Shaha Ashok R, Cohen Tzeela, Ghossein Ronald, Tuttle R Michael
Department of Surgery, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Laryngoscope. 2006 Sep;116(9):1704-7. doi: 10.1097/01.mlg.0000233509.83679.ee.
Sporadic late-onset medullary carcinoma of the thyroid is quite rare. Usually, the patient presents with a thyroid mass or neck node metastasis along with high levels of calcitonin and preoperative fine needle aspiration biopsy suggestive of medullary carcinoma of the thyroid. The role of genetic testing in such individuals, along with testing of other family members, remains somewhat unclear at this stage, especially in patients presenting with familial medullary thyroid carcinoma. Genetic testing with RET proto-oncogene mutational studies is very popular in familial medullary thyroid carcinoma, especially in children, with routine prophylactic thyroidectomy. However, its indications in adults remain unclear at this time.
Recently, a 69-year-old woman presented with a thyroid mass and underwent total thyroidectomy and central compartment dissection. She was found to have medullary carcinoma of the thyroid. The patient had four children, three of whom were found to have a RET mutation similar to their mother's, V804M. In view of the RET mutation, the three children were offered prophylactic thyroidectomy at ages 42, 45, and 47. The patient's son was noted to have extensive C-cell hyperplasia in both lobes of the thyroid. The other two individuals had benign pathology with no evidence of C-cell hyperplasia.
There is no definite consensus of opinion about the need for prophylactic total thyroidectomy in adults with RET mutation. The rarely reported 804 mutation is, however, a predictor of medullary carcinoma of the thyroid. One individual in this group had extensive C-cell hyperplasia, suggesting that he would have developed medullary carcinoma of the thyroid in the future. Prophylactic thyroidectomy should be recommended in patients with RET mutation and a family history of medullary carcinoma of the thyroid; however, its role in adult family members needs to be evaluated with larger registry of prophylactic thyroidectomy. Whether these adults with rare 804-mutation could be observed and followed with serial calcitonin, ultrasound, or calcitonin stimulation tests remains to be studied.
散发性迟发性甲状腺髓样癌相当罕见。通常，患者表现为甲状腺肿块或颈部淋巴结转移，同时伴有降钙素水平升高以及术前细针穿刺活检提示甲状腺髓样癌。在此阶段，基因检测在这类个体以及其他家庭成员检测中的作用仍有些不明确，尤其是在患有家族性甲状腺髓样癌的患者中。RET原癌基因突变研究的基因检测在家族性甲状腺髓样癌中非常普遍，尤其是在儿童中，常进行预防性甲状腺切除术。然而，其在成人中的应用指征目前仍不明确。
最近，一名69岁女性因甲状腺肿块就诊，接受了全甲状腺切除术及中央区淋巴结清扫术。她被诊断为甲状腺髓样癌。该患者有四个孩子，其中三个被发现携带与母亲相似的RET突变，即V804M。鉴于RET突变，这三个孩子分别在42岁、45岁和47岁时接受了预防性甲状腺切除术。患者的儿子甲状腺两叶均有广泛的C细胞增生。另外两人病理结果为良性，无C细胞增生迹象。
对于携带RET突变的成人是否需要进行预防性全甲状腺切除术，目前尚无明确的共识。然而，罕见报道的804突变是甲状腺髓样癌的一个预测指标。该组中有一人有广泛的C细胞增生，表明他将来可能会发展为甲状腺髓样癌。对于有RET突变且有甲状腺髓样癌家族史的患者，应建议进行预防性甲状腺切除术；然而，其在成年家庭成员中的作用需要通过更大规模的预防性甲状腺切除术登记研究来评估。这些携带罕见804突变的成年人是否可以通过连续的降钙素、超声或降钙素刺激试验进行观察和随访，仍有待研究。
