Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology, IRCCS, Padua, Italy.
Front Endocrinol (Lausanne). 2020 May 19;11:234. doi: 10.3389/fendo.2020.00234. eCollection 2020.
Pheochromocytomas (PCCs), paragangliomas (PGLs), ganglioneuroblastomas (GNBs), and ganglioneuromas (GNs) are neuroendocrine neoplasms (NENs) that were thought to share a common embryologic origin from neural crest cells. However, they rarely occur concurrently and recurrently. We describe the case of a 40-years-old woman with "composite PCC-GN" and multiple NENs and neuroblastic tumors. The patient was first referred to our department at the age of 15 years for paroxysmal hypertension, headache, sweating, and watery diarrhea. Her personal history included the diagnosis of a pelvic GNB with lumbar-aortic lymph node metastases at 11 months. Her family history was positive for cerebral glioblastoma multiforme (father). An abdominal ultrasound showed a right adrenal mass that histologically was a "composite adrenal PCC-GN." The symptoms disappeared after surgery. At the age of 20 years, the symptoms returned: computed tomography (CT) and 131I-metaiodobenzylguanidine (MIBG) scintigraphy showed an inter-aortocaval mass, found histologically to be an inter-aortocaval PGL. Her symptoms reappeared again at 28 years: CT and magnetic resonance imaging revealed four left adrenal gland nodules, found histologically to be multifocal PCCs with some atypia. Genetic screening for , and was negative. Mutational analysis of the gene revealed the presence of a novel heterozygous variant, c299G>C (p.Arg100Pro, NM_002382.5) that the bioinformatics prediction programs defined as noxious and causative of pathology. This report represents the first description of a co-occurrence of multiple composite PCC-GN and neuroblastic tumors. The long timeline of the presentation of the NENs/neuroblastic tumors from infancy to adulthood requires a lifelong follow-up for this patient. Moreover, the importance of this case lies in the presence of a novel gene variant deleterious, harmful, and causative of pathology, confirmed by Sanger sequencing and never been associated before with multiple composite PCC-GN. The present case underlines the importance of precision medicine and molecular diagnoses for hereditary pheochromocytomas and paragangliomas, suggesting that when they occur in early childhood, it is necessary to perform an extensive genetic investigation and a lifelong follow-up.
嗜铬细胞瘤（PCCs）、副神经节瘤（PGLs）、神经母细胞瘤（GNBs）和神经节细胞瘤（GNs）是神经内分泌肿瘤（NENs），它们被认为具有共同的神经嵴细胞起源。然而，它们很少同时且反复发生。我们描述了一例 40 岁女性患有“复合 PCC-GN”和多种 NENs 和神经母细胞瘤的病例。该患者 15 岁时首次因阵发性高血压、头痛、出汗和水样腹泻到我们科室就诊。她的个人病史包括 11 个月时诊断为骨盆 GNB 并伴有腰椎主动脉淋巴结转移。她的家族史为脑胶质母细胞瘤多形性（父亲）阳性。腹部超声显示右侧肾上腺肿块，组织学上为“复合肾上腺 PCC-GN”。手术后症状消失。20 岁时，症状再次出现：计算机断层扫描（CT）和 131I-间碘苄胍（MIBG）闪烁显像显示腹主动脉旁肿块，组织学上为腹主动脉旁 PGL。28 岁时，她的症状再次出现：CT 和磁共振成像显示四个左肾上腺结节，组织学上为多灶性 PCC，伴有一些非典型性。 、 和 基因的遗传筛查均为阴性。 基因的突变分析显示存在一种新的杂合变体 c299G>C（p.Arg100Pro，NM_002382.5），生物信息学预测程序将其定义为有害且导致病理学的变体。该报告首次描述了同时发生的多种复合 PCC-GN 和神经母细胞瘤。从婴儿期到成年期，NENs/神经母细胞瘤的表现时间线很长，因此需要对该患者进行终身随访。此外，该病例的重要性在于存在一种新的 基因变体有害、有害且导致病理学，通过 Sanger 测序得到证实，以前从未与多种复合 PCC-GN 相关联。本病例强调了精准医学和遗传性嗜铬细胞瘤和副神经节瘤的分子诊断的重要性，提示当它们在幼年时发生时，有必要进行广泛的遗传研究和终身随访。
