Medullary carcinoma arises from a different type of epithelial cell, the C-cell. C-cells are involved in calcitonin production and normally are found between the follicles of the thyroid.
Epidemiology and Aetiology
Medullary thyroid carcinoma is notable for its strong familial association, usually in association with the MEN 2A and 2B syndromes. Sporadic cases occur at a mean age of 50. Familial cases occur in early childhood (MEN 2B) or in the teenage/young adult years (MEN2A). Familial medullary thyroid carcinoma (FMTC), a distinct entity from MEN 2A/B, occurs at a mean age of 50 (similar to sporadic cases).
The aetiology of sporadic cases is unknown. Radiation exposure does not increase the risk of this disease.
Natural History and Clinical Features
Regional and distant metastases occur early in the course of the disease and are not uncommon. Medullary carcinoma often produces various peptide byproducts and these can lead to paraneoplastic syndromes (eg. Cushing’s syndrome due to ACTH production).
On thyroid functional imaging the malignancy appears as a cold nodule. CT and MRI are helpful for staging.
Tumour Features
Macroscopy
The tumours are usually white to tan and well circumscribed; unlike follicular carcinoma they are not encapsulated. They have a gritty consistency.
Microscopy
The malignant cells are usually arranged in trabeculae, sheets or nests. Cells can be variable in their shape. The clusters of cells are usually separated by a fibrovascular stroma. The nuclei are usually round and uniform with coarse chromatin.
Immunohistochemistry
Neuroendocrine markers are frequently positive, as is CEA and calcitonin stains. TTF1 is usually positive.
Genetics
RET mutations are the hallmark of medullary carcinoma, occurring in 20-80% of sporadic cases. The familial cases are due to MEN 2A, 2B or FMTC. FMTC is a subtype of MEN2. These conditions are all due to different germline mutations of the RET gene.
Staging and Outcomes
Medullary thyroid carcinoma is staged conventionally using TNM. 5 year survival is about 75%.
