转移性嗜铬细胞瘤/副神经节瘤的临床诊断和预后

嗜铬细胞瘤/副神经节瘤(pheochromocytoma and paranganglioma, PPGL)患者由于过度分泌儿茶酚胺, 因而有较高的继发性高血压发生率和死亡率。大约1/4的PPGL具有侵袭转移性, 这类不能切除的转移性病灶的治疗方案包括¹³¹I-间碘苄胍核素治疗、放疗和化疗, 但此类治疗也只能控制肿瘤生长和抑制激素水平。过去10年, PPGL的临床和分子机制研究均取得了诸多进展, 然而预后判断和治疗仍然是临床实践中最大的挑战。转移性PPGL患者的自然病史往往未知, 其预后也不尽相同, 目前诊断依然依赖于转移灶的存在, 因此通常诊断时已是晚期。有研究对患者的临床和分子特征、导致转移性PPGL的特定信号通路的改变进行了探索, 以期随着核素治疗、放疗联合分子靶向治疗的发展, 提高该病的临床预后。

Clinical Diagnosis and Prognosis of Metastatic Pheochromocytoma and Paraganglioma

Hypersecretion of catecholamines from pheochromocytoma and paraganglioma(PPGL) is associated with high morbidity and mortality, even when the tumors are benign. Up to 25% of PPGL are associated with germline mutations in susceptible genes. About one-quarter is metastatic, defined by the presence of distant metastases. Treatment options for unresectable metastatic disease, including chemotherapy, 131I-MIBG, and radiation, can offer limited tumor and hormone control, although none are curative. Over the past 10 years, substantial progress has been made toward understanding the clinical aspects and molecular origins of PPGL. Nevertheless, predicting and managing malignancy remains the biggest challenge in clinical practice. The natural history of patients with metastatic PPGL has not yet been described, and their prognosis varies. Currently, the diagnosis of metastatic PPGL relies on the presence of metastases, and by then, the disease is usually advanced. A better understanding of the clinical and molecular characteristics of patients with metastatic PPGL has spurred several prospective clinical trials. A deeper understanding of the alteration of the specific molecular pathways causing metastatic PPGL might hopefully lead in the future to the development of radiotherapy and multiple molecular-targeted therapies to treat it successfully.