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Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019
| Contributor Information
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Image from the Centers for Disease Control and Prevention (CDC) | Dr. Edwin P. Ewing, Jr.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
The above image demonstrates a gross nephrectomy specimen (bisected) revealing a large renal cell carcinoma (RCC) (arrows).
It was estimated that 65,340 cases of cancer of the kidney and renal pelvis would be diagnosed in the United States in 2018.[1] RCC accounts for approximately 3.8% of all new cancer diagnoses made annually in the United States, with a median age at diagnosis of 64 years.[1]
Most cases of primary renal cancer are RCC, which accounts for approximately 90-95% of all neoplasms arising from the kidney. About 25-30% of patients with RCC are asymptomatic, with the diagnosis being made incidentally.[2]
Established RCC risk factors include smoking and obesity. Among the several hereditary types of RCC that exist, von Hippel-Lindau (VHL) disease is the most common.[3]
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
The most common presentations of RCC (table above) are hematuria, flank pain, weight loss, and flank mass. A varicocele may also develop. Only 10% of patients present with the classic triad of flank pain, hematuria, and flank mass, often indicating a more advanced stage of disease.[2,4]
The signs and symptoms of RCC can be similar to those of many other diseases, making diagnosis potentially difficult. These vague symptoms usually produce a differential diagnosis list that includes more common disease processes (eg, nephrolithiasis, urinary tract infection, renal cysts, or renal abscess). Treatment options must be tailored to the degree of spread; accordingly, early diagnosis is key to insuring the highest likelihood of a good clinical outcome.
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
RCC metastasis to the liver is shown above.
About 33% of patients with RCC develop metastatic disease.[5] The metastatic process frequently involves more than one organ, and although metastasis is often found at the time of diagnosis, about 20-50% of patients develop metastatic disease some time following nephrectomy.[5] Patients with stage IV disease can be risk stratified according to prognostic scoring models, such as the Memorial Sloan Kettering Cancer Center (MSKCC) model.[5,6] The prognosis for "favorable risk" stage IV RCC patients is significantly better, with 2-year survival rates of up to 75%.[6,7] However, for those stage IV patients in the "poor risk" category, median survival time is only 6-12 months, with the 2-year survival rate being 10-20%.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Common locations of RCC metastasis include the lungs, soft tissue, bones, and liver, as well as cutaneous sites and the central nervous system (CNS). Laboratory studies often include a workup for a number of associated paraneoplastic syndromes; RCC is frequently associated with the occurrence of hypercalcemia, nonmetastatic hepatic dysfunction, and erythrocytosis.
After the lungs, the liver is the most common site of visceral metastases. Direct extension into adjacent organs is another mechanism by which RCC may spread. Positron emission tomography (PET) scanning is not useful in the evaluation of primary RCC because the increased radiotracer activity within the collecting system limits sensitivity. However, it may be very useful in the evaluation of metastatic disease.[8]
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Clear cell RCC is the most common histologic subtype, representing approximately 75% of cases.[2] On histology, the tumor is characterized by unusually clear cells with a cytoplasm rich in lipids and glycogen (shown). The tumor is thought to arise from the proximal convoluted tubules within the renal cortex. Clear cell RCC has a higher propensity for vascular, rather than lymphatic, invasion. Compared with other histologic subtypes, clear cell RCC is also more likely to be symptomatic, with patients most commonly experiencing anemia and hepatic dysfunction. The other RCC subtypes (including chromophilic, chromophobic, oncocytic, and collecting duct) are much less common.
Image from Wikimedia Commons | James Heilman, MD.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
A 64-year-old man presents with complaints of left flank pain, which he rates as a 4 out of 10, and associated gross hematuria for the past week. He has not felt any abdominal, back, or chest pain. He has had no changes in urinary frequency and has not experienced dysuria. He has not sustained trauma, has no surgical history, and denies any prior history of renal calculi. He has no other physical complaints. He states that he does not use alcohol or tobacco. His prescribed medications include atorvastatin, atenolol, and aspirin. His vital signs are unremarkable. He provides the urine specimen shown.
What conditions should the differential diagnosis include?
Image from Wikimedia Commons | Bobjgalindo.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Answer: Hematuria with flank pain in a 64-year-old patient should prompt a clinician to consider such diagnoses as urolithiasis, cystitis, pyelonephritis, tumor, and abdominal aortic dissection, to name a few.
