Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

KIDNEYS AND URETERS

to be at an advanced stage. Yet prognosis appears favorable even at this stage.

Hematuria is still the primary presentation for about 60% of these tumors; a minority present with systemic symptoms or a paraneoplastic syndrome. Flank pain or a palpable mass is found in a minority.

Paraneoplastic Syndrome and

Systemic Manifestations

Renal cell carcinoma is associated with several paraneoplastic manifestations. A nephrogenic liver dysfunction syndrome without jaundice (Stauffer’s syndrome) or cholestatic jaundice develops in some patients.

Some renal cell carcinomas produce hormones that have their own manifestations. These include renin (hypertension), parathormone (hypercalcemia), erythropoietin (erythrocytosis), gonadotropin (gynecomastia), and adrenocorticotrophic hormone (Cushing’s syndrome). Hyperglycemia is rare. Hypercalcemia occurs in a number of clinical settings, including such malignancies as lung, breast, ovary, squamous cell, and renal, and some hematologic cancers. Hypercalcemia is rare with other genitourinary malignancies.

Some patients with proven renal cell carcinoma and without an obvious cause of serum alkaline phosphatase elevation, such as metastases or other liver or bone diseases or pregnancy, have an elevated phosphatase level, probably due to a paraneoplastic syndrome. In some patients alkaline phosphatase normalizes after nephrectomy, and metastases develop later without phosphatase elevation.

Etiology

Several syndromes are associated with familial renal cell carcinomas, with the best known being von Hippel-Lindau disease. Renal cell carcinomas in this disease tend to be multicentric and bilateral.

Hereditary papillary renal cell carcinoma is probably in a distinct class of inherited malignancies. Germline missense mutations, allelic losses and duplications of certain chromosomes, and mutation of the VHL gene occur in some renal cell carcinomas. Involved individuals appear to exhibit an autosomal-

dominant transmission with reduced penetrance. A number of these hereditary renal cell cancers are detected incidentally in asymptomatic individuals. Currently a patient presenting with bilateral, multiple, or an early onset of renal cancer should be investigated for von Hippel-Lindau disease and possibly other syndromes. Birt-Hogg-Dubé syndrome, probably familiar only to dermatologists, appears to be associated with familial renal tumors, including oncocytomas and papillary renal cell carcinomas (52).

Patients in chronic renal failure undergoing dialysis who then develop acquired cystic kidney disease are at increased risk of developing renal cell carcinomas. These cancers tend to be hypovascular and difficult to detect early in their course.

Exposure to certain chemicals increases the risk of developing renal cell carcinoma. Thus long-term exposure to trichloroethylene, an industrial solvent, leads to an increased incidence of these tumors. Patients exposed to high and cumulative doses of this solvent have mutations in the VHL gene. An association exists between the number of mutations and the severity of exposure to this solvent (53); the mutations are often multiple and show a loss of heterozygosity.

Radiation therapy–induced renal cell carcinoma is rare. In the few reported patients, radiotherapy occurred several decades earlier.

With the increased survival seen after therapy for childhood neuroblastomas, these patients appear to be at increased risk for subsequent renal cell carcinoma.

Associated Conditions

A synchronous second primary is uncommon, with anecdotal reports describing double primary tumors of the kidney and ovary. A higher than expected synchronous association appears to exist between renal cell carcinoma and non-Hodgkin’s lymphoma. A greater than expected risk of a metachronous second primary also exists in these patients, with the most frequent second neoplasm being in the gastrointestinal tract.

Renal cell carcinoma is association with renal cystic diseases, including simple renal cysts, acquired cystic diseases of the kidney, multilo-

cular cysts, and occasionally even polycystic kidney disease.

Incidental Tumor

Most studies suggest that incidentally discovered renal cell carcinomas tend to be smaller, are more often localized to the kidney, show less vascular invasion, and are of a lower tumor stage, and these patients have greater survival compared to a symptomatic tumor. Some studies suggest, however, that no prognostic differences exist for the same tumor stage. Practically, numerous exceptions exist and it is difficult to generalize.

Over the last several decades the number of incidental renal cell carcinomas detected has increased considerably, while deaths from renal cancer have decreased. A kidney-sparing operation is now much more often feasible than in the past. Of interest is that the examination most responsible for discovering an incidental tumor is US.

