胃肠道炎性肌纤维母细胞瘤研究进展
2017-04-04曾祥宇张鹏高金波刘炜圳帅晓明陶凯雄
曾祥宇 张鹏 高金波 刘炜圳 帅晓明 陶凯雄
·综 述·
胃肠道炎性肌纤维母细胞瘤研究进展
曾祥宇 张鹏 高金波 刘炜圳 帅晓明 陶凯雄
胃肠道炎性肌纤维母细胞瘤 (inflammatory myofibroblastic tumor,IMT)是一种特殊而少见的间叶性肿瘤,发病部位主要位于胃和回盲部,常见于学龄前儿童及青少年,女性多发,临床表现无特异,术前诊断困难,确诊需依据术后病理及免疫组织化学,一般预后良好,偶有复发。本文就胃肠道IMT的临床表现、病理检查及免疫组织化学特点、诊断及鉴别诊断、治疗及预后等作一综述。
炎性肌纤维母细胞瘤; 诊断; 治疗; 预后
炎性肌纤维母细胞瘤 (inflammatory myofibroblastic tumor,IMT)是一种由分化的梭形纤维母细胞或肌纤维母细胞组成的间叶性肿瘤。IMT主要发生在肺部,腹腔内罕见,胃肠道的发病率更低[1]。胃肠道IMT大多为个案报道,缺少大宗病例报道。本文就胃肠道IMT的临床病理特点、诊治及预后等作一综述。
一、胃肠道IMT的临床特点
胃肠道IMT是一种少见而独特的间叶性肿瘤,表现为低度恶性或交界性肿瘤,常见于学龄前儿童及青少年,女性多发[2]。其具体病因不明,多发生于手术、创伤或炎症以后,是人体对损伤的一种异常或者过度的反应[3]。有研究发现其可能与EB病毒感染有关[4]。既往文献报道关于IMT的命名很多,包括组织细胞瘤、黄色瘤、纤维黄色瘤、黄色肉芽肿、浆细胞瘤等[5]。2002年WHO软组织肿瘤国际组织学分类专家正式命名为炎性肌纤维母细胞瘤,定义为“由分化的肌纤维母细胞性梭形细胞组成,常伴大量浆细胞和(或)淋巴细胞的一种肿瘤”[6]。许多学者认为IMT即为以往的炎性假瘤(inflammatory pseudotumor,IPT),其实不然,Höhne等[7]通过涉及938例IMT病人的443篇文章分析指出,IMT与IPT是不同的,首先,IMT是以纤维母细胞瘤增生为主的实质肿瘤,而IPT则是以炎性细胞浸润为主的炎症反应;其次,IMT好发于学龄前儿童及青少年,而IPT好发于中老年;另外,IMT大多须外科手术切除,而IPT可通过保守治疗治愈。
胃肠道IMT以胃及回盲部多见,其临床表现无特异性,但与发病部位密切相关[8]。胃IMT以上腹部不适及消化道出血多见,Bjelovic等[9]报道了1例以上腹部痛及恶心、呕吐就诊的胃IMT病人;十二指肠IMT则以上腹部不适多见;空回肠IMT以腹痛、腹胀及腹部包块多见,Oeconomopoulou等[10]报道了1例以右下腹痛、发热等类似急性阑尾炎症状就诊的回肠末端IMT病人,Unver等[11]则报道了1例回肠IMT合并急性阑尾炎的病例;结肠IMT以右下腹疼痛及右下腹包块多见,陈益民等[12]报道了1例以右下腹疼痛及右下腹包块就诊的回盲部及升结肠IMT病人;直肠IMT以大便带血多见。此外,胃肠道IMT多伴有发热、乏力、消瘦、贫血等全身症状,Qiu等[13]报道了1例以高热为首发症状就诊的胃IMT病人。
二、胃肠道IMT的病理检查及免疫组织化学特点
胃肠道IMT镜检主要为梭形细胞、数量不等的胶原以及淋巴细胞、浆细胞组成的炎性成分,其间质中的淋巴细胞及浆细胞等慢性炎症细胞为其病理学特征[14]。Gleason等[15]将其光镜下病理组织学类型可分为三型:①黏液血管型,瘤组织中血管较丰富,间质广泛黏液变性,其间穿插梭形细胞,可见各种炎症细胞,形态似结节性筋膜炎。②梭形细胞密集型,肿瘤细胞密集排列成束及纵横交错,排列成“人”字形或漩涡状,背景细胞为大量淋巴细胞和浆细胞。③纤维瘢痕型,肿瘤细胞较少,瘤细胞间分布致密成片的胶原纤维类似瘢痕组织。肿瘤的病理分型中可以一种为主,也可两种或三种并存。免疫组织化学指标中S-100、CD34和CD117常表达阴性。梭形细胞胞质标志物Vimentin以及肌源性标志物SMA为胃肠道IMT的特异标记,有研究显示[16],约50%的IMT具有间变型淋巴瘤激酶(ALK)基因的克隆性重排,导致ALK蛋白的激活表达,ALK阳性说明肿瘤呈中度恶性[17]。李明信[18]通过对4例行免疫组织化学的腹腔IMT分析显示,CD117、CD34(-)100%(4/4),Vimentin、SMA(+)100%(4/4)。孙璐等[19]对5例胃IMT分析,免疫组织化学显示CD117、CD34(-)100%(5/5),Vimentin、SMA(+)100%(5/5),ALK100%(5/5)。李焕萍等[20]对30例肺外IMT行免疫组织化学显示,CD117、CD34、S-100(-)100%(30/30),Vimentin(+)100%(30/30),SMA(+)70%(21/30),ALK(+)27%(8/30)。
三、胃肠道IMT的诊断及鉴别诊断
血常规、肝肾功能、肿瘤标志物等实验室检查及B超、CT、MRI等影像学检查对胃肠道IMT均无特异性,穿刺活检由于取材较少且存在局限性,确诊仍需靠术后病理及免疫组化检查。胃肠道IMT术前诊断困难,术前易误诊为恶性肿瘤,李明信[18]对10例腹腔IMT报道显示,其中7例(70%)术前误诊为恶性肿瘤,因此对于学龄前及青少年病人,胃肠道肿块,同时伴有发热、贫血、消瘦等全身症状时应考虑到胃肠道IMT可能。
