腹腔脏器炎性肌纤维母细胞瘤及其相关病变的临床病理、免疫组化及超微结构研究

Intra-abdominal Inflammatory Myofibroblastic Tumor & Related Lesions:Clinicopathologic,Immunohistochemical and Electron Microscopic Study

目的探讨腹腔脏器炎性肌纤维母细胞瘤(IAIMT)、非腹腔炎性肌纤维母细胞瘤(NAIMT)、腹腔内纤维瘤病(AF)、胃肠道型间质肿瘤(GIST)临床病理、免疫组化及超微结构特征及其相互间的鉴别诊断。方法对10例IAIMT、5例NAIMT、5例AF及5例GIST应用免疫组化及电镜观察的方法,结合临床及HE形态进行分析。结果IAIMT、NAIMT、AF和GIST临床表现相似,除NAIMT病例外,多数以腹部包块及腹痛就诊。肿块单发或多发,常与周围组织黏连,手术切除不全可致复发甚至死亡。IAIMT与NAIMT具有相似的病理形态学表现,肿块无包膜,边界欠清,由增生的纤维母细胞和肌纤维母细胞组成,肿瘤间质中散在大量炎症细胞。IAIMT与NAIMT组织学主要分为3型:黏液血管型、梭形细胞密集型和纤维瘢痕型。个别病例肿瘤组织内有钙化、骨化及坏死。AF主要由纤细梭形和星芒状的2种形态的纤维母细胞和肌纤维母细胞组成,间质常有大量胶原。GIST的瘤组织由梭形细胞和上皮样细胞以不同比例组成,胞质内见空泡,梭形瘤细胞交织排列,其间可见具有特征性的上皮细胞团巢。部分病例的肿瘤细胞密集并伴有异型性改变,病理性核分裂像易见(>5/50HPF),可有出血、坏死及囊性变(胃肠道恶性间质瘤)。IAIMT和NAIMT瘤细胞全阳性表达Vimentin(15/15)、SMA(15/15)和MSA(15/15),部分性表达ALK(7/15),Calponin(6/15),Desmin(5/15),CK(5/15);AF肿瘤细胞强阳性表达Vimentin(5/5)、SMA(5/5)、MSA(5/5)、β-catenin(5/5),部分性表达S-100(1/5)、Capo-nin(2/5)、Desmin(1/5)和CK(1/5);GIST全阳性表达Vimentin(5/5)、CD117(5/5),大部分表达CD34(4/5),部分性表达SMA(2/5)、MSA(2/5)、S-100(1/5)、Calponin(3/5)、Caldesmon(3/5)、Desmin(1/5)、Smoothelin(3/5)、Pgp9.5(1/5)和MBP(1/5)。其中,ALK、β-catenin、CD117及CD34的表达具有特征性,分别表达于IMT(包括IAIMT和NAIMT)、AF和GIST的不同肿瘤组织。此外,Caldesmon和Smoothelin表达于具有平滑肌分化的GIST组织,而在具有肌纤维母细胞的病变中不表达。电镜下,IAIMT、NAMIT及AF中瘤细胞均具有纤维母细胞和肌纤维母细胞的特征,但IMT间质中可见大量的炎细胞,而在AF间质中为大量的胶原原纤维,炎症细胞少见;GIST超微结构表现为部分瘤细胞具有致密核心颗粒、微丝、细胞间桥粒样连接等神经性分化特征和具有微丝、密斑和密体等肌性分化结构,尚存在少量未分化的间质细胞。结论IAIMT、NAIMT、AF、GIST均具有各自的临床特点、HE形态、免疫组化标记及超微结构特征,其中病理学形态和免疫组织化学标记是IMT、NAIMT、AF、GIST诊断和鉴别诊断的重要依据。

