Department of Medicine, University Health Network, and Hospital for Sick Children, Toronto, Ontario, Canada.
J Clin Endocrinol Metab. 2012 Feb;97(2):E202-6. doi: 10.1210/jc.2011-2321. Epub 2011 Nov 23.
Carney complex is a genetically heterogenous multiple neoplasia syndrome. Adrenal cortical carcinoma is a rare malignancy with a poor prognosis that is not recognized to be associated with this syndrome.
We report a 22-yr-old female presenting with Carney complex who developed adrenal carcinoma. The response to adjunctive therapy is also described.
We performed a detailed pathology review of the adrenal tumor to examine morphologic changes, Ki-67 labeling, and p53 expression. We also performed genetic testing of candidate genes and describe the response to radiation and kinase inhibition therapy.
The patient presented with an 8.5-cm adrenal mass with a MIB-1 labeling index of 20% and unequivocal angioinvasion classified as a T3NXM0 carcinoma. The nontumorous adrenal cortex revealed characteristic features of primary pigmented nodular adrenocortical disease. Genetic analysis revealed a novel PRKAR1 frame shift mutation resulting in a premature stop codon and a heterozygous p53 polymorphic substitution previously noted in other solid carcinomas. Disease recurrence in the liver showed partial response to combined stereotactic radiotherapy and sorafenib multikinase inhibition.
This represents an initial characterization of a malignancy among patients with Carney complex. Our findings have implications for disease surveillance and management of individuals with this genetic syndrome.
卡尼综合征是一种具有遗传异质性的多发性肿瘤综合征。肾上腺皮质癌是一种罕见的恶性肿瘤，预后不良，与该综合征无关。
我们报告了一例 22 岁的女性患有卡尼综合征，其发展为肾上腺癌。还描述了辅助治疗的反应。
我们对肾上腺肿瘤进行了详细的病理检查，以检查形态变化、Ki-67 标记和 p53 表达。我们还对候选基因进行了基因检测，并描述了对放疗和激酶抑制治疗的反应。
患者出现 8.5 厘米大的肾上腺肿块，MIB-1 标记指数为 20%，具有明确的血管侵犯，归类为 T3NXM0 癌。非肿瘤性肾上腺皮质显示原发性色素性结节性肾上腺皮质疾病的特征性表现。基因分析显示一种新的 PRKAR1 移码突变，导致提前终止密码子和异源 p53 多态性取代，以前在其他实体癌中也有报道。肝内疾病复发显示对联合立体定向放疗和索拉非尼多激酶抑制的部分反应。
这代表了卡尼综合征患者中一种恶性肿瘤的初步特征。我们的发现对该遗传综合征患者的疾病监测和管理具有重要意义。
