(Radiographics. 2000;20:215-243.)
© RSNA, 2000
From the Archives of the AFIP 1
Infiltrative Renal Lesions: Radiologic-Pathologic Correlation
Perry J. Pickhardt, LT, MC, USN ,
Gael J. Lonergan, Lt Col, USAF, MC ,
Charles J. Davis, Jr, MD,
Naoko Kashitani, MD and
Brent J. Wagner, MD
1 From the Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (P.J.P.); the Departments of Radiologic Pathology (G.J.L., N.K., B.J.W.) and Genitourinary Pathology (C.J.D.), Armed Forces Institute of Pathology, Bldg 54, Rm M-121, 14th and Alaska NW, Washington, DC 20306-6000; the Department of Radiology, Guantanamo Bay Naval Hospital, Cuba (P.J.P.); the Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md (G.J.L.); and the Department of Radiology, West Reading Radiology Associates, West Reading, Pa (B.J.W.). Received September 1, 1999; revisions requested September 20 and received October 8; accepted October 13. Address reprint requests to G.J.L.
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Abstract
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Most renal masses exhibit an expansile growth pattern characterized by radial tumor enlargement that displaces normal renal parenchyma and forms spherical, often exophytic, lesions. These expansile masses have pushing margins that impress adjacent normal renal parenchyma but do not infiltrate it; this behavior results in a well-defined, encapsulated appearance at both radiologic and gross pathologic examination. In contrast, certain disease processes involve the kidney in an infiltrative fashion by using the normal renal architecture as scaffolding for interstitial growth. These infiltrative renal lesions lack a sharp border of demarcation with the normal parenchyma and therefore demonstrate ill-defined zones of transition between the lesion and normal parenchyma. Although infiltrative lesions frequently enlarge the kidney, its reniform shape is usually maintained. Cross-sectional imaging can often help distinguish infiltrative from expansile growth patterns through analysis of the parenchymal interface between the process and the kidney, the effect of the lesion on the collecting system and renal sinus, and the overall renal morphology. A wide variety of neoplastic and inflammatory conditions characteristically involve the kidney by cellular infiltration. Although considerable overlap of the imaging features exists among the various infiltrative processes, the correct diagnosis may be suspected when the clinical data and associated radiologic findings are considered together.
Index Terms: Kidney neoplasms, 811.3124, 811.32, 811.34 • Kidney, nephroblastomatosis, 811.325 • Nephritis, 811.212, 811.29 • Sickle cell disease (SS, SC), 811.329
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Introduction
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A lesion involving the kidney can behave as a space-occupying mass with growth by expansion or as a process that permeates the renal parenchyma by interstitial infiltration. Of these two growth patterns, space-occupying masses predominate since the most common primary renal tumors in adults (renal cell adenocarcinoma) and children (Wilms tumor) usually manifest as expansile masses. The most common renal neoplasm overall, metastasis, also usually manifests as an expansile mass. Hallmarks of expansion include a spherical shape (from radial growth), focal bulging of the renal contour, displacement of normal parenchyma and collecting system elements, and pseudocapsule formation (Fig 1). Pseudocapsule formation is the result of tumor growth in an organ, producing compression, ischemia, and necrosis of adjacent normal parenchyma with the resulting deposition of fibrous tissue. In comparison, a true capsule is one formed by an organ as part of its normal development, much like the liver and spleen are surrounded by true capsules.
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Figure 1. Pseudocapsule formation in expansile growth. Photomicrograph (original magnification, x120; hematoxylin-eosin [H-E] stain) of renal cell carcinoma (asterisks) shows fibrous pseudocapsule formation (arrows) around the margins of the tumor.
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Infiltrative growth is a less frequent growth pattern of renal neoplasms but is nonetheless characteristic of certain renal tumors and tumorlike conditions. Hallmarks of cellular infiltration include growth that initially respects the renal contour and invades the normal structures, preservation of the reniform shape when the kidney is enlarged, and a poorly defined interface between the normal renal parenchyma and the lesion (Fig 2). The growth features of infiltrative lesions are reflected in their imaging appearance. In the past, urography and angiography were the primary imaging modalities for the evaluation of renal masses. However, these procedures have largely been replaced by cross-sectional imaging techniques. The typical appearance of an infiltrating mass on excretory urography is nonspecific and may typically manifest as a decreased or absent nephrogram (1). Angiography often demonstrates an ill-defined hypovascular region associated with vascular encasement, pruning, or amputation but without significant vascular displacement (1). However, these radiographic findings may be subtle and underscore the utility of cross-sectional imaging for the evaluation of infiltrative renal lesions (2).
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Figure 2. Infiltrative growth pattern. Photomicrograph (original magnification, x150; H-E stain) of lymphoma (asterisks) shows densely staining nuclei infiltrating around and between glomerulus (straight arrow) and tubules (curved arrows).
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On computed tomographic (CT) scans, a poorly marginated area of diminished enhancement (compared with the normal renal parenchyma) is typically seen. In addition, infiltrative processes more often encase (rather than displace) the intrarenal collecting system. Replacement of the renal sinus fat is also characteristic (2). CT is particularly useful in the evaluation of the perinephric space to exclude extension of disease. At sonographic evaluation, infiltrative processes may demonstrate poorly circumscribed regions of altered echogenicity, either decreased or increased compared with the normal renal parenchyma (2). Some infiltrative lesions, however, may be isoechoic, and such isoechoic infiltration of a normal-sized kidney may be overlooked at ultrasonography (US). Preservation of the reniform shape is readily assessed with direct longitudinal US; this distinction may be less apparent on axial CT images. Magnetic resonance (MR) imaging combines the CT advantages of enhancement characteristics, lesion-parenchyma interface, and simultaneous display of both kidneys with the sonographic advantage of direct multiplanar imaging. Thus, MR imaging is a valuable adjunct in the evaluation of infiltrative lesions.
This article describes the clinical, pathologic, and radiologic features of renal lesions that are characteristically infiltrative at pathologic examination. These lesions and the causes of cellular infiltration can be broadly divided into neoplastic and inflammatory categories (Table). The clinical and radiologic features that influence the formulation of a focused differential diagnosis are emphasized herein.