胃肠道IMT需与间质瘤、平滑肌瘤、息肉、神经鞘瘤及平滑肌肉瘤等鉴别。胃肠间质瘤(gastrointestinal stromal tumor,GIST)为胃肠道最常见的间质源性肿瘤,多呈外生性或“哑铃”状生长,免疫组织化学中,CD117和CD34强阳性表达,基因检测示KIT或PDGFRA突变为最重要的特征[21];平滑肌瘤少见,通常较小且界限清楚,肿瘤常来源于固有肌层,可向腔内或腔外生长,免疫组织化学中CD117和CD34阴性,有助于鉴别诊断;息肉较小,直径小于1 cm,表现为无蒂或有蒂的肿块,病变主要位于黏膜下层,病理检查特点为增生的纤维组织常呈漩涡状围绕血管排列(葱皮样改变);神经鞘瘤通常较大,形态欠规则,钙化多见,易见肿块内多发囊变区,镜下主要变现为瘤组织的周围可见淋巴细胞套;平滑肌肉瘤,瘤细胞丰富,异型性明显,核常呈雪茄样,核分裂象多见,并可见病理性核分裂象。
四、胃肠道IMT的治疗及预后
胃肠道IMT以手术治疗为主,少数病例报道其可通过抗生素[22]、激素[23]或非甾体类抗炎药物[24]治愈,甚至极少数病例无需采用任何治疗而自然转归[25],但是不排除其作者将IMT与IPT相混淆所致。胃肠道IMT虽大多为良性肿瘤,但由于其具有侵袭生长特性,因此在病人身体状况允许的情况下,可以适当扩大手术切除范围。对于胃肠道IMT复发病人,再次手术仍是首选。Wang等[26]报道了1例74岁病人在原发IMT切除30个月后同一部位再发IMT而再次采用外科手术切除的病例。胃肠道IMT对放化疗大多不敏感,但Chen等[27]报道,1例腹膜后IMT病人在原发肿瘤切除后出现原位复发及远处转移,采用表柔比星(表阿霉素)、达卡巴嗪、多烯紫杉醇等化疗药物治疗3个周期后肿瘤大小明显减小。Tao等[28]则报道了1例不可切除的腹膜后IMT病人,经甲氨蝶呤、顺铂等化疗药物治愈长达3年之久。胃肠道IMT大多预后良好,但也可发生复发转移,Gleason等[15]报道,84例肺外IMT中,21例(25%)出现复发。Meis等[29]报道38例腹腔及腹膜后IMT,长期随访27例,其中10例(37%)复发,3例(11%)出现肺、脑转移,5例(19%)最终死于IMT。
总之,胃肠道IMT是一类特殊而少见的间叶性肿瘤,发病部位主要位于胃和回盲部,常见于学龄前儿童及青少年,临床症状及影像学表现无特异性,术前误诊率高,外科手术完整切除是其主要治疗手段,确诊需依据病理及免疫组织化学检查,大多数胃肠道IMT预后良好,但也有复发及转移的报道,需引起外科医师的注意。
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Advances in inflammatory myofibroblastic tumor of gastrointestinal tract
ZengXiangyu,ZhangPeng,GaoJinbo,LiuWeizhen,ShuaiXiaoming,TaoKaixiong.
DepartmentofGastrointestinalSurgery,UnionHospital,TongiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan430022,China
TaoKaixiong,Email:tao_kaixiong@163.com
Inflammatory myofibroblastic tumor (IMT) of gastrointestinal tract is a peculiar and rare kind of tumors from mesenchymal tissue. It mainly occurs in stomach and ileocecum and is more likely associated with preschool children as well as youngsters, showing slight female predominance. The clinical manifestations of gastrointestinal IMT are not specific so that preoperative diagnosis is very difficult. Diagnosis depends on the pathological and histological examinations and usually has favorable prognosis, occasional relapse may happen however. This review discussed the clinicopathological and immunohistochemical characteristics, diagnosis and differential diagnosis, treatment and prognosis of gastrointestinal IMT.
Inflammatory myofibroblastic tumor; Diagnosis; Treatment; Prognosis
国家自然科学基金(81572413);武汉市科技局基金(2015060101010044)
430022 武汉,华中科技大学同济医学院附属协和医院胃肠外科
陶凯雄,Email: tao_kaixiong@163.com
R730.262
A
10.3969/j.issn.1003-5591.2017.02.019
2016-09-09)