Friedrich Reinhard E, Kluwe Lan, Fünsterer C, Mautner V F
Maxillofacial Surgery Clinic, Eppendorf University Hospital, University of Hamburg, Germany.
Anticancer Res. 2005 May-Jun;25(3A):1699-702.
Plexiform neurofibroma (PNF) is a typical feature of neurofibromatosis 1 (NF1). About 10% of patients with NF1 develop malignant peripheral nerve sheath tumors (MPNST), usually arising from PNF, and this is the major cause of poor prognosis. A better prognosis can be achieved if the tumors are diagnosed at an early stage. Our objective was to establish magnetic resonance imaging (MRI) criteria for MPNST, and to test their usefulness in detecting early malignant changes in PNF and to correlate the findings with the mutations of the NF1 gene.
NF1 outpatients were diagnosed according to the NIH criteria. All patients underwent a complete dermatological, ophthalmological and neurological examination and ultrasound of the abdomen between 1997 and 2002. The study was approved by the Institutional Review Board and all patients gave informed consent to analyze clinical records and tumor material for scientific purposes. MRI was performed with devices at 1.5 Tesla field strength (Siemens Magnetom Symphony) or in some patients at 1.0 Tesla field strength (Siemens Impact Expert). T1- and T2-weighted sequences including STIR-sequences were acquired. Ultra-rapid image sequences with HASTE technique were performed for trunk imaging. In patients with no contraindication for the application of contrast media, Gadolinum-DTPA Magnevist was administered intravenously.
MRI was performed on 50 patients with NF1 and nerve sheath tumors, of whom 7 had atypical pain, tumor growth or neurological deficits indicative of malignancy; the other 43 were asymptomatic. On MRI, all 7 symptomatic patients had inhomogeneous lesions, due to necrosis and hemorrhage and patchy contrast enhancement. In one patient, the multiplicity of confluent tumors with inhomogeneous areas in addition to central lesions did not allow the exclusion of malignancy. Only 3 of the 43 asymptomatic patients had comparable changes; the other 40 patients had tumors of relatively homogeneous structure on T1- and T2-weighted images before and after contrast enhancement. All 3 asymptomatic patients with inhomogeneous lesions were shown to have MPNST. Analysis of mutations of the NF1 gene of the 10 MPNST patients revealed a variety of mutations. Concerning the correlation of genetic findings and MPNST in NF1, the sample size of this study group was too small to define genotype-phenotype relations. In this cohort, all types of mutations were found.
This study provides evidence for certain radiographic findings on MRI in PNF of NF1 patients that have to be considered as signs of malignancy, in particular indicating an MPNST. These findings are especially valuable in the long term follow-up control of patients with large tumors (plexiform neurofibromas).
丛状神经纤维瘤（PNF）是神经纤维瘤病1型（NF1）的典型特征。约10%的NF1患者会发生恶性外周神经鞘瘤（MPNST），通常起源于PNF，这是预后不良的主要原因。如果肿瘤能早期诊断，预后会更好。我们的目的是建立MPNST的磁共振成像（MRI）标准，测试其在检测PNF早期恶性变化中的效用，并将结果与NF1基因的突变相关联。
NF1门诊患者根据美国国立卫生研究院（NIH）标准进行诊断。所有患者在1997年至2002年间接受了全面的皮肤科、眼科和神经科检查以及腹部超声检查。该研究经机构审查委员会批准，所有患者均签署知情同意书，同意为科学目的分析临床记录和肿瘤材料。MRI使用1.5特斯拉场强的设备（西门子MAGNETOM Symphony）进行，部分患者使用1.0特斯拉场强的设备（西门子Impact Expert）。采集了T1加权和T2加权序列，包括短反转恢复（STIR）序列。采用快速自旋回波（HASTE）技术的超快速图像序列用于躯干成像。对于无造影剂应用禁忌证的患者，静脉注射钆喷酸葡胺（Gadolinum-DTPA Magnevist）。
对50例患有NF1和神经鞘瘤的患者进行了MRI检查，其中7例有非典型疼痛、肿瘤生长或提示恶性的神经功能缺损；其他43例无症状。在MRI上，所有7例有症状的患者均有不均匀病变，原因是坏死、出血以及斑片状造影剂增强。1例患者，除中央病变外，融合性肿瘤的多样性及不均匀区域无法排除恶性可能。43例无症状患者中只有3例有类似改变；其他40例患者在增强前后的T1加权和T2加权图像上肿瘤结构相对均匀。所有3例有不均匀病变的无症状患者均被证实患有MPNST。对10例MPNST患者的NF1基因突变分析显示存在多种突变。关于NF1中基因发现与MPNST的相关性，本研究组的样本量太小，无法确定基因型与表型的关系。在该队列中，发现了所有类型的突变。
本研究为NF1患者PNF的MRI某些影像学表现提供了证据，这些表现必须被视为恶性征象，尤其是提示MPNST。这些发现对于大肿瘤（丛状神经纤维瘤）患者的长期随访监测特别有价值。