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Infiltrative Renal Neoplasms
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Neoplasms account for a considerable number of infiltrative renal lesions seen on imaging studies (1,2). Specific entities that appear infiltrative include a variety of uncommon tumors (eg, renal medullary carcinoma). However, infiltrative growth may also be an atypical manifestation of more common neoplasms (eg, renal cell carcinoma). Other neoplasms that may exhibit infiltrative growth include epithelial neoplasms of the renal parenchyma, collecting duct carcinoma, renal medullary carcinoma, renal pelvic carcinomas, renal sarcomas, lymphoproliferative diseases, metastatic disease, and several pediatric tumors (Table). Some renal tumors may demonstrate both infiltrative and expansile features at radiologic and pathologic examination; in these cases, an infiltrative component may indicate a more aggressive behavior.
Epithelial Tumors of the Renal Parenchyma
Over 90% of renal neoplasms are adenocarcinomas that arise from the cortex and differentiate toward mature renal tubules. Renal adenocarcinomas are more commonly referred to as renal cell carcinomas (3,4). They account for approximately 3% of adult malignancies, have no racial predilection, and increase in frequency with advancing age (the median age at diagnosis is 55 years). There is a slight male predominance (1.6:1). Metastatic disease is predominantly to the lung, as well as to liver, bone, brain, and skin (5).
There are many histologic subtypes of renal cell carcinoma, including clear cell, papillary, chromophobe cell, and sarcomatoid (also known as spindle cell). The clear cell subtype is the most common and accounts for 70%–80% of renal cell carcinomas. The papillary subtype represents 10%–15% of cases; the chromophobe subtype, about 5%; and the very uncommon sarcomatoid subtype (a poorly differentiated anaplastic variant), approximately 1.5% (5–8).
At histologic analysis, the most common subtype of renal cell carcinoma, clear cell, appears as rounded collections of cells with clear cytoplasm (due to the high content of cytoplasmic lipid and glycogen), which wash away during routine histologic preparation. The cells may be arranged in tubular arrays referred to as the acinar pattern (Fig 3) (5). The more common subtypes—clear cell, papillary, and chromophobe cell—typically appear as well-defined masses and may form a capsule of connective tissue and compressed atrophic renal parenchyma as the tumor grows. Cut sections of renal cell carcinoma appear predominantly solid but often display areas of hemorrhage or necrosis. Occasionally, the tumor appears ill-defined and infiltrative; this appearance is more typical of the uncommon sarcomatoid subtype but may be seen with the other subtypes as well (8).
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Figure 3. Renal cell carcinoma, clear cell type. Photomicrograph (original magnification, x75; H-E stain) shows cells with small nuclei and abundant clear cytoplasm, arranged in rows resembling tubules.
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At imaging, the expansile growth of renal cell carcinoma is manifested as a relatively well-marginated, solitary mass. A focal contour bulge in the renal surface is typical. The less common infiltrative growth pattern displays an ill-defined tumor margin (Fig 4). Calcification is evident in approximately 15%–20% of renal cell carcinomas on radiographs and may be rimlike or central (9). At US, the appearance of renal cell carcinoma is variable: It may be hyper-, iso-, or hypoechoic relative to the normal kidney and may be heterogeneous or homogeneous. At CT, renal cell carcinoma enhances heterogeneously but less than adjacent normal renal parenchyma (10). At MR imaging, renal cell carcinoma is variable in signal intensity: It may be hyper-, iso-, or hypointense relative to normal renal parenchyma and usually appears heterogeneous (11). Invasion of the renal vein (and sometimes the inferior vena cava) is found in up to 16% of tumors and may be diagnosed at US, contrast-enhanced CT, and MR imaging (12). The presence of vascular invasion conveys a poor prognosis. Although renal cell carcinoma typically occurs as an expansile mass, it manifests as an infiltrative lesion in approximately 6% of cases (11). Other renal neoplasms, such as medullary carcinoma, have a greater propensity for infiltrative growth but are considerably less common than renal cell carcinoma. Therefore, renal cell carcinoma remains one of the more frequent causes of an infiltrative neoplasm (3,4). The prognosis for renal cell carcinoma varies with stage and histologic grade. The 5-year survival rate for patients with stage 1 disease (tumor confined within the renal capsule) of low histologic grade is 63%–67% (13). For those patients in whom the tumor has spread into adjacent organs or with distant metastatic disease, the 5-year survival rate drops to approximately 14% (13).
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Figure 4a. Renal cell carcinoma in a 70-year-old man with recent history of lower abdominal pain and 16-lb (7.2-kg) weight loss. (a) Axial contrast material-enhanced CT scan shows a heterogeneous, poorly defined mass (arrows) in the left kidney. (b) Photograph of the bisected specimen shows the infiltrating neoplasm (arrows) in the middle and upper portions of the left kidney.
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Figure 4b. Renal cell carcinoma in a 70-year-old man with recent history of lower abdominal pain and 16-lb (7.2-kg) weight loss. (a) Axial contrast material-enhanced CT scan shows a heterogeneous, poorly defined mass (arrows) in the left kidney. (b) Photograph of the bisected specimen shows the infiltrating neoplasm (arrows) in the middle and upper portions of the left kidney.
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Medullary Tumors of Uncertain Cell Origin
In contrast to typical renal cell carcinomas derived from the cortex, malignant renal tumors arising from the medullary region are rare and account for only 1%–2% of renal cancers (3,4). Two such tumors, collecting duct carcinoma and renal medullary carcinoma, have received considerable attention in recent years. The histologic classification of renal medullary tumors continues to evolve, and the relationship between these two aggressive malignancies remains uncertain (14). The exact histologic origin of these tumors is controversial; they are classified separately from epithelial tumors of the renal parenchyma and renal pelvis (3). Unlike epithelial renal carcinomas, these medullary tumors exhibit a propensity for infiltrative growth (14,15).
