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

Abstract

SUMMARY 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.

Paraneoplastic Syndrome of Angiomatoid Fibrous Histiocytoma May Be Caused by EWSR1-CREB1 Fusion-induced Excessive Interleukin-6 Production

“…8 Cytokine analysis of 2 patients with inflammatory MFH demonstrated elevated serum levels of stem cell factor, granulocyte colony-stimulating factor, IL-6, and tumor necrosis factor in one or both patients. 9 Moreover, cytokine analysis has demonstrated increases in tumor necrosis factor, IL-6, and IL-2, which were produced by leukocytes and tumor cells, in a patient with MFH and severe systemic symptoms. 10 Thus, in our patient we suspected that a paraneoplastic syndrome might have been induced due to some inflammatory-related cytokines.…”

Orthopaedic Case of the Month: A 14-Year-Old Boy With a Medial Thigh Soft Tissue Mass

“…There is no sex predilection [11,19]. Paraneoplastic effects, notably, anemia, weight loss, fever, and chills, secondary to cytokine expression can be the primary presenting symptoms [11,14,19]. AFH is primarily a slow-growing tumor with an indolent course [11,19,20], although more aggressive behaviors have been described [10].…”

Reticular angiomatoid “malignant” fibrous histiocytoma—a case report with cytogenetics and molecular genetic analyses

“…The neoplasm occurs most commonly on the extremities (65%), followed by the trunk (28%) and head and neck (7%), but can also arise in unusual sites, such as lung, bone, and brain [6,8,9,13]. The mediastinum is a particularly unusual site, with only 2 cases reported in the literature [14,15]. To our knowledge, this is the first reported case of a mediastinal angiomatoid malignant fibrous histiocytoma occurring in a ninth-decade patient with confirmatory cytogenetic and molecular studies.…”