INC科普·脑瘤连载:罕见“虎纹征”小脑发育不良性神经节细胞瘤(Lhermitte-Duclos病)

2022-08-12 INC国际神经科学 INC国际神经科学

LDD虽然少见,但其临床表现及影像学特点明显,术前较易诊断,手术是最佳治疗方法,肿瘤全切除较困难,但预后良好。

小脑,是运动的重要调节中枢,它使人体运动保持协调。同时,小脑在维持身体平衡方面也起着重要作用。而一旦小脑周围脑组织或相关联的神经,因各种原因(如小脑萎缩、肿瘤等)被破坏或损伤,患者可表现出头晕、步态不稳、肢体活动不协调、言语功能障碍等小脑性共济失调症状。小脑发育不良性神经节细胞瘤,就是各类小脑肿瘤中相当少见的一种,但其对患者健康的威胁却不容小觑。

小脑发育不良性神经节细胞瘤是良性还是恶性?

小脑发育不良性神经节细胞瘤(dysplastic cerebellar gangliocytoma)又名Lhermitte—Duclos病(Lhermitte—Duclosdisease,LDD),是一种极为罕见的颅内良性肿瘤,由发育不良的神经节细胞构成的良性小脑肿块。WHO分类为I级,虽然已经有一些复发的发育不良的小脑神经节细胞瘤的报道,但预后良好,大多数患者通过手术治愈。

肿瘤位于小脑半球,生长缓慢,通常为单侧(不偏好侧)。很少有双侧肿瘤的报道。手术切除肿瘤为其主要治疗方法。该肿瘤2007年版WHO分类为I级,小脑发育不良性节细胞瘤可呈家族性或散发性方式发病。针对小脑发育不良性节细胞瘤患者的分子研究提示,PTEN/AKT通路(细胞生长的主要调节器)出现异常的频率较高。同样,该肿瘤与Cowden综合征有关,这种常染色体显性遗传病的特征是多发性错构生长病灶,乳腺癌、子宫癌和甲状腺癌的发病率增高,以及PTEN基因种系突变,需要引起关注。

组织起源

目前还不清楚Hermite-Duclos病是错构瘤还是肿瘤。畸形的组织病理学特点,无增生活性或非常低以及无侵袭性支持其归类为错构瘤。然而,偶见复发病例已引起注意,而且发育不良性节细胞瘤可发生在先前MRI扫描正常的成年患者。这就提示我们,起源于小脑颗粒细胞,异常迁移和颗粒细胞肥大是病变形成的原因。PTEN缺失的转基因鼠模型也支持这种假说。

图:小脑发育不良性节细胞瘤的组织学特点。A小脑内颗粒层(图上方)充满了发育不良的神经节细胞:;B高倍视野下的神经节细胞;C免疫组织化学染色显示PTEN在增大的神经元不表达,而在血管中仍表达;D发育不良性神经节细胞磷酸化S6强阳性。

临床表现有哪些?

LDD患者早期症状轻微或无症状,部分于体检时发现。一般首发症状以颅内高压表现(头痛、恶心、呕吐)为主,其原因主要为肿瘤压迫第四脑室造成梗阻性脑积水所致;其次为后组脑神经麻痹(运动障碍、感觉障碍、吞咽困难、咽反射消失等)、小脑压迫症状(共济失调、辨距不良、步态不稳)等;而精神神经症状罕见。国内外多篇文献报道,部分LDD患者可合并Cowden综合征,后者为常染色体显性遗传病,以多种畸形或错构瘤样病变为特征,如巨脑、脊髓空洞症、多指(趾),以及皮肤黏膜或内脏多种肿瘤等。

最常见的表现为发音障碍或其他小脑体征,和/或梗阻性脑积水和颅内压增高的体征和症状。颅神经缺损、大头畸形和癫痫也常出现。术前症状有不同时期的报告,平均持续时间约为40个月。

