Neoplasms of the Kidney PDF

# Neoplasms of the Kidney ## Benign Neoplasms - Angiomyolipoma (vessels+muscle+fat tissue)- Grey/white tumor - Arises from perivascular epithelioid cells - Associated with Tuberous Sclerosis (TSC)-> LOF mutations in TSC1 or TSC2 - Impair fxn and cause bleeding - Symptomatic if >4cm...

# Neoplasms of the Kidney ## Benign Neoplasms - Angiomyolipoma (vessels+muscle+fat tissue)- Grey/white tumor - Arises from perivascular epithelioid cells - Associated with Tuberous Sclerosis (TSC)-> LOF mutations in TSC1 or TSC2 - Impair fxn and cause bleeding - Symptomatic if >4cm (Hematuria, Retroperitoneal bleeding, shock) - Oncocytoma- similar to RCC but is Benign - Arises from intercalated tubular cells @ collecting duct - 75% Asymptomatic-> Abdominal mass, flank pain, painless hematuria - Mitochondria-rich eosinophilic cells-> fast proliferation - Mahogany-brown tumor (area of stellate central scarring) - Can transform into RCC ## Malignant Neoplasms - More are sporadic & 4% arise from AD familial cancers - **Von Hippel-Lindau Syndrome** - Increased tumors & Cysts all over the kidneys - VHL gene @ chromosome 3 affected (1/3 develop tumors) - **Hereditary Leomyiomatosis & Renal Cancer Syndrome** - RCC variant, FH Gene mutations (fumarate hydratase-> @ mitoch.) - Aggressive papillary carcinoma with metastatic potential - **Hereditary Papillary Carcinoma** - Multiple bilateral tumors with papillary histology ("finger-like” projections) - MET protooncogene affected - **Birt-Hogg-Dube Syndrome** - Skin, lungs, + kidney tumors - Mutations in BHD Gene (Express folliculin) ## RCC Classification | Type | Relative Frequency | Cell of origin | Etiology | Macroscopic appearance | Microscopic appearance | Prognosis | |---|---|---|---|---|---|---| | Clear cell renal cell carcinoma | 70% | Proximal convoluted tubule | Sporadic or inherited mutation of VHL gene on chromosome 3p | Yellow or golden due to high intracellular lipid concentration | Clear cells, Polygonal cells arranged as cords or tubules (non-papillary growth), Clear, glycogen and/or lipid-filled cytoplasm, Unifocal, unilateral growth | Depending on tumor stage | | Papillary (chromophilic) RCC | 10-15% | | Trisomy 7, Trisomy 17, Loss of Y chromosome | | Cuboidal, low columnar cells, Cells grow in papillary formations, Bilateral, multifocal growth possible | Type 1 papillary RCC: better than type 2 papillary RCC, Type 2 papillary RCC: aggressive tumor with a poor prognosis | | Chromophobe RCC | 5% | Intercalated cells of the cortical collecting duct | Hypodiploidy | | Large polygonal cells with a prominent cell membrane, Eosinophilic cytoplasm, Perinuclear halo | Excellent prognosis | | Oncocytic RCC | 1% | | Unknown | | Originate from oncocytomas, Similar to chromophobic RCC, but without perinuclear halo, Cells occur as tumor nests | | | Collecting duct carcinoma (Bellini duct carcinoma) | 1% | Medullary collecting duct | Unknown | | Hobnail pattern: irregularly arranged malignant glandular cells within a fibrous stroma, Medullary duct carcinoma: A variant that is associated with sickle cell disease | Aggressive tumor with a poor prognosis | ## Nephroblastoma (Wilms tumor= W11ms) - Most common malignant neoplasm of the kidney in children - Associated syndromes - **WAGR syndrome**: Deletion of the 11p13 band leads to the deletion of the WT1 gene and other genes, such as PAX6. - Nephroblastoma - Aniridia - Genitourinary anomalies - Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis) - Early-onset nephrotic syndrome - Range of intellectual disability - **Denys-Drash syndrome**: point mutation in WT1 gene, which encodes a zinc finger transcription factor - Nephroblastoma - Pseudohermaphroditism, undescended testes in males (due to gonadal dysgenesis) - Early-onset nephrotic syndrome caused by diffuse mesangial sclerosis - **Beckwith-Wiedemann syndrome**: mutations of the WT2 gene-> omphalocele - Clinical features-> Large abdominal mass, hematuria, HT (increased renin) # Vascular Diseases of the Kidney ## Renovascular Diseases - Reduction or loss of renal arterial or venous blood flow is associated with one or more distinct clinical syndromes - A reduction in renal perfusion pressure activates a series of hormonal and neuronal responses that raise systemic arterial pressure to restore RA perfusion pressures. - Renovascular hypertension (RVH) is defined as a syndrome of elevated blood pressure (BP) produced by any condition that leads to reduced perfusion of the kidneys ## Clinical Features of Renovascular Hypertension - Activation of renin angiotensin system (early) - Early-onset (<30 years) or late-onset (>60 years) hypertension - Activation of sympathetic nervous system - Abnormal circadian rhythm: Loss of nocturnal fall - Secondary aldosteronism: Hypokalemia - Accelerated target organ damage - Microvascular disease - Left ventricular hypertrophy - Renal injury - Hyponatremic hypertensive syndrome - Unstable cardiac syndromes - Rarely, nephrotic range proteinuria ## Clinical Presentations of Renovascular Disease - Renovascular hypertension - Ischemic renal disease - Unstable cardiac syndromes - Renal infarction - Atheroembolic renal disease - Renal vein thrombosis - Transplant renovascular disease ## Fibromuscular Dysplasia - Non-inflammatory, non-artherosclerotic arteriopathy with arterial medial smooth muscle cell proliferation and fibrosis - Most common cause of RHV in children and young adults - Involves middle to distal RA or branches - Most common variant: Medial Fibroplasia (85%) - Alternating thin/thick ridges of collagen and elastic deposits resulting in discrete stenoses and aneurysms "String of beads" appearance ## Renal Infarction - Impairment of blood flow to the kidney - Symptoms: Flank, loin, abdominal pain with vomiting and microhematuria & proteinuria, can be asymptomatic - Transient/accelerated RVH occurs from renin release from infarcted portion of the kidney ## Renal Vein Thrombosis - Clinical Features: Loin, testicular, flank pain, testicular swelling (hydrocele), fever, leukocytosis, oliguric AKI, nausea, vomiting, hematuria, proteinuria - Associated with renal edema and swelling - Dx after the patient has developed an acute pulmonary embolus ## Evaluation and Management of Atherosclerotic Renovascular Disease - **Clinical syndrome suggestive of renovascular disease:** - Hypertension (see text) - Ischemic renal disease - **Stable kidney function BP control?** - **Yes:** Optimize medical therapy: RAAS blockade with ACEI/ARB, statin therapy, smoking cessation, aspirin, follow-up imaging (e.g., Doppler) to look for progression - **No:** - **?Progressive disease, ?Total renal mass, Comorbid risk: life expectancy, ?Working kidney function** - **Yes:** Surgery: complex disease, failed stent, aortic disease - **No:** Noninvasive imaging: Duplex ultrasound, CTA/? MRA - **?Bilateral disease, ?High-grade stenosis, ?Progressive disease, ?Working kidney function** - **Yes:** Endovascular: stent (atherosclerosis) - **No:** ?BP/creatinine rise, Re-image: ?Restenosis - **Goal: stable kidney function, excellent BP control** # Cystic Diseases of the Kidney | Disease | Inheritance | Pathological Features | Clinical Features/Complications | Typical Outcomes | |---|---|---|---|---| | Adult polycystic kidney disease | AD | Large multicystic kidneys, liver cysts, berry aneurysms | Hematuria, flank pain, urinary tract infection, renal stones, HTN | Chronic renal failure beginning at 40-60 YOA | | Childhood polycystic kidney disease | AR | Enlarged, cystic kidneys at birth | Liver fibrosis | Variable, death in infancy or childhood | | Medullary sponge kidney | | Medullary cysts on urography | Hematuria, UTI, recurrent renal stones | Benign | | Familial juvenile nephronophthisis | | Corticomedullary cysts, shrunken kidneys | Salt wasting, polyuria, growth retardation, anemia | Progressive renal failure beginning in childhood | | Multicystic renal dysplasia | | Irregular kidneys with cysts of variable size | Association with other renal anomalies | Renal failure if bilateral, surgically curable if unilateral | | Acquired renal cystic disease | | Cystic degeneration in end-stage kidney disease | Hemorrhage, erythrocytosis, neoplasia | Dependence on dialysis | | Simple cysts | | Single or multiple cysts in normal-sized kidneys | Microscopic hematuria | Benign | ## Kidney Cysts - **A. ARPKD (microcysts)** - **B. ADPKD (macrocysts)** - **C. Nephronophthisis** - **D. Distortion Renal calyces (Bardet-Biedl Syndrome)** - **E. Glomerulocystic kidney disease** - **F. Cystic Dysplastic Kidneys** - **G. Multicystic dysplastic kidneys** - **H. Medullary Sponge kidney** # Urolithiasis | Content | Precipitates with | Radiological Finding | Urine crystal | Notes | |---|---|---|---|---| | Calcium | Calcium oxalate: hypocitraturia | Radiopaque/hyperdense | Envelope/dumbbell-shaped | Most common (80%); calcium oxalate > calcium phosphate. Can result from ethylene glycol (antifreeze) ingestion, vitamin C overuse, hypocitraturia. Treatment: thiazides, citrate, low-sodium diet | | Ammonium magnesium phosphate (struvite) | ↓pH | Radiopaque/hyperdense | Coffin-shaped | Account for 15% of stones. Caused by infection with urease+MOs. Treatment: eradication of underlying infection, surgical removal of Stone | | Uric acid | ↓pH | Radiolucent/Visible | Rhomboid/rosettes | 5% of all stones. Risk factors: urine volume, arid climates, acidic pH. Strong association w/hyperuricemia. Treatment: alkalinization of urine, allopurinol. | | Cystine | ↓pH | Faintly radioopaque/Moderately radiodense | Hexagonal | Hereditary condition in which Cystine-reabsorbing PCT transporter loses function, causing cystinuria. Treatment: low sodium diet, alkalinization of urine, chelating agents | ## Kidney Stones | Stone Type | X-Ray/CT | Crystal/Gross Shape | Causes | |---|---|---|---| | Calcium Oxalate (80%) +/- Calcium Phosphate | Radiopaque | Envelope | Low urine pH, Hypercalciuria, Hyperoxaluria | | Calcium Phosphate | Radiopaque | Needle/star | High urine pH | | Struvite: Ammonia, Magnesium, Phosphate | Radiopaque | Coffin-lid | UTI Infection w/ Urease + pathogens. | | Uric Acid | Radiolucent X-ray, Visible on CT | Rhomboid | Low urine pH, Gout, Cancer, metabolic syndrome. | | Cystine | Faintly radiopaque | Hexagonal | Hereditary |