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Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 660

Renal cell carcinoma with paraneoplastic leucocytosis

Department of Medicine, Medical College, Kolkata, West Bengal, India

Date of Web Publication9-Oct-2015

Correspondence Address:
Sanjay Kumar Mandal
Geetanjali Apartment, Flat 3B, 86/13 Brojen Mukherjee Road, Kolkata - 700 034, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.139388

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 > Abstract 

Paraneoplstic leukocytosis, seen in some solid tumors, is due to increased production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 6 and other cytokines by tumor cells. Though its association with malignancy of lung, ovary and bladder is not uncommon, but it is rarely seen with renal cell carcinoma. We are presenting such an association with papillary cell carcinoma of the kidney.

Keywords: Internist′s tumor, paraneoplastic leukocytosis, renal cell carcinoma

How to cite this article:
Mandal SK, Ganguly J, Sil K, Mondal SS, Sardar D, Sarkar P. Renal cell carcinoma with paraneoplastic leucocytosis. J Can Res Ther 2015;11:660

How to cite this URL:
Mandal SK, Ganguly J, Sil K, Mondal SS, Sardar D, Sarkar P. Renal cell carcinoma with paraneoplastic leucocytosis. J Can Res Ther [serial online] 2015 [cited 2020 Jul 10];11:660. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/660/139388

 > Introduction Top

Renal cell carcinomas (RCC) arise within the renal cortex and account for about 90-95% of all primary renal neoplasms. RCC continues to present a diagnostic and therapeutic challenge. [1] The propensity of RCC to manifest with diverse and obscure signs and symptoms has led to its being labeled as the internist's tumor. [2] A number of patients with RCC develop systemic symptoms or paraneoplastic syndromes. Leukocytosis is one such paraneoplastic syndrome. Few case reports are available regarding paraneoplastic leukocytosis in RCC in human being. It is our pleasure to present a case of paraneoplastic leukocytosis in papillary variety of RCC where there was persistent neutrophilic leukocytosis throughout the illness even with subsidence of fever.

 > Case report Top

The present case report is about a 66-year-old male patient who presented with fever and burning sensation during micturition for last 10 days before admission. Fever was intermittent in nature and associated with weakness and anorexia. Patient was known smoker for last 30 years and suffering from chronic obstructive pulmonary disease for last 2 years. He was on bronchodialator and steroid inhaler. He was known hypertensive on angiotensin converting enzyme -inhibitor and suffering from low back pain for last 2 years. Examination revealed mild pallor, few scattered rhonchi on chest auscultation and mild tenderness on deep palpation over right lumbar and iliac region. Investigations done shortly before presenting to us showed hemoglobin (Hb%)-9.4 g/dl, total leukocyte counts (TLC)-25,600/cumm (N89 L8E2M1) platelets-2.9 L/cumm, growth of streptococcus fecalis in urine culture. Left sided enlarged kidney and prostatomegaly were revealed by ultrasonography (USG) of the abdomen and serum prostate specific antigen (PSA) was 0.34 ng/ml. We put the patient on moxifloxacin and amikacin according to urine culture and sensitivity report available to us on admission. Investigations were performed after admission showed Hb%-8.3 g%; TLC-27,000 cumm (N90 L8E1M1); platelets 2.8 L/cumm; erythrocyte sedimentation rate (ESR)-40 mm; mean corpuscular volume-81.6 fl, mean corpuscular hemoglobin-26.3 pg, mean corpuscular hemoglobin concentration-30%; sugar(random)-108 mg/dl; urea-22 mg/dl; creatinine-0.8 mg/dl; post prandial blood sugar-136 mg/dl; Na-122 mEq/L; K4.1 mEq/L; total bilirubin-0.5 (direct-0.2) mg/dl, serum glutamic pyruvic transaminase-52 U/L, serum glutamic oxaloacetic transaminase-56 U/L, alkaline phosphatase-121U/L, total protein-7.2 g/dl, albumin-3.2 g/dl, globulin-4.0 g/dl. Within 3 days of admission, the fever subsided. After 1 week, repeat urine RE/ME showed-pH-5.5, albumin-nil, pus cells-2-3/high power field, red blood cells -nil; urine culture and blood culture showed no growth, but leukocytosis was persistent. USG showed enlarged left kidney ( 10.8 × 7.6 cm) with swollen pelvi-calyceal system. Chest X-ray was within the normal limit. X-ray of the lumbo-sacral spine showed age-related degenerative changes. We also took the opinion from Urology faculties and changed antibiotics to cefoperazone-sulbactam and amikacin according to their opinion.

However after 6 days, the general condition of the patient deteriorated. Patient became drowsy. Peripheral blood picture and basic biochemical parameters were reviewed showing Hb-7.6 g/dl, TLC-25000 (N75 L20 E5 M0), platelet-2.5 L/cumm, ESR-84 mm, urea-25 mg/dl, creatinine-1.0 mg/dl, Na-130.2 mEq/L, K-3.2 mEq/dl. Urine culture showed no growth.

