G-CSF-producing renal cell carcinoma characterized by IL-8-induced marked neutrophil infiltration to tumor tissue

Abstract

Although G-CSF-producing tumor is well-known, co-production of IL-8 by such tumor and IL-8-induced neutrophil chemotaxis to tumor tissue have not been recognized. A 65-year-old male was diagnosed with papillary renal cell carcinoma accompanied by marked intratumoral neutrophil infiltration after left radical nephrectomy. At presentation, laboratory tests showed a white blood cell count of 47.8×10 9 /l with 84.1% neutrophils and a high CRP of 18.3 mg/dl. Serum concentrations of G-CSF, IL-6, and IL-8 were elevated to 143 pg/ml, 474 pg/ml, and 1,260 pg/ml, respectively. After the operation, the white cell count and serum concentrations of these cytokines returned to normal levels. Real-time quantitative PCR of the tumor tissue revealed high gene expressions of G-CSF and IL-8, which appeared to be the cause of the leukocytosis and intratumoral neutrophil infiltration.

Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma

“…Combined G-CSF and CXCL8 mRNA overexpression by an RCC has recently been reported in one case, 11 and these cytokines, on the protein level, were also overexpressed in our index patient as determined by highly elevated serum levels as well as distinctly positive immunostaining of tumor cells in the patients’ renal biopsy. Not only was neutrophilia prominent in this patient but also monocytosis, basophilia, and slight eosinophilia were found.…”

“…11 Gene expression analysis was not performed in our patients, but upregulated RCC gene transcription could be a mechanism behind their elevated cytokine expressions. A broad stimulation of pro-inflammatory genes such as IL-6, CXCL8, and MCP-1 through nuclear factor-κB signaling is common in cancer, 11,43 but further molecular studies are necessary to explain variability of cytokine expression combinations among individual cases and different tumor types with leukemoid reactions. 2,35 As suggested for bladder cancer, autocrine cytokine signaling loops may become future therapeutic targets even for other cancers with leukemoid reactions.…”

“…High messenger RNA (mRNA) levels of these 2 cytokines in RCC were recently reported from tumor tissue in another case. 11 Our case illustrates that a leukemoid reaction may precede a diagnosis of RCC and might contribute to a rapidly progressive course, mandating diagnostic alertness with a multidisciplinary approach and timely treatment considerations.…”

“…2 Twelve cases of G-CSF-producing RCC with leukemoid reactions have been reported, all from Asian countries. 9–11…”

“…2 Twelve cases of G-CSF-producing RCC with leukemoid reactions have been reported, all from Asian countries. [9][10][11] In this study, serum cytokine profiles of 3 consecutive patients with RCC and leukemoid reactions/paraneoplastic leukocytosis were investigated. All 3 patients had high CXCL8 levels, but only 1 had elevated G-CSF.…”