Pathology Thread

Pathology > Study Images > Urinary Tract > Tumors of the Kidney > Malignant Tumors

IV. Malignant Tumors

Objectives:

After completing this tutorial the student will know the following about malignant renal parenchymal tumors:

which are the common and important tumors

the epidemiological features and predisposing factors

the differences in the gross appearances

clinical and histologic features

prognostic factors and prognosis

Epithelial Tumors

Renal Cell Carcinoma

This is a tumor that arises from the renal tubular epithelium but is sometimes called hypernephroma in the mistaken belief that it arises from adrenal rests because of its yellow color and histologic resemblance to clear cells of the adrenal cortex. It occurs in older people with a peak incidence in 50 to 70 years. Males are affected more than females in the ratio 3:1.

Epidemiologic studies show increased frequency in tobacco users with highest risk in pipe and cigar smokers. There is also an increased incidence in patients on renal dialysis for many years. The vast majority of cases are sporadic but a few are inherited. These tend to be multifocal and bilateral and occur at a younger age than sporadic cases. The inherited forms are found in autosomal dominant renal cell carcinoma, von Hippel-Lindau disease (characterized by cerebellar hemangioblastoma, retinal angiomas, renal cell carcinoma, pheochromocytoma and cysts in various organs), and hereditary papillary renal cell carcinoma.

Renal cell carcinoma usually causes no symptoms or dysfunction. The classic triad of back pain, abdominal mass and hematuria is actually seen in only about 10% of patients with this tumor and indicates advanced disease. Hematuria is the single most common symptom and leads to secondary anemia. The tumor is known as one of the great "mimics" in clinical medicine, because of the frequent association with various systemic symptoms from organs not directly involved with tumor - erythrocytosis or polycythemia (from erythropoietin production), hypercalcemia (due to secretion of parathormone-like substance), and hypertension. About a third of patients present with distant metastases.

Question: What causes the hypertension in renal cell carcinoma?

The tumor may arise in any part of the kidney but commonly arises in the in the poles. They are large, spherical masses with well-delineated margins and a pseudocapsule of compressed, atrophic cortical tissue. The cut surface is yellow due to a large amount of intracytoplasmic lipid and there may be focal hemorrhages, necrosis or cyst formation in various combinations. Invasion of the renal capsule with extension into Gerota's fascia is common.

Renal cell carcinoma in the upper pole of a bisected kidney. Note its well circumscription and yellowish color.

Another example of renal cell carcinoma.

Angiography shows a typical vascular pattern with presence of numerous pathologic blood vessels (due to tumor angiogenesis) causing pooling of contrast medium in vessels. Early visualization of the renal vein and inferior vena cava occurs due to arterio-venous shunts within the tumor.

Renal angiography showing a highly vascular tumor. The two arrows point to a filling defect in the renal vein caused by thrombus/invading tumor.

Microscopically, the classic appearances are those of a clear cell carcinoma composed of cells with clearly defined borders, small nuclei and abundant cytoplasm set in a very prominent but delicate vasculature. Less often in other histologic variants, granular cells with homogeneous or granular eosinophilic cytoplasm often with large nuclei may be seen. Tumor cells may be in sheets, cords or as papillary fronds. A small percentage of tumors resemble sarcoma and are composed of spindle cells.

Histology of renal carcinoma showing clear cells. Note the delicate vascular stroma.

Histology of renal cell carcinoma showing granular cells.

Spindle cell or sarcomatoid renal cell carcinoma. No epithelial-looking cells are present.

Venous invasion is often extensive in renal cell carcinoma. Extension of the tumor into the renal vein is common and one of the common features of the disease is its tendency to metastasize hematogenously before giving rise to local symptoms and signs. The most common locations for metastases are the lungs (where "cannon-ball" secondary tumors are produced) with regional lymph nodes, liver and bone showing about equal frequencies next, followed by the adrenal, the other kidney and the brain.

Renal cell carcinoma with venous invasion. The tumor shows the typical yellowish color of renal cell carcinoma with foci of necrosis and cysts. Projecting from its cut surface is the cross-sectioned, thrombosed vein containing tumor.

