Imaging characterization of renal masses. Image atlas
Javier Fernández Mena*, Armando Zuluaga Gómez**, Francisco Valle Díaz de la Guardia**
*Departamento de Radiología y Medicina Física de la Universidad de Granada. Servicio de Radiología Diagnóstica de Clínica Inmaculada Concepción de Granada. **Servicio de Urología. Hospital Universitario San Cecilio. Granada. Spain.
ACTAS UROLÓGICAS ESPAÑOLAS 2009;33(5):482-498
| Abstract |
| The diagnostic study, analysis and characterization of renal masses and their behavior is one of the key elements for elaborating a surgical or therapeutic strategy, determining the prognosis, and for the follow-up of treatment efficacy in patients with benign or malignant disease. At present, computed tomography (CT) and magnetic resonance imaging (MRI) are the two most reliable, effective and efficient instruments in this context - offering sensitivity and specificity values in excess of 87%, with a diagnostic relaibility of over 90% in application to renal masses of a cystic or complex nature, with nonspecific or specific inflammatory characteristics, or of a primary or secondary neoplastic nature. |
| The aim of this study is to present the principal CT and MRI parameters in relation to renal pathology of this kind, correlating them to the clinical, physiopathological and histopathological data with a view to affording architectural, density, signal intensity and biological behavior parametric information of help in understanding the changes occurring in the renal and retroperitoneal regions secondary to such pathologies. |
| Key words: Renal mass. Renal inflammation. Renal cysts. Renal tumors. CT in renal cystic, inflammatory and tumor disease. MRI in renal cystic, inflammatory and tumor disease. Staging of renal tumors. |
As a result of the important increase in the use of imaging techniques at abdominal and thoracic level, renal masses - whether benign or malignant - constitute casual findings in asymptomatic patients in up to 50% of all cases. Patients with hematuria (56% of all subjects with renal cancer), flank pain (38%), weight loss (27%) and other symptoms related to the natural course of renal malignancy are specifically referred to Imaging Diagnosis Units, and in the case of renal cancers associated to familial hereditary syndromes such as Von-Hippel-Lindau syndrome, translocation of chromosome 3, tuberous sclerosis or Birt-Hog-Dubé syndrome, or hereditary renal papillary carcinoma, control of the patient relatives is obligate. In any case, the main body of statistics comes from those cases in which the clinical picture or familial hereditary history does not intervene.
Probably, the exponential increase in the use of ultrasound in our hospital centers, its great accessibility, important diagnostic reliability, low cost and high spatial resolution, together with the proliferation of abdominal computed tomography (CT) explorations performed for different reasons in outpatient and non-urological patient admission units, are making a positive contribution to the identification, characterization, staging and evaluation of the surgical possibilities in relation to such incidentally detected renal masses.
When speaking of renal masses, we necessarily include all benign and malignant processes that occupy, distort and affect the renal parenchyma and its surroundings, regardless of the underlying etiology, shape and volume. This comprises cysts, pseudotumors, neoplasms, inflammatory disorders and traumatisms.
Any renal mass, regardless of its etiology, implies changes in shape and volume, with vascular alterations and the creation of a compartmental syndrome to one extent or other. The diagnostic assessment of these effects is made based on ultrasound and Doppler ultrasound, CT studies with and without iodine contrast administration, intravascular ultrasound (IVUS), and magnetic resonance imaging (MRI)1-16.
Ultrasound (US)
Is a noninvasive technique that does not make use of ionizing radiation. It has great accessibility, low cost, and an important tissue characterization capacity, based on the way in which organs and their lesions interact with the ultrasound waves. Basically, ultrasound is applied to the following:
1. Organ topography
2. Organ morphology
3. Volumetric measurements
4. Differentiation of tissue layers, ultrasound architecture of the organ parenchyma
5. Excretory tract condition
6. Interphases with the renal surroundings or perirenal space
7. Vascular architecture, distribution and flow characteristics
8. Echoenhancer use for the evaluation of ischemic, traumatic, tumor, inflammatory or obstructive lesions
Computed axial tomography (CT)
Is the technique of choice for characterizing kidney lesions. The CT protocol includes imaging both without contrast medium and with medium contrast in two phases:
A. Arterial and cortico-medullary differentiation, and
B. Nephrographic. CT allows the observation of:
1.- The renal cell and morphological and density conditions of the renal fascias, perirenal space, and septae-capsule-fascial, capsule-capsule and transverse interphases
2.- Morphology, countours and volumetric parameters of the organ
3.- Presence of bulging or distortions of the renal axis
4.- Basal density and presence of point calcifications
5.- Basal conditions of the urinary excretory tract
6.- Analysis of the renal mass and the involvement of spaces: (a) renal; (b) renal and sinusal; (c) perirenal; (d) fascial; (e) distant involvement
7.- Analysis of arterial and venous vascular behavior
8.- Analysis of local, locoregional and distant lymphatic involvement
9.- Analysis of local, locoregional and distant venous thrombosis
10.- Analysis of visceral metastatic involvement
Imaging without contrast injection does not allow definitive classification of a mass as being amenable to surgery or not. The findings offer information on etiology and biological behavior. Mass imaging enhancement with contrast injection is the principal criterion for determining whether a mass is amenable to surgical treatment or not. With CT such determination can be based on comparison of the basal density and the use of intravenous iodine contrast injection. Positive enhancement is considered when the mass increases its attenuation coefficients above 20 Hounsfield units (HU). CT density enhancements that are indeterminate and under 10 Hounsfield units are to be subjected to control, or other diagnostic techniques should be incorporated to establish their nature.
