History

Fact Explanation
Haematuria Renal cell carcinoma is the commonest tumor of the kidney in adults. It is more common among men. Haematuria is the commonest presentation of renal cell carcinoma.[1]
Clot colic Renal cell carcinoma may present with gross haematuria.[2] Haematuria may result in clot formation which may obstruct the ureters. The patient develops severe abdominal pain which radiates to the groins. The pain is colicky in nature and mimics a ureteric colic due to ureteric stones.
Abdominal mass/ Abdominal discomfort The tumor mass may be detected by the patient. A large tumor may cause abdominal heaviness.[1]
Lower limb swelling Renal cell carcinoma is characteristically known to grow along the renal vein into the vena cava. This may obstruct lower limb blood flow resulting in edema.[3]
Bone pain/ Bone lump Presentation with features of distant metastases alone is common in renal cell carcinoma. Spread to bone may give rise to severe bone pain. The axial skeleton is most affected – Vertebrae, skull, upper femur, ribs.[4]
Chronic cough/ Haemoptysis/ Dyspnea Due to lung metastasis.[4]
Features of anemia : Palpitations, exertional dyspnea Due to chronic blood loss via the urinary tract.[5]
Hyperviscosity symptoms Presentation with hyperviscosity features such as confusion, spontaneous bleeding through gut or urinary tract, visual disturbances and CNS disturbance is due to ectopic erythropoietin production by the tumor cells.[6] This leads to secondary polycythemia.
Prolonged fever/ Constitutional symptoms Renal cell carcinoma is well known to present with atypical features. Pyrexia of unknown origin is one such presentation.[7] [8]
Presentation due to ectopic hormone production Renal cell carcinoma has being associated with ectopic hormone production – Calcitonin, Renin, Androgens and Sex hormones. The patient may be diagnosed with hypercalcaemia.[9] Features of Cushing’s syndrome such as central obesity, hypertension, acne, hirsutism, easy bruising, osteoporosis etc may occur rarely. Feminization and musculinization are rare presentations.
References
  1. COHEN HERBERT T., MCGOVERN FRANCIS J.. Renal-Cell Carcinoma. N Engl J Med [online] 2005 December, 353(23):2477-2490 [viewed 01 September 2014] Available from: doi:10.1056/NEJMra043172
  2. OTGüN I, ARDA IS, HABERAL N, GüNEY H, HIçSöNMEZ A. Renal cell carcinoma: case report and literature review. J Pediatr Surg [online] 2005 May, 40(5):e13-6 [viewed 05 September 2014] Available from: doi:10.1016/j.jpedsurg.2005.02.013
  3. HEDDERICH GS, O'CONNOR RJ, REID EC, MULDER DS. Caval tumor thrombus complicating renal cell carcinoma: a surgical challenge. Surgery [online] 1987 Oct, 102(4):614-21 [viewed 03 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3660238
  4. FLANIGAN RC, CAMPBELL SC, CLARK JI, PICKEN MM. Metastatic renal cell carcinoma. Curr Treat Options Oncol [online] 2003 Oct, 4(5):385-90 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12941198
  5. KROLL MH, JIJI V, JIJI R. Microcytic hypochromic anemia associated with renal cell carcinoma. South Med J [online] 1984 May, 77(5):635-7 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/6719167
  6. NIELSEN OJ, JESPERSEN FF, HILDEN M. Erythropoietin-induced secondary polycythemia in a patient with a renal cell carcinoma. A case report. APMIS [online] 1988 Aug, 96(8):688-94 [viewed 03 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3046641
  7. CUNHA BA, HAMID N, KROL V, EISENSTEIN L. Fever of unknown origin due to preleukemia/myelodysplastic syndrome: the diagnostic importance of monocytosis with elevated serum ferritin levels. Heart Lung [online] 2006 Jul-Aug, 35(4):277-82 [viewed 03 September 2014] Available from: doi:10.1016/j.hrtlng.2006.02.001
  8. CHANDRANKUNNEL J, CUNHA BA, PETELIN A, KATZ D. Fever of unknown origin (FUO) and a renal mass: renal cell carcinoma, renal tuberculosis, renal malakoplakia, or xanthogranulomatous pyelonephritis? Heart Lung [online] 2012 Nov-Dec, 41(6):606-9 [viewed 03 September 2014] Available from: doi:10.1016/j.hrtlng.2012.03.008
  9. GOLD PJ, FEFER A, THOMPSON JA. Paraneoplastic manifestations of renal cell carcinoma. Semin Urol Oncol [online] 1996 Nov, 14(4):216-22 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8946620

