R7 Renal Tumors, Cysts and Stones

• Tumors
• Congenital anomalies
• Cysts
• Hydronephrosis
• Urinary tract obstruction
• Stones

Most common kidney tumor in children <10 years old; average age 3yrs 

• -Familial
• -Sporadic

• -Deletion of short arm of chromosome 11
• -Loss of supressor gene WT-1

• WT-1 gene, chromosome 11
• Large, solitary well circumscribed mass
• Immature nephroblastic elements
• Epithelium, cartilage, bone, muscle, fibrous tissue
• Tx: radiation chemotherapy and surgery

• WAGR syndrome
• Denys-Drash syndrome
• Beckwith-Wiedeman

• Wilms tumor
• Aniridia - lack of irises 
• Genital anomalies
• Menatl and motor Retardation

gonadal dysgenesis and nephropathy

Organomegaly and cytomegaly

• Cortical adenoma
• Medullary fibroma
• Oncocytoma

• 5-15% of tumors
• slow growing
• tan brown tumors up to 12cm
• Eosinophilic cells filled with mitochondria (red)
• Can be found in endocrine glands (pituitary...)
• Familial or isolated cases; solitary or multicentric
• Always benign

• Angiolyomyofibroma
• Renal adenoma
• Renal fibroma
• Renal oncocytoma

• Tendency to hemorrhage, epilepsy, skin lesions, mental retardation
• TSC 1 or TSC 2 tumor suppressor gene may be defective

May grow and behave like renal cell carcinoma

totally harmless

• RCC represents up to 3% of all newly diagnosed primary cancers
• 85% of all renal tumors are RCC
• 12,000 deaths from RCC; 30,000 new cases every year
• 11th major cause of cancer

• Tobacco: including pipes, cigars and snuff
• Obesity
• Hypertension
• Estrogen treatment
• Asbestos exposure
• Petroleum products
• Heavy metals (cadmium, mercury, lead)
• polycystic disease/dialysis
• Von Hippel Lindaue disease: hemangioblastoma, retina, kidney and cerebellum
• VHL gene
• Men > women (based on risk factors)

• VHL tumor suppressor gene
• -controls ubiquitin ligase which targets certain proteins for destruction

VHL mutations → HIF-1 is high and proangiogenic proteins (VEGF, PDGF, TGF alpha and beta, IGF)... increase their activity and cells and vessels proliferate

VHL mutations increase likely-hood of tumor or cysts

VHL gene: signal transduction/cell adhesion, ubiquitin ligase, involvement in protein degradation

-Chromosome 3p25-26

-Tumor associated with inherited mutations

-Hemangioblastomas

-Angiomas and cysts of viscera

"clear cell" appearance

• Clear cell carcinoma
• -70-80% of renal cancers
• -Associated with VHL gene

• Papillary renal cell ca
• -10-15%
• -Associated with MET protooncogene

• Chromophobe renal cell ca
• -5% (includes oncocytomas)

• Triad: (all 3 present in only 10%)
• 1. Pain
• 2. Hematuria
• 3. Flank mass

• -Hematuria only 90%
• -Sx more likeloy when tumor is near renal pelvis
• -Many tumors located at upper pole of kidney
• -Men>women (based on risk factors)
• -Mid 30s to late middle age

• Paraneoplastic effects of RCC
• -Polycythemia - erythropoietin
• -HTN - renin
• -Hypercalcuria - PTH
• -Feminization/masculinization - gonadotrophin
• -Cushing's syndrome - steroids

• 5 yr survival 45%
• without mets 70%
• mets to lungs...50%
• mets to bone... 30%
• mets to kidney... 10%

• Renal fibroma
• Angiomyolipoma

• Common, harmless
• Usually found at autopsy
• Harmartoma

• Found in patients with tuberous sclerosis
• -25-50% of whom get this tumor

Associated with seizures and skin lesions

• Transitional cell carcinoma
• -uncommon tumor
• -high mortality
• -Presentation: painless hematuria, hydronephrosis
• -5yr survival <10%
• -Risk factors: analgesic uses (all urothelial tumors)

• Transitional epithelium
• papilloma

• Presentation:
• -asymptomatic until...
• -painless hematuria
• -Male>female 3:1

• Pathogenesis:
• -tobacco products
• -chronic cystitis
• -Schistosomiasis (Nile delta)
• -Cyclophosphamide (cancer therapeutic)
• -B-naphthylamine (used in moth balls)

• Tx/prognosis:
• -Surgical removal (part or entire organ)
• -Depth of invasion determines outcome:
• -5yr survival 57%
• -Invasive ca <20%

• Polycystic renal disease
• -Bilateral expanding masses, destroying renal parenchyma

• Epidemiology:
• -1/1000 persons affected
• -APKD accounts for 10% of renal failure cases
• -APKD → HTN, urinary infections

• Genetics:
• -APKD-1 is involved in most cases (chromosome 16)
• -APKD-2 is involved in 10% (chromosome 4)
• -Polycystin gene: lectin-like and fibronectin-like domain... abnl development of ECM by tubules leads to cyst formation

• 10-30% of APKD pts get cerebral aneurism with high rate of subarachnoid hemorrhage
• Hypertension, urinary infections
• Painful rupture of cysts → flank pain and hematuria

• Sx present in 4th decade
• Renal failure by age 50

• Calcium oxalate ± phosphate
• -75%

• Magnesium ammonium phosphate
• -15%

• Uric acid or cystine
• -10%

• Lack of portable water
• hot climate

• Causes:
• -Excessive absorption of calcium
• -Hypercalcuria
• -Defective renal absorption
• -Hyperparathyroidism
• -Vitamin D intoxication
• -High meat diet; vegetable diet somewhat protective

• Associated with urinary tract infections
• -Proteus (and other urea splitting bacteria)
• -Staphylococci
• -Bacteria nidi

• Tamm Horsfal protein
• Crystal matrix protein
• Nephrocalcin
• Uroprontin/osteopontin
• Alpha-1-antitrypsin
• Glycosaminoglycans
• Citrate
• Pyrophosphate
• Zinc/Magnesium

• Mainly affects kidney, but ureter and bladder are possible
• Kidney stones found in 1% of all autopsies
• ♂ > ♀ symptomatic
• Familial factors

Obstruction in the urinary pathway leads to retrograde fluid accumulation  with distention of renal calyces

• Risk factors/causes:
• -Pregnancy
• -Tumors (prostate, uterus)
• -Neurogenic bladder
• -Infection (prostatitis)
• -Obstruction (necrotic papilla, stone

• Atresia of ureter
• Ureteral valves
• Aberrant renal artery compressing ureter
• Renal ptosis with torsion
• Kinking of ureter

• -Fetal lobulation - most are benign; lobulations will disappear as child develops
• 

• -Polycystic renal disease
• 

• -Agenesis (if unilateral, the contralateral kidney will be abnormally large to compensate)
• -Hypoplasia
• -Horseshoe kidney
• -Cysts of the medulla
• -Simple cysts

• Multiple renal arteries and aberrant ureter
• **Ureter is vulnerable to abdomen causing compression

• Horsehoe kidney
• Ureter pass over lower poll of the kidney
• Inferior Mesenteric Artery 'traps' kidneys in base of abdomen/pelvis

Kidney is common site for metastasis for lymphoma

• Multiple myeloma (Bence Jones proteins are toxic  to tubular epithelium)
• -Renal insufficiency
• -Infection common
• -Amyloidosis in 10%