The patient's physical examination revealed only mild left-side abdominal tenderness and left costovertebral tenderness. No abdominal palpable masses or audible bruits were appreciated. The urogenital examination yielded unremarkable findings. Examination of the urinary sediment (shown) revealed more than 50 red blood cells (RBCs) per high-power field (HPF), with no evidence of infection or crystals. Routine laboratory studies, including a complete blood count, coagulation studies, and a complete metabolic chemistry panel with liver function tests, yielded normal results. The patient's flank pain improved only slightly with pain medication.
What would be an appropriate next step toward the diagnosis?
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Answer: An abdominal-pelvic computed tomography (CT) scan.
This contrast-enhanced CT scan reveals a left renal mass (arrow). Detection of clinical stage I (<7.0 cm), solid, enhancing renal masses has increased in frequency and is now a common clinical scenario for the practicing urologist. The biology of these tumors is heterogeneous, and multiple management options are available, ranging from active surveillance to radical nephrectomy. Approximately 20% of clinical stage I renal masses are benign, and only 20-30% of malignant tumors in this size range demonstrate potentially aggressive features, with substantial variance according to patient age, gender, and tumor size.[9,10]
Images courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Contrast-enhanced CT scanning is the imaging modality of choice for the evaluation of RCC. Imaging diagnosis of RCC via CT scanning requires identification of enhancement. Specialized renal protocol CT scans that are typically performed include at least a noncontrast phase and a postcontrast nephrographic phase, although often a delayed excretory phase is also included. The above two CT images show a precontrast Hounsfield unit (HU) value of 45.7 (left) and a postcontrast HU value of 101.7 (right). A difference of more than 10-20 HU (often, 15 HU) between precontrast and postcontrast values is typically considered to be the threshold for indicating enhancement; therefore, this is an enhancing lesion.
RCC can also present as a predominantly cystic mass. The Bosniak classification system was devised to differentiate simple cysts from those that require follow-up imaging or tissue diagnosis.[11]
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Magnetic resonance imaging (MRI) provides an alternative, radiation-free modality for the diagnosis of RCC. As with CT scanning, the goal is to evaluate for enhancement, although strict numerical criteria do not exist for MRI, as they do for CT scanning. On T1-weighted images, RCCs appear isointense or hypointense to the remainder of the kidney. On T2-weighted images, RCCs appear hyperintense (arrows), although the associated hemorrhage and necrosis can make them very heterogeneous. A particularly helpful feature of MRI is its multiplanar capacity when isotropic voxels are obtained.
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
RCC is sometimes incidentally identified on ultrasonography (US) in patients undergoing imaging during workup, due to flank pain, for potential hydronephrosis. Unfortunately, RCC can be protean in appearance; it may show up as hyperechoic, hypoechoic, or isoechoic, depending on the size and degree of necrosis. However, US can usually differentiate solid masses from cysts, thereby providing a cost-effective and radiation-free imaging option. US can also be performed to evaluate for internal vascularity, which can help to differentiate bland from tumoral thrombus.
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
This CT scan from a patient on long-term hemodialysis shows cystic replacement of the kidneys. An RCC has developed in the right kidney and is invading and expanding the inferior vena cava (arrow).
Patients undergoing long-term renal dialysis are at increased risk for acquired renal cystic disease, which in turn predisposes them to RCC.[12] Unfortunately, as the kidneys become progressively replaced by cysts, it can be extremely difficult to differentiate complex cysts from RCC. Any enhancing components must be treated with a high index of suspicion.
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
A horseshoe kidney is a congenital anomaly in which the kidneys are fused at the lower pole (shown). These kidneys have highly variant arterial and venous anatomy. Patients are at risk for traumatic injury, obstruction, nephrolithiasis, Wilms tumor, and, in adults, RCC (arrow). One proposed explanation for the increased incidence of RCC is the constant stasis and resulting low level of chronic inflammation associated with a horseshoe kidney. Treatment can be complicated owing to the variant renal and vascular anatomy.
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Renal oncocytomas are benign renal tumors that arise from the collecting ducts, typically in adults in their seventh or eighth decade of life. They are typically detected incidentally. On imaging, the classic appearance is a solid mass with a central stellate scar (arrow). Unfortunately, these benign tumors cannot be differentiated from RCC by means of imaging alone. Moreover, core-needle biopsy often yields a sample that is indistinguishable from RCC. As a result, most patients with a renal oncocytoma undergo surgical resection before the diagnosis can be made. Fortunately, they do not require any additional treatment, as patients with RCC do.