Examination

Fact Explanation
General examination : Anemia Due to chronic blood loss.[1]
General examination : Polycythemia The conjunctiva may appear flushed. Palmer erythema may be present. Erythropoiesis is stimulated due to excess erythropoietin production.[1]
General examination : Lower limb pitting edema Due to vena caval blood flow obstruction from tumor growth.[2]
General examination : Bone tenderness or bone lumps Bone deposits may present as a definite lump if a superficial bone is affected. Renal cell carcinoma is characteristically associated with highly vascular bone deposits which may be soft in consistency or even be pulsatile.[3]
Respiratory system examination : Features of pleural effusion Metastatic deposits in the lung may cause pleural effusions. The affected side shows reduced chest movement, reduced tactile fremitus, stony dull percussion note and reduced breath sounds. Pleural deposits may also lead to effusion formation.[4]
Abdominal examination : Abdominal mass The tumor mass is felt in the lumbar regions of the abdomen.[1] The mass can be felt as a separate mass from the liver and spleen. It will be hard in consistency and have an irregular surface. The mass is usually ballotable. The mobility of the mass may be limited due to fixation to surrounding structures.
Genital examination : Varicocele The left gonadal vein drains directly into the left renal vein. Varicocele, particularly on the left side may develop due to tumor growth along the renal vein.[5]
References
  1. COHEN HERBERT T., MCGOVERN FRANCIS J.. Renal-Cell Carcinoma. N Engl J Med [online] 2005 December, 353(23):2477-2490 [viewed 01 September 2014] Available from: doi:10.1056/NEJMra043172
  2. HEDDERICH GS, O'CONNOR RJ, REID EC, MULDER DS. Caval tumor thrombus complicating renal cell carcinoma: a surgical challenge. Surgery [online] 1987 Oct, 102(4):614-21 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3660238
  3. ÇıNAR MURAT, DERINCEK ALIHAN, KARAN BELGIN, AKPıNAR SERCAN, TUNCAY CENGIZ. Bone pulsating metastasis due to renal cell carcinoma. Musculoskelet Surg [online] December, 94(2):99-102 [viewed 03 September 2014] Available from: doi:10.1007/s12306-010-0072-9
  4. OHNISHI H, ABE M, HAMADA H, YOKOYAMA A, HIRAYAMA T, ITO R, NISHIMURA K, HIGAKI J. Metastatic renal cell carcinoma presenting as multiple pleural tumours. Respirology [online] 2005 Jan, 10(1):128-31 [viewed 03 September 2014] Available from: doi:10.1111/j.1440-1843.2005.00652.x
  5. ESPINOSA BRAVO R, LEMOURT OLIVA M, PéREZ MONZóN AF, PUENTE GUILLEN M, NAVARRO CUTIñO M, SANDOVAL LóPEZ O, DE LA C FUENTES MILERA A. [Renal cell carcinoma and simultaneous left varicocele]. Arch Esp Urol [online] 2003 Jun, 56(5):533-5 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12918314

