Renal cell carcinoma Classification and external resources
Histopathologic image of clear cell carcinoma of the kidney. Nephrectomy specimen. Hematoxylin-eosin stain.
ICD-10	C64.
ICD-9	189.0
ICD-O:	M8312/3
DiseasesDB	11245
MedlinePlus	000516
eMedicine	med/2002
MeSH	D002292

"Kidney Cancer" redirects here. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The International Classification of Diseases for Oncology (ICD-O is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems The International Classification of Diseases for Oncology (ICD-O is a domain specific extension of the International Statistical Classification of Diseases and Related Health Problems The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books For Wilm's Tumor/Nephroblastoma, see Wilms tumor. Wilms' tumor or nephroblastoma is a Tumor of the Kidneys that typically occurs in Children rarely in Adults Its common name is

Renal cell carcinoma (RCC) is the most common form of kidney cancer arising from the renal tubule. A nephron (from Greek νεφρός (nephros meaning "kidney" is the basic structural and functional unit of the Kidney. It is the most common type of kidney cancer in adults. The kidneys are complicated organs that have numerous biological roles Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Initial treatment is surgery. Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental It is resistant to radiation therapy and chemotherapy, although some cases respond to immunotherapy. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Immunotherapy in medicine refers to an array of treatment strategies based upon the concept of modulating the Immune system to achieve a prophylactic and/or Targeted cancer therapies such as sunitinib have improved the outlook for RCC, although they have not yet demonstrated improved survival. Sunitinib (marketed as Sutent and previously known as SU11248 is an oral small-molecule multi-targeted Receptor tyrosine kinase (RTK inhibitor that was approved by

Signs and symptoms

The classic triad is hematuria (blood in the urine), flank pain and an abdominal mass. In Medicine, hematuria (or "haematuria" is the presence of Red blood cells (erythrocytes in the Urine. This is now known as the 'too late triad' because by the time patients present with symptoms, their disease is often advanced beyond a curative stage. Today, the majority of renal tumors are asymptomatic and are detected incidentally on imaging, usually for an unrelated cause.

Other signs may include:

• Abnormal urine color (dark, rusty, or brown) due to blood in the urine
• Weight loss, malnourished appearance
• The presenting symptom may be due to metastatic disease, such as a pathologic fracture of the hip due to a metastasis to the bone
• Enlargement of one testicle known as varicocele (usually the left, due to blockage of the left gonadal vein by tumor invasion of the left renal vein -- the right gonadal vein drains directly into the inferior vena cava)
• Vision abnormalities
• Pallor or plethora
• Hirsutism - Excessive hair growth (females)
• Constipation
• High blood pressure
• Elevated calcium levels (Hypercalcemia)

Causes

Renal cell carcinoma affects about three in 10,000 people, resulting in about 31,000 new cases in the US per year. In Medicine, hematuria (or "haematuria" is the presence of Red blood cells (erythrocytes in the Urine. Varicocele is an abnormal enlargement of the Veins in the Scrotum draining the Testicles. In Medicine, gonadal vein refers to the Blood vessel that carrying Blood away from the Gonad (testis ovary toward the Heart. The renal veins are Veins that drain the Kidney. They connect the kidney to the Inferior vena cava. The inferior vena cava (or IVC is the large Vein that carries de-oxygenated Blood from the lower half of the body into the Heart. Hirsutism (from Latin hirsutus = shaggy hairy is defined as excessive and increased Hair growth in women in locations where the occurrence of Terminal Hypercalcaemia (in American English '''Hypercalcemia''' is an elevated calcium level in the Blood. A carcinoma is any Malignant Cancer that arises from epithelial cells. The United States of America —commonly referred to as the Every year, about 12,000 people in the US die from renal cell carcinoma. It is more common in men than women, usually affecting men older than 55.

Kidney cancer both RCC & TCC currently is diagnosed in some 6,600 people in Britain/UK per annum and some 3,600 people who die are recorded as having died of kidney cancer in a given year. The morbidity rate recorded is thought to underestimate the percentage who die of kidney cancer. Often the cause of death recorded on the death certificate may not mention kidney cancer but the subsequent metastases. It is clear that well over 50% of those diagnosed with kidney cancer in Britain will die of the disease or as a result of the disease.

