Renal Cell Carcinoma
Clear-cell Cromophillic / Papillary
- 85% of all renal cancers in adults
- Male > female pxs
- Peak in 6th & 7th decades (except hereditary)
Epidemiology
- Hereditary carcinomas → 3-5% of all RCC
Most common renal cell carcinoma Second most common
- Smoking
- Obesity
Risk Factors
- Hypertension
- Acquired cystic kidney disease in dialysis pxs
VHL gene mutation - 60% Type 1: MET proto oncogene [ch7]
- Sporadic - Sporadic MET duplication
- VHL disease - Hereditary papillary renal cell
carcinoma
Etiology Familial clear-cell renal carcinoma Type 2: FH tumor suppressor gene
- 3p translocations - Sporadic
- Hereditary leiomyomatosis and
renal-cell cancer syndrome
Other: SDHB → Hereditary paraganglioma
pVHL protein normally: Mutation: Mu
- O2 sensing → Inhibits HIF → decreases VEGF - Hereditary → one allele is dysfunctional →
and angiogenesis needs second hit
- Ubiquitination and lysis of proteins - Sporadic → two alleles need to be mutated
Mutation: ● MET → proto oncogene →
- Hereditary → one allele is dysfunctional → duplication → carcinogenesis
Pathophysiology
needs second hit ● FH → tumor suppressor gene →
- Sporadic → two alleles need to be inactivated inactivation → carcinogenesis
Loss of pVHL function: Type 1: pale cytoplasm and oval nuclei
- No HIFα regulation → ↑VEGF → ↑angiogenesis Type 2: large cells w/ eosinophilic cytoplasm
- No ubiquitination → protein overexpression → - Poorer prognosis
cell proliferation → Associated w/ trisomies
Triad (not usually seen)
- Flank pain -M
- Hematuria - Oc
- Palpable abdominal mass
VHL disease: - Hereditary leiomyomatosis and RCC Sx
Type 1: w/o pheochromocytome ● Cutaneous and uterine leiomyomas
Clinical Features
- Hemangioblastoma ● Solitary papillary RCC
- Renal cell carcinoma ● Early metastasis
Type 2: w/ pheochromocytoma
- A: + hemangioblastoma
- B: A + renal cell carcinoma
- C: only pheochromocytoma
Based on tumor size and placement. Staging determines 5-year prognosis. Sta
S1
- Stage I → Tumor <7 cm and limited to the kidney S2
- Stage II → Tumor > 7cm and limited to the kidney or lo
Staging
- Stage III → Tumor in major veins or adrenal gland within Gerota's fascia, or 1 regional lymph S3
node involved S4
- Stage IV → Tumor beyond Gerota's fascia or >1 regional lymph node involved site
S5
Histology
Clear-cell Cromophillic / Papillary
- 85% of all renal cancers in adults
- Male > female pxs
- Peak in 6th & 7th decades (except hereditary)
Epidemiology
- Hereditary carcinomas → 3-5% of all RCC
Most common renal cell carcinoma Second most common
- Smoking
- Obesity
Risk Factors
- Hypertension
- Acquired cystic kidney disease in dialysis pxs
VHL gene mutation - 60% Type 1: MET proto oncogene [ch7]
- Sporadic - Sporadic MET duplication
- VHL disease - Hereditary papillary renal cell
carcinoma
Etiology Familial clear-cell renal carcinoma Type 2: FH tumor suppressor gene
- 3p translocations - Sporadic
- Hereditary leiomyomatosis and
renal-cell cancer syndrome
Other: SDHB → Hereditary paraganglioma
pVHL protein normally: Mutation: Mu
- O2 sensing → Inhibits HIF → decreases VEGF - Hereditary → one allele is dysfunctional →
and angiogenesis needs second hit
- Ubiquitination and lysis of proteins - Sporadic → two alleles need to be mutated
Mutation: ● MET → proto oncogene →
- Hereditary → one allele is dysfunctional → duplication → carcinogenesis
Pathophysiology
needs second hit ● FH → tumor suppressor gene →
- Sporadic → two alleles need to be inactivated inactivation → carcinogenesis
Loss of pVHL function: Type 1: pale cytoplasm and oval nuclei
- No HIFα regulation → ↑VEGF → ↑angiogenesis Type 2: large cells w/ eosinophilic cytoplasm
- No ubiquitination → protein overexpression → - Poorer prognosis
cell proliferation → Associated w/ trisomies
Triad (not usually seen)
- Flank pain -M
- Hematuria - Oc
- Palpable abdominal mass
VHL disease: - Hereditary leiomyomatosis and RCC Sx
Type 1: w/o pheochromocytome ● Cutaneous and uterine leiomyomas
Clinical Features
- Hemangioblastoma ● Solitary papillary RCC
- Renal cell carcinoma ● Early metastasis
Type 2: w/ pheochromocytoma
- A: + hemangioblastoma
- B: A + renal cell carcinoma
- C: only pheochromocytoma
Based on tumor size and placement. Staging determines 5-year prognosis. Sta
S1
- Stage I → Tumor <7 cm and limited to the kidney S2
- Stage II → Tumor > 7cm and limited to the kidney or lo
Staging
- Stage III → Tumor in major veins or adrenal gland within Gerota's fascia, or 1 regional lymph S3
node involved S4
- Stage IV → Tumor beyond Gerota's fascia or >1 regional lymph node involved site
S5
Histology
