Medullary Carcinoma Thyroid & Colon Subtypes: Expert Insights

A doctor shows good test results to a sick patient in a hospital bed.

By Kevin FamuyiroSenior Content Strategist

March 13, 2025 1:12 PM PT

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Table of Contents

What Is Medullary Carcinoma Thyroid (MTC)?
Definition and General Makeup
Clinical Presentation and Diagnosis
Key Differences Between Medullary Thyroid Carcinoma and Colon Medullary Carcinoma
Closing Thoughts
References

What Is Medullary Carcinoma Thyroid (MTC)?

Medullary carcinoma is a rare type of cancer that can appear in different parts of the body. It most commonly shows up in the thyroid gland and the colon. Although these two forms share the name “medullary carcinoma,” they each have unique features that set them apart. New advances in science, especially in how we understand the genetic makeup of these cancers, have helped doctors find better ways to treat them.

Medullary Thyroid Carcinoma (often called MTC) is also one of the types of medullary thyroid carcinomas that starts in specific cells of the thyroid gland called parafollicular cells (C cells). These cells make calcitonin, a hormone that helps regulate blood calcium. MTC accounts for about 3–5% of all thyroid cancers ^[1]. This is different from Tubular Carcinoma, where in which cancer cells retain most of the features of normal breast tissue.

Characteristics and Diagnosis

C cells and Calcitonin: Because parafollicular cells produce calcitonin, people with MTC often have high calcitonin levels. Doctors also look at another tumor marker called carcinoembryonic antigen (CEA) to see if MTC might be present ^[4].
Testing and Screening: A tiny sample of the thyroid (taken by a fine-needle aspiration) can show whether the cells are cancerous. Doctors also test for changes (mutations) in the RET proto-oncogene. If someone has a faulty RET gene, they may have a higher chance of developing MTC ^[8].

Grading and Prognosis

Low-Grade vs. High-Grade: Specialists use the International Medullary Thyroid Carcinoma Grading System to classify MTC tumors as low-grade or high-grade. They look at how fast the cancer cells are multiplying and whether parts of the tumor have died (necrosis) ^[5].
Predicting Outcomes: High-grade MTC is linked to a greater chance of spreading (metastasis) and returning (recurrence) after treatment. Low-grade MTC generally has a more favorable outlook.

Treatment

Surgery: The main way to treat MTC is by surgically removing the thyroid gland (or the part affected by cancer). This can help stop the spread of the disease [9].
Targeted Therapies:
- Multi-Kinase Inhibitors: Drugs like vandetanib and cabozantinib block signals that tell cancer cells to grow.
- Selective RET Inhibitors: Medications like selpercatinib and pralsetinib focus on cancer cells with a RET mutation ^[1].
- Emerging Therapies: Ongoing research explores new treatments, including different tyrosine kinase inhibitors, radiotherapy, and immunotherapy ^[9].

Definition and General Makeup

Medullary thyroid cancer (MTC) is a rare and aggressive form of thyroid cancer that originates from the parafollicular C cells of the thyroid gland. These specialized cells are responsible for producing calcitonin, a hormone that helps regulate calcium levels in the body. MTC accounts for approximately 1% to 5% of all thyroid cancers, making it a relatively uncommon but significant type of thyroid malignancy. This cancer can occur sporadically or as part of hereditary syndromes, such as multiple endocrine neoplasia type 2 (MEN2) and familial medullary thyroid cancer (FMTC). One of the critical challenges with MTC is its potential to spread to lymph nodes and other organs, underscoring the importance of early detection and treatment to improve patient outcomes.

Causes and Risk Factors of Medullary Thyroid Cancer

The exact causes of medullary thyroid cancer are not fully understood, but several risk factors have been identified. Genetic mutations play a significant role, particularly mutations in the RET proto-oncogene, which are associated with hereditary forms of MTC, including multiple endocrine neoplasia type 2 (MEN2) and familial medullary thyroid cancer (FMTC). A family history of MTC or MEN2 significantly increases an individual’s risk of developing the disease. Additionally, exposure to radiation, especially during childhood, has been linked to a higher risk of MTC. Certain medical conditions, such as Hashimoto’s thyroiditis, may also elevate the risk of developing this type of thyroid cancer. Understanding these risk factors can help in identifying individuals at higher risk and implementing early screening and preventive measures.

