Medullary carcinoma of the thyroid (MTC) is a distinct thyroid carcinoma that originates in the parafollicular C cells of the thyroid gland. These C cells produce calcitonin.
MTC has a genetic association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but it has an inheritable non-MEN mode of transmission.
Sporadic, or isolated, MTC occurs in 75% of patients, and familial MTC comprises the rest.
Outcome depends on extent of disease, nature of tumor biology, and overall efficacy of surgical treatment.
Pathophysiology: MTC is usually diagnosed on physical examination as a solitary neck nodule, and early spread to regional lymph nodes is common. Distant metastases occur in the liver, lung, bone, and brain.
Sporadic MTC usually is unilateral. In association with MEN syndromes, it always is bilateral and multicentric. MTC typically is the first abnormality observed in both MEN 2A and 2B syndromes.
In addition to producing calcitonin, MTC cells can produce several other hormones, including corticotropin, serotonin, melanin, and prostaglandins; moreover, paraneoplastic syndromes (eg, carcinoid syndrome, Cushing syndrome) can occur in these patients.
History: A specific constellation of symptoms of medullary thyroid carcinoma (MTC) is not usually noted; however, one or more of the following symptoms may be observed:
- Patients may describe a lump at the base of the neck, which may interfere with or become more prominent during swallowing.
- Patients with locally advanced disease may present with hoarseness, dysphagia, and respiratory difficulty.
- Although uncommon, patients may present with various paraneoplastic syndromes, including Cushing or carcinoid syndrome.
- Diarrhea may occur from increased intestinal electrolyte secretion secondary to high plasma calcitonin levels.
- Distant metastases (eg, lung, liver, bone) may produce symptoms of weight loss, lethargy, and bone pain.
Imaging Procedures in general for thyroid nol\\dules:
Because ultrasonography cannot distinguish benign from malignant nodules, the utility of this test is limited in the workup of thyroid nodules. Simple cysts found on ultrasound are benign; however, simple cysts are rarely found. More commonly, cysts are complex with at least some solid component that could potentially harbor malignancy. Ultrasound is highly sensitive for detecting thyroid nodules and can identify nodules only a few millimeters in size. An ultrasound ordered to evaluate a solitary nodule often reveals additional nodules of questionable clinical significance. The accuracy of FNAB results increases when it is guided by ultrasound. Use of ultrasound-guided FNAB can be very useful for biopsy of small or difficult-to-palpate thyroid nodules as well as for FNAB of nodules in children. Ultrasound can also be useful for accurate measurement of thyroid nodules that are being monitored serially.
Radioiodine imaging can determine the functional status of a nodule. Nodules that are nonfunctional do not take up radiolabeled iodine (iodine 123) and appear as cold spots in the thyroid (cold nodules). Nodules that are hyperfunctioning take up higher levels of radioiodine and appear as hot spots (hot nodules). Warm nodules appear similar to the surrounding normal thyroid tissue. Historically, hot or warm nodules were thought to be benign; thus, they did not require further evaluation for malignancy. Ashcraft et al, however, in a review of 5000 patients undergoing thyroidectomy regardless of radioiodine image findings, found that 4% of hot nodules harbored malignancy. Carcinoma cannot be excluded based on radioiodine scans. Thus, radioiodine scans are usually not helpful for the routine evaluation of thyroid nodules. In select situations, however, radioiodine studies can be diagnostic adjuncts. For example, when repeated FNAB of a nodule is nondiagnostic, a radioiodine imaging study can help direct management if a hot nodule would be monitored clinically.
CT scans and MRI can be used to evaluate soft-tissue extension of large or suspicious thyroid masses into the neck, trachea, or esophagus and to assess cervical lymph node metastases. They do not have a role for the routine management of solitary thyroid nodules.
Imaging Studies for medullary carcinoma :
- Preoperatively performing cervical ultrasonography can detect lymph node metastases.
- CT scanning, MRI, and bone scanning can detect distant metastases to the liver, lung, bone, and brain.
Histologic Findings: Grossly, MTC resembles a well-circumscribed off-white nodule with a rough texture. Microscopically, it contains nests of round or ovoid cells. A fibrovascular stroma is usually intercalated between cells. Sometimes, amyloid material, consisting of calcitonin prohormone, may occur in the MTC stroma. Perhaps most importantly, immunohistochemical diagnosis of MTC can be made by demonstrating calcitonin using radioactive calcitonin antiserum against MTC cells.