Question: Renal cell carcinoma is one of the few carcinomas in which hematogenous metastases are more common than regional lymph node metastases. Which other carcinomas behave in this fashion?

The clinical stage is more important than the histologic grade in determining prognosis.

STAGE

DEFINITION

PROGNOSIS

5-YEAR SURVIVAL

I

Tumors confined to the kidney and do not invade the capsule

80%

II

Tumors invade the renal capsule and extend into perinephric fat but confined to Gerota's fascia.

55%

III

Regional node and/or renal vein invasion

35%

IV

Invasion of adjacent organs or distant metastases

20% for adjacent organs

Virtually all those with distant metastases die within 3 years.

Rarely, patients may have a solitary metastasis with long-term survival or even regression of the distant disease after resection of the primary tumor.

Embryonic Tumors

Nephroblastoma (Wilm's Tumor)

This is a malignant mixed embryonic tumor of the kidney. It is one of the most common neoplasms in young children and the most common abdominal neoplasm during the first five years of life. It occurs with equal frequency in males and females, and has a peak incidence in the second year of life. Approximately 75% of cases occur prior to 5 years, but rare adult cases have been reported.

The vast majority of Wilm's tumor (WT) occurs sporadically and tends to be unilateral. A few cases tend to familial and associated with different congenital syndromes:

WAGR - WT, Aniridia, Genitourinary malformations in affected 46XY males, and mental Retardation. This is associated with deletion of the Wilm's tumor-associated gene, WT1, located on the short arm of chromosome 11 (11p13).
Denys-Drash syndrome - This comprises WT, nephropathy and ambiguous genitalia in affected males. DDS is due to mutation of both alleles of the WT1 gene that renders it inactive.
Beckwith-Wiedman syndrome - Composed of WT, organomegaly and body overgrowth (either as gigantism or hemihypertrophy). This is associated with loss of the maternal allele of a locus on 11p15 called WT2, germline duplication of paternal WT2 allele or inheritance of two paternal WT2 alleles and none from the mother.

Precursor lesions in the form of multiple or diffuse foci of nephrogenic rests or blastema within otherwise normal renal parenchyma (nephroblastomatosis) substantially increase the risk of developing WT.

The commonest presentation is a large intraabdominal or flank mass (90% of cases). Other patterns of presentation include abdominal pain, intestinal obstruction, hematuria and hypertension.

Question: What is the cause of the hypertension associated with WT?

Grossly, WT tends to present as large, solitary, well-demarcated mass, which bulges from the kidney and compresses the residual parenchyma to form a surrounding thin rim. The tumor is soft and on section shows a white or "fish flesh" appearance, often with hemorrhage, necrosis or cyst formation. The yellow color of renal cell carcinoma is not seen.

Wilm's tumor showing the white, "fish flesh" color with necrosis and small cysts. The tumor is well circumscribed, compresses the surrounding tissue and nearly replaces the whole kidney.

Another example but less well delineated from the surrounding tissue but showing the typical white, "fish flesh" appearance.

The classic microscopic picture of WT is triphasic with epithelial elements in the form of abortive tubules or glomeruli, spindle-shaped stromal cells and small, round blue blastema in various proportions. This represents attempts to recapitulate the stages of development of the kidney. Occasional tumors contain only two or one of the elements.

Classic triphasic pattern of Wilm's tumor with tubules, spindle-shaped stromal cells and small, round, blue blastema cells.

Another example of classic triphasic Wilm's tumor.

Wilm's tumor showing a monophasic pattern with small, round, blue blastema. Tumor is to the right and renal parenchyma is on the left.

The stage and the presence of anaplasia, which tends to occur in older, nonwhite patients, affect the prognosis of the disease. Other prognostic factors are large tumor, capsule penetration, and spillage of tumor into the abdominal cavity. The tumor is sensitive to both radiation and chemotherapy. Combined surgical resection, radiotherapy and chemotherapy have improved prognosis dramatically. Patients dying of the tumor almost always do so within the first two years.