In the case of solid and homogeneous masses, use can be made of densitometric analysis or mapping of the distribution of the X radiation attenuation coefficients in an extensive region of interest (ROI), though characterization problems may be found in the case of complex cystic, necrotic or hemorrhagic lesions. In these cases we require several measurements, and marking of the region of interest must be made with the same parameters in CT without and with intraveneous iodine contrast. In any case, the density measurements of renal masses sometimes may prove inconsistent and scantly specific, and the problem is further worsened in the case of lesions of small diameter included within the renal parenchyma, without bulging of the contours, and with scant visibility in the basal CT scans.
This problem is compounded by so-called "pseudoenhancement" with increments in excess of 10 HU shown by intraparenchymal cysts measuring less than 20 mm in diameter, in certain cases.
Magnetic resonance imaging (MRI)
Contributes the following parameters to the diagnosis and characterization of renal masses:
1.- Volume and location of the space-occupying lesion
2.- Basal signal characteristics of the mass in T1, density and T2 weighted sequences
3.- Characteristics of the lesion with paramagnetic contrast enhancement (vascular images)
4.- Characteristics of the lesion in inversion-recovery and fat suppression sequences
5.- Mapping of the retroperitoneal, abdominal and visceral region in relation to primary neoplastic disease
6.- Analysis of the venous and lymphatic renal hilum and retroperitoneal lymphatic regions
7.- Analysis of perirenal adipose tissue involvement
8.- Visualization of the renal capsule, tumor pseudocapsule, and alterations in capsule pattern
9.- Identification of cystic regions, necrotic zones and characterization of the tumor stroma and adjacent normal parenchyma
Based on all the above information, it can be seen that on assessing any problem primarily identified as a renal mass with ultrasound, CT and MRI, a first impression can be gained of the following aspects:
• Lesion
• Location
• Size
• Volume
• Ultrasound structural or architectural characteristics
• Density characteristics
• Signal characteristics
• Vascular pattern
• Relations to healthy parenchyma
• Relations extrinsic to the host organ
The above information, correlated to tumor architectural parameters on the basis of histological data, allow us to distinguish basically benign lesions from lesions that are either malignant or tend towards malignant behavior. The range of such lesions comprises cystic disease, nonspecific and specific inflammatory processes, and benign and malignant neoplasms.
CYSTIC LESIONS
Simple renal cysts are the most common presentations. Nevertheless, a cystic lesion may become complicated as a result of infection or bleeding and yield complex radiological manifestations requiring a differential diagnosis and complementary imaging diagnostic techniques.
Bosniak1,2 classified renal cysts by categories, findings, and types of lesion control or follow-up.
CategoryIdefines lesions with water density lacking septae and calcifications, with no solid poles, and no enhanced uptake following the administration of intravenous iodine contrast medium. Ultrasound defines these cysts as a lesion without a distinguishable wall, of a purely anechoic nature, and without alteration of the adjacent renal parenchyma. MRI in turn characterizes these lesions as presenting a homogeneous decrease in signal intensity in T1-weighted sequences, and an increase in signal intensity in T2-weighted acquisitions, without a discernible wall, and no paramagnetic contrast enhancement. The classification of these presentations would be "benign simple cyst", requiring no kind of posterior evaluation.
Category II defines lesions with fine septae, continuous or discontinuous linear calcifications, or homogeneous dense lesions that show no enhanced uptake following the administration of intravenous iodine contrast medium in CT scans or paramagnetic contrast injection in MRI. These are "minimally complicated benign cysts" requiring no surgery or follow-up.
Category II F corresponds to lesions with fine internal sepate, evident enhancement in walls or septae, minimal wall thickening, rough or nodular calcifications, dense intrarenal lesions without enhanced uptake and the absence of measurable enhancement in lesions discovered with increased radiological density. These are "moderately complicated cysts" that require follow-up.
Category III in turn is characterized by smooth or irregular wall thickening or thickening of the internal sepate, and the presence of measurable enhanced uptake in CT scans and MRI. These are "indeterminate masses" that initially require surgery.
Category IV shows nodular enhanced uptake external to the lesion wall and septae interposed within the complex cyst zone. In fact, these are "cystic neoplasms" that require surgery and staging.
When a cyst presents any of the following characteristics:
- Density in excess of 20 HU
- Calcification
- Presence of septae
- Multilocular cysts
- Wall thickening
- Nodularity or enhanced intravenous iodine contrast uptake in CT scans, or enhanced paramagnetic contrast uptake in MRI
the lesion should be referred to as a "cystic mass", and may correspond to some form of renal cell carcinoma.
The cystic lesions corresponding to categories I, II and IV are easy to diagnose and pose no problems in terms of management strategy. However, in the case of lesions corresponding to categories II F and III, which are of a moderately complicated or indeterminate nature and in most cases require surgery, it is difficult to establish an initial decision. Such lesions effectively require the application of an imaging diagnostic protocol, and often require the obtainment of a biopsy for histological assessment. The establishing of a differential diagnosis is relevant in these cases.
While the classification of Bosniak was established on the basis of the CT findings with and without contrast administration, it also must be extended to the parameters analyzed by ultrasound and MRI with and without paramagnetic contrast injection. MRI is usually better than CT in visualizing the septae, their thickening and thickening of the cyst wall. In complex presentations, MRI always should be used for increased precision in defining cystic masses according to the Bosniak classification.
