BACKGROUND: In up to 20% of patients with renal cell cancer (RCC) an inflammatory response consisting of low-grade fever, weight loss and an elevated ESR and CRP may occur with modest granulocytosis and thrombocytosis. Clinical and experimental data suggest a pathogenic role for tumour-derived cytokine production, especially interleukin-6. CASE REPORT: A 79-year-old female with RCC presented with low-grade fever, weight loss and overt granulocytosis and thrombocytosis. Radiological examination revealed a right-sided renal tumour. During nephrectomy a gradient between the IL-6 levels in the renal artery and vein was demonstrated, providing direct evidence for in vivo production of IL-6 by the tumour affected kidney, which was confirmed by the demonstration of IL -6 in the tumour cells by immunohistochemical staining and in the supernatant of the homogenised tumour. Cytogenetic examination revealed complex abnormalities including a gain of chromosome 7. In addition we demonstrated production of IL-1alpha, IL-1beta, IL-8 and ICAM-1 in the tumour with systemic elevated levels of IL-6 and IL-8 with secondary increased serum G-CSF and TPO levels. CONCLUSION: We have provided direct evidence for the production of pro-inflammatory cytokines by renal cancer cells in a patient with RCC and a profound inflammatory response, with a central role of IL-6, probably due to a gain of chromosome 7. The extreme granulocytosis and thrombocytosis may have resulted from the secondary systemic production of G-CSF and TPO.
BACKGROUND: In up to 20% of patients with renal cell cancer (RCC) an inflammatory response consisting of low-grade fever, weight loss and an elevated ESR and CRP may occur with modest granulocytosis and thrombocytosis. Clinical and experimental data suggest a pathogenic role for tumour-derived cytokine production, especially interleukin-6. CASE REPORT: A 79-year-old female with RCC presented with low-grade fever, weight loss and overt granulocytosis and thrombocytosis. Radiological examination revealed a right-sided renal tumour. During nephrectomy a gradient between the IL-6 levels in the renal artery and vein was demonstrated, providing direct evidence for in vivo production of IL-6 by the tumour affected kidney, which was confirmed by the demonstration of IL -6 in the tumour cells by immunohistochemical staining and in the supernatant of the homogenised tumour. Cytogenetic examination revealed complex abnormalities including a gain of chromosome 7. In addition we demonstrated production of IL-1alpha, IL-1beta, IL-8 and ICAM-1 in the tumour with systemic elevated levels of IL-6 and IL-8 with secondary increased serum G-CSF and TPO levels. CONCLUSION: We have provided direct evidence for the production of pro-inflammatory cytokines by renal cancer cells in a patient with RCC and a profound inflammatory response, with a central role of IL-6, probably due to a gain of chromosome 7. The extreme granulocytosis and thrombocytosis may have resulted from the secondary systemic production of G-CSF and TPO.
Authors: A J Zurita; R C Gagnon; Y Liu; H T Tran; R A Figlin; T E Hutson; A M D'Amelio; C N Sternberg; L N Pandite; J V Heymach Journal: Br J Cancer Date: 2017-07-06 Impact factor: 7.640