CAJ | 학술논문

目的研究肺外炎性肌纤维母细胞瘤(IMT)的临床病理特征、免疫表型和分子遗传学改变及其与预后的关系.方法收集30例肺外IMT患者的存档蜡块、病理及临床资料,采用免疫组织化学EnVision法检测相关免疫标志物.运用荧光原位杂交(FISH)检测30例IMT中间变性淋巴瘤激酶(ALK)基因的易位情况.结果 30例IMT患者年龄12 ～ 73岁,平均43.4岁.男女比1.0∶1.1.肿瘤发生于胃肠道、肝、脾、肾、盆腔、腹膜后、纵隔等部位.光镜下梭形的肌纤维母细胞与纤维母细胞以不同比例增生,间质大量炎性细胞弥漫浸润及多量薄壁小血管增生,并见不同程度的胶原化或黏液水肿背景.预后不良的病例镜下主要表现为核仁明显,间质疏松水肿,部分病例可见核分裂象,并可见类似神经节样细胞的大核、怪核及多核细胞.其中1例肿瘤组织中见上皮样或圆细胞形态.淋巴组织增生和组织细胞反应少见.免疫组织化学染色结果:肿瘤细胞波形蛋白、平滑肌肌动蛋白、细胞角蛋白、结蛋白和ALK阳性率分别为100％ (30/30)、70％ (21/30)、13％ (4/30)、27％ (8/30)和27％(8/30).ALK阳性的病例中7例为胞质阳性,其余1例(上皮样或圆细胞形态)为核膜阳性,同时该病例CD30阳性但白细胞共同抗原阴性.上皮细胞膜抗原、CD34、CD117、S-100蛋白和MyoD1均为阴性.FISH检测显示8例免疫组织化学ALK阳性的肿瘤存在ALK分离信号,为阳性病例,其余22例均为阴性.随访21例,14例无瘤生存,4例肿瘤复发,3例死亡.结论预后不良的肿瘤比预后良好的肿瘤形态上更易见到明显的核仁和间质疏松水肿,更易发生ALK蛋白异常表达,而淋巴组织增生和组织细胞反应在良性肿瘤中更易见到.ALK可能是潜在的IMT分子治疗靶点.
목적 연구폐외염성기섬유모세포류(IMT)적림상병리특정、면역표형화분자유전학개변급기여예후적관계.방법 수집30례폐외IMT환자적존당사괴、병리급림상자료,채용면역조직화학EnVision법검측상관면역표지물.운용형광원위잡교(FISH)검측30례IMT중간변성림파류격매(ALK)기인적역위정황.결과 30례IMT환자년령12 ～ 73세,평균43.4세.남녀비1.0∶1.1.종류발생우위장도、간、비、신、분강、복막후、종격등부위.광경하사형적기섬유모세포여섬유모세포이불동비례증생,간질대량염성세포미만침윤급다량박벽소혈관증생,병견불동정도적효원화혹점액수종배경.예후불량적병례경하주요표현위핵인명현,간질소송수종,부분병례가견핵분렬상,병가견유사신경절양세포적대핵、괴핵급다핵세포.기중1례종류조직중견상피양혹원세포형태.림파조직증생화조직세포반응소견.면역조직화학염색결과:종류세포파형단백、평활기기동단백、세포각단백、결단백화ALK양성솔분별위100％ (30/30)、70％ (21/30)、13％ (4/30)、27％ (8/30)화27％(8/30).ALK양성적병례중7례위포질양성,기여1례(상피양혹원세포형태)위핵막양성,동시해병례CD30양성단백세포공동항원음성.상피세포막항원、CD34、CD117、S-100단백화MyoD1균위음성.FISH검측현시8례면역조직화학ALK양성적종류존재ALK분리신호,위양성병례,기여22례균위음성.수방21례,14례무류생존,4례종류복발,3례사망.결론 예후불량적종류비예후량호적종류형태상경역견도명현적핵인화간질소송수종,경역발생ALK단백이상표체,이림파조직증생화조직세포반응재량성종류중경역견도.ALK가능시잠재적IMT분자치료파점.
Objective To investigate the clinicopathologic features,immunohistochemic phenotypes and genetic alterations of extrapulmonary inflammatory myofibroblastic tumor (IMT) and the correlation with prognosis.Methods Thirty cases of IMT with follow-up were analyzed morphologically and immunohistochemically.ALK FISH was also performed to determine the ALK gene status.Results Patients ranged in age from 12 to 73 years (mean 43.4 years).The male-to-female ratio was 1.0∶ 1.1.The tumors were located in various anatomical sites including gastrointestinal tract,liver,spleen,kidney,pelvic,retroperitoneum,mediastinum etc.Histologically,the majority of cases were composed of spindled fibroblastic and myofibroblastic cells accompanied by an inflammatory infiltrate of plasma cells,lymphocytes,and eosinophils.Most cases with aggressive behavior had features including prominent nucleoli and edematous myxoid background.Lymphohistiocytic reactions were usually absent.Some cases showed multinucleation,nuclear pleomorphism and mitoses.One case demonstrated epithelioid morphology with round-to-epithelioid cells.The immunohistochemical study showed vimentin,SMA,CK,desmin,and ALK were expressed in 100％(30/30),70％ (21/30),13％ (4/30),27％ (8/30),and 27％ (8/30) of IMT,respectively.Diffuse cytoplasmic ALK staining was detected in seven cases.One case (containing round-to-epithelioid cells) demonstrated ALK nuclear membrane staining,coupled with positive reaction for C D30 and negative reaction for LCA.EMA,CD34,CD117 and S-100 protein,and MyoD1 were negative for all cases.Six ALK protein positive cases harbored ALK gene rearrangement,but not the remaining 22 cases.Follow-up data were available in 21 patients.After initial resection,14 patients were alive with no evidence of disease,while 4 patients were alive with tumor recurrence and 3 patients died of the disease.Conclusions Most IMT with aggressive behavior have features including prominent nucleoli,edematous myxoid background,and positive expression of ALK.Lymphohistiocytic reaction is usually absent.ALK may be a potential novel therapeutic target for IMT.