Renal cell carcinoma

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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
OMIM 144700 605074
DiseasesDB 11245
MedlinePlus 000516
eMedicine med/2002 
MeSH D002292

Renal cell carcinoma (RCC, also known as hypernephroma) is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer, and the most common type in adults, responsible for approximately 80% of cases.[1]. Initial treatment is most commonly a radical or partial nephrectomy and remains the mainstay of curative treatment.[2] Where the tumour is confined to the renal parenchyma, the 5-year survival rate is 60-70%, but this is lowered considerably where metastases have spread. It is resistant to radiation therapy and chemotherapy, although some cases respond to immunotherapy. Targeted cancer therapies such as sunitinib, temsirolimus, bevacizumab, interferon-alpha, and possibly sorafenib have improved the outlook for RCC (progression-free survival), although they have not yet demonstrated improved survival.

Contents

[edit] Signs and symptoms

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The classic triad is hematuria (blood in the urine), flank pain and an abdominal mass. This is now known, often incorrectly, as the 'too late triad' because by the time patients present with symptoms, their disease is supposedly advanced beyond a curative stage. In addition, whilst this triad is highly suggestive of RCC, it only occurs in around 15% of the sufferers. Today, the majority of renal tumors are asymptomatic and are detected incidentally on imaging, usually for an unrelated cause.

Signs may include:

  • Abnormal urine color (dark, rusty, or brown) due to blood in the urine (found in 60% of cases)
  • Loin pain (found in 40% of cases)
  • Abdominal mass (25% of cases)
  • Malaise, weight loss or anorexia (30% of cases)
  • Polycythemia (5% of cases)
  • Anaemia resulting from depression of erythropoietin (5% of cases)
  • The presenting symptom may be due to metastatic disease, such as a pathologic fracture of the hip due to a metastasis to the bone
  • Varicocele, the enlargement of one testicle, usually on the left (2% of cases[3]). This is due to blockage of the left testicular vein by tumor invasion of the left renal vein; this typically does not occur on the right as the right gonadal vein drains directly into the inferior vena cava.
  • Vision abnormalities
  • Pallor or plethora
  • Hirsutism - Excessive hair growth (females)
  • Constipation
  • Hypertension (high blood pressure) resulting from secretion of renin by the tumour (30% of cases)
  • Elevated calcium levels (Hypercalcemia)
  • Paraneoplastic disease
  • Night Sweats
  • Severe Weight Loss

[edit] Classification

Micrograph of papillary renal cell carcinoma, showing vascular papillae with foam cells. H&E stain.

Recent genetic studies have altered the approaches used in classifying renal cell carcinoma. The following system can be used to classify these tumors:[4][5][6]

Renal epithelial neoplasms have characteristic cytogenetic aberrations that can aid in classification[7]. See also Atlas of Genetics and Cytogenetics in Oncology and Haematology.

  • Clear cell carcinoma: loss of 3p
  • Papillary carcinoma: trisomy 7 and 17
  • Chromophobe carcinoma: hypodiploid with loss of chromosomes 1, 2, 6, 10, 13, 17, 21

Array-based karyotyping can be used to identify characteristic chromosomal aberrations in renal tumors with challenging morphology.[8][9] Array-based karyotyping performs well on paraffin embedded tumors[10] and is amenable to routine clinical use. See also Virtual Karyotype for CLIA certified laboratories offering array-based karyotyping of solid tumors.

Other associated genes include TRC8, OGG1, HNF1A, HNF1B, TFE3, RCCP3, and RCC17.

[edit] Headline text

[edit] Epidemiology

The incidence of renal cell cancer has been rising steadily. Nearly 51190 new diagnoses and 12890 deaths reported in the United States in 2007. It is more common in men than women: the male-to-female ratio is 1.6:1 and has been decreasing over the last decade. Blacks have a slightly higher rate of renal cell cancer than whites. The reasons for this are not clear.[11] Note: in epidemiology, RCC is registered together with renal pelvis carcinoma, which is predominantly transitional cell type.

