Diagnosis

Renal cell carcinoma

Etiology

Cause [oag]

• Sporadic/nonhereditary (96%): associated with structural alterations of chromosome 3

• Hereditary (4%): Genetic defect with translocation between chromosomes 3 and 8

  • Von Hippel-Lindau Syndrome, Hereditary Leiomyomatosis, Aggressive Papillary Carcinoma Syndrome, Hereditary Papillary Carcinoma, Birt-Hogg-Dubé syndrome, Tuberous Sclerosis Syndrome

Type of kidney cancers [oag]

1. Renal cell carcinoma (>90% of all renal malignancies)

   • Clear cell RCC (70-80% of all RCC)

   • Multilocular cystic renal neoplasm of low malignant potential

   • Papillary RCC

   • Hereditary leiomyomatosis RCC

   • Chromophobe RCC

   • Collecting duct carcinoma

   • Renal medullary carcinoma

   • MiT Family translocation carcinomas

   • Succinate dehydrogenase (SDH) deficient RCC

   • Mucinous tubular and spindle cell carcinoma

   • Tubulocystic RCC

   • Acquired cystic disease-associated RCC

   • Clear cell papillary RCC

2. Transitional cell carcinoma of the renal pelvis (behave like bladder cancer)

3. Renal sarcoma (rare)

Pathophysiology [oag]

1. Genetic mutation in the proximal renal tubular epithelium

2. RCC usually remain asymptomatic until late in the disease

3. Clinical presentation:

   • Most are detected incidentally

   • Flank pain/fullness

   • Hematuria

   • Varicocele due to tumor invasion into the renal vein

   • Hypercalcemia (bony metastasis or a paraneoplastic phenomenon)

   • Other symptoms: fatigue, weight loss, fever, night sweats, malaise, hypertension, and anemia

4. Metastatic pattern: [j15]

   • Lung (75%)

   • Soft tissues (36%)

   • Bone (20%)

   • Liver (18%)

   • Cutaneous sites (8%)

   • Central nervous system (8%)

Risk factors [oag]

• Male

• Old age

• Smoking

• Obesity

• Hypertension

• Chronic renal failure

• Alcohol

• Diabetes

• Physical activity

• Exposure to cadmium, asbestos and solvents (trichloroethylene)

Complications [oag]

• Metastasis

• Paraneoplastic phenomenon: erythrocytosis, hypercalcemia, non-metastatic liver involvement (Stauffer syndrome), thrombocytosis, prolonged prothrombin time, and hepatosplenomegaly

• Adverse effects from targeted systemic therapy or surgery: renal failure, hypertension, proteinuria, impaired wound healing, gastrointestinal perforation, hemorrhage, thrombosis, reversible leukoencephalopathy, heart failure, hypothyroidism.

Epidemiology

Incidence per 100.000 [ybe][kbz][svf][84k][zoh][fbk]

Approach

• Blood test: Complete blood cell, electrolytes, kidney function tests, liver function tests, calcium, biomarkers

• Urinanalysis

• Ultrasound abdomen

• CT abdomen

• CT thorax for staging

• PET-CT

• MRI

Staging [oag]

• T1: Tumor ≤7 cm, limited to the kidney

  • T1a: Tumor ≤4 cm, limited to the kidney

  • T1b: Tumor 4-7 cm, limited to the kidney

• T2: Tumor >7 cm, limited to the kidney

  • T2a: Tumor >7 cm but ≤10 cm, limited to the kidney

  • T2b: Tumor >10 cm, limited to the kidney

• T3: Tumor extends into major veins but not into the adrenal gland or  beyond Gerota

  • T3a: Tumor extends into the renal vein or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota fascia

  • T3b: Tumor extends into IVC below the diaphragm

  • T3c: Tumor extends into IVC above the diaphragm or invades the IVC wall

  • T4: Tumor invades beyond Gerota fascia (into the ipsilateral adrenal gland)

• Regional Lymph Nodes (N):

  • NX: Regional lymph nodes cannot be assessed

  • N0: No regional lymph node metastasis

  • N1: Metastases in regional lymph node(s).

• Distant Metastasis (M):

  • M0: No distant metastasis

  • M1: Distant metastasis.

Treatment

1. Surgery: Only known curative treatment for localized RCC [j15]

   • Stage 1a: Partial Nephrectomy

   • Stage 1b, 2, 3: Radical nephrectomy (open/laparoscopic)

   • Palliative nephrectomy (alleviation of symptoms such as pain, hemorrhage, malaise, hypercalcemia, erythrocytosis, or hypertension)

2. Thermal Ablation: small lesions and patients who are not candidates for surgery

3. Molecular-targeted therapy: Stage 4 patients with metastatic disease

   • Sunitinib, Bevacizumab, Pazopanib, Temsirolimus, Everolimus, Lenvatinib, Nivolumab, Avelumab, Cabozantinib, Sorafenib, Axitinib, Avelumab, Pembrolizumab

4. Chemotherapy (Stage 4)

   • Floxuridine, 5-fluorouracil (5-FU), Vinblastine, Paclitaxel, Carboplatin, Ifosfamide, Gemcitabine, Doxorubicin

5. Immunotherapy: Interleukin-2 and Interferon

6. Radiation therapy

7. Renal artery embolization: palliative treatment in patients who are not candidates for surgery

8. Active surveillance

Differential diagnoses

Benign prostatic hyperplasia, Bladder cancer, Cancer origo incerta, Lymphoma, Prostate cancer, Prostatitis, Pyelonephritis, Pyonephrosis, Renal cyst, Renal hemorrhage, Renal infarction, Sarcoma, Urinary tract infection, Urolithiasis, Wilms Tumor