Why the cells become cancerous is not known. A history of smoking greatly increases the risk for developing renal cell carcinoma. Some people may also have inherited an increased risk to develop renal cell carcinoma, and a family history of kidney cancer increases the risk.

Increasingly there is a belief that inhalation of a diversity of chemicals may be causal and it is also noted that there is a steady increase in diagnosis in women. That a disproportionate percentage of those diagnosed with kidney cancer are obese is increasingly believed to be a significant factor.

People with von Hippel-Lindau disease, a hereditary disease that also affects the capillaries of the brain, commonly also develop renal cell carcinoma. Von Hippel-Lindau disease (VHL is a rare inherited Genetic condition involving the abnormal growth of Tumors in parts of the body which are particularly The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain Kidney disorders that require dialysis for treatment also increase the risk for developing renal cell carcinoma. In Medicine, dialysis (from Greek "dialusis" meaning dissolution "dia" meaning through and "lusis" meaning loosening is primarily

Pathology

Renal cell carcinoma

Renal cell carcinoma

Gross examination shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, hemorrhage and scarring. Gross examination or "grossing" is the process by which Pathology specimens are inspected with the naked eye to obtain diagnostic information while being

Light microscopy shows tumor cells forming cords, papillae, tubules or nests, and are atypical, polygonal and large. Because these cells accumulate glycogen and lipids, their cytoplasm appear "clear", lipid-laden, the nuclei remain in the middle of the cells, and the cellular membrane is evident. Glycogen is a Polysaccharide of Glucose (Glc which functions as the secondary short term energy storage in Animal cells Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularized. The tumor compresses the surrounding parenchyma, producing a pseudocapsule. ^[1]

Secretion of vasoactive substances (e. g. renin) may cause arterial hypertension, and release of erythropoietin may cause erythrocytosis (increased production of red blood cells). Renin (pronounced "Ree-nin" or "Rē-nin" (ˈriːnɨn also known as Angiotensinogenase, is a circulating Enzyme that participates in the body's Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Erythropoietin (ɨˌɹɪθɹoʊˈpɔɪɨtɨn /ɨˌɹɪθɹoʊˈpɔɪtən/ or /ɨˌɹiːθɹoʊ-/ or EPO is a Glycoprotein Hormone that controls Polycythemia (or polycythaemia or erythrocytosis) is a condition in which there is a net increase in the total number of Blood cells, primarily Red Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood

Radiology

The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour. It will frequently have an irregular or lobulated margin. 85% of solid renal masses will be RCC. 10% of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat). Following intravenous contrast administration (computed tomography or magnetic resonance imaging), enhancement will be noted, and will increase the conspicuity of the tumor relative to normal renal parenchyma. Computed tomography (CT is a Medical imaging method employing Tomography.

A list of solid renal lesions includes:

• renal cell carcinoma
• metastasis from an extra-renal primary neoplasm
• renal lymphoma
• squamous cell carcinoma
• juxtaglomerular tumor (reninoma)
• transitional cell carcinoma
• angiomyolipoma
• oncocytoma
• Wilm's tumor

In particular, reliably distinguishing renal cell carcinoma from an oncocytoma (a benign lesion) is not possible using current medical imaging or percutaneous biopsy. Transitional cell carcinoma is a type of Cancer that originates in the Kidney, bladder or Ureter. Angiomyolipoma is a benign renal neoplasm previously considered to be a Hamartoma or Choristoma, but now known to be Neoplastic. An oncocytoma is a Kidney or salivary gland Tumor made up of oncocytes, a special kind of cells Presentation An oncocytoma Wilms' tumor or nephroblastoma is a Tumor of the Kidneys that typically occurs in Children rarely in Adults Its common name is

Renal cell carcinoma may also be cystic. As there are several benign cystic renal lesions (simple renal cyst, hemorrhagic renal cyst, multilocular cystic nephroma, polycystic kidney disease), it may occasionally be difficult for the radiologist to differentiate a benign cystic lesion from a malignant one. Radiology is the medical specialty directing Medical imaging technologies to diagnose and treat diseases A classification system for cystic renal lesions that classifies them based specific imaging features into groups that are benign and those that need surgical resection is available^[2]. At diagnosis, 30% of renal cell carcinoma has spread to that kidney's renal vein, and 5-10% has continued on into the inferior vena cava^[3].

