Study on the Staging of Primary Lower Extremity Lymphedema Based on Calf Soft-tissue Thickness Measurement by MRI
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摘要: 目的:探讨基于MRI测量小腿软组织厚度对评估原发性下肢淋巴水肿(PLEL)分期的价值。方法:回顾性收集确诊为PLEL患者90例的临床及MR影像资料,所有患者均行双侧下肢MR检查。采用短时反转恢复序列(STIR)序列测量双侧小腿软组织总厚度(T)、肌骨厚度(M)和皮下软组织厚度(S),分别计算双侧小腿T及S的差值(DT、DS)。参考2020年国际淋巴协会及淋巴外科下肢淋巴水肿的临床分期标准将患者分为Ⅰ、Ⅱ、Ⅲ 期。使用单因素方差分析比较不同临床分期之间的小腿软组织厚度,使用Spearman相关分析小腿软组织厚度与临床分期的相关性,使用ROC曲线确定小腿软组织厚度对临床分期的鉴别效能。结果:3期之间T、S、DT及DS差异均有统计学意义,而M不存在统计学差异;各分期间两两比较,T、S、DT及DS在Ⅰ期与Ⅱ期及Ⅰ期与 Ⅲ 期之间比较均具有统计学差异,而在Ⅱ期与 Ⅲ 期比较无统计学差异。DT(r=0.750)与DS(r=0.772)与临床分期的相关性明显大于T(r=0.669)及S(r=0.734),DS与临床分期相关性最高;M与临床分期无明显相关关系。ROC曲线显示各参数鉴别Ⅰ期与Ⅱ期的AUC值大于鉴别Ⅱ期与 Ⅲ 期的AUC值,所有参数中DS(AUC=0.945)鉴别Ⅰ期与Ⅱ期的曲线下面积(AUC)最高。结论:MRI小腿软组织厚度测量可以作为单侧PLEL临床分期的定量辅助方法,对于单侧PLEL患者,我们推荐DS作为鉴别Ⅰ期与Ⅱ期淋巴水肿的最佳厚度指标。Abstract: Objective: To investigate the value of MRI-based measurement of calf soft-tissue thickness in assessing the clinical staging of primary lower extremity lymphedema (PLEL). Methods: The clinical and MR imaging data of 90 patients diagnosed with PLEL in our hospital were retrospectively collected, and all patients underwent bilateral lower limb MR examinations. Short Time Inversion Recovery (STIR) sequence was used to measure the total soft tissue thickness (T), musculoskeletal thickness (M) and subcutaneous soft tissue thickness (S) of bilateral lower legs, and the difference between T and S of bilateral lower legs (DT, DS) was calculated respectively. Patients were classified into stages Ⅰ, Ⅱ and Ⅲ with reference to the clinical staging criteria of the International Lymphatic Association 2020 and our lymphatic surgery department for lower limb lymphedema, excluding stage 0. One-way ANOVA was used to compare calf soft tissue thickness among different clinical stages, Spearman correlation was used to analyze the correlation between calf soft tissue thickness and clinical stage, and ROC curves were used to evaluate the efficacy of calf soft tissue thickness in discriminating clinical stage. Results: The differences among T, S, DT and DS of the three stages were statistically significant, while there was no statistical difference among M; when comparing two by two in each subperiod, T, S, DT and DS were statistically different between stage Ⅰ and Ⅱ and stage Ⅰ and Ⅲ, while there was no statistical difference between stage II and III. The correlation between DT (r=0.750) and DS (r=0.772) and clinical stage was significantly greater than that between T (r=0.669) and S (r=0.734), with DS showing the highest correlation with clinical stage; there was no significant correlation between M and clinical stage. ROC curves showed that the AUC values for each parameter to identify stage Ⅰ and Ⅱ were greater than those to identify stage Ⅱ and Ⅲ. The AUC value of DS (AUC=0.945) demonstrated the highest area under the curve (AUC) among all parameters to identify stage Ⅰ and stage Ⅱ. Conclusion: MRI soft-tissue thickness measurement of calf can be used as a quantitative adjunct in the clinical staging of unilateral PLEL, and for patients with unilateral PLEL, we recommend DS as the best thickness index to differentiate stage Ⅰ from Ⅱ lymphedema.
