kidney cancer kidney cancer kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. symptoms may include blood in the urine, lump in the abdomen, or back pain. fever, weight loss, and tiredness may also occur. complications can include spread to the lungs or brain. kidney cancerother namesrenal cancermicrograph showing the most common type of kidney cancer (clear cell renal cell carcinoma). h&e stain.specialtyoncology nephrology urologysymptomsblood in the urine, lump in the abdomen, back painusual onsetafter the age of 45typesrenal cell carcinoma (rcc), transitional cell carcinoma (tcc), wilms tumorrisk factorssmoking, certain pain medications, previous bladder cancer, being overweight, high blood pressure, certain chemicals, family historydiagnostic methodtissue biopsytreatmentsurgery, radiation therapy, chemotherapy, immunotherapy, targeted therapyprognosisfive-year survival ~75% (us 2015)frequency403,300 (2018)deaths175,000 the main types of kidney cancer are renal cell cancer (rcc), transitional cell cancer (tcc), and wilms' tumor. rcc makes up approximately 80% of kidney cancers, and tcc accounts for most of the rest. risk factors for rcc and tcc include smoking, certain pain medications, previous bladder cancer, being overweight, high blood pressure, certain chemicals, and a family history. risk factors for wilms' tumor include a family history and certain genetic disorders such as wagr syndrome. diagnosis may be suspected based on symptoms, urine testing, and medical imaging. it is confirmed by tissue biopsy. treatment may include surgery, radiation therapy, chemotherapy, immunotherapy, and targeted therapy. kidney cancer newly affected about 403,300 people and resulted in 175,000 deaths globally in 2018. onset is usually after the age of 45. males are affected more often than females. the overall five-year survival rate is 75% in the united states, 71% in canada, 70% in china, and 60% in europe. for cancers that are confined to the kidney, the five-year survival rate is 93%, if it has spread to the surrounding lymph nodes it is 70%, and if it has spread widely, it is 12%. kidney cancer has been identified as the 13th most common form of cancer, and is responsible for 2% of the world's cancer cases and deaths. the incidence of kidney cancer has continued to increase since 1930. renal cancer is more commonly found in populations of urban areas than rural areas. signs and symptoms early on, kidney masses do not typically cause any symptoms and are undetectable on physical examination. as kidney cancer becomes more advanced it classically results in blood in the urine, flank or back pain, and a mass. other symptoms that are consistent with advanced disease include weight loss, fever, night sweats, palpable swollen lymph nodes in the neck, non-reducing varicocele, bone pain, continuous cough, and bilateral lower leg swelling. the classic triad of visible blood in the urine (hematuria), flank pain and palpable abdominal mass occurs in less than 15% of the cases. rcc may present with signs and symptoms caused by the substances the cancer cell produce (i.e. paraneoplastic syndromes). paraneoplastic syndromes caused by kidney cancer can be broadly classified as endocrine and non-endocrine. endocrine dysfunctions include increase in blood calcium levels (hypercalcemia), high blood pressure (hypertension), increased red bloods (polycythemia), liver dysfunction, milky nipple discharge unrelated normal breast-feeding (galactorrhea), and cushing's syndrome. non-endocrine dysfunctions include deposition of protein in tissue (amyloidosis), decrease in hemoglobin or red blood cells (anemia), disorders of nerves, muscles (neuromyopathies), blood vessels (vasculopathy) and blood clotting mechanisms (coagulopathy). causes factors that increase the risk of kidney cancer include smoking, high blood pressure, obesity, faulty genes, a family history of kidney cancer, having kidney disease that needs dialysis, being infected with hepatitis c, and previous treatment for testicular cancer or cervical cancer. there are also other possible risk factors such as kidney stones being investigated. about 25-30% of kidney cancer is attributed to smoking. smokers have a 1.3 times higher risk of developing kidney cancer compared to non-smokers. moreover, there is a dose-dependent