In Europe the incidence of RCC has doubled in the period from 1975 to 2005.[12] RCC accounted for 3777 deaths in the UK in 2006; male 2372, female 1820.[13][14][15]

[edit] Risk factors

Cigarette smoking and obesity are the strongest risk factors. Hypertension and a family history of the disease are also risk factors.[16]

Dialysis patients with acquired cystic disease of the kidney showed a 30 times greater risk than in the general population for developing RCC. [17]

Exposure to asbestos, polycyclic aromatic hydrocarbons, gasoline has not been shown to be consistently associated with RCC risk.[18]

Patients with certain inherited disorders such as von Hippel-Lindau disease, hereditary papillary renal cancer, a hereditary leiomyoma RCC syndrome and Birt-Hogg-Dubé syndrome, show an enhanced risk of RCC.[19][20][21]

[edit] Pathology

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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.

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. 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.[22]

Secretion of vasoactive substances (e.g. renin) may cause arterial hypertension, and release of erythropoietin may cause erythrocytosis (increased production of red blood cells).

[edit] Radiology

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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 highlight the tumor relative to normal renal parenchyma.[citation needed]

In particular, reliably distinguishing renal cell carcinoma from an oncocytoma (a benign lesion) is not possible using current medical imaging or percutaneous biopsy.[citation needed]

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. 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[23].

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[24].

Percutaneous biopsy can be performed by a radiologist using ultrasound or computed tomography to guide sampling of the tumor for the purpose of diagnosis. 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.

[edit] 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. 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.

[edit] Watchful waiting

Small renal tumors (< 4 cm) are treated increasingly by way of partial nephrectomy.[25][26][27] Most of these small renal masses manifest indolent biological behavior with excellent prognosis.[28] 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%.

[edit] Surgery

Micrograph of embolic material in a kidney removed because of renal cell carcinoma (cancer not shown). H&E stain.

Surgical removal of all or part of the kidney (nephrectomy) is recommended.[2] 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[29], as well as resection of a solitary metastatic lesion. Kidneys are sometimes embolized prior to surgery to minimize blood loss[1] (see image).

Surgery is increasingly performed via laparoscopic techniques. These have the advantage of being less of a burden for the patient and the disease-free survival is comparable to that of open surgery. [2]

[edit] 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. 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). These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible. Therefore, long-term follow-up is crucial to assess completeness of tumour ablation.[30][31]

[edit] 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. 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. Sunitinib (Sutent), sorafenib (Nexavar), and temsirolimus, which are small-molecule inhibitors of proteins, have been approved by the U.S. F.D.A.[32]

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.

A month later, Sunitinib was approved as well. 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. 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. [1][2]

Recently the first Phase III study comparing an RTKI with cytokine therapy was published in the New England Journal of Medicine. This study showed that Sunitinib offered superior efficacy compared with interferon-α. 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. [33]

Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mammalian 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).

Date of Approval: March 30, 2009 Company: Novartis AG Treatment for: Renal Cell Carcinoma Afinitor (everolimus) is an oral once-daily inhibitor of mTOR indicated for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Afinitor approved in US as first treatment for patients with advanced kidney cancer after failure of either sunitinib or sorafenib - March 30, 2009

[edit] Chemotherapy

Most of the currently available cytostatics are ineffective for the treatment of RCC. Their use can not be recommended for the treatment of patients with metastasized RCC.[1] The use of Tyrosine Kinase (TK) inhibitors, such as Sunitinib and Sorafenib, and Temsirolimus are described in a different section

[edit] Vaccine

Cancer vaccines, such as TroVax, have shown promising results in phase 2 trials for treatment of renal cell carcinoma.[34] However, issues of tumor immunosuppression and lack of identified tumor-associated antigens must be addressed before vaccine therapy can be applied successfully in advanced renal cell cancer.[35]

[edit] 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). [36].

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.

[edit] Prognosis

The five year survival rate is around 90-95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%.[citation needed] For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%.[citation needed] 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 %.[citation needed]

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.[citation needed]

[edit] History

Historically, RCC was also known as nephrocellular carcinoma.[37] [Grawitz] first described renal cell carcinoma in 1883.

