Objective: To analyze the clinical features of patients with metastatic pheochromocytoma/paraganglioma (PPGL). Methods: A follow-up study. The clinical data of 250 patients with metastatic PPGL treated at Peking Union Medical College Hospital from January 2018 to August 2023 were retrospectively analyzed, including 124 males and 126 females. The clinical features and treatment status of patients with metastatic PPGL were summarized and analyzed. Kaplan-Meier survival curve was used to evaluate patients' prognosis. Results: The age of onset, age of diagnosis, and age of tumor metastasis in patients with metastatic PPGL were (33.1±14.2) years, (35.4±15.2) years, and (40.7±15.3) years, respectively. Metastasis occurred in 26.4%(66/250) of patients at the time of initial diagnosis. Among patients without metastases at the time of initial diagnosis, the time from primary tumor resection to metastasis[M(Q1, Q3)] was 5.0 (3.0, 9.0) years, among which 20.1%(37/184) of patients had metastases more than 10 years after surgery. Most patients showed increased 24-hour urinary norepinephrine and plasma normetanephrine, accounting for 78.2%(176/225) and 78.7%(85/108), respectively. 42.3%(69/163) of patients had increased neuron specific enolase (NSE)levels. Germline mutations were screened in 201 patients, of which 55.2%(111/201) had germline pathogenic mutations. In patients with gene mutations, 76.5%(85/111) had SDHB mutations. 52.0%(130/250) of metastatic PPGL patients had primary sites outside the adrenal gland, with the Ki-67 index of 5% (3%, 8%). There were 85.6%(214/250) patients had multisystem metastasis, with bone metastasis being the most common site of metastasis, accounting for 60.8%(152/250). In terms of treatment, 32.8%(75/229) of patients underwent two treatment regimens and 8.7%(20/229) of patients underwent three treatment regimens. Most patients had a good prognosis, with a 5-year and 10-year survival rate of 88.0% and 84.0%, respectively. However, some patients had rapid disease progression, and as of August 2023, 30 patients died, and the time from diagnosis to death in deceased patients was 2.0 (1.0, 4.0) years. Conclusions: Patients with metastatic PPGL have a high rate of germline mutations, especially those with SDHB mutations. The metastatic PPGL is usually multisystem metastasis with the characteristics of mostly paraganglioma, large lesion diameter and high Ki-67 index.
目的： 分析转移性嗜铬细胞瘤/副神经节瘤（PPGL）患者的临床特征。 方法： 随访研究。回顾性分析2018年1月至2023年8月于北京协和医院就诊的250例转移性PPGL患者的临床资料，其中男124例，女126例。总结分析转移性PPGL患者的临床特征及治疗情况。应用Kaplan-Meier生存曲线评估患者预后情况。 结果： 转移性PPGL患者中起病年龄、诊断年龄及肿瘤发生转移的年龄分别为（33.1±14.2）岁、（35.4±15.2）岁、（40.7±15.3）岁。26.4%（66/250）的患者在诊断PPGL的同时即发生了转移。诊断PPGL时未发生转移患者中，原发灶手术后至转移的时间［M（Q1，Q3）］为5.0（3.0，9.0）年，其中20.1%（37/184）的患者转移发生在术后10年以上。多数患者以24 h尿去甲肾上腺素及血3-甲氧基去甲肾上腺素升高为主，占78.2%（176/225）及78.7%（85/108），42.3%（69/163）的患者神经元特异性烯醇化酶（NSE）水平升高。201例患者行基因检测，其中55.2%（111/201）患者携带胚系致病性突变，在携带基因突变的患者中，76.5%（85/111）为携带SDHB突变。52.0%（130/250）转移性PPGL患者原发灶位于肾上腺外，转移性PPGL的Ki-67指数为5%（3%，8%）。85.6%（214/250）患者为多系统转移，其中最常见的转移部位为骨转移，占60.8%（152/250）。治疗方面，32.8%（75/229）患者经历2种方案治疗，8.7%（20/229）患者经历3种治疗方案，多数患者预后良好，诊断转移后5年及10年生存率分别为88.0%及84.0%，但部分患者疾病进展迅速，截止到2023年8月，有30例患者死亡，死亡患者诊断转移至死亡的时间为2.0（1.0，4.0）年。 结论： 转移PPGL患者胚系突变率高，特别是携带SDHB突变的发生率高。转移PPGL存在原发灶多为副神经节瘤、病灶直径大、Ki-67指数高的特点，常为多系统转移。.