Contrast enhanced computed tomography (CECT) scan of abdomen [Figure 1] showed swollen kidney on both sides. There was decreased attenuating lesion in the left kidney with perinephric involvement and retroperitoneal lymphadenopathy? inflammatory. However, radiologist advised to exclude neoplastic etiology. The patient was referred to urologist, who suggested review of CECT report with respect to contrast enhancement. Enhancement was 69 with contrast, whereas without contrast it was 33. According to urologist's opinion, CT-guided fine needle aspiration cytology (FNAC) was performed from left kidney after taking proper consent. Repeat blood report showed Hb-7.5 g/dl, TLC-40,000/cumm (N80 L16M2E2). Repeat urine and blood culture showed no growth. Patient's condition deteriorated further and he was shifted to critical care unit where he expired the next day. We collected the report of FNAC later and it showed-loss of normal renal tissue architecture with the presence of papillary projections, along with fibrovascular stalk within them [Figure 2]. Few anaplastic cells with grooved neuclei were also seen. Histopathology was suggestive of RCC (papillary variety). Throughout the course of the disease TLC was persistently high [Table 1].
Figure 1: Contrast enhanced computed tomography abdomen showing low attenuating lesion in left kidney

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Figure 2: Computed tomography guided fine needle aspiration cytology from left renal mass showing papillary projections, nuclear grooving

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Table 1: The different parameters throughout the course

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 > Discussion Top

A paraneoplastic syndrome is an abnormality associated with a tumor present at a distant site. It resolves with removal or control of the tumor and returns with its recurrence. [3] RCC is unique among genitourinary malignancy as close to one-third of patients show signs and symptoms of paraneoplastic syndromes ranging from constitutional symptoms to specific metabolic and biochemical abnormalities such as hypercalcemia, polycythemia, non-metastatic hepatic dysfunction, neuromyopathies, amyloidosis, etc. [4] Paraneoplastic leukocytosis is also one of them, reported in few cases in world literature. Some of them have been described in animals. Data in human beings are still a few. A study done by Petterino et al. has reported a case of paraneoplastic marked neutrophilia with moderate monocytosis in a 7-year-old German shepherd dog presenting with intermittent hematuria associated with papillary cell carcinoma of the kidney. [5] In a study by Peeters et al. found spontaneous resolution of paraneoplastic leukocytosis and hypertrophic osteopathy after resection of a renal Transitional cell carcinoma in young Bull Terrier. [6] In both cases, paraneoplastic leukocytosis was attributed to increased production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by tumor cells. [5],[6] Multiple cytokine study before and after chemo-reductive treatment, was done by Todenhφfer et al., [7] in a case of clear cell carcinoma of kidney associated with excessive peripheral eosinophilia leading to cerebral micro-infarcts. Er O et al. reported a case of rapidly relapsing squamous cell carcinoma of renal pelvis presenting with triple paraneoplastic syndrome of leukocytosis, thrombocytosis and hypercalcemia. [8] Another case of neutrophilic leukocytosis associated with sweet syndrome in RCC, has been reported by van Hirtum et al. [9]

In RCC high leukocyte count may be due to the presence of infection in the body or other inflammatory reaction, apart from paraneoplastic leukocytosis. GM-CSF is helpful to document paraneoplastic leucocytosis. However, this investigation is not available in our institution and patient party could not afford to do it outside. In our patient though initially there was evidence of urinary tract infection, but subsesquently after giving higher antibiotics, repeated blood and urine culture showed no evidence of infection. Fever of the patient was also subsided. Persistent leukocytosis can only be explained by paraneoplstic phenomenon. Sudden deterioration of the patient's condition can be explained by tumor emboli, but the exact cause could not be evaluated because patient expired in a short period and the party did not give consent for post mortem study.

Paraneoplstic leukocytosis is seen in some solid tumors such as lung, ovary and bladder. There is only one such report in world literature associated with papillary cell carcinoma of kidney in a dog. [5] Hence, our case is unique in this regard. Take home message from this case is that we should search for internal malignancy whenever there is persistent leukocytosis irrespective of giving higher antibiotics and negative blood culture.

 > References Top

Whang YE, Godley PA. Renal cell carcinoma. Curr Opin Oncol 2003;15:213-6.  Back to cited text no. 1
Kiely JM. Hypernephroma - The internist's tumor. Med Clin North Am 1966;50:1067-83.  Back to cited text no. 2
Sharkey LC, Rosol TJ, Gröne A, Ward H, Steinmeyer C. Production of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor by carcinomas in a dog and a cat with paraneoplastic leukocytosis. J Vet Intern Med 1996;10:405-8.  Back to cited text no. 3
Palapattu GS, Kristo B, Rajfer J. Paraneoplastic syndromes in urologic malignancy: The many faces of renal cell carcinoma. Rev Urol 2002;4:163-70.  Back to cited text no. 4
Petterino C, Luzio E, Baracchini L, Ferrari A, Ratto A. Paraneoplastic leukocytosis in a dog with a renal carcinoma. Vet Clin Pathol 2011;40:89-94.  Back to cited text no. 5
Peeters D, Clercx C, Thiry A, Hamaide A, Snaps F, Henroteaux M, et al. Resolution of paraneoplastic leukocytosis and hypertrophic osteopathy after resection of a renal transitional cell carcinoma producing granulocyte-macrophage colony-stimulating factor in a young Bull Terrier. J Vet Intern Med 2001;15:407-11.  Back to cited text no. 6
Todenhöfer T, Wirths S, von Weyhern CH, Heckl S, Horger M, Hennenlotter J, et al. Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma. BMC Urol 2012;12:7.  Back to cited text no. 7
Er O, Coºkun HS, Altinbaº M, Akgün H, Cetin M, Eser B, et al . Rapidly relapsing squamous cell carcinoma of the renal pelvis associated with paraneoplastic syndromes of leukocytosis, thrombocytosis and hypercalcemia. Urol Int 2001;67:175-7.  Back to cited text no. 8
van Hirtum PV, Prins M, ten Oever J, Nijziel MR, Vreugdenhil G, Dercksen MW. Sweet syndrome in underlying malignancy. Ned Tijdschr Geneeskd 2010;154:A2112.  Back to cited text no. 9


  [Figure 1], [Figure 2]

  [Table 1]


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