Differential Diagnoses

Fact Explanation
Bladder carcinoma Transitional cell carcinoma of the bladder is an important cause for painless gross haematuria in elderly patients. Bladder cancer is more common among males. Smoking and occupational exposure to chemicals & toxins have being strongly linked with the pathogenesis of bladder carcinoma. Laborers working with petroleum products, leather, rubber and dye products have an increased risk. Presentation is with gross haematuria and clot retention. Tumor spread is mainly loco-regional and may infiltrate the rectum, prostate and female genital tract. Hematogenous and lymphatic spread is rare. Physical examination is usually normal in early disease. Advanced tumors may present with a palpable mass by abdominal, pelvic or bimanual examination. Diagnosis is confirmed by cystoscopy and CT/MRI of the pelvis.[1]
Benign tumors of the kidney Renal cortical adenoma, Oncocytoma, angioma and angiomyolipoma are common benign tumors of the kidney. Majority are asymptomatic and are diagnosed as an incidental finding. Rarely patients may present with abdominal mass or abdominal pain. Angioma have an increased risk of causing gross haematuria.[2] Wilm's tumor/ Nephroblastoma is a malignant paediatric kidney tumor originating from nephrogenic tissue. The tumor usually presents within the first 5 years with abdominal mass, haematuria and hypertension. The tumor is usually unilateral and is sited at the poles of the kidney. Physical examination will reveal an abdominal mass which is large compared to the body size of the child.[3] Diagnosis can be confirmed by imaging modalities - Ultrasound scan or CT scan.
Polycystic kidney disease (PCKD) Polycystic kidney disease is a late onset autosomal dominant condition. Cysts gradually develop within the renal parenchyma and enlarge over time leading to compression of renal tissue. Common presentations are with haematuria, abdominal mass, renal failure, hypertension and recurrent urinary tract infections. Bilateral ballotable masses can be felt during physical examination. PCKD is associated hepatic cysts and berry aneurysms of the cerebral vessels. Diagnosis can be confirmed by ultrasound scan of the abdomen.[4]
References
  1. KAUFMAN DONALD S, SHIPLEY WILLIAM U, FELDMAN ADAM S. Bladder cancer. The Lancet [online] 2009 July, 374(9685):239-249 [viewed 01 September 2014] Available from: doi:10.1016/S0140-6736(09)60491-8
  2. TAMBOLI P, RO JY, AMIN MB, LIGATO S, AYALA AG. Benign tumors and tumor-like lesions of the adult kidney. Part II: Benign mesenchymal and mixed neoplasms, and tumor-like lesions. Adv Anat Pathol [online] 2000 Jan, 7(1):47-66 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10640201
  3. DAVIDOFF AM. Wilms' tumor. Curr Opin Pediatr [online] 2009 Jun, 21(3):357-64 [viewed 03 September 2014] Available from: doi:10.1097/MOP.0b013e32832b323a
  4. GRANTHAM JARED J.. Autosomal Dominant Polycystic Kidney Disease. N Engl J Med [online] 2008 October, 359(14):1477-1485 [viewed 01 September 2014] Available from: doi:10.1056/NEJMcp0804458

Investigations - for Diagnosis

Fact Explanation
Ultrasound scan of the abdomen USS is usually the first imaging modality when an abdominal mass is detected. Information that can be gathered are the origin of the mass, nature of the mass (solid or cystic) and may help in excluding hepatomegaly/ ascites.[1]
Intravenous urogram (IVU) Traditionally IVU has being the main mode of imaging in patients suspected of renal cell carcinoma. The plain radiograph may show distortion of the renal outline and calcification within the tumor. Subsequent films following dye administration may highlight the distorted renal calyceal system and the tumor may appear as a filling defect. The function of the contra-lateral kidney may also be assessed.[2]
CT scan – abdomen Contrast enhanced CT is considered the investigation of choice in diagnosing and staging renal cell carcinoma due to the high sensitivity and specificity.[3] An abdominal mass detected should be first assessed for benign or malignant properties. Assess loco-regional spread of the tumor, growth along the renal vein and lymphadenopathy for staging of the tumor. Assess the anatomy of the opposite kidney.[4]
MRI Provides similar results to CT scan. Lack of availability and high cost limits its routine use in diagnosing renal cell carcinoma. MRI is accurate in determining local tumor spread, growth along the inferior vena cava and is used as the primary diagnostic investigation in certain settings.[5]
Abdominal X-ray Plain radiographs have limited diagnostic value. Distortion of the renal outline and calcifications within the tumor may be seen.[1]
Urinalysis Red blood cells can be seen.[3]
References
  1. HILTON S. Imaging of renal cell carcinoma. Semin Oncol [online] 2000 Apr, 27(2):150-9 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10768594
  2. NG CS, WOOD CG, SILVERMAN PM, TANNIR NM, TAMBOLI P, SANDLER CM. Renal cell carcinoma: diagnosis, staging, and surveillance. AJR Am J Roentgenol [online] 2008 Oct, 191(4):1220-32 [viewed 01 September 2014] Available from: doi:10.2214/AJR.07.3568
  3. RUSSO P. Renal cell carcinoma: presentation, staging, and surgical treatment. Semin Oncol [online] 2000 Apr, 27(2):160-76 [viewed 03 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10768595
  4. REZNEK RH. CT/MRI in staging renal cell carcinoma Cancer Imaging [online] , 4(Spec No A):S25-S32 [viewed 01 September 2014] Available from: doi:10.1102/1470-7330.2004.0012
  5. BAUMGARTNER BR, CHEZMAR JL. Magnetic resonance imaging of the kidneys and adrenal glands. Semin Ultrasound CT MR [online] 1989 Feb, 10(1):43-62 [viewed 03 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2697325