[edit] See also

[edit] References

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  2. ^ a b c Rini BI, Rathmell WK, Godley P (May 2008). "Renal cell carcinoma". Curr Opin Oncol 20 (3): 300–6. doi:10.1097/CCO.0b013e3282f9782b (inactive 2009-06-26). PMID 18391630. 
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  5. ^ Bodmer D, van den Hurk W, van Groningen JJ, et al. (October 2002). "Understanding familial and non-familial renal cell cancer". Hum. Mol. Genet. 11 (20): 2489–98. doi:10.1093/hmg/11.20.2489. PMID 12351585. http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12351585. 
  6. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. pp. 1016. ISBN 0-7216-0187-1. 
  7. ^ van den Berg E, Storkel S . Kidney: Renal cell carcinoma. Atlas Genet Cytogenet Oncol Haematol. June 2003 .
  8. ^ Hagenkord JM, Parwani AV, Lyons-Weiler MA, et al. (2008). "Virtual karyotyping with SNP microarrays reduces uncertainty in the diagnosis of renal epithelial tumors". Diagn Pathol 3: 44. doi:10.1186/1746-1596-3-44. PMID 18990225. 
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  13. ^ Office for National Statistics, Mortality Statistics: Cause England & Wales, 2006. Vol. DH2 No.32. 2006: TSO.
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  16. ^ Lipworth L, Tarone RE, McLaughlin JK (December 2006). "The epidemiology of renal cell carcinoma". J. Urol. 176 (6 Pt 1): 2353–8. doi:10.1016/j.juro.2006.07.130. PMID 17085101. 
  17. ^ Brennan JF, Stilmant MM, Babayan RK, Siroky MB (April 1991). "Acquired renal cystic disease: implications for the urologist". Br J Urol 67 (4): 342–8. doi:10.1111/j.1464-410X.1991.tb15158.x. PMID 2032071. 
  18. ^ McLaughlin JK, Kidney Cancer, Oxford University Press, Oxford, 2006, pp. 1087–1100.
  19. ^ Lamiell JM, Salazar FG, Hsia YE (January 1989). "von Hippel-Lindau disease affecting 43 members of a single kindred". Medicine (Baltimore) 68 (1): 1–29. PMID 2642584. 
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  30. ^ Mogami T, Harada J, Kishimoto K, Sumida S (April 2007). "Percutaneous MR-guided cryoablation for malignancies, with a focus on renal cell carcinoma". Int. J. Clin. Oncol. 12 (2): 79–84. doi:10.1007/s10147-006-0654-6. PMID 17443274. 
  31. ^ Boss A, Clasen S, Kuczyk M, Schick F, Pereira PL (March 2007). "Image-guided radiofrequency ablation of renal cell carcinoma". Eur Radiol 17 (3): 725–33. doi:10.1007/s00330-006-0415-y. PMID 17021704. 
  32. ^ Michaelson MD, Iliopoulos O, McDermott DF, McGovern FJ, Harisinghani MG, Oliva E (May 2008). "Case records of the Massachusetts General Hospital. Case 17-2008. A 63-year-old man with metastatic renal-cell carcinoma". N Engl J Med. 358 (22): 2389–96. doi:10.1056/NEJMcpc0802449. PMID 18509125. http://content.nejm.org/cgi/content/full/358/22/2389. 
  33. ^ Motzer RJ et al. (2007). "Sunitinib versus interferon alfa in metastatic renal-cell carcinoma". N Engl J Med 356 (2): 115–124. doi:10.1056/NEJMoa065044. PMID 17215529. 
  34. ^ Vaccine for kidney and bowel cancers 'within three years' | Mail Online
  35. ^ Amato RJ (September 2008). "Vaccine therapy for renal cancer". Expert Rev Vaccines 7 (7): 925–35. doi:10.1586/14760584.7.7.925. PMID 18767943. 
  36. ^ <http://www.yourcancertoday.com/news/drnakada.html" title=" Dr. Nakada, on Your Cancer Today
  37. ^ Vasil'eva NN (1975). "[Patho-anatomical characteristics of renal cell cancer]" (in Russian). Arkh. Patol. 37 (10): 11–8. PMID 1225265. 
  38. ^ Valladares Ayerbes M, Aparicio Gallego G, Díaz Prado S, Jiménez Fonseca P, García Campelo R, Antón Aparicio LM (November 2008). "Origin of renal cell carcinomas". Clin Transl Oncol 10 (11): 697–712. doi:10.1007/s12094-008-0276-8. PMID 19015066. 
v • d • e
Tumors: urogenital neoplasia: urinary organs (C64-C68/D30, 188-189/223)
Abdominal
Pelvic
Retroperitoneum
v • d • e
Glandular and epithelial neoplasms (ICD-O 8010-8589)
Epithelium
Papilloma/carcinoma
(8010-8139)
Glands
Renal cell carcinoma · Endometrioid tumor · Renal oncocytoma
Other/multiple
Cystic general
Acinar cell (8550-8559)
Other
Complex epithelial (8560-8589)
Retrieved from "http://en.wikipedia.org/wiki/Renal_cell_carcinoma"
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