Small and uncomplicated cysts are usually asymptomatic. Those of large volume may induce pressure sensation, hematuria, polycythemia and excretory tract ectasia, and must be punctured, subjected to sclerosis, or operated upon via the laparoscopic approach.
Complicated renal cysts include hemorrhagic cysts, infected cysts and cysts exhibiting wall calcification. Bleeding is present in 6% of all renal cysts. In patients with polycystic kidney disease, bleeding is found in 68% of all cases. Acute bleeding produces a homogeneous increase in density (40-90 HU) that in turn decreased over the subsequent days. These changes in density are not affected by intravenous iodine contrast medium. Bleeding within a cyst can induce an inflammatory reaction in the cyst wall, with the development of vascular granulation tissue that in turn can show enhanced contrast uptake with thickening of the cyst wall, and finally calcification of the wall. The increase in cyst density may also be due to a high protein content and to "milk of calcium" cysts. MRI is able to differentiate these hemorrhagic formations from tumor lesions. Aspiration of the cyst contents, followed by cytological and biochemical analysis of the latter is essential. Contents corresponding to clotted blood, a high concentration of proteins and lactate dehydrogenase (LDH), cytological positivity, and irregularities of the cyst wall are indicative of a tumor lesion.
Approximately 3% of all cysts present wall calcification, usually in the form of an "eggshell" pattern. These phenomena are seen in combination with homogeneous increments in wall thickness. Most of these findings correspond to changes undergone by a simple cyst secondary to bleeding or infection. In 20% of all cases, wall calcification may be an expression of malignant transformation. Benign calcified cysts show a calcified external membrane and are not accompanied by enhanced uptake of intravenous iodine contrast medium.
Pringle-Bourneville disease / tuberous sclerosis
Is characterized by mental retardation and skin lesions in the form of sebaceous adenomas. Tuberous sclerosis is an autosomal dominant hereditary neurocutaneous disease of variable expression. Renal cysts are frequent in tuberous sclerosis, and are characterized by the presence of eosinophilic cylindrical cells lining the cyst cavities. Angiomyolipomas are renal hamartomas of multiple and bilateral presentation that are found in 40-80% of all patients with Pringle-Bourneville disease. The cysts are over 30 mm in size, but rarely exceed 50 mm, within the cortex and medullary zone, and are accompanied by hamartomas. These cysts can present wall calcifications, and the hamartomas show CT signal densities of between -80 and -110 HU, due to the adipose components.
Von Hippel-Lindau disease
Is another dominant hereditary disease manifesting in the second decade of life and characterized by the following changes: (1) renal cysts, (2) cerebellar hemangioblastoma, (3) retinal angiomatosis, and (4) other lesions in different parts of the body: pancreas, liver, adrenal glands, epididymis, etc.
Von Hippel-Lindau disease
Implies possible malignization to renal adenocarcinoma with or without prior cystic degeneration, and is bilateral in 75% of all patients, multifocal in a kidney in 87% of all cases, and is associated to pheochromocytoma in 10% of all patients.
MULTILOCULAR CYSTIC NEPHROMA
Multilocular cystic nephroma (MLCN) is a space-occupying lesion defined by a thick capsule and containing cystic formations of variable size separated by fibrous septae. These lesions may show important growth, with an average size in excess of 90 mm. The cysts are not inter-communicated, and are lined by an eosinophilic epithelium. They may contain a clear liquid or a mucous and proteinic content. Bleeding is rare in lesions of this type. Hematuria may develop secondary to herniation of the lesion within the collector system, and ulceration may develop.
INFLAMMATORY LESIONS
Among the inflammatory lesions that behave as "renal masses", mention must be made of xanthogranulomatous pyelonephritis (XGP). This chronic inflammatory disease destroys the organ parenchyma and is the result of bacterial infection combined with and obstructive process as its main predisposing factor. The inflammatory process begins in the renal pelvis and causes progressive destruction of the medullary zone and renal cortex. Renal involvement is normally diffuse, though there also may be focal presentations in obstructed calyxes, or in dual excretory tracts.
The calyxes often show irregular margins and appear enlarged, though they may also appear compressed or enveloped by the inflammatory process. The parenchyma is replaced by a yellowish, xanthomatous magma, and multiple necrotic cavities are observed. Histologically, the tissue consists of a chronic inflammatory reaction with lipid-loaded macrophages in the form of xanthomatous or "foam" cells. Fibrous replacement of the parenchyma is found close to the cortex, and the inflammatory process can extend to the neighboring tissues and strata - particularly to the perirenal space, posterior pararenal space, flank region or anterior pararenal space - giving rise to fistulas.
CT shows the kidney to contain multiple hypodense areas (-15 to +20 HU) simulating a hydronephrotic pattern. These areas correspond to dilated calyxes or necrotic cavities. The negative Hounsfield units are related to the presence of adipose tissue and purulent material. Following intravenous iodine contrast injection, intensely enhanced uptake is observed due to the peripheral inflammatory ring or the compressed renal parenchyma.
In diffuse XGP the collector systems sometimes appear massively dilated, with atropy of the parenchyma and replacement of the latter by necrotic tissue and xanthomatous infiltrates.
