Inflammatory myofibroblastic tumor - Comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases
Inflammatory myofibroblastic tumor - Comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases
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DOI：
10.1097/01.pas.0000213393.57322.c7
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发表时间：
2007-04-01
影响因子：
5.6
通讯作者：
Fletcher, Christopher D. M.
中科院分区：
文献类型：
--
作者：
Coffin, Cheryl M.;Hornick, Jason L.;Fletcher, Christopher D. M.
炎症性肌纤维母细胞瘤(INIT)是一种具有中等生物学潜能的肿瘤。在这项研究中，我们报告了一组具有组织学异型性和/或临床侵袭性的IMT，分析了临床病理特征、结果以及间变性淋巴瘤激酶(ALK)和其他标记物的免疫组织化学表达，以确定潜在的病理预后特征。对59例具有典型形态(5例)、不典型组织学特征(21例)、局部复发(27例)和(或)转移(6例)的IMT进行了研究。用免疫组织化学方法检测ALKI和其他标志物(Mib-1、c-Myc)。Cyclin D1、caspase 3、Bcl2、Mcl-1、Survivin、p27、C1356、P53、MDM-2)。59例IMTS的确诊年龄从3周到74岁不等(平均13.2岁，第一个十年的中位数为11岁44%)。肿瘤平均大小为7.8 cm。部位：腹部或骨盆占%，肺占22%，头颈部占8%，四肢占5%。术后随访3个月至11年。平均3.6年，中位数3年。33例局部复发，其中13例为多次局部复发，6例同时存在局部复发和远处转移。6例患者死于疾病，5例局部复发，1例远处转移。7例组织学形态演变为细胞多形性、梭形、多角形或圆形。腹部和盆腔IMTS复发率为85%。复发和转移的IMT较大，平均直径分别为8.7和11 cm。胞浆ALK反应阳性率为56%。ALK阴性的IMT发生在年龄较大的患者(平均年龄20.1岁)，并且具有更大的核多形性、非典型性。和非典型的有丝分裂。6例转移性IMT均为ALK阴性。P53在80%的IMTS中有核表达，但在转移的亚群中仅有25%的表达。C-Myc、细胞周期蛋白D1、MDM-2、Mcl-1、bc-2、CD56、p27在各亚组间表达差异无统计学意义。Caspase 3，或Survivin的表达。综上所述，在这59个IMT中。ALK活性与局部复发有关，但与远处转移无关，后者仅限于ALK阴性的皮损。ALK表达缺失总体上与较高的年龄、细微的组织学差异以及死于疾病或远处转移(在较年轻的亚组中)有关。其他的增殖、凋亡和预后标记物与形态或预后没有很好的相关性。因此，ALK活性可能是INIT和腹盆部IMTS复发更频繁的一个有利的预后指标。
Inflammatory myofibroblastic tumor (INIT) is a neoplasm of intermediate biologic potential. In this study, we report a subset of IMTs with histologic atypia and/or clinical aggressiveness that were analyzed for clinicopathologic features, outcome, and immunohistochemical expression of anaplastic lymphoma kinase (ALK) and other markers to identify potential pathologic prognostic features. Fifty-nine IMTs with classic morphology (5 cases), atypical histologic features (21 cases), local recurrence (27 cases), and/or metastasis (6 cases) were studied. Immunohistochemistry was performed for ALKI and other markers (Mib-1, c-Myc. cyclin D1, caspase 3, Bcl-2, Mcl-1, survivin, p27, C1356 p53, MDM-2) using standard techniques. The 59 IMTs had an age at diagnosis ranging from 3 weeks to 74 years (mean 13.2 y, median 11 y 44% in the first decade). The mean tumor size was 7.8 cm. Sites included the abdomen or pelvis in 64%, lung in 22%, head and neck in 8%, and extremities in 5%. The follow-up ranged from 3 months to 11 years. with a mean of 3.6 years and a median of 3 years. Thirty-three patients had local recurrences, including 13 with multiple local recurrences and 6 patients with both local recurrences and distant metastases. Six patients died of disease, 5 with local recurrences, and 1 with distant metastases. Histologic evolution to a more pleomorphic cellular, spindled, polygonal, or round cell morphologic pattern was observed in 7 cases. Abdominal and pelvic IMTs had a recurrence rate of 85%. Recurrent and metastatic IMTs were larger, with mean diameters of 8.7 and 11 cm, respectively. Cytoplasmic ALK reactivity was seen in 56%. ALK-negative IMTs occurred in older patients (mean age 20.1) years and had greater nuclear pleomorphism, atypia.. and atypical mitoses. All 6 metastatic IMTs were ALK-negative. Nuclear expression of p53 was detected in 80% of IMTs overall, but in only 25% of the metastatic subset. There were no significant differences among the subgroups for c-Myc, cyclin D1., MDM-2, Mcl-1 ` Bcl-2, CD56, p27. caspase 3, or survivin expression. In conclusion, among these 59 IMTs. ALK reactivity was associated with local recurrence, but not distant metastasis, which was confined to ALK-negative lesions. Absent ALK expression was associated with a higher age overall, subtle histologic differences, and death from disease or distant metastases (in a younger subset). Other proliferative, apoptotic, and prognostic markers did not correlate well with morphology or outcome. Thus, ALK reactivity may be a favorable prognostic indicator in INIT and abdominopelvic IMTs recur more frequently.