Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma
© Todenhöfer et al; licensee BioMed Central Ltd. 2012
Received: 7 November 2011
Accepted: 21 March 2012
Published: 21 March 2012
Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma.
A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable.
Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.
KeywordsParaneoplastic Hypereosinophilia Leukocytosis Renal cell carcinoma Leukemoid reaction Encephalopathy
Renal cell carcinoma can cause various paraneoplastic syndromes such as hypercalcemia, hypertension and ectopic hormone production . Renal cell carcinoma can also provoke hematologic disturbances such as polycythemia due to an increased production of erythropoietin . Hypereosinophilia has been reported as a paraneoplastic syndrome in several solid and hematological malignancies. We report the first case of severe paraneoplastic hypereosinophilia with cerebral infarction in a patient with metastatic renal cell carcinoma.
Case presentation and management
Several tests were performed to rule out non-cancer causes of hypereosinophilia such as parasitic infections, allergy (including determination of serum mast cell tryptase), hypereosinophilic syndrome due to FIP1L1/PDGFR receptor mutations and aberrant lymphocytes (no CD4-positive CD3-negative lymphocytes characteristic for lymphoproliferative hypereosinophilic syndrome), which remained all negative. Consequently, the patient was submitted to the department of medical oncology and received steroids and cytoreductive therapy with hydroxyurea. Doses of hydroxyurea and prednisone were increased stepwise up to 3 g/day and 100 mg/day, respectively. Moreover, the patient received vincristine once (2 mg) and 2 doses of cytarabine (2 × 150 mg/24 h) as cytoreductive therapy of symptomatic hypereosinophilia (Figure 3).
Administration of antiproliferative drugs for treatment of hypereosinophilia (cytarabine, hydroxyurea and vincristin) and renal cell carcinoma led to significant reduction of leukocytes and eosinophils as well as pancytopenia (Figure 3).
Levels of multiple cytokines at time of excessive leukocytosis (day 44) and after administration of cytoreductive drugs) (day 74) measured by ultiplex cytokine testing (Progen)
175.8 ± 49.3
27.34 ± 8.00
< LOW >
120 ± 120
< HIGH >
16.8 ± 6.59
< LOW >
< LOW >
< LOW >
9.2 ± 1.5
171.1 ± 6,25
25.5 ± 2.94
< LOW >
16.2 ± 4.0
< LOW >
40.2 ± 8.78
189 ± 22
2.4 ± 0.8
426.5 ± 22.4
3.34 ± 0.84
< LOW >
< LOW >
< LOW >
22.8 ± 7
9.56 ± 0.4
173.2 ± 15.04
< LOW >
< LOW >
88.1 ± 14.31
135.1 ± 29.22
34.32 ± 11.46
76.6 ± 6.07
As swallowing difficulties disappeared, according to his will the patient was set on sunitinib 50 mg/d two months after nephrectomy. The patient could be discharged from hospital in reduced general condition 11 weeks after nephrectomy. Due to further disease progression, the patient died 4 months after primary diagnosis.
Paraneolastic eosinophilia is usually mild without any clinical symptoms, but absolute counts may occasionally exceed 25,000/μl and may cause end-organ damage. In a few reported cases of paraneoplastic hypereosinophilia, neurological symptoms occurred due to thromboembolic events with multiple infarctions [23, 24, 14]. Significantly reduced left ventricular function in our patient may be interpreted as end-organ damage as well.
Several studies have shown that paraneoplastic eosinophilia is a poor prognostic sign and indicates metastatic and extensive disease [25, 26]. In a series of 36 cases with paraneoplastic hypereosinophilia, 32 patients had metastatic disease . The patient reported here had a disseminated disease with pulmonary and bone metastases and presented with extraordinary rapid disease progression with poor response to surgical and systemic treatment. In previously reported cases, peripheral eosinophil count correlated with disease activity . We could not find a clear correlation between tumor mass and absolute granulocyte count in the reported patient.
Symptomatic paraneoplastic eosinophilia could be treated with drugs leading to decreased production and function of eosinophilic granulocytes including glucocorticoids, hydroxyurea, vincristine [29, 30]. Furthermore, reduction of tumor mass either by surgery or systemic treatment has been shown to reduce peripheral eosinophilic counts in paraneoplastic hypereosinophilia [11, 28].
In the present case, a combination of drugs directly targeting function and production of granulocytes (prednisone, hydroxyurea, vincristin, cytarabine) and drugs targeting renal carcinoma (sunitinib and temsirolimus) led to a decrease of absolute leukocytes and eosinophils. Neurologic impairment and general status significantly improved with reduced numbers of eosonophilic granulocytes. First line sunitinib had to be temporarily replaced by temsirolimus, as swallowing difficulties did not permit oral therapy. Temsirolimus led to a short-term response (according to RECIST) 2 weeks after initiation. However, rapid progression was observed only 4 weeks after initiation of systemic therapy. As reduction of prednisone led to significant hypereosinophilia-associated reduction of vigilance with prompt improvement after increase of dosage we consider prednisone as a mainstay of the therapeutic approach. Hence, it leads to reduced eosinophilic count and improvement of hypereosinophilia associated symptoms.
This is the first reported case in the literature of excessive paraneoplastic hypereosinophilia in a patient with metastatic renal cell carcinoma. Paraneoplastic hypereosinophilia due to renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.
Written informed consent was obtained from the next of kin of the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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