Regazzo Daniela, Gardiman Marina Paola, Theodoropoulou Marily, Scaroni Carla, Occhi Gianluca, Ceccato Filippo
Department of Medicine DIMED, Endocrinology Unit, University Hospital of Padova, Padova, Italy.
Department of Medicine DIMED, Surgical Pathology & Cytopathology Unit, University Hospital of Padova, Padova, Italy.
Endocrinol Diabetes Metab Case Rep. 2018 Aug 23;2018. doi: 10.1530/EDM-18-0086. eCollection 2018.
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem hereditary cutaneous condition, characterized by multiple hamartomas. In rare cases, pituitary neuroendocrine tumors (PitNETs) have been described in patients with TSC, but the causal relationship between these two diseases is still under debate. TSC is mostly caused by mutations of two tumor suppressor genes, encoding for hamartin (TSC1) and tuberin (TSC2), controlling cell growth and proliferation. Here, we present the case of a 62-year-old Caucasian woman with TSC and a silent gonadotroph PitNET with suprasellar extension, treated with transsphenoidal endoscopic neurosurgery with complete resection. Therapeutic approaches based on mTOR signaling (i.e. everolimus) have been successfully used in patients with TSC and tested in non-functioning PitNET cellular models with promising results. Here, we observed a reduction of cell viability after an treatment of PitNET's derived primary cells with everolimus. TSC analysis retrieved no disease-associated variants with the exception of the heterozygous intronic variant c.4006-71C>T found in : the computational tools predicted a gain of a new splice site with consequent intron retention, not confirmed by an analysis of patient's lymphocyte-derived RNA. Further analyses are therefore needed to provide insights on the possible mechanisms involving the hamartin-tuberin complex in the pathogenesis of pituitary adenomas. However, our data further support previous observations of an antiproliferative effect of everolimus on PitNET.
Pituitary neuroendocrine tumors (PitNET) in patients with tuberous sclerosis complex (TSC) are rare: only few cases have been reported in literature.Therapeutic approach related to mTOR signaling, such as everolimus, may be used in some patients with PitNETs as well as those with TSC.We reported a woman with both non-secreting PitNET and TSC; PitNET was surgically removed and classified as a silent gonadotroph tumor.Everolimus treatment in PitNET's-derived primary cells revealed a significant decrease in cell viability.Considering our case and available evidence, it is still unclear whether a PitNET is a part of TSC or just a coincidental tumor.
结节性硬化症（TSC）是一种常染色体显性遗传的多系统遗传性皮肤病，其特征为多发性错构瘤。在罕见情况下，TSC患者中曾有垂体神经内分泌肿瘤（PitNETs）的报道，但这两种疾病之间的因果关系仍存在争议。TSC主要由两个肿瘤抑制基因突变引起，这两个基因分别编码错构素（TSC1）和结节素（TSC2），它们控制细胞生长和增殖。在此，我们报告一例62岁白种女性患者，患有TSC及一例向鞍上扩展的无功能促性腺激素细胞垂体神经内分泌肿瘤，经蝶窦内镜神经外科手术完全切除。基于mTOR信号通路的治疗方法（如依维莫司）已成功应用于TSC患者，并在无功能垂体神经内分泌肿瘤细胞模型中进行了测试，结果令人鼓舞。在此，我们观察到用依维莫司处理垂体神经内分泌肿瘤来源的原代细胞后细胞活力降低。除了在[具体位置]发现的杂合内含子变异c.4006 - 71C>T外，TSC分析未检索到与疾病相关的变异；计算工具预测会获得一个新的剪接位点，导致内含子保留，但患者淋巴细胞来源RNA的分析未证实这一点。因此，需要进一步分析以深入了解错构素 - 结节素复合物在垂体腺瘤发病机制中可能涉及的机制。然而，我们的数据进一步支持了之前关于依维莫司对垂体神经内分泌肿瘤具有抗增殖作用的观察结果。
结节性硬化症（TSC）患者中的垂体神经内分泌肿瘤（PitNET）很罕见：文献中仅报道了少数病例。与mTOR信号通路相关的治疗方法，如依维莫司，可用于一些垂体神经内分泌肿瘤患者以及TSC患者。我们报告了一名同时患有无分泌性垂体神经内分泌肿瘤和TSC的女性；垂体神经内分泌肿瘤通过手术切除，分类为无功能促性腺激素细胞肿瘤。依维莫司处理垂体神经内分泌肿瘤来源的原代细胞后，细胞活力显著降低。考虑到我们的病例和现有证据，尚不清楚垂体神经内分泌肿瘤是TSC的一部分还是仅仅是一个巧合的肿瘤。