Focal XGP is infrequent, and affects women and children in a greater proportion. The anatomical and radiological changes are similar to those seen in diffuse XGP, though limited to one concrete area. XGP can be assessed based on the following findings:
Grade I XGP. Pathological changes are seen in the kidney only.
Grade II XGP. Perirenal changes are observed.
Grade III XGP. Peripheral inflammation and inflammatory changes are noted.
Acute focal pyelonephritis or lobar nephronia
Is regarded as a form of uncomplicated pyelonephritis. The area of infection may manifest as a mass. In contrast to renal abscesses, no suppuration is seen, and the lesion is therefore not amenable to drainage. These lesions represent a pre-abscess condition. Basal CT may show a normal or weakly hypodense kidney in the affected region, while studies with intravenous iodine contrast injection reveal rounded hypodense areas with no enhanced uptake or only weakly enhanced uptake. These alterations may either return to normality or progress towards more complex forms, particularly in immune depressed individuals.
Intrarenal abscesses
Are often caused by ascending gramnegative infections. Many microabscesses develop in the course of acute pyelonephritis, and these foci in turn can eventually give rise to a large abscess cavity. The incidence of hematogenous grampositive infections has decreased as a result of antibiotherapy.
Urinary obstructions represent predisposing factors (calculi are found in 25% of all cases), along with diabetes mellitus, cachexia, drug abuse or immune suppression. Multiple abscesses are seen in cases of urinary sepsis. In such cases bulging of the renal contour may be seen, together with an increase in organ size and manifest asymmetry with respect to the contralateral kidney, depending on the size of the lesion.
Following intravenous iodine contrast injection, sharply delimited lesions can be seen, with densities of 0-20-30 HU. The peripherally enhanced uptake is due to perfusion of the dilated vessels that surround the lesion, or to the inflammatory granulation tissue. In peripheral lesions we can see thickening of Gerota's fascia or lateroconal fascia, with striations in the perirenal adipose tissue planes. Abscess extension can give rise to changes in the perirenal or pararenal space, or in the psoas muscle compartment.
Pararenal abscesses
Can develop as a result of direct extension from perirenal inflammatory processes, or derive from other disorders such as Crohn's disease, diverticulitis, costovertebral osteomyelitis, or infections ascending from the sigmoid region.
Pyonephrosis in turn represents the collection of purulent material (pus) within dilated collector systems, in combination with a reduction in renal function. The term "pyocalyx" is used if only one calyx is affected. Affected patients present fever, flank pain, chills and afebrile episodes. Treatment in this case consists of percutaneous drainage under antibiotic coverage. The CT scan shows dilated collector systems, depending on the level of obstruction, and with infected fluid densities in the range of 20-30 HU or more.
RENAL TUMORS
Renal tumors are not frequent. Indeed, they represent a mere 2% of all adult neoplasms. Ninety percent of all renal tumors are renal cell carcinomas with a peak incidence in the 50-70 years age range. Such lesions moreover are twice as frequent in males as in females. Nevertheless, a great variety of both benign and malignant neoplastic processes are located in the kidneys.
Renal adenomais
Observed in 15% of all necropsy studies. These are single or multiple subcapsular lesions, normally measuring less than 10 mm in diameter, and are histologically characterized by the presence of basophilic cells with a papillary or tubular structural pattern. Lesions measuring under 30 mm in size can be regarded as benign tumors, while those of greater diameter are likely to be malignant.
None of the imaging techniques are able to reveal features specific of renal adenoma. The tumor mass may be avascular, hypovascular or hypervascular. A factor to be taken into account when considering the existence of renal adenoma is that patients on dialysis often develop such adenomas, and must be subjected to follow-up. If these tumors increase in size approximately 0.5 cm/year, with a range of 0-1.6 cm/year, or are complicated by hematuria, surgical resection is required.
Renal adenomas are composed of small, uniform cells with scant cytoplasm. The tumor architecture is papillary or tubular, and the lesions may appear very compact or with some cystic formations. Although they are well circumscribed, the lesions lack a capsule.
Oncocytomas
Are histologically characterized by the presence of oncocytes, which are eosinophilic cells of large size containing megamitochondria. Oncocytomas account for 1-14% of all renal tumors identified at autopsy. Macroscopically, these lesions are spherical, with a soft contour, and often present a central scar. Compression of the surrounding renal tissue may give the impression of a pseudocapsule. Oncocytomas do not usually present hemorrhage, necrosis or infiltrating patterns. The lesion tends to be asymptomatic, and the diagnosis is often incidental - though patients occasionally may experience flank pain, flank mass effect or hematuria. The size ranges from a few centimeters to as much as 25 cm. CT both with and without intravenous iodine contrast injection offers important information for the characterization of this type of renal mass. The presence of a central scar within a solid and homogeneous mass, increased contrast uptake within the scar secondary to the presence of vascularized fibrous tissue, homogeneous uptake on the part of the mass, and the absence of calcifications are the basic parameters for diagnosing oncocytoma (Figs. 1a, b, c and d).
FIGURE. 1A. Renal CT showing a large, non-encapsulated homogeneous density tumor with scant and diffuse enhancement in its anterior third portion. Good differentiation with respect to the adjacent parenchyma. Fig. 1B. Macroscopic tumor piece showing absence of necrosis, calcification, clear differentiation with respect to healthy kidney, and an intermediate pink color: ONCOCYTOMA. Fig. 1C. Macroscopic view of ONCOCYTOMA, showing a stellate central zone and "cartwheel" architectural pattern. The countours can be smooth or slightly lobulated. Fig. 1D. Microscopic image of ONCOCYTOMA, showing its compact "archipelago" architecture, with cells presenting an eosinophilic cytoplasm and abundant mitochondria.
