Abstract
肾血管平滑肌脂肪瘤(angiomyolipoma，AML)合并肾静脉、下腔静脉、右心房瘤栓是一种十分罕见的实体肿瘤，其病因及发病机制目前尚不清楚，影像学检查易误诊。中南大学湘雅二医院收治的1例AML合并肾静脉、下腔静脉、右心房瘤栓的女性患者，35岁，无明显诱因右侧腰痛3年余，CT平扫示右肾及右肾静脉-下腔静脉-右心房柱不规则、分叶状、脂肪性密度肿块影，增强扫描示各期脂肪成分无强化，实性成分轻度强化。行右肾根治加瘤栓取出术，术后1年无复发，生活质量可。肾AML 沿肾静脉、下腔静脉生长并延伸至右心房者罕见，影像学检查极为重要，其CT表现具有特征性，但最终明确诊断仍需依靠病理学及免疫组织化学检查。
Keywords: 血管平滑肌脂肪瘤, 肾, 计算机体层摄影
Abstract
Renal angiomyolipoma (AML) with renal vein, inferior vena cava (IVC), and right atrial embolism is a rare solid tumor, whose etiology and pathogenesis are still unclear. Moreover, it is often misdiagnosed. One patient with renal AML complicated with renal vein, IVC, and right atrial embolism was admitted to the Second Xiangya Hospital of Central South University, who was a 35-year-old female, without any previous medical history, presented with right low back pain for more than 3 years. Computed tomography (CT) scan showed irregular lobulated fatty density mass in the right kidney, renal vein, IVC, and right atrium. The contrast-enhanced scan showed no enhancement of fat components at each phase and mild enhancement of solid components. Radical resection of the right kidney and removal of tumor thrombus were performed, and there was no recurrence 1 year after the operation. It is rare for renal AML to grow along the renal vein, IVC, and extend to the right atrium. Imaging examination is extremely important, and the CT findings of this case are characteristic, but the diagnosis eventually depends on pathological and immunohistochemical examinations.
Keywords: angiomyolipoma, kidney, computer tomography
肾血管平滑肌脂肪瘤(angiomyolipoma，AML)属于血管周围上皮样细胞肿瘤(perivascular epithelioid cell tumor，PEComa)的一种类型[1-2]，是最常见的良性肾间质肿瘤，其成分主要包括脂肪组织、畸形血管和平滑肌。Tsui等[3]学者根据脂肪成分比例将AML分为脂肪瘤型(脂肪≥70%)、血管瘤型、平滑肌瘤型(脂肪≤10%)和混合型等。大多数肾AML患者没有症状，常在体检过程中偶然发现，其平均发病年龄为43岁，且以女性为主(男女比例约为4꞉11)[4]。虽然肾AML是良性间叶组织肿瘤，但仍有少数病灶会累及区域淋巴结、肾静脉或下腔静脉，一般累及右心房者少见。本文报告1例具有侵袭性行为的肾AML，其延伸至肾静脉、下腔静脉及右心房，同时回顾性分析其临床、影像表现及病理特征，并结合文献探讨影像学检查在肾AML诊断及鉴别诊断中的应用价值。
1. 病例资料
患者，女，35岁，无明显诱因右侧腰痛3年余，呈间歇性钝痛，按压后加重，可自行缓解，1个月前无明显诱因出现气促，表现为爬楼后呼吸困难，伴胸背部偶发性刺痛，左侧第3脚趾麻木，无发热、恶心呕吐、血尿等。体格检查显示：体温为36.5 ℃，脉搏为80次/min，呼吸为20次/min，血压为107/ 80 mmHg(1 mmHg=0.133 kPa)；右下腹部轻压痛，无反跳痛，右肾区叩击痛，双下肢无水肿。实验室检查显示：白细胞计数为4.83×109/L，血小板为249×109/L，血红蛋白为124 g/L，白蛋白为37.5 g/L；人绒毛膜促性腺激素为0.37 ng/mL，癌胚抗原为0.5 ng/mL，糖类抗原为12 513.26 U/mL，糖类抗原CA199为 13.66 U/mL，甲胎蛋白 1.69 ng/mL；其余未见明显异常。
于2020年11月7日中南大学湘雅二医院(以下简称我院)行CT检查，平扫示右肾不规则分叶状脂肪性密度肿块影(图1A)，CT值约-92 HU，界清，大小约50 mm×32 mm×34 mm，增强扫描示肾皮髓质交界期、增强期及肾盂排泄期脂肪成分无强化，实性成分略强化(图1B~1D)；冠状位及矢状位见右肾静脉-下腔静脉-右心房柱状脂性低密度影，长约12 cm，宽约2.5 cm(图1E和1F)。
图1.