Clinical Presentation and Diagnosis

Symptoms and Signs

The symptoms of medullary thyroid cancer can vary depending on the stage of the disease. Common symptoms include:

A lump or nodule in the thyroid gland
Difficulty swallowing or breathing
Hoarseness or voice changes
Coughing or wheezing
Weight loss
Fatigue

These symptoms can often be mistaken for other conditions, making it crucial to seek medical evaluation if they persist.

Diagnostic Tests

Diagnosing medullary thyroid cancer typically involves a combination of tests to confirm the presence of cancer and assess its extent. A fine-needle aspiration biopsy (FNAB) is often performed to obtain a sample from the thyroid nodule or lymph node, which is then examined for cancer cells. Imaging studies, such as ultrasound, CT, or MRI scans, are used to evaluate the size and spread of the tumor. Blood tests measuring calcitonin and carcinoembryonic antigen (CEA) levels are also crucial in confirming the diagnosis and monitoring for recurrence. Additionally, genetic testing for mutations in the RET proto-oncogene can identify individuals at risk of developing hereditary MTC, allowing for early intervention and management.

Medullary Carcinoma of the Colon

A rarer form of colon cancer called medullary carcinoma can appear in the large intestine. Most colon cancers are known as adenocarcinomas, but medullary carcinoma looks and behaves in a special way ^[2].^[6] .

Epidemiology and Characteristics
- How Rare Is It? Medullary carcinoma of the colon is very uncommon, making up less than 1% of all colon cancers. It is often found on the right side of the colon and is more common in females ^[7].
- Presentation: Although it can appear at a later stage, it does not often spread to faraway parts of the body right away. This unusual behavior can lead to better outcomes for some patients ^[2].
Molecular Features
- Microsatellite Instability (MSI): A large number of medullary colon tumors have high microsatellite instability, which means they carry frequent DNA errors because the body’s system for fixing these errors is not working well ^[3].
- Mismatch Repair Deficiency: This deficiency leads to the high MSI often seen in medullary carcinoma of the colon ^[3].
- BRAF (V600E) Mutations: Many of these tumors also show changes in a gene called BRAF. Drugs that specifically target BRAF mutations can be part of a patient’s treatment plan ^[7].
Prognosis
- Outlook for Patients: Even though these tumors may present at advanced stages, they often have a better survival rate compared to other poorly differentiated or undifferentiated colon cancers ^[3], ^[6].

Key Differences Between Medullary Thyroid Carcinoma and Colon Medullary Carcinoma

While both are called medullary carcinoma, these cancers differ in many ways:

Feature	Medullary Thyroid Carcinoma (MTC)	Medullary Carcinoma of the Colon	Differentiated Thyroid Carcinoma
Origin	Parafollicular (C cells)	Cells in the colon lining (colorectal epithelium)	Follicular cells
Common Biomarker	Calcitonin	Microsatellite instability (MSI)	Thyroglobulin
Molecular Drivers	RET mutations	Mismatch repair deficiency, BRAF	BRAF, RAS mutations
Treatment	Surgery, RET inhibitors	Surgery, MSI-targeted therapies	Surgery, radioactive iodine
Prognosis	Varies (worse if high-grade)	Often better than other aggressive colon cancers	Better established treatment pathway, generally better prognosis than MTC

Closing Thoughts

Medullary carcinoma, whether it appears in the thyroid gland or the colon, holds a unique spot among rare cancers. Medullary Thyroid Carcinoma (MTC) can be discovered through elevated levels of calcitonin, changes in the RET gene, or abnormal cells found on biopsy. Sporadic medullary thyroid carcinoma, which occurs without an identifiable family history, often presents with more extensive disease at diagnosis and involves specific genetic mutations, particularly in the RET proto-oncogene. Although these subtypes have different origins, each one benefits from ongoing discoveries in genetic testing and targeted therapies.

