1. a. Hereditary papillary renal cell carcinoma is a cancer syndrome mapped to chromosome 7q31.1-q34, a region containing the MET oncogene, which is mutated in hereditary papillary renal cell carcinoma families. Although trisomy 7 is commonly associated with sporadic papillary renal cell carcinomas, only 13% of sporadic papillary tumors have MET mutations, suggesting that sporadic and hereditary disease may develop by different mechanisms. Cytogenetic features of most common renal neoplasm are as follows: WT1 gene on chromosome 11p13 in nephroblastoma, p57/kip2 gene on chromosome 11p15 in nephroblastoma associated with Beckwith-Wiedemann syndrome, VHL gene on chromosome 3p25 in clear cell renal cell carcinoma associated with von Hippel-Lindau syndrome, MET gene on chromosome 7q31 in papillary renal cell carcinoma associated with hereditary papillary renal cell carcinoma.

2. a. See comment in Answer 4.

3. a. See comment in Answer 4.

4. d. Renal cell carcinoma clear cell type (conventional type), is characterized by a multinodular/multicolored tumor mass with a predominantly yellow-colored cut surface. In general, the yellow color corresponds to the lipid-rich tumor cells. The growth pattern is usually solid but occasionally a cystic growth pattern composed of multiple cysts varying in size up to 2 to 3 cm in diameter occurs. On light microscopy, the clear cell areas are the result of extensive, intracytoplasmic accumulation of glycogen, phospholipids, and neutral lipids because of characteristic disturbances of increased glucose 6-phosphate levels, activated glycosis, and reduced gluconeogenesis. As the malignancy becomes more anaplastic (grade 1-3), the amount of cholesterol decreases. Conventional renal cell carcinoma are composed of a mixture of clear cells and granular cells. This granular cell pattern can be found in chromophobe renal cell carcinoma, oncocytoma, and papillary renal cell carcinoma.

5. a. The incidence rate of simple renal cysts increases with age. In general, they are asymptomatic. They can be solitary to multiple and are usually located in the cortex. The size varies but is usually <5 cm.

6. d. Genetic renal cystic diseases include adult (autosomal dominant) polycystic kidney disease, infantile (autosomal recessive) polycystic kidney disease, juvenile nephronophthisis (autosomal recessive), medullary cystic disease (autosomal dominant), and autosomal recessive and rare multicystic disorders (von Hippel Lindau, tuberous sclerosis, etc.). Nongenetic renal cystic diseases include multicystic dysplastic kidney, benign multilocular cyst, simple cyst, medullary sponge kidney, sporadic glomerulocystic kidney disease, acquired renal cystic disease, and calyceal diverticulum.

7. a. Autosomal dominant polycystic kidney disease is associated with hepatic cysts that become evident with increased age. Autosomal recessive polycystic kidney disease is associated with congenital hepatic fibrosis in all affected surviving individuals.

8. a. The common sites are lung, liver, bone, lymph nodes, adrenal, brain, opposite kidney, heart, spleen, and skin. Liver metastasis is associated with an ominous prognosis. Adrenal metastasis occurs in <19% in ipsilateral and 10% to 11% in contralateral adrenal. Adrenal metastasis is more common with large upper pole tumors in patients with metastatic disease. The most common sites and approximate frequency of metastasis of renal cell carcinoma are lung in 50% to 60%, lymph nodes, liver, and bone in 30% to 40% each, opposite kidney in 10% to 25%, and brain in 5%.

9. c. Ninety-five percent of hemangiomas present with intermittent gross hematuria. There is no gender or side predilection. Twelve percent are multifocal and a few bilateral. Sometimes the lesions are seen in the renal pelvis. The tumor diameter ranges from 1 to 2 cm. Treatment can be embolization, laser ablation, or partial nephrectomy. However, this depends on location and size.

10. e. This is an autosomal dominant inherited disease associated typically with multiple and bilateral angiomyolipomas, mental retardation, and adenoma sebaceum. Angiomyolipoma in these patients frequently develops in late childhood. Although this tumor occurs in 80% of patients with tuberous sclerosis, <40% of patients with angiomyolipoma have features of tuberous sclerosis.

11. e. The abundant mitochondria are responsible for the eosinophilic cytoplasm seen in the polygonal, uniform cells of oncocytomas. Mitotic figures are rare.

12. d. Approximately 10% of oncocytomas occur concurrently with renal cell carcinoma in either the ipsilateral or contralateral kidney. The renal cell carcinoma can be a separate tumor or can be embedded in the oncocytoma.

13. b. The estimated incidence approaches 7 per 1,000,000. Wilms tumor is the most common renal malignancy in childhood. Fifteen percent of nephroblastomas are associated with congenital anomalies. Nephroblastoma is approximately 2 to 8 times more common in patients with horseshoe or fused kidneys. Several other genitourinary abnormalities such as renal hypoplasia, ectopia, duplications, hypospadias, and cryptorchidism have been reported in association with Wilms tumor.

14. a. Most children with WAGR syndrome have a chromosomal deletion on chromosome 11p13, the chromosomal abnormalities most commonly reported associated with nephroblastoma. The gene at this locus has been cloned and designated the WT1 tumor suppressor gene. A second Wilms tumor locus, WT2, has been identified on chromosome 11p15.5. Approximately 20% of patients with Wilms tumor have loss of heterozygosity (LOH) on chromosome 16q, and 11% of Wilms tumor patients have LOH on chromosome 1p.

15. a. The incidence of bilateral sporadic nephroblastomas is 5% (4% synchronous, 1% metachronous). Most of these are found in kidneys with the perilobar type of nephrogenic rests. Forty percent of cases with nephrogenic rests have unilateral Wilms tumors. Nephrogenic rests are found in 90% of patients with bilateral Wilms tumors.

16. a. Xanthogranulomatous pyelonephritis is commonly seen in patients with staghorn calculi. Characteristic band of golden yellow tissue outlines the dilated calyces and renal pelvis. The mucosa is ulcerated. Histologically, the lesion shows a zonal change involving all areas of the kidney. There is hyalinization or fibrosis of the cortex with only a few glomeruli remaining. A middle zone shows inflammation, many foam cells (vacuolated macrophages), proliferating small vessels, and a deep zone contains necrotic debris, blood, and fibrin in the area of destroyed medulla and calyces.

17. a. Nephroblastoma, a favorable histology. Grossly, the tumor has an encephaloid appearance. The typical nephroblastoma consists of three elements, all seen on this slide: epithelial, stromal, and blastemal. The darkly staining, intensely cellular areas are the undifferentiated nephrogenic component. In places, these appear to differentiate into tubules, occasionally glomeruloid structures—all lined by neoplastic cells. The above structures are contained in a poorly differentiated spindled mesenchymal stroma. This has a myxoid or fibroblastic appearance. Occasionally, this stromal component may show differentiation to skeletal muscle or cartilage. The presence of nuclear anaplasia is defined as hyperchromasia, nuclear enlargement to three times that of the nonanaplastic cells and multipolar aneuploid mitoses. Recognition of diffuse unfavorable histology is important because it is associated with poor response to treatment.