患者肾血管平滑肌脂肪瘤并下腔静脉、右心房瘤栓患者计算机断层血管造影
Figure 1 Computed tomography angiography in the patient with renal angiomyolipoma combined with inferior vena cava and right atrial embolism A: Right renal mass in precontrast phase dominated with fat density (red arrow) by CT; B: Slight enhancement of the solid mass (red arrow) in cortico medullary phase by contrast-enhanced CT; C: Slight enhancement of the solid mass (red arrow) in nephrographic phase by contrast-enhanced CT; D: No delayed enhancement of the solid mass (red arrow) in excretory phase by contrast-enhanced CT; E: A columnar lipid low-density filling defect from the right renal vein-inferior vena cava to the right atrium (yellow arrow) in coronary position of CT; F: A columnar lipid low-density filling defect in the inferior vena cava (yellow arrow) in sagittal position of CT.
2020年11月9日于我院行腹部及肾血管超声检查，下腔静脉近心段及肝后段可见长条形高回声物(图2A，红色箭头)，约占管腔4/5，彩色多普勒血流成像(color Doppler flow imaging，CDFI)示下腔静脉切面内血流充盈缺损。右房内大小约31 mm×22 mm的高回声物，边界清，形态规则(图2B)。
图2.
患者肾血管平滑肌脂肪瘤并下腔静脉、右心房瘤栓患者的超声图像
Figure 2 Ultrasound image in the patient with renal angiomyolipoma combined with inferior vena cava and right atrial embolism
A: A long hyperechoic lesion in the proximal and posterior hepatic segments of the vein (red arrow) by abdominal vascular ultrasound; B: A filling defect of IVC by CDFI. A hyperechoic lesion with 3.1 cm in length and 2.2 cm in width is also seen in the right atrium (yellow arrow). IVC: Inferior vena cava; CDFI: Color Doppler flow imaging.
手术所见(图3)：纵行剖开下腔静脉，见黄色瘤栓，瘤栓完整，心房内瘤栓活动可，用镊子从下腔静脉完整脱出瘤栓，瘤栓附着部为右肾静脉出口部，蒂部直径约3 mm，离断蒂部，完整取出瘤栓。病理结果显示右肾及瘤栓为AML，肾肿瘤体积为5.5 cm×5.5 cm×4.0 cm，瘤栓体积为11.0 cm× 2.0 cm×2.0 cm。HE染色镜下可见血管壁组织、纤维组织增生及玻璃样变性，少许灶性淋巴细胞浸润(图4A)。活组织病理检查及免疫组织化学结果显示(图4B)：波形蛋白(vimentin，Vim)(+)、神经组织来源标记物S-100蛋白(+)、平滑肌肌动蛋白(smooth muscle actin，SMA)(+)、人黑色素瘤相关抗原(human melanoma black，HMB)(散在+)、间叶组织来源标记物Melan-A(+)、神经元特异性烯醇化酶(neuron-specific enolase，NSE)(-)、钙调蛋白(calponin)(+)、CD34(+)、肿瘤增殖抗原Ki-67(1%+)、细胞角蛋白(cytokeratin，CK)(-)、肾母细胞瘤(Wilm’s tumor-1，WT-1)蛋白(-)。其中Vim(+)表明肿瘤可能起源于间叶组织；S100(+)、SMA(+)、HMB(散在+)、Melan-A(+)提示肿瘤含有脂肪成分；CD34(+)表明肿瘤血管内皮细胞生成；Ki-67增殖指数低，提示肿瘤的增殖活性较低。
图3.
患者肾血管平滑肌脂肪瘤并下腔静脉、右心房瘤栓患者的大体标本
Figure 3 Gross specimen of patient with renal angiomyolipoma combined with inferior vena cava and right atrial embolism
The right renal mass and the entire right kidney with a fatty tumor thrombus extend from the mass into the renal vein (axial position) in the gross specimen.
图4.
患者肾血管平滑肌脂肪瘤并下腔静脉、右心房瘤栓患者的HE染色和免疫组织化学染色
Figure 4 HE staining and immunohistochemistry result of a patient with renal angiomyolipoma combined with inferior vena cava and right atrial embolism
A: Vascular wall tissues, fibrous hyperplasia and hyalinization as well as lymphocyte infiltration by HE staining; B: Positive expression of Melan-A in tumor cytoplasm by immunohistochemical staining.