Collecting Duct Carcinoma.—Collecting duct carcinoma is a tumor arising from the medullary region of the kidney. In the older pathology literature, it was referred to as Bellini duct carcinoma, reflecting the belief that it arose from the duct of Bellini. Today, the cell of origin is uncertain, although histologically the tumor often resembles collecting ducts. There are just over 100 cases reported in the literature, with a male predominance (2:1) (16–19). The mean age at diagnosis is 55 years, although the age range is wide, with cases reported in children as young as 13 years old and adults over 80 years of age (5,14). Patients present with abdominal pain, flank mass, and hematuria. Collecting duct carcinomas demonstrate an aggressive clinical course. Less than one-third of patients survive more than 2 years beyond diagnosis, and up to 40% have metastatic disease at presentation (14).
Collecting duct carcinoma is an infiltrative neoplasm that is usually centered in the renal medulla, although extension into the cortex is seen in nearly all cases (19). The histologic criteria for diagnosing collecting duct carcinoma are controversial (3). Tubular or ductlike structures are present, usually associated with a papillary element that frequently projects into the pelvis (3). The tumor generally recapitulates the morphology of the ducts of Bellini, although some areas may resemble renal cell carcinoma (3). Most tumors are of high grade and metastasize early (5,14).
The imaging features of collecting duct carcinoma are not well characterized in the literature, with the largest radiologic series consisting of five cases (20,21). In our experience, based on a review of 16 cases at the Armed Forces Institute of Pathology, the tumors are usually large at presentation. At CT, renal medullary involvement with an infiltrative appearance and renal sinus encroachment are the most common findings (Fig 5). The tumors may also demonstrate a coexisting expansile component, such that a collecting duct carcinoma may appear infiltrative in some areas and well defined in others (20,21). Collecting duct carcinoma in our cases appeared hyperechoic relative to normal parenchyma at sonography, hypovascular at angiography, and hypointense relative to normal renal parenchyma at T2-weighted MR imaging.
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Figure 5a. Collecting duct carcinoma in a 68-year-old man with vague abdominal pain for several months. (a) Longitudinal sonogram through the right kidney reveals an ill-defined hyperechoic mass (arrows) in the upper pole. (b) Axial contrast-enhanced CT scan shows the low-attenuation mass (arrows) in the right kidney involving the medulla and cortex and effacing or abutting the renal sinus. (c) Axial T1-weighted MR image shows the mass (arrowheads), which is isointense relative to the renal parenchyma. (d) On a coronal T2-weighted MR image, the mass (arrow) has low signal intensity and extends into the renal sinus. (e) Photograph of the bisected gross specimen shows the infiltrating mass (arrows) in the upper half of the kidney.
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Figure 5b. Collecting duct carcinoma in a 68-year-old man with vague abdominal pain for several months. (a) Longitudinal sonogram through the right kidney reveals an ill-defined hyperechoic mass (arrows) in the upper pole. (b) Axial contrast-enhanced CT scan shows the low-attenuation mass (arrows) in the right kidney involving the medulla and cortex and effacing or abutting the renal sinus. (c) Axial T1-weighted MR image shows the mass (arrowheads), which is isointense relative to the renal parenchyma. (d) On a coronal T2-weighted MR image, the mass (arrow) has low signal intensity and extends into the renal sinus. (e) Photograph of the bisected gross specimen shows the infiltrating mass (arrows) in the upper half of the kidney.
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Figure 5c. Collecting duct carcinoma in a 68-year-old man with vague abdominal pain for several months. (a) Longitudinal sonogram through the right kidney reveals an ill-defined hyperechoic mass (arrows) in the upper pole. (b) Axial contrast-enhanced CT scan shows the low-attenuation mass (arrows) in the right kidney involving the medulla and cortex and effacing or abutting the renal sinus. (c) Axial T1-weighted MR image shows the mass (arrowheads), which is isointense relative to the renal parenchyma. (d) On a coronal T2-weighted MR image, the mass (arrow) has low signal intensity and extends into the renal sinus. (e) Photograph of the bisected gross specimen shows the infiltrating mass (arrows) in the upper half of the kidney.
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Figure 5d. Collecting duct carcinoma in a 68-year-old man with vague abdominal pain for several months. (a) Longitudinal sonogram through the right kidney reveals an ill-defined hyperechoic mass (arrows) in the upper pole. (b) Axial contrast-enhanced CT scan shows the low-attenuation mass (arrows) in the right kidney involving the medulla and cortex and effacing or abutting the renal sinus. (c) Axial T1-weighted MR image shows the mass (arrowheads), which is isointense relative to the renal parenchyma. (d) On a coronal T2-weighted MR image, the mass (arrow) has low signal intensity and extends into the renal sinus. (e) Photograph of the bisected gross specimen shows the infiltrating mass (arrows) in the upper half of the kidney.
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Figure 5e. Collecting duct carcinoma in a 68-year-old man with vague abdominal pain for several months. (a) Longitudinal sonogram through the right kidney reveals an ill-defined hyperechoic mass (arrows) in the upper pole. (b) Axial contrast-enhanced CT scan shows the low-attenuation mass (arrows) in the right kidney involving the medulla and cortex and effacing or abutting the renal sinus. (c) Axial T1-weighted MR image shows the mass (arrowheads), which is isointense relative to the renal parenchyma. (d) On a coronal T2-weighted MR image, the mass (arrow) has low signal intensity and extends into the renal sinus. (e) Photograph of the bisected gross specimen shows the infiltrating mass (arrows) in the upper half of the kidney.
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Differentiating collecting duct carcinoma from an invasive pelvic urothelial tumor on the basis of imaging findings may not be possible. However, such a distinction is important because the latter carries an increased risk of synchronous urothelial tumors and is treated with nephroureterectomy instead of nephrectomy. Because pelvic urothelial tumors are considerably more common than collecting duct carcinoma, an invasive renal pelvic tumor is usually treated presumptively as a urothelial tumor with nephroureterectomy.