Microscopically, the cells are distributed in the form of alveolar-type nests, trabeculae or tubular formations separated by a lax and edematous stromal component. The immunohistochemical pattern in turn is dominated by negativity for vimentin and cytokeratin 7, while cytokeratins 8 and 18 prove positive. This allows differentiation with respect to granular cell tumors.
Metanephrogenic adenoma
Is a special form of adenoma. The imaging findings (CT and MRI) may show different patterns of enhanced intravenous iodine and paramagnetic contrast uptake. No infiltration is observed, and necrosis or calcification is unusual.
Angiolipoma
Is another histologically benign type of renal mass. Angiolipomas may present as single or multiple masses affecting one or both kidneys, and associated with more complex diseases such as Pringle-Bourneville disease / tuberous sclerosis. This latter presentation is characterized by with the presence of multiple, small tumor lesions in young patients. Large, solitary and unilateral angiomyolipomas are predominantly found an middle-aged women. If the tumor is voluminous, necrotic or hemorrhagic changes may be seen within the lesion, though calcification is rare.
Angiomyolipomas (AMLs)
Are histologically characterized by the presence of adipose tissue in variable proportions, smooth muscle and blood vessels, i.e., they exhibit a hamartoma-like structure, with tissues of normal histological appearance but in abnormal proportions and locations. The CT image reveals an adipose environment interspaced with elements of increased density in the form of striations representing muscle fibers and vessels (Figs. 2a and b).
FIGURE. 2A and B. CT view showing the presence of two capsular-subcapsular masses with a predominantly adipose tissue architecture (negative densities between -190 and -110 HU). Both masses show internal vascular structures and intermediate density elements corresponding to left renal ANGIOMYOLIPOMAS. MACROSCOPIC. (2C) AND MICROSCOPIC. (2D) VIEW OF ANGIOMYOLIPOMA. Characterization is based on the proportions of its tissue components. The color is generally yellowish. This is a non-encapsulated but well delimited lesion showing no atypias.
The patients may present a palpable mass effect, flank pain, hematuria or anemia, or may be asymptomatic. Bleeding secondary to traumatic rupture or hypertension is one of the most significant complications of this type of tumor.
Angiomyolipomas are fundamentally hypodense lesions with CT signal attenuation values of between -40 and -120 HU. In order to detect the accumulation of adipose tissue, CT imaging slices of 4-5 mm are required, without intravenous iodine contrast enhancement. Following iodine contrast injection, enhanced uptake may not be seen, in proportion to the accumulation of adipose tissue and lessening of the vascular component; alternatively, the study may reveal important vascular bundles or a relevant fibromuscular presence (Fig.s 2 c and d).
Renal carcinoma
Is a malignant epithelial tumor of the renal parenchyma. These carcinomas are classified according to the type of tumor cell present (large-cell, fusiform cell, clear cell), and the observed architectural or growth pattern (acinar, papillary or sarcomatoid). Advances in genetic knowledge have changed the basic concept of this type of pathology, as well evidenced by the Heidelberg classification, which combines genetic and morphological findings.
Renal clear cell adenocarcinoma
Accounts for 90% of all renal tumors. Its peak incidence is recorded between 50-70 years of age, and males are affected twice as often as females. The incidence of these tumors in turn increases in the presence of Von Hippel-Lindau disease or Pringle-Bourneville disease / tuberous sclerosis, and in patients on dialysis.
Exhaustive knowledge of the morphology, histology, biochemistry, immunology and ultrastructure of renal cell carcinoma (RCC), and the diversity of its morphological-structural characteristics, offer clinicians an improved idea of the prognosis of the disease and its relation to the above mentioned parameters, the tumor stage and nuclear grade.
Renal neoplasms show considerable variability in growth rate (from 0-1.6 cm/year), as determined from linear measurements in the longest axial diameter. The standard deviation is estimated to be ± 2 mm, and the reference slice thickness is 5 mm. The relative changes in size must be evaluated over periods in excess of two years. A neoplasm that doubles its diameter from 1.0 to 2.0 cm can increase its volume from 0.52 to 4.19 cm3, assuming a spherical growth pattern expressed by V = 4/3 π r3.
Low-grade and well differentiated tumors fundamentally appear homogeneous, with well defined margins, in contrast to the more heterogeneous poorly differentiated lesions. Tumor grade and host resistance are the factors that ultimately determine the growth rate of these lesions.
The definition of adenoma was at one time based only on the parameter size. Renal cell carcinoma is indistinguishable from renal adenoma, and the diagnosis of adenoma is fundamentally suggested by a small or zero growth rate, and the absence of metastatic spread. Renal cell carcinomas exhibit linear growth ranges of 3.5-7.0 cm in the case of tumors diagnosed with a maximum diameter of 3 cm, and the growth rate is 0.5-4.0 cm/year. Another influencing factor is considered to be host resistance. The lesion may grow extremely slowly over prolonged periods of time, arrest its growth, or generate evidence of remission - a situation referred to as "semifrozen renal cell carcinoma".
