Renal Tumors

A. Renal Cell Carcinoma

1- Derived from renal tubular epithelium
2- Located predominately in the cortex
3- 80-85% of all primary malignant tumors of the kidney
4- 2-3% of all cancers in adults
5- 30,000 cases/year
6- 40% of patients die from the disease
7- Most common in the 6th-7th decades of life
8- Men affected twice as common as women
9- Increased risk:
0o Smokers
1o Occupational exposure to cadmium
2o Acquired polycystic disease secondary to chronic dialysis (30 fold
increased risk)
3
10 Renal cell carcinoma classifications
11. Clear cell carcinoma
22. Papillary renal cell carcinoma
33. Chromophobe renal cell carcinoma
1
21. Clear cell carcinoma:
1- Most common type of renal cell carcinoma (70-80%)
2- Morphology:
1o Usually solitary and large
2o Grossly is yellow to orange to gray-white with areas of cystic
softening and hemorrhage
3o Well defined margins
4o Some may develop satellite nodules
5o Can invade into the renal vein (may extend into the IVC to the
heart)
6o Can directly invade into the perinephric fat
7o Microscopically: cells appear vacuolated or may be solid…depends
on the amount of lipid and glycogen present
8o Nuclei are small and round
3- Majority = sporadic
 4- Also occur in familial forms or in association with von Hippel-Lindau
disease (VHL)
1o VHL Disease:
2 Autosomal dominant
3 Predisposition to a variety of neoplasms:
hemangioblastomas of the cerebellum and retina
4 Hundreds of bilateral renal cysts and bilateral, often multiple
clear cell carcinomas develop in 40-60% of the cases
5 Patients with VHL inherit a germ line mutation of the VHL
gene (3p25, a tumor suppressor gene) and lose the second
allele by a somatic mutation
6 Loss of both copies can give rise to clear cell carcinoma
7 Loss of chromosomal segment of 3p14 to 3p26 is often seen
in sporadic clear cell carcinoma

12. Papillary Renal Cell Carcinoma

1- 10-15% of all renal cell carcinomas
2- Frequently multifocal and bilateral
3- Familial and sporadic forms
4- Chromosome involved: 7q31 = MET protooncogene
1o MET gene = tyrosine kinase receptor
2o An "overdose" of the MET gene (2-3 fold gain) in chromosome 7
can spur abnormal growth of tubular epithelial cell precursors of
papillary renal cell carcinoma
3o Trisomy of chromosome 7 along with mutations of the MET gene
are seen commonly in familial papillary renal cell carcinoma
5- Morphology:
1o Papillary formations with fibrovascular cores
2o Can have clear cells or more commonly cells with a pink cytoplasm

13. Chromophobe Renal Cell Carcinoma

1- Least common type (5%)
2- Cells stain more darkly than clear cell type
3- Tumor cells have multiple losses of entire chromosomes hypodiploidy
4- Good prognosis (in general)

Renal Cell Carcinoma Clinical Course

1- Most frequent presenting manifestation = hematuria (>50% of cases)
2- If tumor is large = flank pain and a palpable mass
3- Nonspecific extrarenal effects of tumor = fever and polycythemia
 1o Polycythemia from erythropoietin produced by tumor cells (5-10% of
cases)
4- In many cases, the primary tumor remains silent…only to be diagnosed
after it metastasizes
5- Prevalent metastatic sites: lungs and bone
6- Tumor presents in many fashions, but the following triad is characteristic:
1o PAINLESS HEMATURIA
2o LONG-STANDING FEVER
3o DULL FLANK PAIN

B. Wilms Tumor
1- 3rd most common organ cancer in children < 10 years old
2- Infrequent in adults
3- Variety of cell and tissue components which are all derived from mesoderm
4
0III. Tumors of the Urinary Bladder and
1Collecting System
2
5- Transitional epithelium lines the collecting system
6- Collecting system tumors above the bladder = relatively uncommon
7- Dominant clinical presentation = painless hematuria

Bladder Tumors
1- Bladder tumors = more frequent cause of death than kidney tumors
2- Bladder tumors range from benign papillomas to invasive cancers

Benign Papillomas
1 Rare
2 Frond like structures with a delicate fibrovascular core that
are covered by multiple layers of well- differentiated transitional
epithelium
3 Usually solitary and rarely recur after removal

Malignant tumors
1 Used to be called transitional cell carcinomas
2 New terminology: urothelial carcinoma
3 Range from flat to papillary, from noninvasive to invasive,
and from well differentiated to highly anaplastic
4 Grading of tumors
0o Grade I: well differentiated
1o Grade II
2o Grade III: highly anaplastic and aggressive
1- Bladder Cancer Clinical Course:
1o Men 3x as frequent as women
2o 50-70 years old
3o 50x more common in those exposed to B-naphthylamine
4o Increased incidence with: smoking, chronic cystitis,
schistosomiasis, and certain drugs (cyclophosphamide)
5o Clinical significance of bladder cancer depends on:
6 Histologic grade and differentiation of tumor
7 Depth of invasion (**most important**)
2o Deep bladder wall infiltration = 5 year survival rate < 20%
3o Overall survival rate: 57%