Renal cell carcinomas (RCC) (historically also known as hypernephroma or Grawitz tumor) are primary malignant adenocarcinomas derived from the renal tubular epithelium and are the most common malignant renal tumor. They usually occur in 50-70-year old patients and macroscopic hematuria occurs in 60% of the cases.
On imaging, they have a variety of radiographic appearances, from solid and relatively homogeneous to markedly heterogeneous with areas of necrosis, cystic change, and hemorrhage.
Patients are typically 50-70 years of age at presentation 1,2, with a moderate male predilection of 2:1 2.
Renal cell carcinomas are thought to be the 8th most common adult malignancy, representing 2% of all cancers, and account for 80-90% of primary malignant adult renal neoplasms 4,7.
- cigarette smoking 2
- dialysis-related cystic disease 2
- treatment with cyclophosphamide (chemotherapy agent) 14
- hypertension 26
- post-renal transplant 31
Presentation is classically described as the triad of:
- macroscopic hematuria: 60%
- flank pain: 40%
- palpable flank mass: 30-40%
This triad is however only found in 10-15% of patients 1,2, and increasingly the diagnosis is being made on CT for assessment of hematuria alone or as an incidental finding. The majority of cases are sporadic. In contemporary medicine, almost half of all identified renal cell carcinomas are found incidentally on imaging performed for other purposes.
Around 25% of RCC patients will develop a paraneoplastic syndrome 19-21:
- hypercalcemia (20%)
- hypertension (20%)
- polycythemia: from erythropoietin secretion (~5%)
- Stauffer syndrome: hepatic dysfunction not related to metastases
- limbic encephalitis
Renal cell carcinomas arise from tubular epithelium, and encompasses a number of distinct histological varieties, including 4-6:
clear cell renal carcinoma (conventional): 70-80%
- arises from proximal convoluted tubules
- large uniform cells with clear cytoplasm (thus the name and T2 appearance (see below)
- highly vascular
- subtype: clear cell multilocular renal cell carcinoma
papillary renal cell carcinoma: 13-20%
- arises from distal convoluted tubules
- can be multifocal and bilateral
- most common form in dialysis-associated RCC
- type I: sporadic, generally good prognosis 4
- type II: inherited, bilateral and multifocal
chromophobe renal cell carcinoma: 5%
- arises from intercalated cells of collecting ducts
- similar histologically to renal oncocytomas 4
- best prognosis 5
collecting duct renal cell carcinoma (Bellini duct): <1%
- often younger patients
- worst prognosis 5
renal medullary carcinoma: rare
- seen primarily in patients with sickle cell disease or sickle cell trait 4
sarcomatoid renal cell carcinoma (sRCC) 15
- advanced RCC may dedifferentiate into this highly aggressive subtype 15
Macroscopically, renal cell carcinomas are variable in appearance, ranging from solid and relatively homogeneous to markedly heterogeneous with areas of necrosis, cystic change, and hemorrhage 4.
Low grade, smaller tumors typically have a pseudocapsule composed of compressed and ischemic normal renal tissue. The presence of a pseudocapsule is only seen in renal cell carcinomas, renal adenomas, and oncocytomas 8.
Renal cell carcinoma is one of the more common causes of cannonball metastases to the lung.
Histological nuclear grading
The most widely used and most predictive grading system for renal cell cancer is the "Fuhrman nuclear grade" which is on a scale of I-IV, where grade I carries the best prognosis and grade IV the worst.
In some instances RCCs are associated with 2:
- von Hippel-Lindau syndrome: greater tendency for bilateral RCC as well as a presentation at a younger age; clear cell subtype
- Xp11.2 translocation
- familial clear cell cancer
- tuberous sclerosis
- hereditary renal cell cancer syndromes
Main metastatic sites
The most common sites of metastasis are, in order: the lungs, the bones, lymph nodes, the liver, adrenals, and the brain 25.
Although ultrasound is very frequently requested to assess the renal tract, it is not as sensitive or specific as CT or MRI. Furthermore, it struggles to accurately locally stage the disease in many instances 4.
Renal cell carcinoma has a widely varying sonographic appearance. It may appear solid or partially cystic and may be hyper-, iso-, or hypoechogenic to the surrounding renal parenchyma 22. The tumor pseudocapsule can sometimes be visualized with ultrasound as a hypoechoic halo. Although this is a relatively specific sign, it not particularly sensitive (~20%). Use of harmonic scanning has been reported to increase sensitivity to up to 85% 8.