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Keywords:
- MRI /
- lymphedema /
- primary /
- lower extremity /
- stage
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多形性黄色星形细胞瘤(pleomorphic xanthoastrocytoma,PXA)是一类低级别神经上皮肿瘤,起源于软脑膜下星形细胞或其前体,临床罕见,易复发及脑脊液播散。它由Kepes等[1]于1979年首次报道。1993年被WHO纳入中枢神经系统2级肿瘤。后经大量的研究及经验积累,2016年WHO将PXA(2级)和间变型PXA(3级)分为两个不同的实体,后者预后较差并被定义为“具有≥5个有丝分裂/10个高倍视野的PXA”。2021年WHO删除“间变型”一词,直接将PXA分为2和3级。PXA的主要临床表现为不同程度及类型的癫痫发作。该肿瘤常见于儿童及年轻人,预后相对较好。病灶多位于大脑半球浅表部位,以颞叶居多。
目前国内外PXA的相关报道较少,大样本量的研究缺乏,临床对其认识不足。为提高对其认识,现将我院收治1例PXA患者分析报道,主要对其MR特点进行总结归纳。
1. 病历资料
1.1 临床表现及实验室检查
患者,男性,16岁,以“突发癫痫一次”为主诉入院”,神经系统查体及实验室检查均为阴性。
1.2 MRI表现
头颅MRI增强检查提示左侧颞叶囊实性占位,实性成分T1WI等信号,T2WI等信号,增强后实性成分明显强化,实性成分旁软脑膜呈线状明显强化(图1)。
1.3 治疗
行标准前颞叶切除术,病理提示“多形性黄色星形细胞瘤,WHO 2级”,分子病理结果为BRAF(v600 e突变),FISH-CDKN2 A缺失。
1.4 随访
患者一年后门诊复诊,无癫痫发作,头颅MRI增强提示未见肿瘤复发。
2. 讨论
2.1 病因及发病机制
Kepes等[2]认为PXA是起源于软脑膜下的星形细胞,因为软脑膜下星形胶质细胞和PXA肿瘤细胞具有共同的超微结构特征。这一假设可以解释大多数肿瘤位于大脑皮层浅表位置的原因。随着分子病理学检测技术的不断发展,BRAF(v600 e)突变和CDKN2 A/B纯合缺失,被认为是PXA的特征性分子改变[3-4]。
2.2 临床特征
PXA是一类罕见的脑肿瘤,在原发性中枢神经系统肿瘤中占比<0.3%,在所有星形细胞肿瘤中占比<1%,年发病率<0.7例/10万。PXA在每个年龄段均可发病,常见于儿童及年轻人,Perkins等[5]报道该肿瘤诊断时的平均年龄为26.3岁,无性别差异。PXA常发生于大脑半球浅表部位,以颞叶居多,常累及临近软脑膜[6],其次也可发生于额叶及顶叶,其他部位如小脑、脊髓、视网膜等少见。当肿瘤复发或发生恶变时,少数病例可出现脑脊液播散。由于PXA常位于大脑浅表部位,症状多表现为不同程度及类型的癫痫发作。其他症状包括肿瘤增大,可引起颅内压增高相关的头痛、恶心、呕吐等,很少有患者是靠影像学检查偶然发现,也很少有患者在首诊时已经出现脑脊液播散。
2.3 影像学表现
PXA的影像学表现分为3种类型:大囊伴附壁结节,附壁结节常靠近或附着于软脑膜上(该类型最常见);实性肿块伴小囊变;单囊或多囊性病变。CT平扫实性部分为稍低或等密度,偶可见钙化,囊性部分为低密度,但略高于脑脊液密度。MR平扫实性部分(包括附壁结节或厚囊壁)T1WI呈稍低信号或等信号,T2WI呈稍高信号或等信号;囊性部分T1WI呈低信号,T2WI呈高信号。增强后实性部分在CT和MR上均为明显强化,囊壁可或不强化;部分病例可出现临近软脑膜强化。多数病灶瘤周水肿较轻,但3级PXA肿瘤体积常较大,瘤周水肿多明显。由于肿瘤位置常较表浅,少数病例可出现颅骨的受压变薄。本病例的MRI表现符合PXA中大囊伴附壁结节的类型特点,附壁结节T2WI呈等信号,T1WI呈等信号,增强后附壁结节及临近脑沟内的软脑膜明显强化,囊壁无强化。
2.4 治疗及转归
