==== Front Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.39726 Oncology Hematology Paraneoplastic Hypereosinophilia in Locally Advanced Clear Cell Renal Carcinoma Muacevic Alexander Adler John R Ellez Halil İbrahim 1 Bayram Esra 2 Demirciler Erkut 1 Semiz Hüseyin Salih 3 1 Medical Oncology, Dokuz Eylul University, İzmir, TUR 2 Internal Medicine, Dokuz Eylul University, İzmir, TUR 3 Institute of Oncology, Dokuz Eylül University, İzmir, TUR Halil İbrahim Ellez h.ibrahimellez@gmail.com 30 5 2023 5 2023 15 5 e3972630 5 2023 Copyright © 2023, Ellez et al. 2023 Ellez et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from https://www.cureus.com/articles/160248-paraneoplastic-hypereosinophilia-in-locally-advanced-clear-cell-renal-carcinoma Renal cell carcinoma (RCC) can cause various paraneoplastic syndromes, including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. Hypereosinophilia due to RCC is very rare and is only available as case reports in the literature. A 66-year-old male patient's thoracoabdominal computed tomography (CT) performed showed an increase in size in the right kidney and a heterogeneous contrasting solid mass of approximately 12 cm × 9 cm, which formed lobulations in its contours. The patient was diagnosed with clear-cell renal carcinoma as a result of a kidney biopsy. In the patient with stage cT4NxM0, the leukocyte count was 40.000/µl and the eosinophil count was 20% in biochemical tests. With these results, the patient was evaluated as having severe paraneoplastic hypereosinophilia due to RCC. The patient was started on sunitinib 50 mg for two weeks on/one week off. No symptoms were observed due to hypereosinophilia. In the evaluation made two weeks after the start of the treatment, it was observed that eosinophil levels decreased to normal rates. Paraneoplastic hypereosinophilia due to renal cell carcinoma may indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required for symptomatic patients. cytokin locally advanced tumors renal cell carcinoma (rcc) hyper-eosinophilia paraneoplastic syndromes ==== Body pmcIntroduction Paraneoplastic syndromes occur with the release of peptides, hormones, or cytokines secreted from tumor tissue or due to cross-reactivity between tumor cells and normal tissues [1]. Paraneoplastic syndromes are seen in approximately 40% of renal cell carcinomas (RCC) [2]. The most common paraneoplastic syndrome in RCC is fatigue. Other findings related to hypercalcemia, hypertension, and ectopic hormone secretion are also frequently observed. The most common hematological disorder in RCC is polycythemia due to an increase in hypoxia-inducible factor (HIF). Hypereosinophilia due to RCC is very rare and is only available as case reports in the literature. We will also describe a case describing asymptomatic hypereosinophilia in locally advanced renal cell carcinoma and its condition after sunitinib use. Case presentation A 66-year-old male patient, on thoracoabdominal computed tomography (CT) performed for edema in both legs, weakness, and weight loss, which started in May 2022, showed an increase in size in the right kidney and a heterogeneous contrasting solid mass of approximately 12 cm × 9 cm, which formed lobulations in its contours (Figure 1). On the right, a tumor thrombus is seen in the renal vein and the inferior vena cava. The tumor thrombus reaches up to the atrium in the right part of the heart (Figure 2). Figure 1 Thrombus in the right atrium and vena cava seen on CT (red arrow: thrombus in vena cava; blue arrow: thrombus in right atrium) Figure 2 Mass in the right kidney viewed in the coronal plane on computed tomography (red arrows: renal mass in right kidney) Table 1 Case laboratory parameters at the diagnosis WBC: white blood count, NEU: neutrophil, LYM: lymphocyte, EOS: eosinophil, MONO: monocyte, HGB: hemoglobin, PLT: thrombocyte Laboratuar parameters Value (/µl) Normal range (/µl) WBC 40,000 4000–11,000 NEU 20,000 1500–8000 LYM 7000 1000–4800 EOS 8000 0–500 MONO 5000 0–1000 HGB 8.2 11.2–15.4 PLT 558,000 150,000–400,000 Table 2 Case laboratory parameters at the first month treatment WBC: white blood count, NEU: neutrophil, LYM: lymphocyte, EOS: eosinophil, MONO: monocyte, HGB: hemoglobin, PLT: thrombocyte Laboratuar parameters Value (/µl) Normal range (/µl) WBC 10,300 4000–11,000 NEU 7000 1500–8000 LYM 2000 1000–4800 EOS 300 0–500 MONO 1000 0–1000 HGB 9.4 11.2–15.4 PLT 350,000 150,000–400,000 The patient was diagnosed with clear-cell renal carcinoma as a result of a kidney biopsy performed in June 