Investigations - Fitness for Management

Fact Explanation
Full blood count Look for anemia or polycythemia.[1] The hemoglobin level and platelet level are important parameters to consider prior to surgery.
Renal function tests Assess renal functions in preparation of surgery as a baseline investigation.[2]
Serum electrolytes Serum calcium level may be elevated as part of a paraneoplastic syndrome.[3]
Liver function tests : AST/ALT/Serum protein Assess liver function prior to surgery. A low serum protein level is a risk factor for poor wound healing.[4]
Blood group and save Radical nephrectomy carries the risk of severe bleeding if aberrant arteries are not secured.[5] Reserve blood for replacement of blood loss during surgery.
References
  1. MARSHALL FF, WALSH PC. Extrarenal manifestations of renal cell carcinoma. J Urol [online] 1977 Apr, 117(4):439-40 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/850316
  2. SHIRASAKI Y, TSUSHIMA T, SAIKA T, NASU Y, KUMON H. Kidney function after nephrectomy for renal cell carcinoma. Urology [online] 2004 Jul, 64(1):43-7; discussion 48 [viewed 05 September 2014] Available from: doi:10.1016/j.urology.2004.02.039
  3. WALTHER MM, PATEL B, CHOYKE PL, LUBENSKY IA, VOCKE CD, HARRIS C, VENZON D, BURTIS WJ, LINEHAN WM. Hypercalcemia in patients with metastatic renal cell carcinoma: effect of nephrectomy and metabolic evaluation. J Urol [online] 1997 Sep, 158(3 Pt 1):733-9 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9258070
  4. RUSSELL L. The importance of patients' nutritional status in wound healing. Br J Nurs [online] 2001 Mar, 10(6 Suppl):S42, S44-9 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12070399
  5. CHEN XF, ZHOU FJ, HAN H, QIN ZK, LIU ZW, YU SL, LI YH, WANG H, HOU GL. [Transabdominal radical nephrectomy for renal cell carcinoma: an experience on 155 patients]. Ai Zheng [online] 2007 May, 26(5):528-32 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/17672946

Investigations - Screening/Staging

Fact Explanation
Chest X-ray To rule out lung deposits which appear as cannon ball secondaries.[1]
Bone scan To investigate for bone deposits.[1]
Inferior venacavography/ Magnetic resonance angiography Prior to surgery it is important to determine the presence of cancer growth along the renal vein into the inferior vena cava.[2]
References
  1. ISHAK AI, MD PAUZI SH, MASIR N, GOH BS. Multiple Metastatic Deposits in the Head and Neck Region from a Renal Cell Carcinoma Malays J Med Sci [online] 2010, 17(4):71-74 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216188
  2. HORAN JJ, ROBERTSON CN, CHOYKE PL, FRANK JA, MILLER DL, PASS HI, LINEHAN WM. The detection of renal carcinoma extension into the renal vein and inferior vena cava: a prospective comparison of venacavography and magnetic resonance imaging. J Urol [online] 1989 Oct, 142(4):943-7; discussion 947-8 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2795748

Management - General Measures

Fact Explanation
Patient counseling and education The diagnosis of renal cancer should be informed to the patient and relatives sensitively. Provide psychological support during the initial stages. Provide information regarding the natural course, aetiology, complications of the tumor and investigations required. Counsel the patient regarding the stage o f the cancer and treatment options available. Renal cell carcinoma nomograms are used to predict the future progression and accurate prognostication.[1]
Preparation for surgery Optimize pre-existing medical conditions prior to radical surgery. Achieve control of blood pressure and blood glucose level. If present anemia should be corrected. Blood transfusions may be required if the hemoglobin level is very low.[2]
References
  1. LANE BR, KATTAN MW. Predicting outcomes in renal cell carcinoma. Curr Opin Urol [online] 2005 Sep, 15(5):289-97 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16093851
  2. SWEITZER BJ. Preoperative screening, evaluation, and optimization of the patient's medical status before outpatient surgery. Curr Opin Anaesthesiol [online] 2008 Dec, 21(6):711-8 [viewed 05 September 2014] Available from: doi:10.1097/ACO.0b013e3283126cf3