Percutaneous biopsy can be performed by a radiologist using ultrasound or computed tomography to guide sampling of the tumor for the purpose of diagnosis. Radiology is the medical specialty directing Medical imaging technologies to diagnose and treat diseases Computed tomography (CT is a Medical imaging method employing Tomography. However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient make it unfavorable from a risk-benefit perspective. This is not completely accurate, there are new experimental treatments.

Treatment

If it is only in the kidneys, which is about 40% of cases, it can be cured roughly 90% of the time with surgery. Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental If it has spread outside of the kidneys, often into the lymph nodes or the main vein of the kidney, then it must be treated with adjunctive therapy, including cytoreductive surgery

Watchful waiting

Small renal tumors represent the majority of tumors that are treated today by way of partial nephrectomy. A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. Nephrectomy is the surgical removal of a Kidney. Indications There are various indications for this procedure such as Renal cell carcinoma, a The average growth of these masses is about 4-5 mm per year, and a significant proportion (up to 40%) of tumors less than 4cm in diameter are benign. More centers of excellence are incorporating needle biopsy to confirm the presence of malignant histology prior to recommending definitive surgical extirpation. In the elderly, patients with co-morbidities and in poor surgical candidates, small renal tumors may be monitored carefully with serial imaging. Most clinicians conservatively follow tumors up to a size threshold between 3-5 cm, beyond which the risk of distant spread (metastases) is about 5%.

Surgery

Surgical removal of all or part of the kidney (nephrectomy) is recommended. Nephrectomy is the surgical removal of a Kidney. Indications There are various indications for this procedure such as Renal cell carcinoma, a This may include removal of the adrenal gland, retroperitoneal lymph nodes, and possibly tissues involved by direct extension (invasion) of the tumor into the surrounding tissues. In cases where the tumor has spread into the renal vein, inferior vena cava, and possibly the right atrium (angioinvasion), this portion of the tumor can be surgically removed, as well. In case of metastases surgical resection of the kidney ("cytoreductive nephrectomy") may improve survival^[4], as well as resection of a solitary metastatic lesion.

Percutaneous therapies

Percutaneous, image-guided therapies, usually managed by radiologists, are being offered to patients with localized tumor, but who are not good candidates for a surgical procedure. In Surgery, percutaneous pertains to any medical procedure where access to inner organs or other tissue is done via needle-puncture of the skin rather than by using an "open" Radiology is the medical specialty directing Medical imaging technologies to diagnose and treat diseases This sort of procedure involves placing a probe through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by computed tomography, ultrasound, or even magnetic resonance imaging guidance, and then destroying the tumor with heat (radiofrequency ablation) or cold (cryotherapy). Computed tomography (CT is a Medical imaging method employing Tomography. Not to be confused with Supersonic. Ultrasound is cyclic Sound pressure with a Frequency greater than the upper Radio Frequency Ablation ( RFA) of Lung kidney breast bone and Liver tumors RFA is performed to cure tumors in lung liver kidney bone and rarely in other Cryotherapy is the use of cold in a variety of modalities to treat a medical condition These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible.

Medications

RCC "elicits an immune response, which occasionally results in dramatic spontaneous remissions. " This has encouraged a strategy of using immunomodulating therapies, such as cancer vaccines and interleukin-2 (IL-2), to reproduce this response. The term cancer vaccine refers to a Vaccine that either prevents infections with cancer-causing viruses or treats existing Cancer. Interleukin-2 ( IL-2) is an Interleukin, a type of Cytokine Immune system signaling molecule that is instrumental in the body's natural response IL-2 has produced "durable remissions" in a small number of patients, but with substantial toxicity. Another strategy is to restore the function of the VHL gene, which is to destroy proteins that promote inappropriate vascularization. Bevacizumab, an antibody to VEGF, has significantly prolonged time to progression, but phase 3 trials have not been published. Bevacizumab (Avastin Genentech/Roche is a Monoclonal antibody against Vascular endothelial growth factor (VEGF Vascular endothelial growth factor ( VEGF) a sub-family of Growth factors, more specifically of Platelet-derived growth factor family of cystine-knot growth Sutinib (Sutent), sorafenib (Nexavar), and temsirolimus, which are small-molecule inhibitors of proteins, have been approved by the U. S. F. D. A. ^[5]