Contrast-enhanced ultrasound 16 may typically show a lesion heterogeneously hypervascular in the arterial phase with early washout in the delayed phase.
CT is frequently used to both diagnose and stage renal cell carcinomas.
On non-contrast CT, the lesions are soft tissue attenuation between 20-70 HU 23,24. Larger lesions frequently have areas of necrosis. Approximately 30% demonstrate some calcification 7.
During the corticomedullary phase of enhancement, 25-70 seconds after administration of contrast, renal cell carcinomas demonstrate variable enhancement, usually less than the normal cortex. Small lesions may enhance a similar amount and can be difficult to detect 7. In general small lesions enhance homogeneously, whereas larger lesions have irregular enhancement due to areas of necrosis. The clear cell subtype may show much stronger enhancement 5.
The corticomedullary phase is also best for assessing vascular anatomy, both for renal vein involvement, and for arterial variation if partial nephrectomy is being contemplated 7. Intraluminal growth into the venous circulation, in particular, the renal vein, occurs in 4-15% 12. The prognosis is significantly worse for those with IVC involvement compared to renal vein involvement alone, making identification on CT important 13.
The nephrogenic phase (80-180 seconds) is the most sensitive phase for detection of abnormal contrast enhancement.
Excretory phase is of less worth, but important in assessing the collecting system anatomy especially if the candidate is a potential candidate for partial nephrectomy.
Follow-up imaging after treatment is typically done with CT, with dual-phase imaging of the abdomen advocated to maximize the detection of solid organ metastases 9. Renal cell carcinoma typically causes hypervascular metastases, best appreciated on arterial phase imaging of the upper abdomen.
MRI is not only excellent at imaging the kidneys and locally staging tumors, but is also able to suggest the likely histology, on the grounds of T2 differences.
- T1: often heterogeneous due to necrosis, hemorrhage, and solid components
T2: appearances depend on histology 6
- clear cell RCC: hyperintense
- papillary RCC: hypointense
- T1 C+ (Gd): often shows prompt arterial enhancement
Tumor pseudo capsule, essentially only seen in low-grade renal cell carcinomas, renal adenomas, and oncocytomas appear as a hypointense rim between the tumor and the adjacent normal renal parenchyma 8.
MRI is also useful for imaging renal vein and IVC tumor thrombus and the rostral extension (important in preoperative planning). The presence of enhancement in the thrombus is able to distinguish between bland and tumor thrombus 4.
The use of diffusion-weighted sequences has been explored in assisting with characterizing indeterminate small renal lesions, which may be inflammatory or malignant in nature, both exhibit restricted diffusion, albeit the restriction is greater with abscess than tumor 10.
Unlike many other malignancies, FDG PET may have limited value in primary renal carcinoma mostly as result of physiological excretion of FDG from the kidneys, which decreases contrast between renal lesions and normal tissue, and may obscure or mask the lesions of the kidneys 32. However certain publications suggest it can effectively be used for postoperative surveillance and restaging as an adjunct when conventional imaging is not conclusive and in some situations such as differentiating benign or bland emboli from tumor emboli 32.
Treatment and prognosis
Treatment of renal cell carcinomas is usually with radical nephrectomy if feasible. However, in elderly patients or those with co-morbidities, and especially those with smaller tumors suggestive of papillary histology (see MRI findings above) then organ-sparing treatment can be entertained. This ranges from adrenal sparing nephrectomy to partial nephrectomy, performed both open or laparoscopically. Additionally, percutaneous radiofrequency or cryoablation (typically under CT guidance), which can be carried out with only local anesthetic and sedation, has been introduced in selected cases 11.
Prognosis can be variable depending on both on histological subtype and stage.
The papillary variant carries the best prognosis (5-year survival of 90%), followed by clear cell (conventional) RCC (5-year survival 70%) while collecting duct subtype carries the worst 6.
As far as the effects of tumor stage (see renal cell carcinoma staging) are concerned, there is a dramatic difference between stage I and IV tumors:
- stage I: 90% 5-year survival
- stage II: 50% 5-year survival
- stage III: 30% 5-year survival
- stage IV: 5% 5-year survival
Approximately one-third of the newly diagnosed cases of the RCC have metastatic disease at the time of initial presentation (synchronous metastases) 30.