Renal Medullary Carcinoma.—In 1995, an Armed Forces Institute of Pathology review of renal pelvic carcinomas in patients younger than 40 years revealed a distinct clinical and pathologic subset of predominantly young black patients with sickle cell trait (HbSA and HbSC) who developed highly aggressive and infiltrative tumors (15). The tumors arose from the renal medulla, either from the distal collecting ducts or from the epithelium of the renal papillae. The name renal medullary carcinoma was coined, and multiple case reports and small series have followed (22–25). Interestingly, sickle cell anemia (HbSS) is not associated with this tumor. It is important to note that patients with sickle cell trait may not know of their heterozygous status, as sickle cell trait may be clinically occult. The presence of a few sickled red blood cells in the pathologic specimens identifies the patient as having sickle cell trait to the reviewing pathologists.
Renal medullary carcinoma occurs in relatively young patients, ranging from 11 to 39 years old. In patients between the ages of 11 and 24 years, there is a male predominance of 3:1; beyond the age of 24 years, there is no gender predilection. Flank pain and hematuria are the most common presenting complaints (15). Renal medullary carcinoma confers a dismal prognosis, with advanced metastatic disease common at presentation and an overall mean survival after surgery of slightly less than 4 months (15). Metastatic involvement of regional lymph nodes, liver, and lung are common associated findings (15,24,25).
Renal medullary carcinomas are large central tumors with varying amounts of hemorrhage and necrosis (15,23). At histologic analysis, poorly differentiated tumor cells within a desmoplastic stroma are mixed with several other cellular morphologic patterns, including reticular, yolk sac–like, and adenoid cystic components (Fig 6) (15). It has been suggested that renal medullary carcinoma represents a particularly aggressive form of collecting duct carcinoma (14).
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Figure 6. Medullary carcinoma, adenoid cystic pattern. Photomicrograph (original magnification, x40; H-E stain) shows lightly staining, irregularly shaped cells arranged in clusters (arrows) and separated by desmoplastic stromal reaction.
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The radiologic appearance of renal medullary carcinoma is that of a prototypical infiltrative lesion. An ill-defined mass centered in the renal medulla with extension into the renal sinus and cortex is characteristic; caliectasis may be seen, presumably as a result of the sinus invasion. Larger tumors expand the kidney but tend to maintain its reniform shape. The tumors are heterogeneous at US and contrast-enhanced CT, reflecting characteristic tumor necrosis (Fig 7) (24).
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Figure 7a. Medullary carcinoma in a 29-year-old black woman with flank pain and gross hematuria. (a) Longitudinal sonogram shows the right kidney (arrows), which is markedly enlarged and heterogeneously echogenic. (b) On an axial contrast-enhanced CT scan, the right kidney (arrow) enhances heterogeneously and is enlarged. (c) Photograph of the bisected gross specimen shows the infiltrative mass (arrows) replacing much of the renal parenchyma.
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Figure 7b. Medullary carcinoma in a 29-year-old black woman with flank pain and gross hematuria. (a) Longitudinal sonogram shows the right kidney (arrows), which is markedly enlarged and heterogeneously echogenic. (b) On an axial contrast-enhanced CT scan, the right kidney (arrow) enhances heterogeneously and is enlarged. (c) Photograph of the bisected gross specimen shows the infiltrative mass (arrows) replacing much of the renal parenchyma.
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Figure 7c. Medullary carcinoma in a 29-year-old black woman with flank pain and gross hematuria. (a) Longitudinal sonogram shows the right kidney (arrows), which is markedly enlarged and heterogeneously echogenic. (b) On an axial contrast-enhanced CT scan, the right kidney (arrow) enhances heterogeneously and is enlarged. (c) Photograph of the bisected gross specimen shows the infiltrative mass (arrows) replacing much of the renal parenchyma.
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Although rare, the unique constellation of clinical (younger black patient, whose sickle cell trait may be known or clinically occult) and radiologic (infiltrative medullary mass) findings suggest the diagnosis of renal medullary carcinoma. A renal mass in an older black patient is more likely to be renal cell carcinoma, since it is considerably more common than medullary carcinoma.
Epithelial Tumors of the Renal Pelvis
Malignant tumors arising from the urothelium of the renal pelvis account for only 5% of urinary tract neoplasms (26), with the most common of these being transitional cell carcinoma and squamous cell carcinoma. Aggressive tumors of the renal pelvis may directly invade the kidney and appear as infiltrative renal masses on imaging studies. Renal pelvic tumors (rather than renal parenchymal tumors) should be suspected when the tumor is centered in the pelvis and appears to secondarily invade the renal sinus and parenchyma.
Transitional Cell Carcinoma.—Of the tumors that arise from the renal pelvic urothelium, approximately 90% are transitional cell carcinomas (27). These tumors share the same epidemiologic features associated with transitional cell carcinomas of the ureter and bladder (history of exposure to chemicals in the dye, rubber, and petroleum industries, tobacco use, high amounts of coffee consumption, and chronic inflammation or infection). Patients with a history of analgesic abuse are also at risk for transitional cell carcinoma of the renal pelvis. The typical patient age at diagnosis of transitional cell carcinoma is the 6th or 7th decade of life, with a mean age of 68 years. Men are more commonly affected than women (2.7:1), and the tumor is more common in whites than blacks (5). Presentation with painless hematuria is characteristic, although flank pain may also bring the patient to clinical attention (28). Metastases occur to regional lymph nodes, peritoneum, and liver (5,26).
Most renal pelvic transitional cell carcinomas are of the papillary type and demonstrate predominantly exophytic intrapelvic growth (29). Transitional cell carcinoma may invade the renal sinus and parenchyma; this is more typical of high-grade transitional cell carcinoma, which is more anaplastic than noninvasive transitional cell carcinoma (5). At microscopic examination of invasive transitional cell carcinoma, the cells are arranged in nests and cords. An infiltrative pattern of growth is apparent, with indistinct tumor margins due to inflammation and desmoplastic changes of the stroma at the tumor-parenchyma interface (Fig 8) (5).
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Figure 8. Transitional cell carcinoma of the renal pelvis. Photomicrograph (original magnification, x75; H-E stain) shows pleomorphic cells (arrows) infiltrating the renal parenchyma in two separate areas.