Multicentric Tumors

Renal cell adenomas and carcinomas occur bilaterally and are often multicentric (Fig. 10.10). Multiple synchronous renal cell carcinomas occur in von Hippel-Lindau disease and the acquired cystic conditions developing in endstage renal disease. The reported prevalence of multicentricity varies, ranging from 10% to almost 50%. Whether a relationship exists between multicentricity and the size or stage of a primary tumor is not clear, realizing that whether a partial or total nephrectomy is performed is often based on the size of the carcinoma.

A rare patient is found to have multiple renal cell adenomas or adenomatosis. This condition is more common in a setting of end-stage renal disease.

Growth

Renal cell carcinomas tend to be relatively slowgrowing tumors. Typical tumor volume doubling time is over 1 year; on the other hand, metastases grow considerably faster, and the microenvironment appears to play a role in their growth rate. Because of their slow growth, watchful waiting appears appropriate for some

ADVANCED IMAGING OF THE ABDOMEN

of these patients. Nevertheless, tumor size is related both to tumor stage and survival, with larger tumors generally being of an increased stage and associated with a worse prognosis; keep in mind that some very large renal cell carcinomas tend to have a favorable prognosis.

Rare spontaneous regression of a renal cell adenocarcinoma is reported. Most contain calcifications or a cystic, necrotic cavity and few viable carcinoma cells.

Screening

Several sonographic screening studies have eventually led to a renal cell carcinoma diagnosis in <0.2% of healthy adults. Most detected hyperechoic renal tumors are angiomyolipomas, with others being some other tumor, a cyst, or simply a normal variant.

Pathologic Study

Renal adenomas are defined as those having a low nuclear grade tubulopapillary histology, and <5mm in diameter (54); most are located in the cortex and have a discrete border. Autopsy studies commonly identify what appear to be cortical adenomas. Pathologists use the term renal cortical neoplasm of low malignant potential for similar low-grade histology but slightly larger tumors (54).

Renal cell carcinomas show considerable histologic variability. Many adenocarcinomas have varying degrees of tubular differentiation. Some are difficult to classify. Some require immunohistochemical staining and electron microscopy for adequate evaluation.

One grading scheme consists of applying the worst grade that occupies more than 10% of a tumor; the presence of a higher grade, the number of satellite tumors, and vein invasion are directly proportional to tumor size. Thus small carcinomas tend to contain more grade 1 carcinomas, with their frequency decreasing with increasing tumor diameter as grade 3 cancers increase in frequency; venous involvement and risk of metastases also correlates directly with tumor size. Multifocal carcinomas are also more prevalent in larger tumors. Necrosis, hemorrhage, and cystic degeneration are common in larger cancers. They invade locally, spread to regional lymph nodes, and metastasize mostly hematogenously.

these tumors are malignant, thus affecting prognostic considerations.

Although hematuria has numerous causes, generally a neoplasm needs to be excluded and both upper and lower urinary tracts must be studied. Traditionally, IV urography was the initial study for the upper urinary tracts but it has been supplanted in some institutions by US, although the documentation for such a change is rather weak. In either case, if one study is negative and a bladder tumor has been excluded, then the other study is indicated. Some investigators believe that with a negative first study, CT should be the second study, but here also firm evidence is lacking. With an ambiguous first study, on the other hand, CT seems reasonable.

A minority of renal cell carcinomas contain calcifications, with the prevalence increasing with tumor size. Calcifications range from punctate to linear and are located either in the center or on the periphery. Peripheral calcifications are seen more often in association with cysts but do occur in cystic adenocarcinomas. Calcifications are less common in most other solid renal tumors, and detection of calcifications makes a renal cell carcinoma more likely.

Renal function tends to be preserved except with very extensive tumors. Lack of function should suggest renal vein thrombosis.

Using current imaging techniques, in general, any solid non–fat-containing renal tumor

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should be considered malignant. Adenomas have a similar imaging appearance to that of carcinomas (Fig. 10.11). Serial follow-up is problematic because some renal cell carcinomas show little or no size change over a year or more. Renal cell cancers tend to be larger, are more round and more encapsulated than metastases. Enlarged perirenal lymph nodes, on the other hand, are more common with metastases.

Ultrasonography is generally the first imaging test obtained in children with a palpable abdominal tumor. Except for a suspected cystic tumor, either contrast CT or MRA is obtained next.

Computed Tomography

Computed tomography is considered to be accurate in detecting renal tumors. Some studies have reported CT sensitivities and specificities >98% in detecting these tumors, but enthusiasm for these high percentages should be tempered by an inherent build-in patient selection bias. Detection varies with tumor size, with a majority of tumors <5mm not detected.

