Renal Tumors

The vast majority of renal tumors are malignant adenocarcinomas (historically termed hypernephroma or renal cell carcinoma). Other malignant renal tumors include lymphoma and metastases. Benign solid masses (oncocytoma, angiomyolipoma) of the kidney are uncommon. Tumors of the renal pelvis are categorized separately.

Epidemiology

Renal adenocarcinoma is the 10th most common cancer, accounting for 3% of all malignancies in adults, with a median age at diagnosis of 65 years. The male:female ratio is 2:1. Incidence is increasing--sixfold from 1935 to 1989 in men (from 1.6 to 9.6 cases/100,000) and in women (from 0.7 to 4.2 cases/100,000).

No strong risk factors have been identified for the development of renal adenocarcinomas, although obesity and smoking contribute modestly. The strongest risk factors appear to be genetic; multifocal renal adenocarcinomas have a hereditary basis, which is being studied intensively. Several multiorgan syndromes are associated with a high risk of renal malignancies--the most prominent is von Hippel-Lindau disease (an autosomally dominant hereditary disease originating from chromosome 3p, beginning in the teenage years, and characterized by the development of central nervous system hemangioblastomas, renal adenocarcinomas, and other anomalies).

Pathology

Because of the isolated anatomic location of the kidney, renal adenocarcinomas can grow large while remaining clinically silent. Most demonstrate a characteristic hypervascularity. Renal adenocarcinomas have a predilection for vascular invasion and tend to grow intravascularly within the renal vein and into the vena cava. Because these tumor thrombi may extend as far as the right atrium, they present a unique surgical challenge.

Although essentially every organ site can be affected, the most common sites of metastases are the lungs, adrenal glands, liver, and bones (where the lesions are predominantly lytic and prone to pathologic fracture).

Symptoms and Signs

The historic symptom triad of renal adenocarcinoma is hematuria, flank pain, and the presence of a flank mass--most cases with these symptoms are advanced and incurable. Rarely, a patient presenting with heart failure has an underlying renal malignancy as the cause (ie, high-output failure due to a functional arteriovenous fistula). Paraneoplastic disorders are relatively common; hypercalcemia, fever, anemia, weakness, and erythrocytosis occur most often (see Table 101-1). A small percentage of tumors secrete inappropriate levels of erythropoietin.

Diagnosis and Staging

Increasingly, localized (not metastatic and not involving the lymph nodes) renal adenocarcinoma is being diagnosed in patients having no symptoms attributable to the tumor; these tumors are often discovered incidentally during imaging evaluation of patients' other complaints.

Gross hematuria is rarely a symptom of renal adenocarcinoma until an advanced stage. Because gross hematuria can occur in patients receiving anticoagulation therapy, it is important to consider renal adenocarcinoma and not to dismiss hematuria as an adverse effect of anticoagulation therapy. Patients with gross hematuria are best evaluated by a urologist. An appropriate approach is cystoscopy followed by an upper urinary tract imaging study (usually intravenous urography with tomography).

Microhematuria is problematic. Although the differential diagnosis includes tumors of the kidney, renal pelvis, ureter, bladder, and prostate, the vast majority of cases have a benign or idiopathic etiology. Microhematuria occurs in many patients with nephrosclerosis, benign prostatic hyperplasia, and small clinically insignificant renal arteriovenous malformations. Small, asymptomatic renal stones are another cause of benign microhematuria. The patient's evaluation should be individualized and should consider comorbidities, age, and previous medical history.

Incidental renal masses: The use of imaging studies (eg, ultrasonography, CT, intravenous urography) for evaluation of abdominal complaints or renal colic has significantly increased the incidental discovery of renal masses. Most masses are simple uncomplicated cysts, which become increasingly frequent after age 65. However, because the vast majority of curable (ie, still localized) renal adenocarcinomas are found incidentally, appropriate cost-effective management of these patients is important.

Usually, these incidentally discovered lesions are characterized adequately by imaging studies, without the need for biopsy or exploration. Cysts fulfilling all radiographic criteria of simple uncomplicated lesions (using either dedicated renal ultrasonography or CT) need no further evaluation; however, atypical cysts need further evaluation, as do solid masses, because cystic adenocarcinomas often have an indeterminate image.

The vast majority of solid masses are malignant and require definitive evaluation and treatment. The rare benign solid mass (eg, benign hamartomas [angiomyolipomas]) can be diagnosed by imaging studies alone. Performing a percutaneous biopsy on a solid renal mass is rarely cost-effective because it is unlikely to change future treatment unless there is evidence of advanced disease. Exceptions are patients with a previous history of another malignancy, multifocal disease, or associated extensive nodal adenopathy suggestive of lymphoma.

A CT (with or without contrast), a plain chest x-ray, and, in some cases, a bone scan are used to stage renal adenocarcinoma. Abdominal MRI rarely provides additional information (unless a tumor thrombus into the renal vein and vena cava is suspected), but MRI is appropriate when use of contrast is precluded (eg, for patients with an allergy to IV contrast or for patients with renal insufficiency).

Prognosis

In most cases of localized renal adenocarcinoma, the 5-year survival rate is > 60%. The natural history of renal adenocarcinoma is far more unpredictable than that of most solid tumors. Disease may recur > 15 years after removal of the original primary lesion. Various host immune factors may contribute to this recurrence.

Metastatic disease has a poor prognosis and is rarely curable. Metastatic recurrence at a remotely distant time is not uncommon.

Treatment

Because renal adenocarcinoma is relatively radioresistant, radiation therapy has little or no role in its treatment.

Localized disease: Surgery is the sole intervention capable of cure. The standard procedure is radical nephrectomy--removal of the whole affected kidney along with adjacent lymph nodes and tissue. In the patient with renal insufficiency or a solitary kidney, partial nephrectomy (a far more complex procedure) may be indicated. For patients with a genetic predisposition and multifocal disease (usually affecting both kidneys), sophisticated renal-sparing surgery is necessary. Laparoscopy is used in extremely carefully selected cases of small incidentally found lesions when the contralateral kidney is healthy.

No consensus exists for monitoring of recurrence or progression after surgery, but most oncologists obtain a chest x-ray and liver function tests (and occasionally a sedimentation rate) every 4 to 6 months. Performing imaging studies, particularly CT, at periodic intervals is controversial and must be individualized based on the patient's estimated prognosis and the tumor's original pathologic stage.

Metastatic disease: Renal adenocarcinoma is resistant to cytotoxic chemotherapeutic drugs. Immunotherapeutic approaches have been used, but few tumors have been cured. Interleukin-2 (IL-2) and -interferon are two cytokines that produce a low but reproducible response. Although sustained complete responses can occur, few cases are curable. Surgery to resect metastatic disease is highly controversial.

Patients with bony metastasis and substantial cortical destruction (particularly of the long bones) may require preemptive medullary rod placement and local radiation therapy to prevent pathologic fractures, thereby protecting these patients from incapacitation.