影像学特点:过目不忘的虎纹征

1、虎纹征 :LDD的占位效应明显,可累及小脑蚓部、桥臂、第四脑室等结构,造成不同程度的梗阻性脑积水,部分可导致小脑扁桃体下疝。“虎纹征”为LDD 的典型MRI表现,T1WI 呈条纹状相间的等、低信号或层状排列结构,T2WI 呈条纹状相间的等、高信号,表现为在高信号区域里可见低信号的条纹状结构,即为“虎纹征”;这是由于小脑叶片异常神经元细胞的增生和过度髓鞘化,以及中央白质萎缩形成的疏松结构间的脑脊液所致。增强扫描见线样、条状强化或无强化病变,病变的强化可能与蛛网膜下腔小血管的异常有关。

2、肿瘤无强化:也是LDD的特征性MRI表现,由于病变区血脑屏障无明显破坏,无细胞外水肿,因此增强后肿瘤无明显强化。

需要与哪些疾病鉴别诊断?

LDD需与小脑肿瘤(如髓母细胞瘤、小脑星形细胞瘤及血管母细胞瘤等)、结节性硬化、小脑片状脑梗死以及小脑脑炎相鉴别。小脑肿瘤易发生坏死、囊变,信号不均匀,增强后实性成分强化明显,其中髓母细胞瘤好发于小脑蚓部,多见于儿童。结节性硬化好发于皮质下和室管膜下,其特征性表现为智力低下、癫痫、皮脂腺瘤三联征,可见结节影和钙化影。小脑片状脑梗死及小脑脑炎一般起病较急,而LDD进展缓慢。

不同治疗及预后如何?

本病既往的治疗方法有:肿瘤活检加放射治疗、后颅窝减压术、分流手术。

1肿瘤活检加放疗

肿瘤活检加放疗的方法曾被广泛应用,但现已少用,原因如下:现代神经外科技术的进步使肿瘤切除术成为一个相对安全的手术,且手术死亡率较低,而以前的文献报道约有1/3左右的患者死于术后并发症。该肿瘤对放疗不敏感,活检除证实肿瘤的性质外不能解决临床症状。

2后颅窝减压术

后颅窝减压术可以很好地缓解临床症状并能有效地延长患者的生存期,但目前已被淘汰,因为该肿瘤生长缓慢,后颅窝减压术创伤较大,且不能解决肿瘤生长的问题。

3分流手术

分流手术可用于肿瘤切除前后缓解脑积水的症状,但是单纯分流手术不能缓解因小脑受压迫导致的临床症状。肿瘤切除术是该病的有效治疗方法,术后临床症状消失或减轻,死亡率极低。

目前首选治疗方法:手术全切

LDD属于WHOⅠ级良性肿瘤,手术全切除为最佳的治疗方法。鉴于该病的生长特性,全切除肿瘤的情况下不行放疗仍可治愈。

LDD病理可见肿瘤与周围小脑组织没有清晰的界限,存在一个逐渐过渡的区域,在术中多发现肿瘤与周围组织界限不清,这是肿瘤难以全切及术后复发的原因。术者应根据肿瘤质地尽量大范围切除,既要避免脑干等重要结构的损伤,又要避免肿瘤的残留,此时,术者的经验与术中导航超声等辅助设备显得尤为重要。否则,残余肿瘤极易复发。当然,对于合并梗阻性脑积水的患者,更应积极手术治疗,切除肿瘤的同时解除高颅压,挽救生命。全切肿瘤,则患者预后较好,但也要当心复发的可能。因此,对于小脑发育不良性神经节细胞瘤术后患者来说,遵照医嘱长期随诊仍然十分必要。

综上,LDD虽然少见,但其临床表现及影像学特点明显,术前较易诊断,手术是最佳治疗方法,肿瘤全切除较困难,但预后良好。因此想要最大程度降低手术并发症、且全切肿瘤的前提是选择一个手术经验丰富且技术高超的神经外科手术团队以及具备一系列先进术中神经导航设备等的医院。

参考资料:

1.Helmut Bertalanffy.Dysplastic cerebellar gangliocytoma(Lhermitte-Duclos disease).Gliomas, glioneuronal tumours, and neuronal tumours

2.DOI:103760/cmajcn112050 2020103000559

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    2022-08-13 gracezdd
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    2022-08-06 jxrzshh
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    2022-08-06 neurowu
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    2022-08-06 syscxl
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