Microscopically, renal cell carcinoma shows a heterogeneous architecture, with areas of hemorrhage, necrosis and secondary cystic changes, fibrosis and calcification. Papillary adenocarcinoma is fast-growing and presents a high incidence of cystic components. These lesions show defined margins in relation to the renal parenchyma, due to the pseudocapsule created by compression of the adjacent kidney tissue and the fibrotic reaction in response to tumor growth. All these macroscopic features have their corresponding representation in the different imaging diagnostic techniques (Figs. 3 a and b).
FIGURE. 3A and B. CT images with intravenous iodine contrast showing respective right renal masses: (A) in upper 1/3 and posterior middle zone of right kidney, and (B) showing right kidney hilar occupation. Both masses show heterogeneously enhanced contrast uptake inferior to that of the renal parenchyma, and present hypodense necrotic areas.
Renal cell carcinomas originate from the proximal tubular cells, and are classified according to the cell type, growth characteristics and cytological criteria. The most frequent cellular variety is clear cell carcinoma (71%), followed by chromophobic cell tumors (15%) (Figs 3 c, d, e and f).
FIGURE 3C and D.: MACROSCOPIC VIEWS OF CLEAR CELL RENAL CARCINOMA. The color can be light orange, often showing areas of bleeding and necrosis, with infiltrating margins. Internal cystic areas are occasionally seen. Fig. 3E. Microscopic view of clear cell renal carcinoma with a foamy or eosinophilic and granular cytoplasm. The vascular architecture is delicate and shows tubulo-cystic compactness. Clear cell carcinoma is graded according to the classification of Furhrman, which contemplates 4 grades according to nuclear criteria, presence / absence of a nucleolus, size and contour. Grade 1 clear cell carcinoma with 10 μm nucleus and no nucleolus.
In order to differentiate among the different histological subtypes, the CT pattern of enhanced contrast uptake is the most useful option. In this context, the clear cell variant shows the strongest enhancement, and may appear heterogeneous due to the presence of necrotic or cystic areas. Clear cell renal carcinoma shows enhancement values of over 85 HU in the cortico-medullary differentiation phase, while papillary carcinoma is typically hypovascular and shows peripherally increased contrast uptake. The chromophobic subtype in turn shows moderate and homogeneous enhancement, with a radiological behavior similar to that associated with oncocytoma. Multilocular cystic renal cell carcinoma is an encapsulated, benign-behaving tumor showing septae that separate chambers of variable size (Figs 4a and b)(Figs 4c and 4d).
FIGURE. 4A. CT view with intravenous iodine contrast showing a left renal tumor with: (1) parenchymal infiltration, (2) necrotic areas, and (3) dystrophic calcium plaques at the necrotic margins. Left kidney clear cell adenocarcinoma. Hilar adenopathies. Fig. 4B. Right inferior pole renal mass. Ultrasound exploration. Homogeneous ultrasound architecture showing intense echogenicity without areas of necrosis, and similar to the architecture of oncocytoma. Fig. 4C. Macroscopic view of chromophobic adenocarcinoma, representing 5% of the global epithelial tumors. The lesion is solid, well circumscribed and of a variable grayish color. Fig. 4D. Microscopic view of chromophobic adenocarcinoma, showing a solid pattern, eosinophilic cytoplasm and perinuclear halo. Fig. 4E and F showing tumor bleeding, manifesting as renal, subcapsular, capsular and perirenal hemorrhage. Mass effect and heterogeneous densities due to the hematic and iron concentration, with clot retraction and serum fraction.
Perirenal bleeding is an atypical presentation of renal cell carcinoma, unrelated to the size of the tumor. CT is the fundamental diagnostic tool in this case, with a sensitivity of 100%. In effect, CT is the technique of choice for diagnosing renal tumors. Its sensitivity in diagnosing tumors is 94%, with a reliability of 90% in relation to tumor staging - this sometimes proving inferior to the performance of MRI (Figs 4e and f).
The main questions we must ask are the following: Is there a renal tumor? If so, is it malignant or benign? Does its growth extend beyond the kidney? Are the lymph node chains affected? Are there distant metastases? Is the collector system infiltrated by the tumor? Is the perirenal adipose tissue infiltrated? Is there tumor thrombosis of the renal vein or inferior vena cava? All these aspects must be reflected in renal tumor staging.
Renal cell carcinoma induces changes in organ contour, shape and orientation, depending on the volume and location of the lesion. The basal CT scan may show the tumor to be hypodense, isodense or hyperdense with respect to the adjacent parenchyma. The hyperdense areas usually correspond to intratumor hemorrhagic foci. Cystic areas or cystic tumors in turn are related to papillary forms of renal cancer.
Calcifications are clearly identified with CT. In most cases, the calcifications are amorphous and are located centrally in the form of clusters. An "eggshell" pattern is associated with small tumors.
Following the bolus administration of iodine contrast, most tumors show enhanced uptake in the later periods of the parenchymal phase. The adjacent renal parenchyma tends to show greater enhancement, with a net contrast between tumor and healthy organ tissue. The necrotic areas do not show enhanced uptake following contrast injection. A blurry appearance or erasure of the renal contour is associated with perirenal infiltration (Fig.s 5a and b).
FIGURE. 5A. CT image showing a left renal tumor with perirenal spread (thickening of perirenal septae), and the presence of perirenal venous vessels. Internal cystic and necrotic areas. Moderate-intermediate vascular enhanced uptake of the tumor tissue. Fig. 5B. Tumor spread beyond the capsule. Images of perirenal, fascial and left flank infiltration.
