Li Huanping, Shen Qin, Xia Qiuyuan, Shi Shanshan, Zhang Rusong, Yu Bo, Ma Henghui, Lu Zhenfeng, Wang Xuan, He Yan, Zhou Xiaojun, Rao Qiu
Department of Pathology, Medicine School of Nanjing University/Nanjing Jinling Hospital, Nanjing 210002, China.
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Zhonghua Bing Li Xue Za Zhi. 2014 Jun;43(6):370-4.
To investigate the clinicopathologic features, immunohistochemic phenotypes and genetic alterations of extrapulmonary inflammatory myofibroblastic tumor (IMT) and the correlation with prognosis.
Thirty cases of IMT with follow-up were analyzed morphologically and immunohistochemically. ALK FISH was also performed to determine the ALK gene status.
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 CD30 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.
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.
探讨肺外炎性肌纤维母细胞瘤(IMT)的临床病理特征、免疫组化表型及基因改变,并分析其与预后的相关性。
对30例有随访资料的IMT进行形态学和免疫组化分析。同时采用ALK荧光原位杂交(FISH)检测ALK基因状态。
患者年龄12~73岁(平均43.4岁),男女比例为1.0∶1.1。肿瘤位于多个解剖部位,包括胃肠道、肝脏、脾脏、肾脏、盆腔、腹膜后、纵隔等。组织学上,大多数病例由梭形的成纤维细胞和肌纤维母细胞组成,并伴有浆细胞、淋巴细胞和嗜酸性粒细胞的炎性浸润。多数具有侵袭性行为的病例具有核仁明显、黏液样水肿背景等特征。通常无淋巴组织细胞反应。部分病例可见多核、核异型性及核分裂象。1例表现为上皮样形态,由圆形至上皮样细胞构成。免疫组化研究显示,波形蛋白、平滑肌肌动蛋白(SMA)、细胞角蛋白(CK)、结蛋白及ALK在IMT中的表达率分别为100%(30/30)、70%(21/30)、13%(4/30)、27%(8/30)和27%(8/30)。7例检测到ALK弥漫性胞质染色。1例(含圆形至上皮样细胞)显示ALK核膜染色,同时CD30阳性、白细胞共同抗原(LCA)阴性。所有病例上皮膜抗原(EMA)、CD34、CD117、S-100蛋白及肌分化抗原(MyoD1)均为阴性。6例ALK蛋白阳性病例存在ALK基因重排,其余22例无此现象。21例患者有随访资料。初次切除术后,14例患者存活且无疾病证据,4例患者存活但肿瘤复发,3例患者死于该疾病。
多数具有侵袭性行为的IMT具有核仁明显、黏液样水肿背景及ALK阳性表达等特征。通常无淋巴组织细胞反应。ALK可能是IMT潜在的新型治疗靶点。