虽然PXA被认为是惰性肿瘤,但与其他低级胶质瘤相比,PXA的复发率、恶变率及死亡率更高。WHO肿瘤分级是PXA患者生存率(overall survival,OS)的最重要预测指标[7-8]。在一项回顾性研究[7]中,作者发现与2级PXA患者相比,3级PXA患者的OS显著降低,其次肿瘤出现坏死与PXA患者预后不良密切相关,无坏死肿瘤的5年OS为90.2%,坏死肿瘤的5年OS为42.2%。在年龄方面,诊断PXA时患者年龄越大,其OS越短[8-9]。
由于PXA在临床罕见,易复发、恶变,目前还没有标准的治疗指南。PXA的常规治疗主要为外科手术行肿瘤全切除,术后联合影像学检查以检测肿瘤复发和进展情况。其他辅助治疗如放疗、化疗等通常用于术后残留、复发或3级PXA的患者,但由于缺乏数据支持,辅助治疗的疗效目前仍不确定。本文报道的PXA病例WHO肿瘤分级为2级,在肿瘤全切除术后1年来我院复诊,患者病情稳定,无癫痫发作,复查头颅MRI未见肿瘤复发。
2.5 诊断与鉴别诊断
虽然PXA的MRI表现具有一定特点,但其临床表现、影像学表现都极易误诊[10],确诊主要依靠病理,少数患者组织病理学诊断仍困难,需进一步行分子病理学检测。
儿童或年轻患者,以癫痫发病,MRI表现为发生于颞叶的大囊伴附壁结节病灶,与软脑膜关系密切,增强后结节明显强化,应考虑PXA的可能性,但此时仍需与以下疾病进行鉴别。①节细胞胶质瘤(ganglioglioma,GG),以囊实性多见,与PXA相比,GG常见钙化,肿瘤累及皮层时常伴脑回变宽,低级别GG无或轻度强化,软脑膜受累少见。②胚胎发育不良性神经上皮瘤,WHO 1级,其病灶常呈“三角形”或“楔形征”,尖角多凸向脑实质,瘤内多发微囊伴分隔,一般无壁结节及强化,肿瘤周围脑组织常见皮质发育不良,而PXA常为大囊,存在明显强化的附壁结节,且不伴有皮层发育不良。③青少年多形性低级别神经上皮肿瘤,女性为主,典型CT表现为肿瘤中央见结节样钙化[11],增强扫描一般无强化或轻度斑片状强化,与PXA的偶见钙化,实性成分明显强化较易鉴别。
总之,PXA是一种罕见的在儿童和年轻人中呈惰性生长的肿瘤,具有复发和脑内播散的潜力。临床表现常以癫痫发作起病但无特异性,典型MR表现为大囊伴结节,结节明显强化,可伴临近软脑膜强化。术前PXA易被误诊,MRI可为其侵袭性和分级提供有价值信息,有助于临床对患者进行综合管理和预后预测。肿瘤全切除为该病的主要治疗方式,3级PXA常需联合辅助治疗。
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图 1 小腿软组织总厚度(T)、肌肉厚度(M)和皮下组织厚度(S)的测量方法
在小腿轴面STIR图像上,通过小腿上1/3及下1/3层面正中位置(虚线)画一条水平线,测量两层面软组织的厚度。这些线分别与小腿的内侧(a)和外侧(d)皮肤、内侧(b)和外侧(c)浅筋膜相交,(a)与(d)之间的距离表示T的值;(b)与(c)之间的距离表示M的值。S为T减M。健侧小腿的T、M和T的测量方法同患侧小腿。
Figure 1. Total soft tissue thickness (T), muscle thickness (M) and subcutaneous tissue thickness (S) of calf were measured
表 1 2020年国际淋巴协会肢体淋巴水肿临床分期标准
Table 1 Clinical staging criteria for limb lymphedema by the International Lymphatic Society 2020
分期 临床表现 0期 亚临床状态,淋巴系统受损,组织液或成分发生微小变化,但肿胀不明显。可在水肿发生(I~Ⅲ 期)之前存在数月或数年。 Ⅰ期 水肿部位柔软,按压可凹陷,无皮肤纤维化,抬高患肢后肿胀可缓解,又称可逆性水肿。 Ⅱ期 抬高患肢肿胀消退不明显,后期由于皮下脂肪过多和纤维化,水肿可呈非凹陷性。 Ⅲ 期 水肿不可凹陷,病变肢体皮肤改变如脂肪沉积,色素沉着、棘皮病、疣状增生,呈现淋巴象皮肿。 表 2 不同分期的原发性下肢淋巴水肿的临床资料