CT offers a sensitivity of 78-95% in detecting tumor thrombosis, with a specificity of 96%. Thrombi are seen as a filling defect or as a vascular tumor following bolus injection of the contrast medium, due to arterialization of the thrombus within the renal vein or inferior vena cava. Right renal vein thrombi are more difficult to evaluate, due to their short trajectory and oblique position, and patients with obstructed liver venous flow towards the inferior cava may develop Budd-Chiari syndrome.
STAGING OF RENAL CELL CARCINOMAS
The main factors influencing the prognosis of renal cell carcinoma are the following:
- Nuclear grade, histological subtype
- Anatomical extent of the tumor
Ten histological subtypes of renal cell carcinoma are presently considered:
1.- Clear cell carcinoma, originating from the proximal tubular cells
2.- Papillary carcinoma, likewise originating from the proximal tubular cells
3.- Chromophobic cell carcinoma, derived from the cortical collector tubules
4.- Multilocular cystic carcinoma
5.- Collector tubule carcinoma, derived from the medullary collector tubules
6.- Mucinous tubular carcinoma, derived from the loop of Henle
7.- Renal cell carcinoma associated to neuroblastoma
8.- Translocation carcinoma
9.- Hereditary syndromes
10.- Non-classifiable lesions
The most important individual prognostic factor in relation to any of the mentioned histological subtypes is the extent of the tumor at the time of diagnosis. Advances in surgery have made it possible to indicate successful conservative surgery in patients with organ-confined neoplasms, single-kidney lesions, with renal failure, or with bilateral multiple tumors.
CT is the diagnostic technique of choice for staging renal cancer, with a reliability of 91%, though under special circumstances MRI may help define elements of interest: (a) visualization of pseudocapsule integrity in papillary renal cell carcinoma; (b) visualization of the tumor thrombus in the renal vein and inferior vena cava; (c) alteration of the perirenal adipose tissue signal in the case of infiltration; and (d) lymphatic and metastatic evaluation. The CT exploration protocol includes a basal study with contrast medium in the following phases: (1) cortico-medullary, (2) nephrographic, and (3) excretory, with multiplanar reconstructions (Figs. 6a, b, c and d).
FIGURE. 6A and B. Basic CT and MRI images for assessing renal architecture, morphology, volume, contour and excretory tract condition. CT with intravenous iodine contrast allows clear cortico-medullary differentiation, and visualization of the hilar and retroperitoneal regions. MRI in T1-weighted sequencing allows us to study the organ in all its planes, and offers cortico-medullary differentiation without contrast injection. Fig. 6C and D. MIP (maximum intensity projection) reconstructions in aorto-renal MR-Angio. Preoperative evaluation of renal, tumor and retroperitoneal vascularization in search of anomalies, accessory vessels and abnormal vascular supply networks.
Perirenal adipose tissue invasion is decisive for defining the required surgical technique. Infiltration of the perirenal compartment is indicative of the need for radical nephrectomy. Imaging identification of adipose tissue involvement constitutes an important source of false-positive and false-negative results, however. The presence of nodules with enhanced contrast uptake within the adipose tissue is more specific, but may be due to non-neoplastic changes secondary to vascular ingurgitation or edema, in those cases characterized by prior inflammation (Figs. 7a and b).
FIGURE. 7A and B. Coronal plane MRI images and basal T1-weighted sequences, showing right (7C) and left perirenal involvement (7D). Note thickening of the perirenal septae, the presence of venous vessels and involvement of the renal vascia. The perirenal adipose tissue shows reduced MRI signal intensity.
Regional lymph node assessment using CT or MRI and the administration of contrast media based on iron oxide nanoparticles (USPIO) is decisive for establishing a prognosis. Metastatic lymph node involvement is indicative of a poor prognosis, with a survival of 5-30% after 5 years. The diagnosis of lymph node invasion is based on criteria of size. CT and MRI offer a reliability of 83-88%. Positron emission tomography (PET-CT-FDG) offers a sensitivity of 85% and a specificity of 100%. The use of iron oxide contrast media exhibits increased specificity in the context of MRI. This type of lymphatic assessment is based on nanoparticle phagocytosis by the cells of the reticuloendothelial system. A normal lymph node decreases its signal homogeneously as a result of the positive ferromagnetic effects of the contrast. In contrast, a partially or totally affected lymph node shows a high signal intensity due to the fact that the reticuloendothelial cells have been replaced by tumor cells (Figs. 8a and b).
FIGURE. 8A. CT image showing a left inferior polar renal tumor with retroperitoneal lymph node involvement. The lymphadenopathies are of variable volume, and the retroperitoneal extranodal adipose tissue exhibits increased density with fine striations characterizing extranodal neoplastic activity. Fig. 8B. MRI image showing a left renal tumor with perirenal and lymphatic spread.
Tumor invasion is based evaluated by MRI. As regards the difference between tumor and non-tumor thrombosis, the former is heterogeneous, hyperintense in T2-weighted sequences, and shows enhanced contrast uptake. On the other hand, a non-tumor thrombus is hypointense due to the concentration of hematic iron, homogeneous, and shows no increased uptake (Figs. 9a, b and c).
FIGURE. 9A. Coronal T1-weighted MRI. Tumor thrombus in IVC. 9B. Renal CT with intravenous iodine contrast showing tumor thrombus in right renal vein and IVC. 9C. Sagittal T1-weighted MRI showing metastatic tumor thrombus in portal vein and varicose transformation changes of the network.
