Melhem M F, Meisler A I, Saito R, Finley G G, Hockman H R, Koski R A
Department of Pathology, University of Pittsburgh School of Medicine, PA.
Blood. 1993 Oct 1;82(7):2038-44.
Inflammatory malignant fibrous histiocytomas (IMFH) are rare tumors and are frequently associated with leukocytosis. In rare cases, leukemoid reactions were attributed to tumor production of unidentified hematopoietic factors. In this study, we used immunohistochemical techniques to show cytokine immunoreactivity in the malignant cells of two cases of IMFH presenting with leukemoid reactions and compared them with two malignant fibrous histocytomas, noninflammatory type. All four tumors stained positively for stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-4, IL-5, interferon-alpha (IFN-alpha), and insulin-like growth factor-I. Other cytokines detected only in the two IMFH included IL-6, IL-7, IL-8, IFN-gamma, and keratinocyte growth factor. Granulocyte-macrophage-CSF, IL-3, and transforming growth factor-beta staining was present in one of the two IMFH tumors and was not present in the noninflammatory tumors. The immunohistochemical staining was localized to the malignant cells, suggesting deregulated cytokine expression consistent with their monocytic/histocytic origin. Expression of certain cytokines in the IMFH may account for the local inflammatory infiltrate, tumor fibrosis, and the aggressive nature of the malignant cells. We also detected elevated serum levels of SCF, G-CSF, IL-6, and tumor necrosis factor in one or both of the IMFH patients. These latter observations may explain the bone marrow hypercellularity and other paraneoplastic symptoms, including fever, malaise, and weight loss, observed in both patients. Different cytokines present in the two IMFH tumors appear to be responsible for the eosinophilic leukemoid reaction observed in one case and for the granulocytic leukemoid reaction observed in the other patient. They may also be responsible for expansion of the tumor-cell population, fibroblast proliferation, and enhanced secretion of extracellular collagen.
炎性恶性纤维组织细胞瘤（IMFH）是罕见肿瘤，常伴有白细胞增多。在罕见情况下，类白血病反应被归因于肿瘤产生的不明造血因子。在本研究中，我们使用免疫组化技术显示了两例伴有类白血病反应的IMFH恶性细胞中的细胞因子免疫反应性，并将其与两例非炎性型恶性纤维组织细胞瘤进行了比较。所有四个肿瘤对干细胞因子（SCF）、粒细胞集落刺激因子（G-CSF）、白细胞介素-2（IL-2）、IL-4、IL-5、α干扰素（IFN-α）和胰岛素样生长因子-I均呈阳性染色。仅在两例IMFH中检测到的其他细胞因子包括IL-6、IL-7、IL-8、IFN-γ和角质形成细胞生长因子。粒细胞-巨噬细胞集落刺激因子、IL-3和转化生长因子-β染色在两例IMFH肿瘤中的一例中存在，而在非炎性肿瘤中不存在。免疫组化染色定位于恶性细胞，提示细胞因子表达失调与其单核细胞/组织细胞起源一致。IMFH中某些细胞因子的表达可能解释了局部炎性浸润、肿瘤纤维化以及恶性细胞的侵袭性。我们还在一例或两例IMFH患者中检测到血清SCF、G-CSF、IL-6和肿瘤坏死因子水平升高。后述观察结果可能解释了两名患者均观察到的骨髓细胞增多和其他副肿瘤症状，包括发热、不适和体重减轻。两例IMFH肿瘤中存在的不同细胞因子似乎分别导致了一例患者中观察到的嗜酸性类白血病反应和另一例患者中观察到的粒细胞类白血病反应。它们也可能导致肿瘤细胞群体的扩增、成纤维细胞增殖以及细胞外胶原蛋白分泌增加。