2022. An intermediate stage was observed according to the Memorial Sloan-Kettering Cancer Center's (MSKCC) risk classification. In the patient with stage cT4NxM0, the leukocyte count was 40,000/µl and the eosinophil count was 20% in biochemical tests. He also had anemia and thrombocytopenia. Bone marrow aspiration and biopsy were performed on the patient with the pre-diagnosis of myeloproliferative disease and paraneoplastic syndrome associated with RCC concurrently with the diagnosis of RCC. BCR/ABL (P210), Janus Kinase 2 (JAK2) V617F mutation, and calreticulin (CALR) mutation were studied from peripheral blood and bone marrow aspiration, and the results were negative. Apart from this, anti-nuclear antibody (ANA) (immunofixation), anti-neutrophil cytoplasmic antibody (ANCA) (immunofixation), and C3 and C4 levels for rheumatologic paraneoplastic syndromes were not significant. It was evaluated by urology as unsuitable for nephrectomy. The bone marrow biopsy result was consistent with hypercellular bone marrow. Dysplastic cells were not observed, and the ratio of the myeloid/erythroid series was increased in favor of the myeloid series (M:E approximately 7-8:1). Eosinophil leukocytes at different stages of maturation were slightly increased in focal areas (Figure 3). The serum tryptase value was 3 ng/ml (normal range: 0-5 ng/ml). No positive results were found in stool or blood tests for allergic infections. FIP1L1/PDGFR receptor mutations were not detected. CD3 and CD4 levels could not be measured because they were not studied in our country. Figure 3 Hypereosinophilia in bone marrow aspiration (BM biopsy, hematoxylin and eosin, original magnification ×400) Red arrow: eosinophil in bone marrow aspiration The patient's thrombus, starting from the inferior vena cava and extending to the right atrium, was not associated with hypereosinophilia. Due to problems in the social security system in Turkey, the patient was started on sunitinib 50 mg for two weeks on/one week off. No symptoms were observed due to hypereosinophilia. In the evaluation made two weeks after the start of the treatment, the leukocyte count was 20,000 µ/l and the eosinophil level was 10%. In the first-month evaluation made in July 2022, it was observed that eosinophil levels decreased to normal rates. With these results and treatment response, the patient was evaluated as having severe paraneoplastic hypereosinophilia due to RCC. Discussion Hypereosinophilia is most commonly seen in allergic diseases or parasitic infections. In addition, hypereosinophilia can be seen in drugs, some pulmonary and gastrointestinal diseases, and malignancies [3]. Mild to moderate hypereosinophilia (500-1500 µ/l) is seen in approximately 5% of all malignancies. In recent years, some molecular disorders that cause hypereosinophilia have been detected by molecular tests. The most common and best-revealing of these are those seen as a result of platelet-derived growth factor receptor (PDGFR) rearrangement [4]. Severe hypereosinophilia due to malignancy (5000 µ/l≤) is frequently seen in bronchial carcinomas, gastrointestinal cancers, prostate cancer, and sarcomas [5-7]. Hypereosinophilia due to malignancy is thought to develop due to cytokines such as interleukin-3 (IL-3), interleukin-5 (IL-5), granulocyte-stimulating factor (G-CSF), and granulocyte-macrophage stimulating factor (GM-CSF) [8]. In this case, we cannot comment on this issue since the cytokine level could not be studied under the conditions in Turkey. In a case report made in Germany in 2012, hypereosinophilia was detected in a patient with metastatic RCC, and G-CSF and GM-CSF levels in the peripheral blood were found to be high and decreased to an undetectable level in the blood with treatment [9]. The cytokine levels measured in hypereosinophilia due to malignancy may not always be significant in the diagnosis and treatment follow-up since it is impossible to determine the source of these cytokines due to the cytokines secreted by the increased eosinophils [10]. It has been shown that hypereosinophilia is observed due to tumor necrosis, and, accordingly, the lymphocyte-tumor relationship clusters around tumor necrosis [11]. In our case, tumor necrosis could not be differentiated by imaging methods. No tumor necrosis was observed in the kidney biopsy. Since the patient did not undergo a nephrectomy, we cannot comment on this. Paraneoplastic eosinophilia is usually mild without any clinical symptoms. However, thromboembolic events and related organ damage can be seen when