2. 讨 论
世界卫生组织将肾AML定义为生物学良性的间叶源性肿瘤，在普通人群中发病率为0.1%~2.2%，其中约80%为女性[5]。临床表现根据肿瘤部位及大小不同而异，常因肿瘤渐进性增大而导致疼痛为首发症状，本研究中患者以肾肿块渐进性增大而引发腰部不适就诊。此外根据是否合并有结节性硬化将AML分为两型。在AML患者中有20%~30%合并有结节性硬化，而在所有结节性硬化的患者中，有40%~60%的患者合并有AML，本例患者未合并有结节性硬化。
从Kutcher等[6-9]在1982年首次报道肾AML沿肾静脉及下腔静脉生长的病例至今，已有42例类似的病例报道。出现肾AML沿肾静脉、下腔静脉生长并延伸至右心房的情况比较罕见，其具体机制尚不明确。部分学者[10-11]认为本病可能是血流长期冲击带蒂瘤栓，导致瘤栓逐渐沿肾静脉及下腔静脉生长蔓延至右心房，瘤栓实质上是AML成分。Luo等[12]回顾性分析了9例肾AML合并肾静脉或下腔静脉栓塞的患者，在术后的随访中，5例(55.56%)存活且未出现任何并发症，2例(22.22%)在术中或术后死亡。Lei等[13]对43例肾AML患者进行了为期44.3个月的随访，只有2例患者出现了复发而死亡。另外本例患者手术过程中发现下腔静脉瘤栓完整，心房内瘤栓活动可，术中用镊子可完整取出，且未见明确的肾与静脉内肿瘤侵袭性生长的证据，因此笔者认为这些特点可支持本例患者的病变为多中心生长的良性病变。
目前肾AML的临床诊断主要依赖病理检查，其确诊依据为存在表达HMB45的平滑肌样细胞[14]。一般AML大体观察显示为切面多呈红褐色、灰黄或灰白色，界清，质地较为柔软，没有明显包膜；镜下观察其肿瘤由厚壁血管、平滑肌和成熟脂肪组织等成分组成；免疫组织化学染色显示血管内皮细胞标记(CD34)以及平滑肌肌动蛋白(SMA)等多呈阳性。
随着影像学检查技术的不断提高，肾AML的检出率显著提高，典型的肾AML脂肪成分明显，在CT上具有特征性，因此诊断较为容易，但是当肾AML为血管瘤型或肌瘤型时，诊断较为困难。本病例脂肪成分明显，易于诊断，但是其沿肾静脉、下腔静脉及右心房生长，与低度恶性脂肪肉瘤鉴别困难。一般肾AML有以下特点：1)肿瘤多表现为类圆形或不规则肿块，呈膨胀性生长，边界较清，本例中肿瘤与肾分界清晰；瘤体与肾交界呈尖嘴征，提示病灶起源于肾。另外，当肿瘤大于4 cm时易发生瘤内出血，因此当伴有自发性破裂出血时，应考虑肾AML可能。2)肿瘤中存在脂肪成分，因此CT值通常为负值；肿瘤的实性成分呈不均匀轻中度强化，但是脂肪无强化。
肾AML一般要与以下肿瘤相鉴别：1)肾细胞癌。肾细胞癌多表现为无痛性肉眼血尿，单侧发病，出血、坏死、囊变常见，平扫密度不等，可有钙化及脂肪成分，增强肿块明显不均匀强化，动脉期CT值常超过100 HU，典型者呈“快进快出”征象。2)畸胎瘤。CT上畸胎瘤病灶呈混杂密度，内可见脂性低密度影、骨骼样高密度影，增强扫描示脂性低密度灶，未见明显强化，软组织呈不均匀强化。3)脂肪肉瘤。CT扫描示脂肪肉瘤体积常十分巨大，平均直径约20 cm，密度取决于分化程度，可呈实性、混合、脂性密度，增强扫描病灶呈不均匀强化，软组织呈不同程度强化，边界模糊，易侵犯临近的组织结构。
尽管肾AML是良性肿瘤，但其治疗仍首选手术，尤其是当肿瘤直径大于4 cm，或病变沿肾静脉、下腔静脉至右心房生长时[15]，即使患者无症状，也应手术切除，因为其可导致肺动脉栓塞的发生，这种情况下很容易引发患者猝死。此外射频消融术、冷冻消融术、栓塞等介入治疗手段对体积较小的AML也有较好效果。而对于类似本例沿着肾静脉、下腔静脉及右心房生长的肾AML患者，一般行肾部分或根治性切除加腔静脉瘤栓清除术[16-18]，预后效果较好，本例患者手术后1年无复发。
综上所述，肾AML的临床症状没有特异性，多数患者仅在体检时发现，少数出现腰部胀痛等症状。CT检查有助于评估肿瘤内部成分、自身血供情况，以及与周围脏器和大血管的关系，为手术方案设计及风险评估提供了有力的依据。对于具有类似文中病例特征的肾AML，应该谨慎处理，并及时进行手术干预，以防止肺动脉栓塞的发生。
基金资助
湖南省自然科学基金(2019JJ40444)。
This work was supported by the Natural Science Foundation of Hunan Province, China (2019JJ40444).
利益冲突声明
作者声称无任何利益冲突。
作者贡献
刘欢 数据采集和整理，论文构想、撰写及修订；肖恩华 论文指导与审校。所有作者阅读并同意最终的文本。
原文网址
http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/2022121763.pdf
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