Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France.
University of Lille, Lille, France.
Front Endocrinol (Lausanne). 2021 May 6;12:678869. doi: 10.3389/fendo.2021.678869. eCollection 2021.
Phakomatoses encompass a group of rare genetic diseases, such as von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC) and Cowden syndrome (CS). These disorders are due to molecular abnormalities on the RAS-PI3K-Akt-mTOR pathway for NF1, TSC and CS, and to hypoxia sensing for VHL. Phakomatoses share some phenotypic traits such as neurological, ophthalmological and cutaneous features. Patients with these diseases are also predisposed to developing multiple endocrine tissue tumors, e.g., pheochromocytomas/paragangliomas are frequent in VHL and NF1. All forms of phakomatoses except CS may be associated with digestive neuroendocrine tumors. More rarely, thyroid cancer and pituitary or parathyroid adenomas have been reported. These susceptibilities are noteworthy, because their occurrence rate, prognosis and management differ slightly from the sporadic forms. The aim of this review is to summarize current knowledge on endocrine glands tumors associated with VHL, NF1, TSC, and CS, especially neuroendocrine tumors and pheochromocytomas/paragangliomas. We particularly detail recent advances concerning prognosis and management, especially parenchyma-sparing surgery and medical targeted therapies such as mTOR, MEK and HIF-2 α inhibitors, which have shown truly encouraging results.
痣样病变包括一组罕见的遗传疾病，如 von Hippel-Lindau 综合征 (VHL)、神经纤维瘤病 1 型 (NF1)、结节性硬化症 (TSC) 和考登综合征 (CS)。这些疾病是由于 NF1、TSC 和 CS 的 RAS-PI3K-Akt-mTOR 通路和 VHL 的缺氧感应的分子异常引起的。痣样病变具有一些表型特征，如神经、眼科和皮肤特征。这些疾病的患者也易发生多种内分泌组织肿瘤，例如嗜铬细胞瘤/副神经节瘤在 VHL 和 NF1 中很常见。除 CS 外，所有形式的痣样病变都可能与消化道神经内分泌肿瘤有关。更罕见的是，甲状腺癌和垂体或甲状旁腺腺瘤也有报道。这些易感性值得注意，因为它们的发生率、预后和管理与散发性形式略有不同。本文综述的目的是总结与 VHL、NF1、TSC 和 CS 相关的内分泌腺体肿瘤的最新知识，特别是神经内分泌肿瘤和嗜铬细胞瘤/副神经节瘤。我们特别详细介绍了最近在预后和管理方面的进展，特别是保留实质的手术和针对 mTOR、MEK 和 HIF-2α抑制剂等的医学靶向治疗，这些治疗方法取得了非常令人鼓舞的结果。