- renal tumors
- renal adenoma: should be considered small, early renal cell carcinomas
- renal oncocytoma: particularly for chromophobe type
- usually has a large component of fat
- 4-5% have little or no fat however 6
- renal metastasis
- renal lymphoma
- solitary fibrous tumor of the kidney: rare
- multilocular cystic nephroma: indistinguishable from multilocular clear cell carcinoma
- renal pseudotumors
- direct extension of neighboring tumors
- 1. Federle MP, Jeffrey RB, Woodward PJ et-al. Diagnostic Imaging: Abdomen, Published by Amirsys®. Lippincott Williams & Wilkins. (2009) ISBN:1931884714. Read it at Google Books - Find it at Amazon
- 2. McPhee SJ, Papadakis MA. Current Medical Diagnosis and Treatment 2009. McGraw-Hill Professional. (2008) ISBN:0071591249. Read it at Google Books - Find it at Amazon
- 3. Tanagho EA, McAninch JW. Smith's general urology. McGraw-Hill Medical. (2004) ISBN:0071396489. Read it at Google Books - Find it at Amazon
- 4. Ng CS, Wood CG, Silverman PM et-al. Renal cell carcinoma: diagnosis, staging, and surveillance. AJR Am J Roentgenol. 2008;191 (4): 1220-32. doi:10.2214/AJR.07.3568 - Pubmed citation
- 5. Kim JK, Kim TK, Ahn HJ et-al. Differentiation of subtypes of renal cell carcinoma on helical CT scans. AJR Am J Roentgenol. 2002;178 (6): 1499-506. AJR Am J Roentgenol (full text) - Pubmed citation
- 6. Oliva MR, Glickman JN, Zou KH et-al. Renal cell carcinoma: t1 and t2 signal intensity characteristics of papillary and clear cell types correlated with pathology. AJR Am J Roentgenol. 2009;192 (6): 1524-30. doi:10.2214/AJR.08.1727 - Pubmed citation
- 7. Sheth S, Scatarige JC, Horton KM et-al. Current concepts in the diagnosis and management of renal cell carcinoma: role of multidetector ct and three-dimensional CT. Radiographics. 2001;21 Spec No (suppl 1): S237-54. Radiographics (full text) - Pubmed citation
- 8. Ascenti G, Gaeta M, Magno C et-al. Contrast-enhanced second-harmonic sonography in the detection of pseudocapsule in renal cell carcinoma. AJR Am J Roentgenol. 2004;182 (6): 1525-30. AJR Am J Roentgenol (full text) - Pubmed citation
- 9. Jain Y, Liew S, Taylor MB et-al. Is dual-phase abdominal CT necessary for the optimal detection of metastases from renal cell carcinoma?. Clin Radiol. 2011;66 (11): 1055-9. doi:10.1016/j.crad.2011.06.002 - Pubmed citation
- 10. Goyal A, Sharma R, Bhalla AS et-al. Diffusion-weighted MRI in inflammatory renal lesions: all that glitters is not RCC!. Eur Radiol. 2013;23 (1): 272-9. Eur Radiol (full text) - doi:10.1007/s00330-012-2577-0 - Pubmed citation
- 11. Venkatesan AM, Wood BJ, Gervais DA. Percutaneous ablation in the kidney. Radiology. 2011;261 (2): 375-91. Radiology (full text) - doi:10.1148/radiol.11091207 - Free text at pubmed - Pubmed citation
- 12. Kim HL, Zisman A, Han KR et-al. Prognostic significance of venous thrombus in renal cell carcinoma. Are renal vein and inferior vena cava involvement different?. J. Urol. 2004;171 (2): 588-91. doi:10.1097/01.ju.0000104672.37029.4b - Pubmed citation
- 13. Wagner B, Patard JJ, Méjean A et-al. Prognostic value of renal vein and inferior vena cava involvement in renal cell carcinoma. Eur. Urol. 2009;55 (2): 452-9. doi:10.1016/j.eururo.2008.07.053 - Pubmed citation
- 14. Travis LB, Curtis RE, Glimelius B et-al. Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. J. Natl. Cancer Inst. 1995;87 (7): 524-30. Pubmed citation