Table 2 Clinical data of patients with primary lymphedema of the lower extremity at different clinical stages
项目 分期临床资料 Ⅰ(n=33) Ⅱ(n=44) Ⅲ(n=13) 年龄/岁* 20.00±19.00 35.50±27.00 29.50±29.00 病程/年* 2.00±9.40 9.00±21.25 9.00±15.00 性别/n(%)a 女 21(63.64) 26(59.09) 7(53.84) 男 12(36.36) 18(40.91) 6(46.16) 注:*-数据采用中位数±四分位间距表示;a-计数资料采用频数(构成比)表示。 表 3 原发性下肢淋巴水肿患者不同临床分期小腿软组织厚度比较
Table 3 Comparison of calf soft tissue thickness in patients with primary lymphedema of the lower extremity at different clinical stages
参数 分期 统计检验 Ⅰ(n=33) Ⅱ(n=44) Ⅲ(n=13) F/χ P T/cm 10.66±0.91a,b 13.04±1.89a 14.53±2.67b 28.821 <0.001 M/cm 8.08±0.77 8.42±1.30 8.24±0.87 0.944 0.393 S/cm 2.58±0.69a,b 4.62±1.39a 6.29±2.47b 37.970 <0.001 DT/cm 0.95±0.801,a,b 3.50±1.62a 4.94±2.55b 52.2311 <0.001 DS/cm 1.00±0.65a,b 3.18±1.34a 3.40±3.001,b 54.8611 <0.001 注:1-数据采用(中位数±四分位数间距)表示,组间比较采用非参数检验;余数据采用均数±标准差表示,组间
比较采用单因素方差分析。a-Ⅰ期与Ⅱ期比较,P<0.05;b-Ⅰ期与 Ⅲ 期比较,P<0.05。表 4 原发性下肢淋巴水肿患者小腿软组织厚度鉴别Ⅰ期及Ⅱ期的ROC曲线分析
Table 4 ROC curve analysis of stage Ⅰ and Ⅱ differentiation of leg soft tissue thickness in patients with primary lower extremity lymphedema
参数 AUC 95% CI P Youden指数 临界值/cm 敏感性/% 特异性/% T 0.882 0.788~0.944 <0.0001 0.6515 11.55 77.27 87.88 S 0.916 0.830~0.967 <0.0001 0.7121 3.55 77.27 93.94 DT 0.935 0.855~0.979 <0.0001 0.8106 1.65 93.18 87.88 DS 0.945 0.869~0.984 <0.0001 0.7879 1.60 90.91 87.88 表 5 原发性下肢淋巴水肿患者小腿软组织厚度鉴别Ⅱ期及 Ⅲ 期的ROC曲线分析
Table 5 ROC curve analysis of leg soft tissue thickness in stage Ⅱ and Ⅲ differentiation of primary lymphedema of lower extremities
参数 AUC 95% CI P Youden指数 临界值/cm 敏感性/% 特异性/% T 0.667 0.530~0.786 0.063 0.325 14.90 46.15 86.36 S 0.705 0.570~0.819 0.018 0.362 7.35 38.46 97.73 DT 0.685 0.549~0.802 0.020 0.400 2.95 92.31 47.73 DS 0.717 0.582~0.828 0.007 0.432 2.60 100.00 43.18 -
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