Sorafenib was FDA approved in December 2005 for treatment of advanced renal cell cancer, the first receptor tyrosine kinase (RTK) inhibitor indicated for this use. Sorafenib (Nexavar Bayer) is a drug approved for the treatment of primary kidney cancer (advanced Renal cell carcinoma) and advanced primary liver cancer ( Hepatocellular In Chemistry and Biochemistry, a kinase, alternatively known as a phosphotransferase, is a type of Enzyme that transfers Phosphate

A month later, Sunitinib was approved as well. Sunitinib (marketed as Sutent and previously known as SU11248 is an oral small-molecule multi-targeted Receptor tyrosine kinase (RTK inhibitor that was approved by Sunitinib—an oral, small-molecule, multi-targeted (RTK) inhibitor—and sorafenib both interfere with tumor growth by inhibiting angiogenesis as well as tumor cell proliferation. Angiogenesis is a physiological process involving the growth of new Blood vessels from pre-existing vessels Sunitinib appears to offer greater potency against advanced RCC, perhaps because it inhibits more receptors than sorafenib. However, these agents have not been directly compared against one another in a single trial. [2][3]

Recently the first Phase III study comparing an RTKI with cytokine therapy was published in the New England Journal of Medicine. The New England Journal of Medicine ( N Engl J Med or NEJM) is an English-language Peer-reviewed Medical journal published This study proved that Sunitinib offers superior efficacy compared with interferon-α. Sunitinib (marketed as Sutent and previously known as SU11248 is an oral small-molecule multi-targeted Receptor tyrosine kinase (RTK inhibitor that was approved by Progression-free survival (primary endpoint) was more than doubled. The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline. 28% of sunitinib patients had significant tumor shrinkage compared with only 5% of patients who received interferon-α. Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNa. ^[6] Based on these results, lead investigator Dr. Robert Motzer announced at ASCO 2006 that “Sunitinib is the new reference standard for the first-line treatment of mRCC. ” ^[7]

Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mamallian target of rapamycin) that was shown to prolong overall survival vs. interferon-α in patients with previously untreated metastatic renal cell carcinoma with three or more poor prognostic features. The results of this Phase III randomized study were presented at the 2006 annual meeting of the American Society of Clinical Oncology (www. ASCO. org).

Chemotherapy

Chemotherapy may be used in some cases, but cure is unlikely unless all the cancer can be removed with surgery. Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. The use of Tyrosine Kinase (TK) inhibitors, such as Sunitinib and Sorafenib, and Temsirolimus are described in a different section.

Vaccine

Cancer vaccines, such as TroVax, are in phase 3 trials for treatment of renal cell carcinoma. The term cancer vaccine refers to a Vaccine that either prevents infections with cancer-causing viruses or treats existing Cancer. TroVax is a Cancer vaccine being developed by Oxford BioMedica. ^[8]

Cryoablation

This involves destroying the kidney tumor without surgery, by freezing the tumor. The process can remove 95% of tumors in one treatment and can be tolerated by patients who are not good candidates for surgery (older or weak patients). ^[9].

Prognosis

The outcome varies depending on the size of the tumor, whether it is confined to the kidney or not, and the presence or absence of metastatic spread. The Fuhrman grading, which measures the aggressiveness of the tumor, may also affect survival, though the data is not as strong to support this.

The five year survival rate is around 90-95% for tumors less than 4 cm. The five-year Survival rate is a term used in medicine for estimating the Prognosis of a particular disease For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%. For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%. Fascia (făsh'ē-ə pl fas·ci·ae (făsh'ē-ē adj fascial (făsh'ē-əl (from Latin: a band is the Soft tissue component of If it has metastasized to the lymph nodes, the 5-year survival is around 5 % to 15 %. If it has spread metastatically to other organs, the 5-year survival rate is less than 5 %.

For those that have tumor recurrence after surgery, the prognosis is generally poor. Renal cell carcinoma does not generally respond to chemotherapy or radiation. Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise. Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series.

See also

• Stauffer syndrome

External links

• Photo at: Atlas of Pathology
• www.411cancer.com - General Cancer Information
• Vaccine for kidney cancer
• Offers a massive aggregation of media articles and data collated by patients for patients & Forum for patients and carers
• Renal Cell Carcinoma (translocation associated) — ArQule Clinical Research Study

References