increased risk of cancer development. men who smoke more than 20 cigarettes per day have twice the risk. likewise, women who smoke more than 20 cigarettes per day have 1.5 times the risk of non-smokers. after 10 years of smoking cessation a substantial reduction is seen in the risk of developing kidney cancer. diagnosis due to the increase in ultrasound and ct imaging for nonspecific abdominal complaints, kidney masses are frequently incidentally diagnosed on medical imaging. more than 60% of renal cell carcinoma (the most common type of kidney cancer), are diagnosed incidentally by abdominal imaging for nonspecific abdominal complaints. kidney masses can be classified by the nature of the cells in the growth, or by its appearance on radiography. the term cancer refers to a malignant tumor, which is an uncontrolled growth of abnormal cells. however, kidney masses can be due to growth of normal tissue (benign), inflammatory (a reaction of the immune system), or vascular (cells of the blood vessels). medical imaging since there is a large differential diagnosis for a kidney tumor, the first step is to characterize the mass with medical imaging to assess its likelihood of being benign or malignant. ultrasonography is sometimes used to evaluate a suspected kidney mass, as it can characterize cystic and solid kidney masses without radiation exposure and at relative low cost. radiologically tumors are grouped based on appearance into simple cystic, complex cystic, or solid. the most important differentiating feature of a cancerous and non-cancerous tumor on imaging is enhancement. simple cysts, which are defined by strict criteria are safe to be monitored if the person does not have any symptoms. however, all masses that are not clearly simple cysts should be further evaluated and confirmed by alternate imaging techniques. computed tomography (ct) of the abdomen administered with and without iv contrast is the ideal imaging to diagnose and stage kidney cancer. there is tentative evidence that iodinated contrast agents may cause worsening of kidney function in people with chronic kidney disease (ckd) with a glomerular filtration rate (gfr) less than 45ml/min/1.73m2 and should therefore be given cautiously in this group. abdominal magnetic resonance imaging (mri) is an alternative imaging method that can be used to characterize and stage a kidney mass. it may be suggested if contrast material cannot be given. mri can also evaluate the inferior vena cava if the mass is suspected to extend outside the kidney. since the lungs are the most common organ for kidney cancer to spread to, a chest x-ray or ct scan may be ordered based on the person's risk for metastatic disease. histopathologic classification micrograph of a kidney cancer (chromophobe renal cell carcinoma, oncocytic variant), that may be challenging to differentiate from a benign kidney tumour (renal oncocytoma). h&e stain. micrograph of papillary renal cell carcinoma, a form of kidney cancer. h&e stain. the most common type of kidney malignancy is renal cell carcinoma, which is thought to originate from cells in the proximal convoluted tubule of the nephron. another type of kidney cancer although less common, is transitional cell cancer (tcc) or urothelial carcinoma of the renal pelvis. the renal pelvis is the part of the kidney that collects urine and drains it into a tube called the ureter. the cells that line the renal pelvis are called transitional cells, and are also sometimes called urothelial cells. the transitional/urothelial cells in the renal pelvis are the same type of cells that line the ureter and bladder. for this reason tcc of the renal pelvis is distinct from rcc and is thought to behave more like bladder cancer. other rare types of kidney cancers that can arise from the urothelial cells of the renal pelvis are squamous cell carcinoma and adenocarcinoma. other causes of kidney cancer include the following: sarcoma- for example leiomyosarcoma, liposarcoma, angiosarcoma, clear-cell sarcoma and rhabdomyosarcoma are types of sarcomas that have occurred in the kidney metastatic tumor from distant organ lymphoma wilms tumor- an embryonic tumor that is the most common type of kidney cancer in children carcinoid tumor of the renal pelvis carcinosarcoma inverted urothelial papilloma- was