Treating metastatic medullary thyroid cancer presents significant challenges, but protein kinase inhibitors like Vandetanib and Cabozantinib have shown promise in improving survival rates for patients with advanced stages of MTC. Meanwhile, medullary carcinoma of the colon is closely tied to microsatellite instability and mismatch repair deficiency, which can guide how doctors choose treatments. As researchers continue to learn more, patients and their families can look forward to new treatment options and a brighter outlook.

References

^{[1] Pelizzo, M. R., Mazza, E. I., Mian, C., & Merante Boschin, I. (2023). Medullary thyroid carcinoma.}^{Expert review of anticancer therapy}^,²³^{(9), 943–957.}^{https://doi.org/10.1080/14737140.2023.2247566}

^{[2] Cunningham, J., Kantekure, K., & Saif, M. W. (2014). Medullary carcinoma of the colon: a case series and review of the literature.}^{In vivo (Athens, Greece)}^,²⁸^{(3), 311–314.}^{https://pubmed.ncbi.nlm.nih.gov/24815832/}

^{[3] Jabbal, I. S., Nagarajan, A., Rivera, C., Yaghi, M., Liang, H., Nahleh, Z., Bejarano, P., Berho, M., & Wexner, S. (2022). Medullary carcinoma of the colon: A comprehensive analysis of the National Cancer Database.}^{Surgical oncology}^,⁴⁵^{, 101856.}^{https://doi.org/10.1016/j.suronc.2022.101856}

^{[4] Thomas, C. M., Asa, S. L., Ezzat, S., Sawka, A. M., & Goldstein, D. (2019). Diagnosis and pathologic characteristics of medullary thyroid carcinoma-review of current guidelines.}^{Current oncology (Toronto, Ont.)}^,²⁶^{(5), 338–344.}^{https://doi.org/10.3747/co.26.5539}

^{[5] Xu, B., Fuchs, T. L., Ahmadi, S., Alghamdi, M., Alzumaili, B., Bani, M. A., Baudin, E., Chou, A., De Leo, A., Fagin, J. A., Ganly, I., Glover, A., Hartl, D., Kanaan, C., Khneisser, P., Najdawi, F., Nigam, A., Papachristos, A., Repaci, A., Spanheimer, P. M., … Ghossein, R. A. (2022). International Medullary Thyroid Carcinoma Grading System: A Validated Grading System for Medullary Thyroid Carcinoma.}^{Journal of clinical oncology : official journal of the American Society of Clinical Oncology}^,⁴⁰^{(1), 96–104.}^{https://doi.org/10.1200/JCO.21.01329}

^{[6] Pyo, J. S., Sohn, J. H., & Kang, G. (2016). Medullary carcinoma in the colorectum: a systematic review and meta-analysis.}^{Human pathology}^,⁵³^{, 91–96.}^{https://doi.org/10.1016/j.humpath.2016.02.018}

^{[7] Kaliszewski, K., Ludwig, M., Ludwig, B., Mikuła, A., Greniuk, M., & Rudnicki, J. (2022). Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?}^Cancers^,¹⁴^{(15), 3643.}^{https://doi.org/10.3390/cancers14153643}

^{[8] Jayasinghe, R., Basnayake, O., Jayarajah, U., & Seneviratne, S. (2022). Management of medullary carcinoma of the thyroid: a review.}^{The Journal of international medical research}^,⁵⁰^{(7), 3000605221110698.}^{https://doi.org/10.1177/03000605221110698}

^{[9] Ringel M. D. (2021). New Horizons: Emerging Therapies and Targets in Thyroid Cancer.}^{The Journal of clinical endocrinology and metabolism}^,¹⁰⁶^{(1), e382–e388.}^{https://doi.org/10.1210/clinem/dgaa687}