Medullary thyroid carcinoma in multiple endocrine neoplasia types 2A and 2B

Abstract

Background: Considerable emphasis has been placed on early diagnosis and surgery for multiple endocrine neoplasia (MEN)-related medullary thyroid carcinoma (MTC) during the past two decades. Genetic screening now promises earlier and more accurate diagnosis. We examine our experience with MTC in MEN 2A and MEN 2B and assess the benefits of biochemical screening during the past 20 years.

Patients and methods: Seventy-seven patients undergoing 63 primary total thyroidectomies and 14 reoperative procedures for MEN-related invasive MTC and/or preinvasive C-cell hyperplasia are reported. Fifty-eight patients had MEN 2A and 19 had MEN 2B; 79% of patients had a family history of MTC; 27% had pheochromocytoma, and 25% had hyperparathyroidism.

Results: Patients with MEN 2B had more advanced disease than those with MEN 2A, in spite of presentation at a younger age (15 years versus 24 years). Every patient with MEN 2B had invasive carcinoma, whereas 14% of patients with MEN 2A had C-cell hyperplasia without invasive disease. Nodal metastases were found less frequently in MEN 2A (14%) than MEN 2B (38%), and biochemical cure was achieved in 56% of patients with MEN 2A compared with none in patients with MEN 2B. Among patients with MEN 2A the occurrence of invasive carcinoma increased with age (p = 0.0003); 40% of patients for less than 5 years had invasive MTC compared with 100% at more than 20 years. Cause-specific mortality among patients with MEN and invasive tumors at 6, 12, and 18 years was 2%, 4%, and 7%, respectively, lower than that of patients with sporadic MTC (12%, 17%, and 23%, respectively) treated during the same time period (p = 0.028).

Conclusions: Intensive biochemical screening of MEN 2 kindreds for MTC can result in detection of early disease and a significant prospect of surgical cure. Genetic testing promises additional benefits through more reliable detection of preinvasive disease, allowing prophylactic thyroidectomy in infancy. In MEN 2B, MTC is considerably more aggressive than in MEN 2A. A policy of routine thyroidectomy in infants with MEN 2B, regardless of serum calcitonin levels, is justified.