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Invasive pelvic transitional cell carcinoma usually results in decreased or absent excretion at urography. Sonography depicts invasive transitional cell carcinoma as a poorly defined hypo- or hyperechoic mass that replaces the renal sinus fat but does not disrupt the normal renal contour (Fig 9). Caliectasis without pelviectasis may be present. Characteristic CT features include a large low-attenuation tumor centered in the renal pelvis with obliteration of the renal sinus fat and ill-defined extension into the renal medulla and cortex (29–31).
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Figure 9a. Transitional cell carcinoma of the renal pelvis in a 48-year-old woman with a 1-month history of right flank pain and intermittent gross hematuria. (a) Longitudinal sonogram shows an ill-defined hyperechoic mass (arrows) in the upper pole and midportion of the right kidney. (b) Axial contrast-enhanced CT scan demonstrates the low-attenuation mass (arrow) in the upper portion of the right kidney. (c) Photograph of the bivalved specimen demonstrates the infiltrative mass (arrows) in the upper half of the kidney.
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Figure 9b. Transitional cell carcinoma of the renal pelvis in a 48-year-old woman with a 1-month history of right flank pain and intermittent gross hematuria. (a) Longitudinal sonogram shows an ill-defined hyperechoic mass (arrows) in the upper pole and midportion of the right kidney. (b) Axial contrast-enhanced CT scan demonstrates the low-attenuation mass (arrow) in the upper portion of the right kidney. (c) Photograph of the bivalved specimen demonstrates the infiltrative mass (arrows) in the upper half of the kidney.
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Figure 9c. Transitional cell carcinoma of the renal pelvis in a 48-year-old woman with a 1-month history of right flank pain and intermittent gross hematuria. (a) Longitudinal sonogram shows an ill-defined hyperechoic mass (arrows) in the upper pole and midportion of the right kidney. (b) Axial contrast-enhanced CT scan demonstrates the low-attenuation mass (arrow) in the upper portion of the right kidney. (c) Photograph of the bivalved specimen demonstrates the infiltrative mass (arrows) in the upper half of the kidney.
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Prognosis varies with tumor invasion of the muscularis mucosa of the renal pelvis epithelium. For patients without such invasion, the 5-year survival rate is 77%–80%. Once invasion occurs, the 5-year survival rate drops to 5%.
Squamous Cell Carcinoma.—Squamous cell carcinoma is the second most common malignancy of the pelvic urothelium and accounts for 5%–10% of such cases in the United States (33). There is an increased prevalence among patients with renal calculi, and chronic irritation of the urothelium appears to be an important etiologic factor in the development of squamous cell carcinoma (5,33). As with transitional cell carcinoma, there is a male predominance, although it is not as strong (less than 2:1), and the age at diagnosis is 60–70 years (5). Presentation is typically with painless hematuria or flank pain associated with ureteropelvic junction obstruction (5,33). The prognosis is worse than that of patients with transitional cell carcinoma, as only one-third of patients survive 1 year beyond diagnosis (33).
Much like squamous cell carcinoma elsewhere in the human body, the tumor is locally invasive, and it may demonstrate extensive infiltration of the renal parenchyma. At histologic analysis, the tumor is characterized by sheets of epithelium that often become keratinized, recapitulating epidermis (5).
At cross-sectional imaging evaluation, the kidney is enlarged but maintains its reniform shape (Fig 10) (2). The kidney may not excrete contrast material, because it is often nonfunctional as a result of obstruction of the renal pelvis from the tumor and associated renal calculi. A tumor mass is not often evident, as squamous cell carcinoma tends to grow from the urothelium directly into the sinus and parenchyma (34). It may be impossible to radiologically distinguish squamous cell carcinoma of the renal pelvis from xanthogranulomatous pyelonephritis, as the radiologic features of an infiltrating renal pelvic process, nonfunctional kidney, and renal calculus (present in 40%–80% of renal pelvis squamous cell carcinomas) are characteristic of both (30,34). The correct diagnosis is easily made histologically.
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Figure 10a. Squamous cell carcinoma of the renal pelvis in a 69-year-old woman with recent weight loss. (a) Longitudinal sonogram of the left kidney shows dilated calices (arrowheads), echogenic renal calculi (curved arrow), and an ill-defined soft-tissue mass (straight arrows) filling much of the renal pelvis. (b) On an axial contrast-enhanced CT scan, the low-attenuation mass (arrow) is seen arising medial to the calculi, in the region of the middle and lower renal pelvis. (c) Photograph of the bivalved surgical specimen shows the large mass (straight arrows) replacing the lower half of the left kidney and upper pole caliectasis (curved arrow).
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Figure 10b. Squamous cell carcinoma of the renal pelvis in a 69-year-old woman with recent weight loss. (a) Longitudinal sonogram of the left kidney shows dilated calices (arrowheads), echogenic renal calculi (curved arrow), and an ill-defined soft-tissue mass (straight arrows) filling much of the renal pelvis. (b) On an axial contrast-enhanced CT scan, the low-attenuation mass (arrow) is seen arising medial to the calculi, in the region of the middle and lower renal pelvis. (c) Photograph of the bivalved surgical specimen shows the large mass (straight arrows) replacing the lower half of the left kidney and upper pole caliectasis (curved arrow).
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Figure 10c. Squamous cell carcinoma of the renal pelvis in a 69-year-old woman with recent weight loss. (a) Longitudinal sonogram of the left kidney shows dilated calices (arrowheads), echogenic renal calculi (curved arrow), and an ill-defined soft-tissue mass (straight arrows) filling much of the renal pelvis. (b) On an axial contrast-enhanced CT scan, the low-attenuation mass (arrow) is seen arising medial to the calculi, in the region of the middle and lower renal pelvis. (c) Photograph of the bivalved surgical specimen shows the large mass (straight arrows) replacing the lower half of the left kidney and upper pole caliectasis (curved arrow).