Management - Specific Treatments

Fact Explanation
Treatment options The main treatment options available for renal cell carcinoma are surgery, immunotherapy, chemotherapy and radiotherapy. The most appropriate measure should be selected based on the stage of the tumor, patient fitness and preferences.[1] Majority of patients are diagnosed in the early stages of disease and are suitable for curative surgery. Renal cell carcinoma has good prognosis if the tumor can be excised completely. The survival rate after 5 years is approximately 60%.
Surgery : Nephrectomy Tumors confined to the kidney are treated with nephrectomy and removal of the perinephric fat. Complete removal of even large tumors by radical surgery carries a good prognosis. The kidney can be approached by either an abdominal or loin incision. Achieving control of the renal pedicle is the initial step. The renal artery is identified and ligated. Next the renal vein is identified and palpated along its length to look for tumor growth along the vein. If no growth is detected the renal vein followed by the artery can be ligated and dissected. By careful dissection of the vascular pedicle, the risk of bleeding and tumor cell embolization can be minimized. The ureter is identified and traced downwards and divided. The kidney is then mobilized with its coverings. It is important to exclude the presence of aberrant renal arteries and tumor extension into the inferior vena cava. Cytoreductive nephrectomy is used for treating metastatic renal cell carcinoma. Patients with resectable metastatic deposits are treated with radical nephrectomy and metastasectomy.[2]
Immunotherapy Immunotherapy is being increasingly used for treatment of renal cell carcinoma. Interleukin 2 and interferons are used for this purpose. These agents have also shown to be effective as an adjuvant treatment option to surgery. In combination molecular agents such as everolimus, sorafenib, pazopanib, temsirolimus, axitinib, sunitinib etc can be used. Further evaluation is required to determine its optimum role in the management of renal cell carcinoma.[3]
Chemotherapy Adenocarcinoma of the kidney has poor response to conventional chemotherapeutic agents.[4] Trials have being conducted with gemcitabine, fluorouracil, floxuridine, vinblastine, paclitaxel etc in varies combinations and the response rate has being poor.
Radiotherapy Radiotherapy can be used as a primary treatment option in inoperable disease and as an adjuvant following surgery. It is useful to treat locally infiltrative malignancy where there is tumor infiltration into surrounding structures. Radiotherapy can used to treat bone and brain deposits for palliation of troublesome symptoms.[5]
Renal artery embolization Renal artery embolization is reserved for patients with disseminated malignancy. Further studies are required to determine its role in management of renal cell carcinoma.[6]
Management of widely metastatic disease Immunotherapy is considered the first line treatment for metastatic malignancy. Treatment with agents such as Sunitinib has shown success for treating metastatic renal carcinoma. Further evaluation is required to determine the appropriate regimes and duration of therapy required.[7] Surgery to de-bulk the tumor can be used as a palliative treatment option. Surgery and radiotherapy can be used as a local measure for bone deposits and brain netastases.
References
  1. RUSSO P. Renal cell carcinoma: presentation, staging, and surgical treatment. Semin Oncol [online] 2000 Apr, 27(2):160-76 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10768595
  2. CAMPBELL SC, FLANIGAN RC, CLARK JI. Nephrectomy in metastatic renal cell carcinoma. Curr Treat Options Oncol [online] 2003 Oct, 4(5):363-72 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12941196
  3. ESCUDIER B. Emerging immunotherapies for renal cell carcinoma. Ann Oncol [online] 2012 Sep:viii35-40 [viewed 01 September 2014] Available from: doi:10.1093/annonc/mds261
  4. AMATO RJ. Chemotherapy for renal cell carcinoma. Semin Oncol [online] 2000 Apr, 27(2):177-86 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10768596
  5. ONUFREY V, MOHIUDDIN M. Radiation therapy in the treatment of metastatic renal cell carcinoma. Int J Radiat Oncol Biol Phys [online] 1985 Nov, 11(11):2007-9 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2414257
  6. KALMAN D, VARENHORST E. The role of arterial embolization in renal cell carcinoma. Scand J Urol Nephrol [online] 1999 Jun, 33(3):162-70 [viewed 01 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10452291
  7. KOLLMANNSBERGER C, SOULIERES D, WONG R, SCALERA A, GASPO R, BJARNASON G. Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects. Can Urol Assoc J [online] 2007 Jun, 1(2 Suppl):S41-54 [viewed 05 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18542784