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A rare mediastinal tumour presenting with systemic effects due to IL‐6 and tumour necrosis factor (TNF) production

Patients presenting with prolonged systemic illnesses with no specific clinical or serological defining features may be diagnosed as having atypical systemic vasculitides, but often turn out to have occult malignancies. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study we describe a patient presenting after 2 years of a severe systemic illness with a marked acute phase response, due to an occult mediastinal angiomatoid malignant fibrous histiocytoma. Tumour resection was curative. We evaluated in detail the local and systemic production of cytokines induced by this tumour. Blood samples were taken pre‐ and postoperatively for cytokine studies. In vitro production of IL‐2, IL‐2R, IL‐1β, IL‐6 and TNF‐α by cultured monocytes from the patient, as well as plasma cytokine levels, were measured by ELISA. Tumour cytokine production was also evaluated immunocytochemically, and by in situ hybridization with specific cDNA probes. Plasma IL‐2R and IL‐6, and IL‐6 and TNF‐α production by peripheral blood monocytes were markedly elevated before tumour resection, normalizing postoperatively. Most tumour cells and infiltrating lymphocytes stained with antibodies to IL‐6, IL‐6R and TNF‐α, and expressed HLA class II. IL‐6 and TNF‐ α mRNA production in the tumour was confirmed by in situ hybridization studies. We have described the first case of an occult angiomatoid malignant fibrous histiocytoma in the mediastinum. Studies of cytokine expression suggested that chronic TNF, IL‐6, and IL‐2 production by leucocytes and tumour cells in this patient was responsible for the severe systemic illness with which she presented.