traditionally regarded as a benign growth. however, there may be an increased risk for recurrence and transformation to tcc. in children, wilms tumor is the most common type of kidney cancer. mesoblastic nephroma, although rare, also typically presents in childhood. renal cell carcinoma has been further divided into sub-types based on histological features and genetic abnormalities. the 2004 who classification of the renal tumors of the adults describes these categories: clear cell rcc multilocular clear cell rcc papillary rcc chromophobe rcc carcinoma of the collecting ducts of bellini renal medullary carcinoma xp11 translocation carcinomas carcinoma associated with neuroblastoma mucinous tubular and spindle cell carcinoma mixed epithelial stromal tumor tumors that are considered benign include angiomyolipoma, oncocytoma, reninoma (juxtaglomerular cell tumor), and renal adenoma. immunohistochemistry typical immunohistochemistry for various kidney cancer types. pax8 cd10 caix rcc melanocytic markers vimentin ck7 hmwck cd117 / kit amacr gata3 clear cell rcc + + + (box-like) + - + - - - -/+ - papillary rcc + + +/- + - + + - - + - clear cell papillary rcc + - + (cup-like) +/- - + + +/- - - +/- chromophobe rcc + -/+ - +/- - - + - + - +/- oncocytoma + -/+ - - - - focal - + -/+ - angiomyolipoma - - -/+ - + -/+ - - - - - collecting duct carcinoma + - -/+ - - + +/- + - - - tubulocystic carcinoma + + +/- + - +/- -/+ - - +/- - translocation rcc + +/- -/+ +/- +/- + - - - +/- - mtscc + -/+ -/+ +/- - + + -/+ - +/- - legend: + = usually positive +/- = frequently positive -/+ = occasionally positive - = usually negative laboratory studies people with suspected kidney cancer should also have their kidney function evaluated to help determine treatment options. blood tests to determine kidney function include a comprehensive metabolic panel (cmp), a complete blood count (cbc). in addition, these tests help understand the overall health of the person, which can be affected by metastatic disease (disease that is outside of the kidney). for example, liver or bone involvement could result in abnormal liver enzymes, electrolyte abnormalities, or anemia. a urine sample should also be collected for urinalysis. biopsy the utility of renal mass biopsy (rmb) lies in that it can confirm malignancy with reliability, can direct therapy based on diagnosis, and can provide drainage. once imaging has been completed, renal mass biopsy should be considered if there is a high likelihood that the mass is hematologic, metastatic, inflammatory, or infectious. these types of lesions would not be managed surgically, differing from cancer originating from the kidney. cancer originating outside the kidney and lymphoma are managed systemically. rmb can accurately diagnose malignancy, however, it cannot reliably diagnose benign disease. in other words, if the biopsy shows cancer, there is a 99.8% chance that kidney cancer is present (positive predictive value= 99.8%). a negative biopsy does not rule out a diagnosis of cancer. staging staging is the process that helps determine the extent and spread of the disease. renal cell carcinoma is the only type of kidney cancer that can be staged. the first step of staging follows the tnm staging system proposed by the union international contre le cancer that is widely used among cancers in other organs. the tnm staging system classifies the primary tumor (t), lymph nodes (n) and distant metastasis (m) of the disease. the american joint committee on cancer (ajcc) published a cancer staging manual revision in 2010 that describes the values of tmn for renal cell carcinoma. lymph node involvement is classified as either regional lymph node metastasis (n1), or no involvement (n0). similarly, m1 describes distant metastasis, while m0 describes no distant metastasis. the primary tumor of renal cell carcinoma is categorized in the table below, as according to the ajcc 8th edition cancer staging manual: stagetnmdescription tx, n0, m0 tumor cannot be assessed t0, n0, m0 no evidence of primary tumor i t1, n0, m0 tumor ≤7 cm; limited to kidney t1a, n0, m0 tumor ≤4 cm; limited to kidney t1b, n0, m0 tumor 4-≤7 cm; limited to kidney ii t2, n0, m0 tumor >7 cm; limited to kidney t2a, n0, m0 tumor 7-≤10 cm; limited to kidney t2b, n0, m0 tumor >10 cm; limited to kidney iii