Image from Wikimedia Commons | Hellerhoff.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Renal angiomyolipomas (AMLs) are the most common benign tumors of the kidney and thus are the lesions most commonly mistaken for RCC. They are usually asymptomatic and are frequently found incidentally on imaging. (AML is also sometimes mistaken for the rare benign lesion adrenal myelolipoma.) Identification of fat on a well-circumscribed lesion (arrows) on either CT (shown) or MRI scan is pathognomonic for renal AML and excludes RCC. Patients with multiple AMLs are more likely to have tuberous sclerosis, although most AMLs are incidental. Tumors smaller than 4 cm can be managed conservatively; larger tumors are often excised because of the risk of hemorrhage.[13]
Image courtesy of Stephen Thomas, MD, Department of Radiology, University of Chicago.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
A 55-year-old man undergoes contrast-enhanced CT scanning, which shows a left renal mass.
On the basis of the imaging features, what is the Bosniak classification of this mass? Is any follow-up required?
Image courtesy of Stephen Thomas, MD, Department of Radiology, University of Chicago.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Answer: The lesion has a nonenhancing, thin hairline septum (arrow) and would be classified as a Bosniak II cyst. A Bosniak II cyst is a lesion with some abnormal features. These can be thin hairline septa that do not enhance or thin calcifications in the septa or wall. The risk of malignancy in a Bosniak II cyst is nearly zero, and no suspicious features are apparent. Therefore, follow-up is not necessary in this case.
Image courtesy of Stephen Thomas, MD, Department of Radiology, University of Chicago.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
A 68-year-old woman undergoes contrast-enhanced CT scanning, which shows a left renal lesion. On the basis of the imaging features, how would this lesion be classified?
Image courtesy of Stephen Thomas, MD, Department of Radiology, University of Chicago.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Answer: The left renal lesion is a slightly complex cystic lesion that would be categorized as Bosniak IIF.
There are several thin septa (arrows) but no solid nodules or masses. The right renal lesion is simple, without any enhancing septa, and would be a Bosniak I lesion. The left lesion cannot be fully characterized as benign, because there are some complex features; however, it does not have enough features to be malignant and thus would be placed in an intermediate category, Bosniak IIF. Between 5% and 25% of lesions in this category will prove to be malignant. Bosniak IIF lesions include cystic lesions with multiple thin septa, septa thicker than hairline, a slightly thick cyst wall, or calcification, which may be thick; they also include totally intrarenal, nonenhancing, high-attenuation cysts of 3 cm or larger.
Image courtesy of Stephen Thomas, MD, Department of Radiology, University of Chicago.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
An axial, contrast-enhanced CT scan is obtained in a 72-year-old woman being evaluated for a mass in the left kidney.
Does the lesion show any features that would make it suspicious? What is its Bosniak classification? Is any follow-up required?
Image courtesy of Stephen Thomas, MD, Department of Radiology, University of Chicago.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Answer: This complex left cystic renal mass has enhancing, thick internal septa (arrow), which make it a suspicious lesion. Bosniak III lesions have features that include uniform wall thickening or mural nodules, thick or irregular calcification, and thick septa that enhance. About 50% of these lesions are malignant, and resection would be indicated.
Image courtesy of Stephen Thomas, MD, Department of Radiology, University of Chicago.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
A contrast-enhanced CT scan obtained in a 30-year-old woman with a complaint of abdominal pain shows a right renal mass.
What is the Bosniak classification of this mass? What follow-up would be indicated?
Image courtesy of Stephen Thomas, MD, Department of Radiology, University of Chicago.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
Answer: This right renal mass has solid, enhancing components (arrow) and meets the criteria for a Bosniak IV lesion. Bosniak IV lesions have all the characteristics of Bosniak III lesions and are clearly malignant cystic masses. They also contain enhancing soft-tissue components adjacent to, but independent of, the wall or septa. Bosniak IV lesions carry a greater than 90% risk of malignancy and are treated surgically. The lesion shown was resected and found to be a cystic RCC.
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
The above image shows a gross pathology specimen of a radical nephrectomy (bisected), with a localized RCC seen in the upper pole (arrows).
