancers are distinguished from other thyroid cancers in pathological examination, with tissue showing eosinophilic staining and amyloid positivity. In medullary thyroid cancers, the protein stored with amyloid is usually calcitonin and procalcitonin produced by C cells. Diagnosis is made by detecting calcitonin in histochemical examinations.
Medullary thyroid cancer is a cancer with a variable course. It can be aggressive or slow progressing. While the 5-year survival rate is around 50% in sporadic cases, there is a more variable process in familial cases.
The most aggressive form in MEdullary thyroid cancers is the MEN 2B family cases. The slowest course is the familial isolated form.
Medullary thyroid cancer can spread to regional lymph nodes and lungs. It can even metastasize to regional tissues and internal organs such as the liver and brain. Chronic diarrhea can sometimes be seen in metastatic cases.
Medullary thyroid cancers secrete calcitonin as the main product. Along with calcitonin, it also produces substances such as prostaglandins, serotonin, histamine, ACTH, somatostatin, corticotropic releazing hormone. Therefore, some paraneoplastic syndromes, such as Cushing’s syndrome and carcinoid syndrome, may develop as medullary thyroid cancer in the future, and they can also produce hormones such as corticotropin, serotonin, prostaglandins, and melanin.
Diagnosis of medullary thyroid cancer:
Calcitonin detection is the main determinant of medullary thyroid cancer. Calcitonin secretion increases in stimulation tests with pentagastrin. While calcitonin level may remain normal in medullary thyroid cancers detected in the early stages, very high calcitonin levels are seen in advanced stages.
The diagnosis of medullary thyroid cancer is made by histological examination in fine needle aspiration biopsy. In cases where biopsy cannot be performed or the diagnosis cannot be made, the diagnosis can be made by examining the tissue sample after surgery. In addition, serum calcitonin levels and carcinoembryonic antigen (CEA) studies are also supportive for diagnosis.
In addition, the diagnosis can be made by examining genetic mutations with RET oncogene analysis. By examining these mutations in risky patients or families, the risk carriers of individuals can be evaluated. As a precaution, total thyroidectomy and lymph node dissection can be performed in high-risk patients who are found to be carriers. In high-risk patients, surgical procedures can be performed even in childhood.
Medullary thyroid cancer is a type of cancer that can be screened early. Familial screening is performed because even the randomly detected cases may have a familial background at a rate of 25%.
Other imaging of the neck, such as ultrasonography or computed tomography, may be evaluated after the histological diagnosis is made to evaluate cervical lymph node involvement. In patients with suspected metastatic disease, evaluation of systemic disease using neck CT and imaging of the liver with CT or MRI can be performed.
Treatment of medullary thyroid cancer:
The main treatment for medullary thyroid carcinoma is surgical resection. It does not respond to radioactive iodine (RAI) or conventional chemotherapy. Thyroid-stimulating hormone (TSH) suppression is not necessary for medullary thyroid cancer because C cells lack thyroid-stimulating hormone receptors. In addition, all patients should be evaluated for hyperparathyroidism and pheochromocytoma. If a pheochromocytoma is found, it should be removed before thyroidectomy.
After the evaluation of patients who are found to be at risk by genetic tests, prophylactic surgery can be applied in suitable patients.
Serum CEA and calcitonin levels should be evaluated two to three months after surgery. If CEA is within normal limits and calcitonin is not detectable, the patient is considered cured and has the best prognosis. This group should be monitored with annual CEA, calcitonin, and potentially annual ultrasound (based on symptoms and physical examination). For multiple endocrine neoplasia 2A and 2B, annual examinations are required for hyperparathyroidism and pheochromocytoma.
Radiotherapy or chemotherapy can be applied in patients who cannot be completely cleared surgically or who develop recurrence later. Tyrosine kinase inhibitors such as vandetanib and cabozantinib can be used for chemotherapy in unresectable and symptomatic patients.
Elderly patients, those with high-grade lesions and incomplete surgical resection have a worse prognosis.