Geurts Jennifer L
Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
J Gastrointest Oncol. 2020 Jun;11(3):559-566. doi: 10.21037/jgo.2020.03.09.
Inherited syndromes are important to recognize in the setting of a pancreatic neuroendocrine tumor (PNET) as there are significant implications for the patient's medical management and opportunity for early detection of subsequent manifestations. Although most PNETs are sporadic, approximately 10% are due to an inherited syndrome, which include multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 4 (MEN4), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). The general hallmarks of a hereditary endocrine neoplasia predisposition syndrome include any one of the following: multiple primary tumors (in the same or different organs), rare tumors (prevalence of less than 1 in 1,000 people in the general population), earlier age of diagnosis (usually under the age of 40), characteristic pattern of disease in the individual or family (phenotype and inheritance pattern). These syndromes are monogenic (due to a single gene disorder), highly penetrant (with all carriers of the disease exhibiting at least part of the phenotype) and can display variable expressivity (where affected individuals may have different presentations and features of the disease). A thoughtful approach to management is required, even if the presenting symptom is resolved, as these syndromes often involve multi-organ disease with a lifelong risk for tumor development. Additionally, the natural history of tumors in the setting of a hereditary condition may be different than would be expected in a sporadic form of the disease. For example, in some circumstances the risk of metastatic disease is lower, and therefor longer observation is the preferred approach over early surgical intervention. The unique aspects to management, challenges in hereditary disease recognition and accurate diagnosis, and rarity of these syndromes are all reasons to support referral to high-volume centers with the experience and knowledge to treat patients with hereditary endocrine neoplasia syndromes.
在胰腺神经内分泌肿瘤（PNET）的背景下，识别遗传性综合征很重要，因为这对患者的医疗管理以及早期发现后续表现的机会具有重大意义。虽然大多数PNET是散发性的，但约10%是由遗传性综合征引起的，其中包括1型多发性内分泌腺瘤病（MEN1）、4型多发性内分泌腺瘤病（MEN4）、冯·希佩尔-林道病（VHL）、1型神经纤维瘤病（NF1）和结节性硬化症（TSC）。遗传性内分泌肿瘤易感性综合征的一般特征包括以下任何一项：多个原发性肿瘤（在同一或不同器官）、罕见肿瘤（在普通人群中患病率低于千分之一）、诊断年龄较早（通常在40岁以下）、个体或家族中疾病的特征模式（表型和遗传模式）。这些综合征是单基因的（由于单一基因疾病）、高度外显的（所有疾病携带者至少表现出部分表型），并且可能表现出可变表达性（受影响个体可能有不同的疾病表现和特征）。即使当前症状已缓解，也需要采取周全的管理方法，因为这些综合征通常涉及多器官疾病，终身有肿瘤发生风险。此外，遗传性疾病背景下肿瘤的自然史可能与散发性疾病预期的不同。例如，在某些情况下，转移性疾病的风险较低，因此较长时间的观察是比早期手术干预更可取的方法。管理的独特方面、遗传性疾病识别和准确诊断中的挑战以及这些综合征的罕见性，都是支持将患者转诊至有经验和知识治疗遗传性内分泌肿瘤综合征患者的高容量中心的理由。