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Renal Sarcoma
Primary renal sarcomas are rare (accounting for approximately 1% of malignant renal parenchymal tumors) mesenchymal tumors that generally convey a poor prognosis. Subtypes of renal sarcoma include leiomyosarcoma (the most common type), angiosarcoma, hemangiopericytoma, rhabdomyosarcoma, fibrosarcoma, and osteosarcoma (35). The biologic behavior of the various types of sarcoma is highly variable.
Diagnosis requires exclusion of sarcomatoid renal carcinoma and direct extension from a primary retroperitoneal sarcoma, both of which are more common than primary renal sarcoma. Leiomyosarcoma accounts for over 50% of all renal sarcomas but generally manifests as a well-circumscribed expansile lesion (36). Rhabdomyosarcoma and angiosarcoma of the kidney are the most likely sarcomas to display an infiltrative growth pattern (Fig 11) (5,37). Most other renal sarcomas appear as expansile masses (37). A typical imaging appearance of renal sarcoma is not readily definable, because the various subtypes vary considerably in appearance depending on their cellular constituents.
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Figure 11a. Undifferentiated renal sarcoma in a 58-year-old woman with left flank pain. (a) Axial contrast-enhanced CT scan shows an enlarged, heterogeneously enhancing left kidney (straight arrow) and soft-tissue nodules adjacent to the aorta (curved arrow). The latter subsequently proved to be metastatic adenopathy. (b) Photograph of the bisected gross specimen reveals the lobulated, poorly defined mass (arrows) replacing the upper half of the left kidney.
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Figure 11b. Undifferentiated renal sarcoma in a 58-year-old woman with left flank pain. (a) Axial contrast-enhanced CT scan shows an enlarged, heterogeneously enhancing left kidney (straight arrow) and soft-tissue nodules adjacent to the aorta (curved arrow). The latter subsequently proved to be metastatic adenopathy. (b) Photograph of the bisected gross specimen reveals the lobulated, poorly defined mass (arrows) replacing the upper half of the left kidney.
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Lymphoproliferative Diseases
Lymphoma, leukemia, and plasma cell dyscrasias may all infiltrate the kidney. Of these three diseases, lymphoma is the most frequently encountered in renal imaging.
Renal Lymphoma.—The malignant lymphomas comprise a heterogeneous group of neoplasms involving lymphoid cells that are broadly divided into non-Hodgkin lymphoma and Hodgkin disease. Extranodal disease, including renal involvement, occurs more frequently with non-Hodgkin lymphoma than with Hodgkin disease (38,39). Renal involvement with lymphoma is almost always secondary to systemic disease because the kidney does not contain lymphoid tissue. Primary renal lymphoma is rare, usually arising in the renal hilar lymph nodes; it may also arise in the renal parenchyma itself (40,41). Patients with renal involvement from systemic lymphoma do not usually manifest urinary tract symptoms (38,41).
Although non-Hodgkin lymphoma affects the kidney much more frequently than Hodgkin disease, their pathologic patterns of involvement are similar (38). Bilateral renal involvement was reported in 75% of all patients with lymphoma in one autopsy series (39); at presentation, renal lymphoma is evident in approximately 5% of patients at initial staging CT (42). At histologic analysis, lymphoma is characterized by cells with prominent nuclei and scant cytoplasm. Renal lymphoma grows by both infiltration and expansion. Initially, lymphomatous proliferation within the kidney is interstitial, with sparing of the renal glomeruli and tubules. As the disease progresses, growth may continue in an infiltrative pattern, uniformly enlarging the kidney, or the lymphoma may focally proliferate, forming masses that may appear infiltrative or expansile (38,39,42).
As a result of these variable growth features, renal lymphoma has varied manifestations on imaging studies. The most common appearance is that of multiple expansile homogeneous masses that are hypoechoic at sonography and of low attenuation at CT (42–45). These focal masses are usually well defined but may show infiltrative margins, appearing as focal infiltrative processes. When lymphoma is diffusely infiltrative, the kidneys are enlarged but usually maintain their reniform shape (Fig 12) and show diminished enhancement at CT (43,44). Perinephric lymphoma and renal involvement from contiguous spread of retroperitoneal disease are also relatively common (38,45). The presence of infiltrative renal lesions on cross-sectional images, when seen with concomitant bulky perinephric disease, widespread lymphadenopathy, or contralateral renal involvement, is very suggestive of lymphoma.
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Figure 12a. Lymphoma in a 69-year-old man with right flank pain. (a) Axial contrast-enhanced CT scan shows a low-attenuation mass arising from the right kidney, extending through the renal capsule and into the retroperitoneum (arrows). (b) Photograph of the bisected gross specimen shows the ill-defined tumor mass (arrows) in the upper half of the kidney. The retroperitoneal neoplasm is not visible on this view.
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Figure 12b. Lymphoma in a 69-year-old man with right flank pain. (a) Axial contrast-enhanced CT scan shows a low-attenuation mass arising from the right kidney, extending through the renal capsule and into the retroperitoneum (arrows). (b) Photograph of the bisected gross specimen shows the ill-defined tumor mass (arrows) in the upper half of the kidney. The retroperitoneal neoplasm is not visible on this view.
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Renal Leukemia.—Leukemia of the lymphatic system is characterized by clonal proliferation of lymphoblasts (acute leukemia) or small lymphocytes (chronic leukemia). Leukemic infiltration of the kidneys is present at autopsy in over 50% of children and up to 65% of adults who die of their disease (46–48). Acute lymphoblastic forms account for the majority of cases of renal leukemia.
The true frequency of renal involvement in patients with leukemia, however, is difficult to assess because abdominal imaging is not routinely performed for staging of disease. When renal involvement is detected on cross-sectional images, diffuse bilateral infiltration with moderate or massive nephromegaly is the most common finding (Figs 13, 14) (46,49). CT and sonographic features resemble those of infiltrative renal lymphoma. However, unlike renal lymphoma, discrete renal masses from leukemia are unusual (46,49).
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Figure 13. Leukemia in a 3-year-old boy who presented with hypertension. Longitudinal sonogram of the right kidney (arrowheads) shows an enlarged, heterogeneous kidney and loss of normal corticomedullary differentiation. Similar findings were present in the left kidney.
