What is medullary thyroid carcinoma (MTC)?

From the Guidelines

Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer that originates from the parafollicular C cells of the thyroid gland, which normally produce the hormone calcitonin, and accounts for approximately 5-8% of all thyroid malignancies, as stated in the most recent and highest quality study 1.

Key Characteristics of MTC

• MTC is not derived from thyroid follicular cells and can occur sporadically (about 75% of cases) or as part of inherited genetic syndromes such as Multiple Endocrine Neoplasia type 2 (MEN2A or MEN2B) or Familial Medullary Thyroid Carcinoma (FMTC) 1.
• MTC typically presents as a thyroid nodule, sometimes with cervical lymph node involvement, and may cause symptoms like diarrhea or facial flushing due to hormone secretion.
• Diagnosis involves measuring calcitonin levels, thyroid ultrasound, fine-needle aspiration biopsy, and genetic testing for RET mutations, with measurement of serum calcitonin being a reliable tool for the diagnosis of MTC, as stated in 1 and 1.

Treatment and Management

• Treatment primarily consists of total thyroidectomy with central neck dissection, as MTC does not respond well to radioactive iodine therapy used for other thyroid cancers, as stated in 1.
• Long-term monitoring includes regular calcitonin and carcinoembryonic antigen (CEA) measurements, with the goal of detecting persistent or recurrent disease, as stated in 1.
• For hereditary forms, early genetic screening of family members is crucial, as prophylactic thyroidectomy may be recommended for those carrying RET mutations before cancer develops, as stated in 1 and 1.

Prognosis and Survival

• MTC has a survival rate of 82% at 10 years, as stated in 1, which is lower than that of differentiated thyroid carcinomas (DTC), but still relatively favorable with appropriate treatment and management.
• The prognosis of MTC depends on various factors, including the extent of disease, presence of lymph node metastases, and distant metastases, as stated in 1 and 1.

From the FDA Drug Label

CAPRELSA is a prescription medicine used to treat medullary thyroid cancer that cannot be removed by surgery or that has spread to other parts of the body. INDICATIONS AND USAGE CAPRELSA is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. Medullary thyroid carcinoma is a type of thyroid cancer that cannot be removed by surgery or has spread to other parts of the body, and is treated with CAPRELSA (2), (2).

• Medullary thyroid cancer is a condition where cancer cells are found in the thyroid gland, specifically in the medullary cells.
• It can be symptomatic or progressive, and may be unresectable, locally advanced, or metastatic (2), (2).

From the Research

Definition and Origin of Medullary Thyroid Carcinoma

• Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells, also known as C cells 3, 4, 5.
• It represents 2-5% of all thyroid malignancies 3, 4, 6.
• MTC is a rare neuroendocrine tumor with a distinct biology compared to differentiated thyroid cancer 5, 6.

Types and Genetic Mutations

• MTC can be sporadic or inherited, with the latter being part of the MEN 2 syndromes 4.
• Germline mutations in the RET proto-oncogene are driver mutations in hereditary MTC, while somatic RET mutations and RAS mutations are found in sporadic MTC 4.
• Genetic screening for germline mutations in the RET proto-oncogene can identify gene carriers and enable primary or secondary prevention of the disease 4.

Diagnosis and Treatment

• MTC should be suspected in individuals with thyroid nodules, family histories of MTC, and certain phenotypic characteristics 3.
• Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation 3.
• Surgery is the only curative therapeutic strategy, and radical surgery with complete tumor resection is pivotal in attaining cure for MTC 3, 4, 6.
• Treatment options for metastatic disease are limited and focused on disease control, with multikinase inhibitors and selective RET-inhibitors being used in some cases 4.