Treatment options for RCC are complicated and are guided by the probability of cure, which is directly related to the disease stage. The management of stage IV disease has significantly evolved in recent times. Surgery may have a role in select patients even in the setting of metastatic disease. For tumors localized to the kidney, partial or complete nephrectomy is recommended.[14] Cytoreductive therapy may be employed for patients with surgically resectable disease, before systemic therapy is initiated. For previously untreated patients with clear cell RCC, targeted therapies, such as with the antiangiogenic drug sunitinib, may be utilized.[14,15] Patients who have advanced-stage disease or are unable to tolerate surgical therapy may be eligible only for palliation via radiation therapy or renal artery embolization.
Image courtesy of Medscape.
Recognizing Renal Cell Carcinoma
Stephen Thomas, MD; Lars Grimm, MD, MHS; Mark P Brady, PA-C | March 28, 2019 | Contributor Information
The above image is a gross pathology specimen of clear cell RCC demonstrating central necrosis after treatment with the antiangiogenic agent sunitinib.
Tumor size is one of the most important factors influencing survival in RCC. Whereas the 5-year survival rate is 77% for tumors smaller than 4 cm, it is 54% for tumors 4-7 cm in size and 46% for tumors larger than 7 cm.[16] These statistics emphasize the importance of diagnosing RCC early. Early diagnosis requires that clinicians remain vigilant, especially in patients with risk factors. Fortunately, newer, targeted therapies, such as sunitinib and pazopanib, are steadily improving the median survival rate in RCC, especially for patients with late-stage disease.
In addition to the common ragweed, other pollinating weeds (eg, Russian thistle), trees, grasses, and molds can cause seasonal allergies. Learn about the different seasonal allergens and their current treatments.Slideshows, March 2019
Renal cell carcinoma is the most common type of kidney cancer in adults. It accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. Renal cell carcinoma may remain clinically occult for most of its course. Only 10% of patients present with the classic triad of flank pain, hematuria, and flank mass.Diseases/Conditions, February 2019
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Contributor Information
Authors
Stephen Thomas, MD
Assistant Professor of Radiology
University of Chicago Medical Center
Chicago, IL
Disclosure: Stephen Thomas, MD, has disclosed no relevant financial relationships.
Lars Grimm, MD, MHS
Assistant Professor
Department of Diagnostic Radiology
Duke University Medical Center
Durham, NC
Disclosure: Lars Grimm, MD, MHS, has disclosed no relevant financial relationships.
Mark P Brady, PA-C
Adjunct Faculty and Preceptor
Physician Assistant Program
University of New England
Physician Assistant
Department of Emergency Medicine
Cambridge Hospital, Cambridge Health Alliance
Cambridge, MA
Disclosure: Mark P Brady, PA-C, has disclosed no relevant financial relationships.
Reviewer
Ali Ahmad, MD, FACS
Clinical Assistant Professor of Surgery
University of Kansas School of Medicine-Wichita
Wichita, KS
Disclosure: Ali Ahmad, MD, FACS, has disclosed no relevant financial relationships.
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References
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Lane BR, Babineau D, Kattan MW, et al. A preoperative prognostic nomogram for solid enhancing renal tumors 7 cm or less amenable to partial nephrectomy. J Urol. 2007 Aug;178(2):429-34. PMID: 17561141
Muglia VF, Westphalen AC. Bosniak classification for complex renal cysts: history and critical analysis. Radiol Bras. 2014 Nov-Dec;47(6):368-73. PMID: 25741120 [Full Text].
Kojima Y, Takahara S, Miyake O, Nonomura N, Morimoto A, Mori H. Renal cell carcinoma in dialysis patients: a single center experience. Int J Urol. 2006 Aug;13(8):1045-8. PMID: 16903927.
Yamakado K, Tanaka N, Nakagawa T, Kobayashi S, Yanagawa M, Takeda K. Renal angiomyolipoma: relationships between tumor size, aneurysm formation, and rupture. Radiology. 2002 Oct;225(1):78-82. PMID: 12354988
Tsuchiya N, Yuasa T, Maita S, et al. Organ-specific and tumor-size-dependent responses to sunitinib in clear cell renal cell carcinoma. BMC Urol. 2014 Mar 11;14:26. PMID: 24612599 [Full Text].
Jonasch E, Matin SF, Pagliaro LC, Wood CG, Tannir NM. Renal cell carcinoma. In: Kantarjian HM, Wolff RA, Koller CA, eds. The MD Anderson Manual of Medical Oncology. 2nd ed. New York: McGraw-Hill; 2011.
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