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Renal Plasmacytoma.—Plasma cell neoplasia consists of a group of malignant disorders involving differentiated B lymphocytes or plasma cells that most often arise in bone either as a solitary lesion (plasmacytoma) or multiple lesions (multiple myeloma). Multiple myeloma and plasmacytoma of bone account for approximately 95% of plasma cell neoplasms (50). Multiple myeloma may involve nonskeletal sites, including the kidney, usually as microscopic foci of plasma cells. This has been reported in up to 17% of patients dying of multiple myeloma. Primary extramedullary plasmacytomas represent about 5% of plasma cell neoplasms and most often arise in the upper respiratory tract. Rarely, plasmacytomas may arise in the renal interstitium (51,52). In cases of isolated renal plasmacytoma, a monoclonal immunoglobulin may be detected at serum electrophoresis or there may be Bence-Jones proteinuria, findings that establish the diagnosis. If the tumor does not manufacture immunoglobulin, the diagnosis may not be established preoperatively (51).
Radiologic findings in renal plasmacytoma may be indistinguishable from those of other infiltrative lesions. Renal plasmacytomas may appear well circumscribed or infiltrative and may be difficult to distinguish from other renal primary tumors (Fig 15) (51,52).
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Figure 15a. Plasmacytoma in a 59-year-old man with a recent 20-lb (9-kg) weight loss. (a) Axial unenhanced CT scan shows an enlarged and irregular right kidney (straight arrow) with a low-attenuation, lobulated mass (curved arrow) in the region of the renal hilum. (b) Photograph of the bivalved specimen shows the mass (black arrows) in the midportion of the kidney, with extension into the renal pelvis (white arrow).
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Figure 15b. Plasmacytoma in a 59-year-old man with a recent 20-lb (9-kg) weight loss. (a) Axial unenhanced CT scan shows an enlarged and irregular right kidney (straight arrow) with a low-attenuation, lobulated mass (curved arrow) in the region of the renal hilum. (b) Photograph of the bivalved specimen shows the mass (black arrows) in the midportion of the kidney, with extension into the renal pelvis (white arrow).
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Renal Metastases
The frequency of metastases to the kidney in cancer patients is 7%–13% in large autopsy series (53–55). Before the advent of routine cross-sectional imaging, antemortem diagnosis of renal metastatic disease was unusual because of its characteristically indolent clinical behavior (53). When renal metastases are seen on imaging studies, patients typically have advanced disease. Rarely, a solitary renal metastasis will arise many years after diagnosis of the primary neoplasm (Fig 16) (56). The most common primary malignancy to involve the kidney is bronchogenic carcinoma, followed by breast and gastrointestinal cancers (55).
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Figure 16a. Metastatic disease in a 48-year-old man with a history of bronchogenic carcinoma 6 years earlier who presented with flank pain and gross hematuria. (a) Axial sonogram of the left kidney reveals an echogenic mass (arrows). (b) On an axial contrast-enhanced CT scan, the mass is seen as an ill-defined, low-attenuation region (arrows). (c) Photograph of the axially bisected specimen shows the light tan metastatic focus in the renal parenchyma and adjacent perinephric fat (arrows).
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Figure 16b. Metastatic disease in a 48-year-old man with a history of bronchogenic carcinoma 6 years earlier who presented with flank pain and gross hematuria. (a) Axial sonogram of the left kidney reveals an echogenic mass (arrows). (b) On an axial contrast-enhanced CT scan, the mass is seen as an ill-defined, low-attenuation region (arrows). (c) Photograph of the axially bisected specimen shows the light tan metastatic focus in the renal parenchyma and adjacent perinephric fat (arrows).
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Figure 16c. Metastatic disease in a 48-year-old man with a history of bronchogenic carcinoma 6 years earlier who presented with flank pain and gross hematuria. (a) Axial sonogram of the left kidney reveals an echogenic mass (arrows). (b) On an axial contrast-enhanced CT scan, the mass is seen as an ill-defined, low-attenuation region (arrows). (c) Photograph of the axially bisected specimen shows the light tan metastatic focus in the renal parenchyma and adjacent perinephric fat (arrows).
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As with lymphoma, renal metastases can display either expansile or infiltrative growth patterns (53,57,58). The most frequent pattern is that of multiple discrete bilateral lesions. Solitary exophytic metastases are more common in patients with colon cancer, and perinephric tumor extension is typical of melanoma (57). An infiltrative growth pattern, sometimes with renal enlargement, is a somewhat less common manifestation of metastatic disease.
Radiologic features of renal metastases reflect their pathologic pattern of involvement. Most lesions will appear as circumscribed rounded masses, but truly infiltrative lesions are occasionally seen. The presence of an associated exophytic component, cystic necrosis, hemorrhage, or calcification at CT depends on the nature of the underlying primary tumor (57,58). Patients with a known extrarenal primary malignancy who present with a solitary renal lesion constitute a greater diagnostic challenge, since the possibility of a synchronous primary renal cancer must also be considered. A circumscribed hypovascular metastasis may be indistinguishable from a papillary renal cell carcinoma or lymphoma. Because infiltrative growth is an uncommon manifestation of renal cortical tumors in general, a solitary infiltrative renal lesion in a patient with a history of cancer most likely represents metastatic disease. Tissue sampling is usually necessary in such cases.
Pediatric Renal Tumors
The most common renal malignancy in children, Wilms tumor, produces an expansile growth pattern more commonly than an infiltrative pattern. However, Wilms tumor represents an important cause of infiltrative pediatric renal lesions, since it is an infrequent manifestation of a common tumor. Other pediatric neoplasms that characteristically grow by infiltration include mesoblastic nephroma, rhabdoid tumor of the kidney, nephroblastomatosis, and primitive neuroectodermal tumor (59).
