Medullary Thyroid Cancer (MTC) is a distinct and relatively rare form of thyroid malignancy. Unlike the more common papillary or follicular carcinomas, MTC is classified as a neuroendocrine tumor because it originates from different cells than the surrounding thyroid tissue. This unique cellular origin affects its behavior and treatment approach.
Overall Incidence of Medullary Thyroid Cancer
MTC is considered a rare disease, accounting for only 1% to 5% of all thyroid cancer diagnoses. Its incidence rate is low, estimated at approximately 0.225 cases per 100,000 people annually in the United States, translating to roughly 1,000 to 1,600 new diagnoses each year. Despite this low incidence, MTC is responsible for a disproportionately higher percentage of thyroid cancer-related deaths, highlighting its aggressive nature compared to the differentiated types. Because MTC is so uncommon, it is often treated differently than the more prevalent thyroid cancers.
The Unique Cellular Origin of MTC
MTC originates from the parafollicular C cells, unlike papillary and follicular cancers, which develop from the abundant follicular cells. These C cells are neuroendocrine cells scattered throughout the thyroid gland and are far less numerous than the follicular cells. The primary function of the C cells is the production and secretion of the hormone calcitonin, which helps regulate calcium levels in the blood. Because MTC cells retain this function, elevated serum calcitonin levels are a characteristic marker for diagnosis and monitoring of the disease. Since the tumor cells do not arise from hormone-producing follicular cells, they do not absorb radioactive iodine (RAI), which is a common and effective therapy for other thyroid cancers. Surgical removal is the primary treatment, and calcitonin serves as a reliable biomarker to track disease recurrence.
The Sporadic and Hereditary Breakdown
MTC cases are clearly divided into sporadic and hereditary forms. Approximately 75% of cases are sporadic, meaning they occur randomly in individuals with no family history of the disease. The remaining 25% are hereditary, which are directly linked to inherited genetic mutations. The hereditary form is almost always caused by a germline mutation in the RET proto-oncogene. This inherited mutation can result in Multiple Endocrine Neoplasia type 2 (MEN 2), an autosomal dominant disorder. MEN 2 is further divided into subtypes, such as MEN 2A and MEN 2B, which involve MTC along with tumors in other endocrine glands. In families with a known RET mutation, at-risk individuals can be identified through genetic testing and undergo prophylactic thyroidectomy, or preventive surgery, at a young age. This early intervention means hereditary MTC is often diagnosed earlier and in a less advanced state than its sporadic counterpart, where the average age of diagnosis tends to be older.
Demographic and Global Prevalence
The incidence of MTC shows some variation across different demographic groups. Globally, MTC has been observed in virtually all ethnic groups. While thyroid cancer overall has a significant female predominance, MTC shows a less dramatic sex difference, especially when considering the hereditary forms. Sporadic MTC is typically diagnosed in older adults, often between 40 and 60 years of age. Conversely, hereditary MTC, particularly the aggressive MEN 2B subtype, can present in childhood or young adulthood due to proactive genetic screening. Geographic differences in prevalence are often linked to access to genetic screening and surveillance programs. Regions with limited access to RET gene testing may see a higher proportion of sporadic cases diagnosed later in life. Men and certain racial/ethnic groups, such as Hispanic individuals, may present with more advanced disease at diagnosis, including larger tumors and more frequent lymph node or distant metastases.