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.