Objective: Evaluation of treatment of children who are proven carriers of a multiple endocrine neoplasia type 2 (MEN 2)-associated rearranged during transfection (RET) gene mutation.
Design: Retrospective case study and review of the literature.
Method: Between 1976 and 2005, 6 boys and 14 girls with a proven RET mutation or biochemical indication of MEN 2 had thyroid surgery at the University Medical Center, Groningen, The Netherlands. The median age was 10 years (range: 0-08). Preoperative assessment, surgical procedure, pathological findings, postoperative complications and treatment results were studied and compared with data from the literature.
Results: All 20 children underwent total thyroidectomy. In 17 children with preoperatively abnormal basal or stimulated calcitonin levels, total thyroidectomy was combined with tracheo-oesophageal exploration (n = 6) or central compartment dissection (n = 11). C-cell hyperplasia was found in 19 cases (95%) and medullary thyroid carcinoma in 14 (70%; aged 3-18 years). Lymph-node metastases were found in 3 children (15%), all over the age of 10. They underwent additional selective lateral neck dissection, unilateral in 2 cases and bilateral in 1. Two children developed hypoparathyroidism postoperatively, no recurrent laryngeal-nerve palsy was observed. All patients are clinically free of disease after a median follow-up of 9 years (range: 0.6-27). The patients with node metastases still have biochemical evidence of disease. The literature indicates that the progression of the malignant transformation to medullary thyroid carcinoma is connected to the type of RET-mutation. The treatment plan depends on the type of mutation.
Conclusion: Medullary thyroid cancer occurs at a very young age in carriers ofgermline RET mutations. In patients with high-risk mutations prophylactic thyroidectomy is likely to be recommended before the child reaches the age of 2. Elective central lymph-node dissection can be omitted in this instance. After this age, however, the risk of lymph-node metastases increases and, for cases with increased basal or stimulated calcitonin levels, total thyroidectomy with central compartment dissection is indicated.