Normal liver is present admixed with metastatic medullary thyroid carcinoma. Early spread to lymph nodes is common in and sites and distant metastasis occurs in the liver, lung, bone and brain.

Medullary thyroid carcinoma often shows nodules of plump spindled cells. Although not demonstrated in this metastatic infiltrate, acellular amyloid deposits (derived from altered calcitonin) can often be found in adjacent to tumor cells, blending into the fibrous stroma.

GROSS IMAGE: The resected liver harbors a solid oval nodule just under the capsule.

GROSS IMAGE: Cross section shows a solid tan appearance with hemorrhagic foci. Foci of necrosis and hemorrhage are common in larger lesions.

Medullary thyroid carcinoma (MTC) is a neuroendocrine neoplasm that originates from the parafollicular C cells of the thyroid. Parafollicular C cells are derived from neurocrest cells, and mostly produce calcitonin, although other peptide hormones have been found to be also produced in small quantities in certain C cell populations.1 Thus, not surprisingly, MTCs have been known to elaborate somatostain, serotonin, corticotropin, thereby causing paraneoplastic syndromes such as carcinoid syndrome and Cushing syndrome. Paradoxically, hypocalcemia is not a frequent feature despite elevated calcitonin levels.2

80% of the MTCs are sporadic and 20% are familial, occurring in association with multiple endocrine neoplasia syndromes, specifically, MEN type IIA and MEN type IIB, and familial medullary thyroid carcinoma (FMTC).

• MEN type IIA (Sipple syndrome) is defined by MTC, pheochromocytoma (50%) and parathyroid hyperplasia (20%).
• MEN type IIB, is also defined by MTC and pheochromotcytomas. However, parathyroid hyperplasia is supremely rare and there are additional associated abnormalities including a marfanoid body habitus and mucosal neuromas. Furthermore, the form of medullary thyroid carcinoma in MEN IIb is much more aggressive than MTC in MEN IIa.4
• Familial MTC is simply hereditary medullary thyroid carcinoma without any other associated endocrine neoplasms.

MEN syndromes are inherited in an autosomal dominant fashion. In MEN type I, the responsible gene is MENIN. In MEN type II, the culprit are germline point mutations in RET, which is a proto-oncogene. Somatic (and not germline) RET mutations are also involved in sporadic forms of MTC. In familial medullary thyroid carcinomas, one often detects multi-centric C-cell hyperplasia, thought to be precursor lesions. In sporadic MTCs, C-cell hyperplasia is not usually found.2

IHC: Tumor cells would stain for calcitonin in both lesional cells and the stromal amyloid. CEA and chromogranin would also be positive.

In sporadic forms of MTC, lesions tend to be unilobular and occur later in life (5-6th decades); in MTC associated with MEN IIA or IIB, the lesions tend to be bilateral and multicentric, occurring in younger patients (2-3rd decades).2,3

Presents as a mass in the neck or paraneoplastic syndrome caused by a particular secreted hormone such as carcinoid or Cushing's syndrome.

Thyroidectomy. Tumor is not very response to radioactive iodine or chemoradiation.5

The measure of calcitonin levels can be helpful in diagnosis and postoperative management of patients. Prophylactic thyroidectomy is offered to MEN-2 patients with RET mutations.