The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease
The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease
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DOI：
10.3171/jns.2003.98.1.0082
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发表时间：
2003-01-01
影响因子：
4.1
通讯作者：
Oldfield, EH
中科院分区：
文献类型：
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作者：
Wanebo, JE;Lonser, RR;Oldfield, EH
Object.本研究的目的是确定与von Hippel-Lindau（VHL）病相关的中枢神经系统（CNS）血管母细胞瘤的自然史和生长模式，并将与症状发展相关的血管母细胞瘤特征关联起来。和治疗的需要。方法。作者回顾了连续160例VHL病患者的系列磁共振图像和临床病史，这些患者均患有CNS成血管细胞瘤，并连续测量了肿瘤和相关囊肿的体积。（250例肿瘤），脑干（64例肿瘤，均位于延髓后部），脊髓（331个肿瘤，其中96%位于脊髓后半部）和幕上脑（10个肿瘤）。这些症状与肿块效应有关。在小脑、脑干和脊髓肿瘤中，随着患者从无症状进展到有症状并需要手术，成血管细胞瘤的大小连续增加（p < 0.0001）。29例小脑肿瘤中有21例（72%）伴有囊肿，而221例无症状的小脑肿瘤中只有28例（13%）伴有囊肿（p < 0.0001）。12例有症状的脑干肿瘤中有9例（75%）伴有囊肿，而52例无症状的脑干病变中只有4例（8%）伴有囊肿（p < 0.0001）。当症状出现并需要手术时，囊肿大于致病肿瘤;小脑和脑干囊肿分别是手术时相关肿瘤的34倍和19倍。95%的脊髓血管母细胞瘤合并脊髓空洞症，其临床表现是动态的。在88例接受连续成像6个月或更长时间（中位数32个月）的患者中，373例血管母细胞瘤中有164例（44%），55例肿瘤相关囊肿中有37例（67%）扩大。无肿瘤或囊肿自发缩小。有症状的小脑和脑干肿瘤的生长速度分别是相同区域无症状肿瘤的6倍和9倍。囊肿扩大7倍（小脑）和15倍（脑干）比血管母细胞瘤导致他们。血管母细胞瘤经常表现出一种生长模式，其中它们会在一段时间内扩大（生长期），然后在生长停滞期（静止期）稳定下来。在69例有肿瘤生长记录的患者中，18例（26%）具有至少两个生长期的肿瘤。在160例血管母细胞瘤患者中，34例（中位随访51个月）发现115例新发血管母细胞瘤，15例新发肿瘤相关囊肿。在这项研究中，作者定义了与VHL疾病相关的CNS血管母细胞瘤的自然史。囊肿不仅常与小脑、脑干和脊髓成血管细胞瘤相关，而且囊肿的扩大速度比成血管细胞瘤快得多。当症状出现时，大多数产生肿块效应的症状来自囊肿，而不是来自引起囊肿的肿瘤。这些肿瘤通常具有多个肿瘤生长期，这些肿瘤生长期被生长停滞期隔开，并且许多未经治疗的肿瘤可能在几年内保持相同的大小。在确定个体患者的最佳筛查时间以及评估治疗时间和结果时，必须考虑这些特征。
Object. The goals of this study were to define the natural history and growth pattern of hemangioblastomas of the central nervous system (CNS) that are associated with von Hippel-Lindau (VHL) disease and to correlate features of hemangioblastomas that are associated with the development of symptoms and the need for treatment.Methods. The authors reviewed serial magnetic resonance images and clinical histories of 160 consecutive patients with VHL disease who harbored CNS hemangioblastomas and serially measured the volumes of tumors and associated cysts.Six hundred fifty-five hemangioblastomas were identified in the cerebellum (250 tumors), brainstem (64 tumors, all of which were located in the posterior medulla oblongata), spinal cord (331 tumors, 96% of which were located in the posterior half of spinal cord), and the supratentorial brain (10 tumors). The symptoms were related to a mass effect. A serial increase in hemangioblastoma size was observed in cerebellar, brainstem, and spinal cord tumors as patients progressed from being asymptomatic to symptomatic and requiring surgery (p < 0.0001). Twenty-one (72%) of 29 symptom-producing cerebellar tumors had an associated cyst, whereas only 28 (13%) of 221 nonsymptomatic cerebellar tumors had tumor-associated cysts (p < 0.0001). Nine (75%) of 12 symptomatic brainstem tumors had associated cysts, compared with only four (8%) of 52 nonsymptomatic brainstem lesions (p < 0.0001). By the time the symptoms appeared and surgery was required, the cyst was larger than the causative tumor; cerebellar and brainstem cysts measured 34 and 19 times the size of their associated tumors at surgery, respectively. Ninety-five percent of symptom-producing spinal hemangioblastomas were associated with syringomyelia.The clinical circumstance was dynamic. Among the 88 patients who had undergone serial imaging for 6 months or longer (median 32 months), 164 (44%) of 373 hemangioblastomas and 37 (67%) of 55 tumor-associated cysts enlarged. No tumors or cysts spontaneously diminished in size. Symptomatic cerebellar and brainstem tumors grew at rates six and nine times greater, respectively, than asymptomatic tumors in the same regions. Cysts enlarged seven (cerebellum) and 15 (brainstem) times faster than the hemangioblastomas causing them. Hemangioblastomas frequently demonstrated a pattern of growth in which they would enlarge for a period of time (growth phase) and then stabilize in a period of arrested growth (quiescent phase). Of 69 patients with documented tumor growth, 18 (26%) harbored tumors with at least two growth phases. Of 160 patients with hemangioblastomas, 34 patients (median follow up 51 months) were found to have 115 new hemangioblastomas and 15 patients new tumor-associated cysts.Conclusions. In this study the authors define the natural history of CNS hemangioblastomas associated with VHL disease. Not only were cysts commonly associated with cerebellar, brainstem, and spinal hemangioblastomas, the pace of enlargement was much faster for cysts than for hemangioblastomas. By the time symptoms appeared, the majority of mass effect-producing symptoms derived from the cyst, rather than from the tumor causing the cyst. These tumors often have multiple periods of tumor growth separated by periods of arrested growth, and many untreated tumors may remain the same size for several years. These characteristics must be considered when determining the optimal timing of screening for individual patients and for evaluating the timing and results of treatment.