the eosinophil count is 25,000 µ/l and above. In our case, the eosinophil level was 8000 µ/l at the time of diagnosis. The tumor thrombus had no relationship with eosinophilia. In our case, a significant increase in neutrophils and other series could not be proven because a nephrectomy could not be performed on the patient. However, hypereosinophilia is thought to contribute to this condition. Paraneoplastic eosinophilia is an indicator of a poor prognosis and, generally, of metastatic disease [12]. In our case, the patient is in a locally advanced stage and has been followed up for two months under treatment. A clinical response was observed with treatment. However, the patient cannot reach standard primary care treatment due to treatment payment problems within the scope of social security in our country. Because of this situation, the prognosis is estimated to be poor. Symptomatic paraneoplastic eosinophilia can be treated with drugs that cause decreased production and function of eosinophilic granulocytes, including glucocorticoids, hydroxyurea, and vincristine [13]. Apart from this, with treatment for the disease (surgery, chemotherapy, and radiotherapy), there may be a regression in both the number of eosinophils and the symptoms. In our case, a decrease of approximately 50% was detected in the eosinophil value measured in the second week after the treatment, and it returned to normal levels in the first-month control. During the follow-up, it was observed that the weight loss stopped and the constitutional symptoms decreased significantly. This suggests that eosinophil levels may be associated with treatment response in patients with paraneoplastic eosinophilia. Conclusions In the literature review on paraneoplastic hypereosinophilia in RCC, we were able to detect eight cases in a total of five studies. All patients seen in these studies were in the metastatic stage. In our study, our patient was in a locally advanced stage and received a dramatic response in the first month of treatment. Paraneoplastic hypereosinophilia due to renal cell carcinoma may indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required for symptomatic patients. Human Ethics Consent was obtained or waived by all participants in this study The authors have declared that no competing interests exist. ==== Refs References 1 Paraneoplastic syndromes: an approach to diagnosis and treatment Mayo Clin Proc Pelosof LC Gerber DE 838 854 85 2010 20810794 2 [Paraneoplastic syndrome in renal cell carcinoma] Urologe A Bedke J Buse S Kurosch M Haferkamp A Jäger D Hohenfellner M 45 48 46 2007 17186189 3 Eosinophilia: secondary, clonal and idiopathic Br J Haematol Tefferi A Patnaik MM Pardanani A 468 492 133 2006 16681635 4 Eosinophilia N Engl J Med Rothenberg ME 1592 1600 338 1998 9603798 5 Intratumoral production of interleukin-5 leading to paraneoplastic peripheral eosinophilia in hepatocellular carcinoma J Hepatol Balian A Bonte E Naveau S 355 356 34 2001 11281573 6 Disseminated colon cancer with severe peripheral blood eosinophilia and elevated serum levels of interleukine-2, interleukine-3, interleukine-5, and GM-CSF J Surg Oncol Anagnostopoulos GK Sakorafas GH Kostopoulos P 273 275 89 2005 15726608 7 Hypereosinophilic encephalopathy with multiple cerebral infarctions in neighbouring vascular territories associated with prostate cancer Rev Neurol Rojas GJ Castro DM Vigo-Guevara GL Ferrua M Barriga-Maldonado V Rotta-Escalante R 762 764 43 2006 https://pubmed.ncbi.nlm.nih.gov/17160930/ 17160930 8 Production of granulocyte-macrophage colony-stimulating factor in a patient with metastatic chest wall large cell carcinoma Jpn J Clin Oncol Watanabe M Ono K Ozeki Y Tanaka S Aida S Okuno Y 559 562 28 1998 9793030 9 Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma BMC Urol Todenhöfer T Wirths S von Weyhern CH 7 12 2012 22436420 10 TNF-induced IL-8 and MCP-1 production in the eosinophilic cell line, EOL-1 Mediators Inflamm Goldstein LA Strieter RM Evanoff HL Kunkel SL Lukacs NW 218 223 5 1996 18475720 11 Hypereosinophilia associated with cardiac rhabdomyosarcoma Am J Hematol Lo Re V 3rd Fox KR Ferrari VA Scott CH Kossev PM Kostman JR 64 67 74 2003 12949893 12 Tumour-associated eosinophilia: a review J Clin Pathol Lowe D Jorizzo J Hutt MS 1343 1348 34 1981 https://jcp.bmj.com/content/34/12/1343.info 7035499 13 Eosinophils express a functional receptor for interferon alpha: inhibitory role of interferon alpha on the release of mediators Blood Aldebert D Lamkhioued B Desaint C 2354 2360 87 1996 8630398