Sen Indrani, Young William F, Kasperbauer Jan L, Polonis Katarzyna, Harmsen William S, Colglazier Jill J, DeMartino Randall R, Oderich Gustavo S, Kalra Manju, Bower Thomas C
Department of Vascular Surgery, Mayo Clinic, Rochester, Minn.
Department of Endocrinology, Mayo Clinic, Rochester, Minn.
J Vasc Surg. 2020 May;71(5):1602-1612.e2. doi: 10.1016/j.jvs.2019.08.232. Epub 2020 Feb 5.
Genetic testing to identify succinate dehydrogenase (SDH) mutations in patients with head and neck paraganglioma (HNP) has been in clinical practice for more than a decade. However, the recurrence and metachronous tumor occurrence risks in surgically treated mutation-positive patients are not well studied.
Clinical and procedural details of consecutive patients who underwent excision for HNP from January 1996 to October 2016 were retrospectively reviewed. End points included recurrence, metachronous tumor detection, and mortality. Germline DNA was tested to identify mutations in SDHx genes. Patients were divided into three groups on the basis of genetic testing: group I, positive; group II, negative; and group III, unknown or offered but not tested.
HNP was diagnosed in 268 patients, 214 (147 female; mean age, 47 years) included in this study. Directed genetic testing was performed in 68; mutations were detected in SDH in 47 (69%), a majority SDHD. In group I, 47 patients had 64 procedures for 81 tumors (52 carotid body tumors [CBTs]); 17 (36%) were bilateral, 7 (15%) multiple, 3 (6%) functional, and 7 (15%) malignant. Residual tumor in 10 was significant in 2, managed by radiation therapy and reoperation. Local recurrence was detected in 12 patients (25%) at a median of 8 years; 11 metachronous mediastinal and retroperitoneal paragangliomas were detected in 8 (17%) at a median of 13 years. Systemic metastases occurred in five (10%). Six patients (13%) had more than one recurrence. In group II, 21 patients had 22 procedures for 23 tumors, 17 CBTs. Two (9%) were bilateral and two (9%) malignant. Excision was complete in all with no recurrence or systemic metastasis at last follow-up. For group III, 146 patients underwent 153 procedures for 156 tumors, 95 CBTs; 7 (5%) were bilateral, 2 (1%) multiple, 8 (5%) functional, and 1 (0.6%) malignant. Local recurrence was detected in nine (6%) at a median of 9 years and metachronous HNP in three (2%) at a median of 5 years. Systemic metastases occurred in two (1%). Mortality was 4% in group I and 3% in group III, none procedure or tumor related. Group I (mutation positive) had 10-year overall, recurrence-free, and metachronous tumor-free survival rates of 93%, 69.4%, and 73%, respectively, lower than the other groups (P < .001).
Bilateral, functional, malignant, recurrent, and metachronous tumors are more common in SDH mutation-positive patients with HNP. Overall survival in patients with HNP is high. Metachronous tumors or local recurrences occur late, and long-term follow-up is necessary.
用于识别头颈部副神经节瘤（HNP）患者琥珀酸脱氢酶（SDH）突变的基因检测已在临床应用超过十年。然而，手术治疗的突变阳性患者的复发和异时性肿瘤发生风险尚未得到充分研究。
回顾性分析1996年1月至2016年10月期间因HNP接受手术切除的连续患者的临床和手术细节。终点包括复发、异时性肿瘤检测和死亡率。检测种系DNA以识别SDHx基因中的突变。根据基因检测结果将患者分为三组：第一组，阳性；第二组，阴性；第三组，未知或已提供检测但未进行检测。
268例患者被诊断为HNP，本研究纳入214例（147例女性；平均年龄47岁）。对68例患者进行了定向基因检测；47例（69%）检测到SDH突变，大多数为SDHD。在第一组中，47例患者因81个肿瘤接受了64次手术（52例颈动脉体瘤[CBT]）；17例（36%）为双侧，7例（15%）为多发，3例（6%）有功能，7例（15%）为恶性。10例有残留肿瘤，2例残留肿瘤明显，通过放疗和再次手术处理。12例患者（25%）在中位时间8年时出现局部复发；8例患者（17%）在中位时间13年时检测到11例异时性纵隔和腹膜后副神经节瘤。5例（10%）发生全身转移。6例患者（13%）有不止一次复发。在第二组中，21例患者因23个肿瘤接受了22次手术，17例为CBT。2例（9%）为双侧，2例（9%）为恶性。所有患者切除均完整，最后一次随访时无复发或全身转移。对于第三组，146例患者因156个肿瘤接受了153次手术，95例为CBT；7例（5%）为双侧，2例（1%）为多发，8例（5%）有功能，1例（0.6%）为恶性。9例患者（6%）在中位时间9年时出现局部复发，3例患者（2%）在中位时间5年时出现异时性HNP。2例（1%）发生全身转移。第一组死亡率为4%，第三组为3%，均与手术或肿瘤无关。第一组（突变阳性）的10年总生存率、无复发生存率和无异时性肿瘤生存率分别为93%、69.4%和73%，低于其他组（P <.001）。
SDH突变阳性的HNP患者中，双侧、有功能、恶性、复发和异时性肿瘤更为常见。HNP患者的总体生存率较高。异时性肿瘤或局部复发出现较晚，需要长期随访。