Adrenal gland invasion may be synchronous and ipsilateral. In this context, CT offers a negative predictive value of 100% and a positive predictive value of 92.8%. Direct tumor spread outside Gerota's fascia and towards the neighboring organs can be studied more reliably with MRI. Erasure of the adipose tissue planes in relation to the adjacent organs is suggestive of direct infiltration.
At the time of presentation of the renal tumor, 25-30% of all patients have isochronic metastases. CT evaluation must include staging of the lung fields, liver, adrenal glands and retroperitoneum (Figs. 10a and b).
FIGURE 10A and B. CT IMAGES OF METASTATIC RENAL CANCER. Multiple space-occupying lesions in liver. Dorsal vertebral metastasis with spinal canal and radicular involvement.
KIDNEY AND LYMPHOMA
Primary renal lymphomas are very rare. Secondary renal involvement, particularly in the form of non-Hodgkin lymphoma, is more frequent. These presentations may result from hematogenous spread or direct contiguity infiltration from the neighboring lymph nodes.
With CT, renal lymphoma manifests in a number of forms, with bilateral involvement in 75% of cases. Imaging in the absence of contrast medium may show apparently normal kidneys or kidneys of moderately increased volume. Perirenal tissue infiltration induces increased adipose tissue density. There may be multinodular changes, often with lobulated renal contours. This is the most common pattern (45%), in contrast to circumscribed renal lesions, which are seen in only 15% of all patients, or bilateral diffuse infiltrations (10%). Renal infiltration from retroperitoneal locations is found in 25% of cases. The manifestations of extrarenal lymphoma imply the liver-splenic axis and lymh nodes of the mesenteric, paraaortic, pelvic and adrenal regions (Figs. 11a and b).
FIGURE. 11A. Right renal ultrasound view of primary organ non-Hodgkin lymphoma. Prenchymal destructuring. Diffuse infiltrating pattern with non-homogeneous ultrasound structure. Preservation of the perirenal adipose tissue. Fig. 11B. Retroperitoneal non-Hodgkin lymphoma with extranodal bilateral renal infiltration (secondary renal non-Hodgkin lymphoma).
INFREQUENT RENAL TUMORS
This section comprises fibroma, hemangiopericytoma, renal pheochromocytoma, reninoma, leiomyoma, hemangioma, lymphangioma, renal sarcoma, carcinoid lesions, benign fibrous histiocytoma and teratomas.
Renal sarcoma represents a mere 1% of all adult renal neoplasms. It probably originates in the renal capsule. These are usually voluminous tumors, and one-third are palpable. Renal sarcomas have a variable histological composition: leiomyosarcoma (Figs. 12a, b, c and d), liposarcoma, rhabdomyosarcoma, malignant fibrous histiocytoma or fibroxanthosarcoma. The prognosis is moreover very poor if there is early metastatic spread.
FIGURE. 12A. Right renal leiomyosarcoma in a single-kidney patient. Tumor isodense with muscle, homogeneus, well circumscribed and defined, and without evidence of necrosis. Fig. 12B. Left renal leiomyosarcoma. Non-homogeneously enhanced contrast uptake within the tumor, with no evidence of necrotic areas. Microscopic views of two samples of leiomyosarcoma. Fig. 12C. Leiomyoma appearance. Note the focal hemorrhage and necrosis. Fig. 12D. Evidence of fusiform-type cells. A myxoid variant is observed. Note the necrosis and tissue pleomorphism with variable degrees of mitosis.
SUMMARY AND CONCLUSIONS
In the presence of any mass effect in the renal region, detected by routine ultrasound or on the basis of CT scans specific or nonspecific of renal disease, strict patient protocolization is required in order to secure a sequence of data allowing us to establish an anatomical-radiological correlation of the process. The classification criteria for non-complicated and complicated cyst disease, and the characteristics of specific disorders such as hamartomatosis, renal polycystosis, and nonspecific and specific inflammatory processes such as tuberculosis and xanthogranulomatous pyelonephritis, can be easily covered by ultrasound. CT and MRI in turn contribute abundant information determined by the etiology and course of the disease.
Such characterization proves most important in relation to benign and malignant renal tumor disease. Radiological differentiation between adenoma and carcinoma is difficult in the early stages, when the lesion is no larger than 20 mm in diameter. More in-depth evaluation of the radiological-pathological correlations, and the study and visualization of tumor architecture with the different imaging techniques, afford key information on the specific biological behavior and histological features of these lesions. Probably, much more information on tumor biology can be obtained from the emerging cell- and molecular-based MRI and spectroscopic technologies, the use of specific contrast media in ultrasound, and the application of SPECT or PET-CT-FDG techniques.
Factors relevant to surgical management, such as perirenal tumor spread, lymphatic spread, or venous or metastatic tumor progression can be demonstrated relatively efficiently with multidetector CT or MRI techniques. We face a genuine challenge: detection, location, extent, characterization, surgical planning, prognosis - a complete chain of decisions based on a multidisciplinary approach in which urologists, radiologists, pathologists, oncologists, biologists, physiopathologists and specialists in emerging areas in basic science and research will have to analyze and characterize kidney lesions.
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Correspondencia author: Dr. Javier Fernández Mena
Departamento de Radiología y Medicina Física
Universidad de Granada
Author e-mail: jfm.rad--at--gmail.com
Paper information: Original
Manuscript received: march
Manuscript accepted: april
