Interleukin-8 producing malignant fibrous histiocytoma with prolonged fever

Abstract

We present a case of malignant fibrous histiocytoma accompanied by prolonged spiking fevers, which disappeared after tumor resection. Sarcoma with fever as a primary symptom is rare. Furthermore, in this case, fever was closely related to the clinical course of the tumor. In order to detect possible production of febriferous substance(s), we used blood and tumor tissue samples to investigate nine candidate cytokines possibly responsible for the fever. Expression of IL-8 mRNA was detected in preoperative peripheral blood mononuclear cells by RT-PCR. Expressions of IL-6, IL-8, IFN-gamma and TNF-alpha mRNAs were also detected in tumor tissue, while IL-1alpha, IL-1beta, IL-2, IL-4 and COX-2 mRNAs were not. We suspected IL-8 to be a causative factor, and examined its localization by immunohistochemical staining, paraffin sections of tumor tissue stained positive for IL-8. Since infiltrating mononuclear cells were positive for IL-8, this may explain the tumor-associated fever. This case involves intratumoral production of IL-8 as a causative factor, and IL-6, IL-8, IFN-gamma and TNF-alpha cytokine production might have resulted from stimulation with a substance(s) derived from tumor tissue, since the fever disappeared postoperatively. To date the patient is alive and in good health for 7 years and 2 months since the surgery.

Fig. 1

T2-weighted MRI shows a high intensity mass (black and white arrows).

Fig. 2

Atypical cells undergoing mitosis and many infiltrating inflammatory cells in the tumor mass (arrows) (H&E: high power view).

Fig. 3

Ultrastructural examination reveals no myofilaments (×5000).

Fig. 4

RT-PCR findings, obtained with preoperative peripheral blood mononuclear cells, were positive only for IL-8 (243 bp) mRNA.

Fig. 5

Expressions of IL-6 (610 bp), IL-8 (243 bp), IFN-γ (330 bp) and TNF-α (429 bp) mRNAs were detected in a tumor tissue sample. No IL-1α, IL-1β, IL-2, IL-4 or COX-2 mRNA was detected in either sample.

Fig. 6

Immunohistolochemically, paraffin sections of tumor tissue stained positive for IL-8 (immunohistochemical staining: high power view).