- 15. Shuch B, Bratslavsky G, Linehan WM et-al. Sarcomatoid renal cell carcinoma: a comprehensive review of the biology and current treatment strategies. Oncologist. 2012;17 (1): 46-54. doi:10.1634/theoncologist.2011-0227 - Free text at pubmed - Pubmed citation
- 16. Malhi H, Grant EG, Duddalwar V. Contrast-Enhanced Ultrasound of the Liver and Kidney. Radiol. Clin. North Am. 2014;52 (6): 1177-1190. doi:10.1016/j.rcl.2014.07.005 - Pubmed citation
- 17. Aster JC. Robbins Basic Pathology. Saunders. (2012) ISBN:1437717810. Read it at Google Books - Find it at Amazon
- 19. Palapattu GS, Kristo B, Rajfer J. Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell carcinoma. Rev Urol. 2011;4 (4): 163-70. Free text at pubmed - Pubmed citation
- 20. McCardle O. Oncology. Churchill Livingstone. ISBN:0443103747. Read it at Google Books - Find it at Amazon
- 21. Gultekin SH, Rosenfeld MR, Voltz R et-al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000;123 ( Pt 7) (7): 1481-94. doi:10.1093/brain/123.7.1481 - Pubmed citation
- 22. Hertzberg, Middleton. Ultrasound: The Requisites, 3rd Edition, Elsevier. ISBN:0323086187. Read it at Google Books - Find it at Amazon
- 23. O'Connor SD, Silverman SG, Ip IK, Maehara CK, Khorasani R. Simple cyst-appearing renal masses at unenhanced CT: can they be presumed to be benign?. Radiology. 269 (3): 793-800. doi:10.1148/radiol.13122633 - Pubmed
- 24. Jonisch AI, Rubinowitz AN, Mutalik PG, Israel GM. Can high-attenuation renal cysts be differentiated from renal cell carcinoma at unenhanced CT?. Radiology. 243 (2): 445-50. doi:10.1148/radiol.2432060559 - Pubmed
- 25. Bianchi M, Sun M, Jeldres CKasiske B et-al. Cancer After Kidney Transplantation in the United States. (2004) American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. doi:10.1111/j.1600-6143.2004.00450.x - Pubmed . Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. (2012) Annals of oncology : official journal of the European Society for Medical Oncology. 23 (4): 973-80. doi:10.1093/annonc/mdr362 - Pubmed
- 26. Macleod LC, Hotaling JM, Wright JL et-al. Risk factors for renal cell carcinoma in the VITAL study. (2013) The Journal of urology. 190 (5): 1657-61. doi:10.1016/j.juro.2013.04.130 - Pubmed
- 27. Irzi M, Mhanna T, Aynaou M et-al. Renal cell carcinoma revealed by sternal tumefaction: A rare case report and literature review. (2020) Urology case reports. 31: 101137. doi:10.1016/j.eucr.2020.101137 - Pubmed
- 28. Andreas Fottner, Melinda Szalantzy, Lilly Wirthmann, Michael Stähler, Andrea Baur-Melnyk, Volkmar Jansson, Hans Roland Dürr. Bone metastases from renal cell carcinoma: patient survival after surgical treatment. (2010) BMC Musculoskeletal Disorders. 11 (1): 1. doi:10.1186/1471-2474-11-145 - Pubmed
- 29. Raquel Ribeiro Batista, Edson Marchiori, Tatiana Chinem Takayassu, et-al. Sternal metastasis as an initial presentation of renal cell carcinoma: a case report. (2009) Cases Journal. 2 (1): 1. doi:10.4076/1757-1626-2-9045 - Pubmed
- 30. Bianchi M, Sun M, Jeldres C et-al. Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. (2012) Annals of oncology : official journal of the European Society for Medical Oncology. 23 (4): 973-80. doi:10.1093/annonc/mdr362 - Pubmed
- 31. Kasiske B, Kasiske SJ, Kasiske GD et-al. Cancer After Kidney Transplantation in the United States. (2004) American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. doi:10.1111/j.1600-6143.2004.00450.x - Pubmed
- 32. Liu Y. The Place of FDG PET/CT in Renal Cell Carcinoma: Value and Limitations. (2016) Frontiers in oncology. 6: 201. doi:10.3389/fonc.2016.00201 - Pubmed