嗜铬细胞瘤/副神节瘤的围手术期处理

嗜铬细胞瘤/副神节瘤是由神经嵴起源的嗜铬细胞产生的肿瘤,具有分泌儿茶酚胺的功能,而儿茶酚胺作用于血管、心脏,常常引起血液循环系统及代谢的改变。嗜铬细胞瘤手术前后血液中儿茶酚胺浓度的变化会引起相应血液动力学的改变,若没有充分的术前准备和术后监护,心血管意外事件的发生几率很高。因此,了解嗜铬细胞瘤/副神节瘤的病理学特点,术前进行良好的药物准备,术中轻柔的手术操作及与麻醉师的良好配合,术后ICU的严密监护,是嗜铬细胞瘤围手术期处理的关键,也是嗜铬细胞瘤/副神节瘤成功治疗的基本保障。     

Precision medicine in pheochromocytoma and paraganglioma: current and future concepts

Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics‐based taxonomy, PPGL can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro‐mitogenic and anti‐apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome‐related tumours. Genotype‐tailored treatment options, follow‐up and preventive care are being investigated. Future new developments in precision medicine for PPGL will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large‐scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions.     

Novel mutation in the TMEM127 gene associated with phaeochromocytoma

Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours that arise from the adrenal glands or paraganglia (paragangliomas) within the abdomen, thorax and neck. Although it was originally suggested that approximately 10% of these tumours were inherited, it is now recognised that up to approximately 30% of these tumours are associated with a germline mutation in one of the phaeochromocytoma/paraganglioma susceptibility genes. Of the 12 currently known genes predisposing to these tumours, the TMEM127 gene is one of the more recently identified and appears to be present in approximately 2% of apparently sporadic phaeochromocytomas. We report a 33‐year‐old man who presented with an apparently sporadic adrenal phaeochromocytoma and was identified as carrying a novel TMEM127 germline mutation, p.Gln139X. Patients harbouring a germline TMEM127 mutation most commonly present with an apparently sporadic solitary adrenal phaeochromocytoma. Testing patients who present with a phaeochromocytoma or paraganglioma for an underlying germline mutation needs to be considered in all patients due to implications for family members, but a strategy based on clinical and immunohistochemical findings would be prudent to limit costs.     

膀胱副神经节瘤组织中SDHB、EPAS1及Ki⁃67表达的研究

目的：探讨膀胱副神经节瘤临床病理特征以及琥珀酸脱氢酶B（succinate dehyrogenase B,SDHB）、内皮PAS区域蛋白1（EPAS1）及Ki?67在膀胱副神经节瘤中的表达情况,以及三者作为预测恶性副神经节瘤指标的意义。方法：回顾性分析本院收治的43例膀胱副神经节瘤患者的临床病理资料,对43例标本行SDHB、EPAS1、CgA、Ki?67免疫组化检测,并分析其作为预测恶性副神经节瘤指标的意义。结果：43例中,男24例,女19例;年龄26~81岁,中位年龄68岁;随访时间2~84个月,中位随访时间51.3个月;3例死亡,9例术后转移,4例术后反复复发,无转移;其余无复发及转移。良性30例,镜下表现为肿瘤细胞呈经典的巢状排列,核分裂及坏死罕见,瘤细胞巢周围有支持细胞包绕。SDHB阴性（-）4例,EPAS1强阳性（+++）14例,CgA强阳性（+++）18例,2例Ki?67≥3%。恶性13例,镜下表现为肿瘤细胞呈弥漫浸润性生长或大巢状分布,核分裂多见,可见肿瘤性坏死及脉管内瘤栓。SDHB阴性（-）8例,EPAS1强阳性（+++）9例;CgA强阳性（+++）10例;11例Ki?67≥3%。SDHB阴性（-）肿瘤中66.7%为恶性,SDHB阳性（+）的肿瘤中16.1%为恶性,两组比较差异有统计学意义（P＜0.05）。SDHB 阴性（-）肿瘤中EPAS1、CgA表达强度以及Ki?67≥3%的比例明显高于SDHB阳性（+）肿瘤。恶性膀胱副神经节瘤中EPAS1、CgA、Ki?67阳性表达率明显高于良性膀胱副神经节瘤。结论：恶性膀胱副神经节瘤组织中SDHB免疫组化阴性率为66.7%,SDHB阴性的膀胱副神经节瘤组织中EPAS1过表达,EPAS1阳性表达强度与CgA及Ki?67高表达呈正相关。SDHB、EPAS1、Ki?67是预测恶性膀胱副神经节瘤的生物学指标。     

Extra-adrenal Composite Paraganglioma with Ganglioneuroma Component Presenting as a Pancreatic Mass

Paragangliomas may have composite forms in which they combine features of a typical paraganglioma with those of a neural component consisting of either neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. These variants are rare and generally located in the adrenal. Herein, we describe a retroperitoneal, extra-adrenal composite paraganglioma–ganglioneuroma of a 57-year-old woman. Radiological evaluation revealed a nodular mass with apparent pancreatic location, with findings suggestive of an endocrine tumor, yielding the diagnosis of a pancreatic endocrine tumor. At histology the neoplasm, strictly adhering to the external surface of the pancreatic gland but well demarcated, displayed a main central region with typical paraganglioma features and cells arranged in cords and in a nesting “zellballen” pattern, positive for neuroendocrine markers, and a distinct peripheral area consisting of dense bundles of wavy spindled Schwann cells, with scattered ganglionic cells.     

An unusual case of Carney triad with high level catecholamine- secreting but no existence of extra-adrenal paraganglioma

In 1977, Carney originally described the association of .gastric epithelioid leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma, and this unusual syndrome was subsequently called ＂Carney triad＂. At present, the diagnosis of Carney triad, requires at least two of three components-gastrointestinal stromal tumor （GIST）, pulmonary chondroma and extra-adrenal paraganglioma. Up to now, fewer than 80 cases of Carney triad have been reported worldwide.1 ^We described a case of incomplete Carney triad with multiple pulmonary chondromas and GIST. Although the patient was detected in high level secreting of catecholamine, no extra-adrenal paraganglioma has been found.     

Aorticopulmonary Paraganglioma (Aortic Body Tumor): Report of a Case

A case of aorticopulmonary paraganglioma in a 57-year-old man is described. The tumor comprised nests of uniform cells in a fibrovascular stroma. Electron microscopy revealed abundant neurosecretory granules, and S-100 protein staining demonstrated scattered sustentacular cells at the periphery of typical zellballen. The findings in this case correlated with those of studies on the prognosis for extraadrenal paragangliomas.