Because most renal cell carcinomas originate from the cortex, a renal contour bulge is common. On precontrast CT most small tumors are isodense to renal parenchyma. Larger tumors tend to necrose and bleed and are heterogeneous in appearance. Postcontrast, carcinomas exhibit variable CT enhancement,

generally less than normal renal parenchyma (Figs. 10.12 and 10.13). Small tumors tend to have homogeneous contrast enhancement, while larger ones are heterogeneous. A nonenhancing central scar surrounded by an irregular enhancing rim is found in some. Larger tumors tend to have an indistinct margin between the tumor and the adjacent normal parenchyma. A not uncommon appearance for a renal carcinoma at initial presentation is that of a large

Figure 10.13. Right renal cell carcinoma. Computed tomography identifies a poorly enhancing tumor (arrow). (Courtesy of Algidas Basevicius, M.D., Kaunas Medical University, Kaunas, Lithuania.)

hypervascular tumor having inhomogeneous contrast enhancement.

Computed tomography often detects collateral renal capsular veins, and at times even gonadal vein collaterals. These collateral veins are a manifestation of the extensive high-flow state and arteriovenous shunting present in many of these highly vascular tumors; they tend to be more prominent with larger tumors. An arteriovenous fistula is detected in some cancers.

A common assumption is that radiographically visible fat does not occur in a renal cell carcinoma, and the presence of fat, if detected by CT, essentially excludes a carcinoma. Yet exceptions do occur. Some renal cell carcinomas encase adjacent fat. Metaplasia within a necrotic tumor results in fat. The presence of fat is even more relevant with MR studies (discussed later).

Ultrasonography

Renal cell carcinomas range from hypoechoic to hyperechoic compared to normal renal parenchyma. Acoustic shadowing is not found. Smaller tumors tend toward a hyperechoic appearance, and US cannot differentiate small renal cell carcinomas from angiomyolipomas. An anechoic or hypoechoic rim is detected in a minority of solid renal cell carcinomas, a finding not seen with angiomyolipomas. Con-

trast enhanced second harmonic US detected a rim of perilesional enhancement, mostly in the tardive phase, in 86% of renal cell carcinomas but not in noncarcinomas (55).

Doppler US detection of blood flow within a cyst suggests a malignancy. Hypervascularity, intratumoral high flow arterial signals, and a high pulsatility index within a complex cyst also suggest a malignancy. Some inflammatory tumors, however, have similar findings; also, hypovascular malignancies will be missed. In particular, small tumors are difficult to characterize.

Magnetic Resonance

Magnetic resonance is useful in renal cancer detection and preoperative evaluation when other imaging modalities are limited by artifacts or the use of iodinated contrast agents is contraindicated. Current MRI techniques achieve accuracies in renal tumor detection and characterization similar to those of CT.

Small renal cell carcinomas tend to be hypoto isointense on T1-weighted MR images and isoto hyperintense on T2-weighted images; regions of high signal intensity on precontrast T1-weighted images represent intratumoral hemorrhage, while hypointensity on T2weighted image is caused by hemosiderin, hemorrhage, or necrosis. Considerable intensity

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variation exists, however, and some small tumors are missed on noncontrast images (Figs. 10.14 and 10.15). Larger tumors tend toward a heterogeneous appearance. The use of gadolinium improves tumor detection and characterization. Postcontrast, carcinomas <3cm in diameter range from hypervascular (enhancement greater than that of renal cortex) to hypovascular (56), while those >3cm tend more toward hypovascularity.

Some renal cell carcinomas contain sufficient fat that they undergo a loss of signal intensity on chemical shift opposed-phase MRI (Figs. 10.16 and Fig. 10.17); generally insufficient fat is present to be detected by CT. Magnetic resonance findings in these tumors overlap those seen with little or no fat-containing angiomyolipomas, and thus the dictum that renal cell adenocarcinomas rarely contain fat should be modified when applied to MR. These intracellular lipid-containing carcinomas are mostly chromophobe (clear cell) carcinomas, and thus chemical shift imaging tends to differentiate them from other renal cell carcinomas. Chemical shift gradient-echo MRI reveals a significantly higher signal loss in clear cell carcinomas compared to non–clear cell carcinomas (57); a significant correlation exists between specimen fat staining and signal loss. Signal intensity loss on opposed phase images is not seen with all clear cell carcinomas and even in