Sporadic and familial medullary thyroid carcinoma: state of the art

Abstract

Medullary thyroid cancer (MTC) accounts for 5% to 10% of all thyroid cancers. The high frequency of familial cases mandates screening and genetic testing. The aggressiveness and age of onset of familial MTC differs depending on the specific genetic mutation, and this should determine the timing and extent of surgery. Sporadic MTC can present at any age, and it is usually associated with a palpable mass and the presence of nodal metastases. Surgery is standard treatment for any patient presenting with resectable MTC. Further studies are needed to investigate the role of radiation therapy in the palliation and local control of postresection and advanced-stage MTC. New systemic therapies for metastatic disease are being investigated. Targeted molecular therapies, based on knowledge of the pathways affected by RET mutations, are being tested in multiple clinical trials.

Figure 1

Features of MEN 2A and 2B syndromes. A. Bisected thyroidectomy specimen showing multifocal, bilateral MTC tumors. B. Adrenalectomy specimen showing pheochromocytoma. C. Megacolon in patient with MEN 2B. D. Tongue nodules in patient with MEN 2B. (Photograph A courtesy of Dr. S.A. Wells. Photographs B, C and D courtesy of Dr. R. Thompson) (reprinted with permission from Moley, JF, Medullary thyroid cancer, from Textbook of Endocrine Surgery, ed. Clark, OH, and Duh, Q-Y, WB Saunders Co, Philadelphia, 1997)

Figure 2

Schematic representation of the anatomic landmarks and lymph node compartments in the neck and upper mediastinum encountered in surgical reinterventions in medullary thyroid carcinoma. The central compartment is delimited inferiorly by the innominate vein, superiorly by the hyoid bone, laterally by the carotid sheaths, and dorsally by the prevertebral fascia. It comprises lymphatic and soft tissues around the esophagus as well as pretracheal and paratracheal lymph nodes which drain the thyroid bed (level VI). The submandibular nodal group (level I) is subsumed in the central compartment by some classifications. The lateral compartments span the area between the carotid sheath, the sternocleidomastoid muscle and the trapezius muscle. The inferior border is defined by the subclavian vein, and the hypoglossal nerve determines the superior boundary. The lymph node chain adjacent to the jugular vein is divided cranially to caudally in superior jugular nodes (level II), midjugular nodes (level III), and inferior jugular nodes (level IV). Lymph nodes situated in the posterior triangle between the dorsolateral sternocleidomastoid muscle, the trapezius muscle and the subclavian vein are classified as level V nodes. Mediastinal lymphatic tissue is referred to as level VII lymph nodes (Reprinted with permission from Musholt TJ, Moley JF. Prob Gen Surg 14, 1997).

Figure 3

Total thyroidectomy and central neck dissection in a MEN 2A patient with palpable MTC. (Photos by author)

Figure 4

Photograph of central neck compartment after redo central neck dissection for persistent medullary thyroid carcinoma. Thyroid and central neck lymph nodes have been removed, parathyroids were removed and autotransplanted. (Photo by author)