IV. Malignant Tumors
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
Histology of renal cell carcinoma showing granular cells.
Spindle cell or sarcomatoid renal cell carcinoma. No epithelial-looking cells
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
Tumors confined to the kidney and do not invade the capsule
Tumors invade the renal capsule and extend into perinephric fat but
confined to Gerota's fascia.
Regional node and/or renal vein invasion
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
- 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
- Messenchymal Tumors
Primary malignant messenchymal tumors occur but are rare and form less than
1% of malignant tumors of the kidney.