Weinhäusel Andreas, Behmel Annemarie, Ponder Bruce A J, Haas Oskar A, Niederle Bruno, Gessl Alois, Vierhapper Heinrich, Pfragner Roswitha
CCRI St. Anna Children's Hospital, Vienna, Austria.
Endocr Pathol. 2003 Winter;14(4):375-82. doi: 10.1385/ep:14:4:375.
A unilateral, apparently sporadic pheochromocytoma was removed from the right adrenal of a 73-yr-old Caucasian woman. At the time of surgery, germline DNA from the patient was not available. However, a continuous cell line (KNA) established from the tumor showed a heterozygous sequence variant TGC (cysteine) to TGG (tryptophan) in exon 10, codon 611 of the RET proto-oncogene. Subsequent genetic testing of the patient and her offspring revealed the same base-change in herself, one daughter, one son, and the only grandson, confirming hereditary disease classified as MEN2A-2. Clinical follow up of the patient revealed elevated serum calcitonin after 6 yr. Thyroidectomy was performed and revealed a small medullary thyroid carcinoma. The patient's children thus far show no evidence of MEN2, but C-cell hyperplasia has been diagnosed in the grandson. Our serendipitous finding of a MEN2A-2 mutation in a patient with initial diagnosis of late onset, unilateral, "sporadic" pheochromocytoma would argue for routine mutation screening of even elderly patients presenting with a pheochromocytoma.
从一名73岁白种女性的右侧肾上腺切除了一个单侧、明显散发的嗜铬细胞瘤。手术时，无法获取患者的生殖系DNA。然而，从肿瘤建立的连续细胞系（KNA）显示，RET原癌基因第10外显子第611密码子存在杂合序列变异，即从TGC（半胱氨酸）变为TGG（色氨酸）。随后对患者及其后代进行的基因检测显示，患者本人、一个女儿、一个儿子和唯一的孙子都存在相同的碱基变化，证实为遗传性疾病，归类为MEN2A-2。对患者的临床随访显示，6年后血清降钙素升高。进行了甲状腺切除术，发现了一个小的甲状腺髓样癌。到目前为止，患者的子女未表现出MEN2的迹象，但已在孙子中诊断出C细胞增生。我们在最初诊断为迟发性、单侧“散发”嗜铬细胞瘤的患者中偶然发现MEN2A-2突变，这表明即使是患有嗜铬细胞瘤的老年患者也应进行常规突变筛查。