Objective To investigate the clinicopathologic and electron microscopic features of intra-abdominal inflammatory myofibroblastic tumor （IAIMT）, Non-Abdominal inflammatory myofibroblastic tumor（ NAIMT）, Abdominal fibromatosis （AF）, Gastrointestinal stromal tumor（GIST） and to discuss their differential diagnosis. Methods IAIMT, NAIMT, AF and GIST were observed by light mlcroscopy,immunohistochemistry and electron microscopy. Results Objective To investigate the clinico- pathologic and electron microscopic features of intra-abdominal inflammatory myofibroblastic tumor （IAIMT） , Non-Abdominal inflammatory myofibroblastic tumor （NAIMT） , Abdominal fibromatosis （ AF ） , Gastrointestinal stromal tumor （ GIST ） and to discuss their differential diagnosis. Methods IAIMT, NAIMT, AF and GIST were observed by light microscopy, immunohistochemistry and electron microscopy. Results The clinical manifestations of IAIMT, NAIMT, AF and GIST were similar： Except the patients with NAIMT , the presenting symptoms in majority cases were abdominal mass , vague abdominal pain . The masses were either solitary or multiple and adherent to the surrounding tissues. Incomplete resection of the lesions can result in recurrence of the tumor and even death of the patients. There were similar characters in pathologic morphology between IAIMT and NAIMT, which composed of myofibroblasts, fibroblasts and a large num- ber of inflammatory cells. The tumors had no capsules and clear boundary. There were three basic histological pantterns of IAIMT and NAIMT： ①myxoid-vascular pattern, ② compact spindle cell pattern,③ hypocellular-fibroscar pattern. Calcification, ossification and necrosis were present in few cases. The masses of AF were composed of spindle and corpulent shaped cells,separated by a variable amount of collagenous tissue. GIST were composed of spindle cells and epithelioid cells. The vacuoles appeared in the cytoplasm of the neoplastic cells. The spindle cells were arranged in plexiform or bunchiness, Among them there are some cell nests which were the character of epithelial cells. High cell density, obvious atypia, high karyokinesis （≥5/50HPF）, cystification, hemorrage or necrosis in few cases were easy to be found （the character of malignant gastrointestinal stromal tumors）. In immunohistochemical analyses,all of IAIMT and NAIMT showed diffused strong positive for vimentin（ 15/15 ） ,SMA（ 15/15 ） and MSA （ 15/15 ）, focal positive for ALK （ 7/15 ）, Calponin （ 6/15 ）, Desmin （ 5/15 ）, CK （ 5/15 ）, and negative for S-100, CD34, CD117, Caldesmon,β-catenin, Smoothelin, Pgp9.5 and MBP ; AF showed diffuse strong positive for Vimentin （ 5/5 ）, SMA （ 5/5 ）, MSA （5/ 5 ）, β-catenin （5/5）, focal positive for S-100 （ 1/5 ）, Caponin （ 2/5 ）, Desmin （ 1/5 ） and CK （ 1/5 ） ; GIST showed diffuse strong positive for Vimentin（5/5）,CDI17（5/5）,focal positive for CD34（4/5）SMA（2/5） ,MSA（2/5） ,S-100（1/5） ,Calponin（3/5）, Caldesmon（3/5 ）, Desmin （ 1/5 ）, Smoothelin （ 3/5 ）, Pgp9.5 （ 1/5 ） and MBP （ 1/5 ）. The characteristic expressions of ALK, β- catenin, CD117 and CD34 were detected in IMT（ IAIMT＆NAIMT）, AF and GIST respectively. Moreover, Caldesmon and Smoothelin were both focal positive in GIST with smooth muscle-differentiation, but negative in tumors with myofibroblastic differentiation. Electron microscopically, IAIMT, NAMIT and AF all showed the characteristic uhrastructure of myofibroblasts and fibroblasts, but a large number of inflammatory cells and a amount of extracellular collagen appear in IMT and AF. Electronic micwscopy of GIST show the presence of interdigitating cell processes, in some areas, synapse-like structure and numerous desmosome-like junctions as well as a few gap junctions and small round neurosecretory granules. There were also abundant intermediate fdaments and thin filaments of actin-type with longitudina condensations （dense bodies） and a spot of undifferentiated mesenchymal cells. Conclusion A certain specific clinical characteristics, pathologic morphology, immunohistochemistry and ultrastructural change appear in IAIMT, NAIMT, AF and GIST. Among them, pathologic morphology and immunohistochemical phenotype are two important means to diagnose and differentiate IMT（IAIMT＆NAIMT） from AF and GIST.