Wilms Tumor.—Wilms tumor, named for the German surgeon Wilms who was one of the first physicians to describe the tumor, is a malignant neoplasm composed of embryonal nephrogenic elements. It may also be referred to as nephroblastoma (59). The mean age at diagnosis is just over 3 years. It is slightly more common in boys than girls and is more common in blacks worldwide. It is relatively less common in Japan and other Asian countries. There is a significant association of Wilms tumor with certain syndromes, including Beckwith-Wiedemann, hemihypertrophy, and Drash syndromes. Wilms tumor is the most frequent abdominal solid malignancy in children. It metastasizes mainly to the lung and liver (5,59). The prognosis for patients with Wilms tumor is relatively good. The overall 4-year survival rate is 83.6% for patients with stage 4 (metastatic) disease and over 90% for patients with less extensive disease (60).
Wilms tumor is composed of immature renal elements, including blastema, primitive tubules, and stroma (Fig 17). The vast majority of Wilms tumors are expansile masses with well-circumscribed peripheral margins, due to the formation of a surrounding pseudocapsule composed of fibrous tissue and compressed adjacent normal parenchyma. Occasionally, an infiltrative pattern of growth is seen (59,61).
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Figure 17. Wilms tumor. Photomicrograph (original magnification, x100; H-E stain) depicts densely staining blastema (arrows) and primitive tubules (arrowheads) on a background of primitive stroma.
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Wilms tumor is typically a predominantly solid but heterogeneous tumor at US and CT (Fig 18). The echogenicity is variable; in tumors with areas of necrosis, hypo- and anechoic areas may be seen (62). Calcification is visible in up to 9% of cases of Wilms tumor at CT (63). Invasion of the renal vein and inferior vena cava may also occur (59,62).
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Figure 18a. Wilms tumor in a 7-year-old girl with right abdominal pain for 3 weeks. (a) Longitudinal sonogram of the right kidney reveals a mass (arrows) replacing the upper portion of the kidney. (b) Axial contrast-enhanced CT scan shows that the mass (arrows) is heterogeneous and poorly defined, replacing normal renal parenchyma at this level. The very low attenuation areas (arrowhead) in the mass represent areas of tumor necrosis. (c) Photograph of the bivalved gross specimen shows the tumor (arrows) replacing and expanding the renal parenchyma in the upper two-thirds of the kidney.
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Figure 18b. Wilms tumor in a 7-year-old girl with right abdominal pain for 3 weeks. (a) Longitudinal sonogram of the right kidney reveals a mass (arrows) replacing the upper portion of the kidney. (b) Axial contrast-enhanced CT scan shows that the mass (arrows) is heterogeneous and poorly defined, replacing normal renal parenchyma at this level. The very low attenuation areas (arrowhead) in the mass represent areas of tumor necrosis. (c) Photograph of the bivalved gross specimen shows the tumor (arrows) replacing and expanding the renal parenchyma in the upper two-thirds of the kidney.
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Figure 18c. Wilms tumor in a 7-year-old girl with right abdominal pain for 3 weeks. (a) Longitudinal sonogram of the right kidney reveals a mass (arrows) replacing the upper portion of the kidney. (b) Axial contrast-enhanced CT scan shows that the mass (arrows) is heterogeneous and poorly defined, replacing normal renal parenchyma at this level. The very low attenuation areas (arrowhead) in the mass represent areas of tumor necrosis. (c) Photograph of the bivalved gross specimen shows the tumor (arrows) replacing and expanding the renal parenchyma in the upper two-thirds of the kidney.
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Mesoblastic Nephroma.—Mesoblastic nephroma is the most common renal neoplasm that affects patients in the first 3 months of life and rarely occurs after the age of 6 months; the median age at diagnosis is 2 months (64). It is usually discovered because of a palpable abdominal mass.
Mesoblastic nephroma is a benign tumor characterized by interlacing bundles of spindle cells that grow between nephrons and replace the parenchyma, infiltrating between the glomeruli and tubules (Fig 19) (65). At pathologic examination, the tumor is typically solid, unencapsulated, and replaces most of the renal parenchyma. The tumor margins are indistinct, and its cut surface demonstrates a characteristic solid, whorled appearance. Hemorrhage and necrosis are usually not present, but there may be cystic areas. Although surgical resection is curative, local recurrence is possible if tongues of tumor tissue are left behind at the surgical margin (5,64).
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Figure 19. Mesoblastic nephroma. Photomicrograph (original magnification, x25; H-E stain) shows spindle cells (straight black arrow) infiltrating between clusters of normal tubules (curved arrow) and glomeruli (white arrow).
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The sonographic appearance of mesoblastic nephroma varies from a homogeneously hypoechoic lesion to a complex, heterogeneous mass with cystic areas (Fig 20) (65). One study described a sonographic pattern consisting of concentric rings of alternating echogenicity (66). Mesoblastic nephroma is usually a heterogeneous low-attenuation mass at contrast-enhanced CT (67,68). Imaging findings alone, however, do not allow mesoblastic nephroma to be reliably distinguished from Wilms tumor or other solid renal masses.
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Figure 20a. Mesoblastic nephroma in a 2-year-old boy who presented with gross hematuria. (a) Sonogram of the left kidney depicts a mass (arrows) arising from the upper half of the kidney. (b) On an axial contrast-enhanced CT scan, the mass (arrow) has low attenuation. (c) On an axial T1-weighted MR image, the mass (arrow) is low in signal intensity compared with normal renal parenchyma. (d) On an axial T2-weighted MR image, the mass (arrow) is heterogeneous and slightly hyperintense. (e) Photograph of the bisected specimen shows the heterogeneous mass (arrows) in the middle and upper portions of the left kidney.
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Figure 20b. Mesoblastic nephroma in a 2-year-old boy who presented with gross hematuria. (a) Sonogram of the left kidney depicts a mass (arrows) arising from the upper half of the kidney. (b) On an axial contrast-enhanced CT scan, the mass (arrow) has low attenuation. (c) On an axial T1-weighted MR image, the mass (arrow) is low in signal intensity compared with normal renal parenchyma. (d) On an axial T2-weighted MR image, the mass (arrow) is heterogeneous and slightly hyperintense. (e) Photograph of the bisected specimen shows the heterogeneous mass (arrows) in the middle and upper portions of the left kidney.
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Abstract
Introduction
