Renal cell carcinomas account for 90–95% of malignant neoplasms arising from the kidney. Notable features include diagnosis without symptoms, resistance to cytotoxic agents, infrequent responses to biologic response modifiers such as interleukin (IL)-2, robust activity of antiangiogenesis-targeted agents, and a variable clinical course for patients with metastatic disease, including anecdotal reports of spontaneous regression. The remaining 5–10% of malignant neoplasms arising from the kidney are transitional cell carcinomas (urothelial carcinomas) originating in the lining of the renal pelvis. See Chap. 82 for transitional cell carcinomas.
The incidence of renal cell carcinoma rose for three decades but has now reached a plateau of ~63,000 cases annually in the United States, resulting in >14,000 deaths per year. It is the ninth most common cancer overall in the United States, seventh most common in males, and tenth most common in females; the male-to-female ratio is 2:1. Though this malignancy may be diagnosed at any age, it is uncommon in those aged <45 years, and incidence peaks between the ages of 50 and 70 years. Many factors have been investigated as possible contributing causes; associations include cigarette smoking, obesity, and hypertension. Risk is also increased for patients who have acquired cystic disease of the kidney associated with end-stage renal disease and for those with tuberous sclerosis.
Most cases of renal cell carcinoma are sporadic, although familial forms have been reported (Table 81-1). One such form is associated with von Hippel-Lindau (VHL) syndrome, an autosomal dominant disorder. Genetic studies identified the VHL gene on the short arm of chromosome 3. Approximately 35% of individuals with VHL disease develop clear cell renal cell carcinoma. Other VHL-associated neoplasms include retinal hemangioma, hemangioblastoma of the spinal cord and cerebellum, pheochromocytoma, and neuroendocrine tumors and cysts. Birt-Hogg-Dubé syndrome is a rare human autosomal dominant genetic disorder characterized by fibrofolliculomas (benign tumors arising in hair follicles), pulmonary cysts, and kidney tumors. The renal tumors are usually of the chromophobe type, but they can exist as hybrids with other cell types. This disorder is associated with mutations in the FLCN gene, which codes for folliculin.
Table Graphic Jump Location TABLE 81-1Hereditary Renal Cell Tumors ||Download (.pdf) TABLE 81-1 Hereditary Renal Cell Tumors
|Syndrome ||Chromosome(s) ||Gene ||Protein ||Kidney Tumor Type ||Additional Findings |
|von Hippel-Lindau syndrome ||3p25 ||VHL ||von Hippel-Lindau protein ||Clear cell ||Hemangioblastoma of the retina and central nervous system; pheochromocytoma; pancreatic and renal cysts; neuroendocrine tumors |
|Hereditary papillary RCC ||7p31 ||MET ||MET ||Papillary (type I) || |
|Hereditary leiomyomatosis and RCC ||1q42 ||FH ||Fumarate hydratase ||Papillary (non−type I) ||Leiomyoma; uterine leiomyoma/leiomyosarcoma |
|Birt-Hogg-Dubé syndrome ||17p11 ||FLCN ||Folliculin ||Chromophobe, oncocytoma ||Facial fibrofolliculoma; pulmonary cysts |
|Tuberous sclerosis || |
|Angiomyolipomas; lymphangioleiomyomatosis; rare RCC with variety of histologic appearances ||Angiofibroma, subungual fibroma; cardiac rhabdomyoma; adenomatous small intestine polyps; pulmonary and renal cysts; cortical tuber; subependymal giant cell astrocytomas |
|Constitutional chromosome 3 translocations...|