Acta Radiológica Portuguesa, Vol.XIX, nº 74, pág. 90-107, Abr.-Jun., 2007 Cystic Renal Disease of Childhood Ellen Chung Armed Forces Institute of Pathology Terminology Cyst Polycystic kidney disease ARPKD and ADPKD only Multicystic kidney Calyceal Diverticulum Cyst that communicates with collecting system Need contrast study to distinguish from cyst Urine stasis leads to infection and stone formation Look for stone in tic on US, KUB, or non-con CT Delayed images show contrast-filling of the cyst and a neck Treatment surgical ablation if symptomatic Genetically-based Classification 2 Nongenetic Multicystic dysplasia Multilocular cyst (tumor) Simple cyst/calyceal diverticulum Medullary sponge kidney Acquired cystic disease Genetic Autosomal recessive polycystic kidneys Autosomal dominant polycystic kidneys Juvenile nephronophthisis (AR)-medullary cystic disease (AD) complex Cysts associated with multiple malformation syndromes 2 Glassberg KI, Stephens FC, Lebowitz RL, et al. Renal dysgenesis and cystic disease of the kidney: a report of the Committee on Terminology, Nomenclature and Classification, Section on Urology, American Academy of Pediatrics. J Urol 1987, Oct; 138:1085 Simple Renal Cyst Observed on PNUS screen for malformation syndrome US criteria for simple cyst no further imaging unless recurrent symptoms of infection Otherwise CT to exclude tumor No treatment unless symptomatic or obstructing collecting system ARP 99
Medullary Sponge Kidney Congenital focal dilation of collecting tubules usualllly presenting in adulthood Associated with stones or infection but may be found incidentally Usually bilateral Medullary nephrocalcinosis radially aligned Streaky linear densities in involved pyramids US may show calcifications before plain film Multicystic Dysplastic Kidney Most common form of cystic renal disease in infants and children Most common cause of renal mass in first week of life Rarely bilateral Due to early severe in utero obstruction Extreme end of spectrum of UPJO Multicystic Dysplastic Kidney Risk of abnormality of contralateral kidney 20-50% Negligible renal function Nodular blastemal elements in 3-5% - risk of Wilms tumor Acquired Renal Cysts AIDS Hemo- and peritoneal dialysis Increase in number and size with length of time on dialysis Complications intracyst or subcapsular or perinephric hemorrhage MCDK - Presentation PNUS Neonate with abdominal mass Incidentally in older child mimics agenesis 100 ARP
MCDK Gross Pathology Macrocysts of variable size Randomly distributed Cysts do not communicate Hydronephrotic variant large central cyst Rarely segmental upper pole of duplex or lower crossed fused ectopic No identifiable normal parenchyma Associated atresia of ureter or infundibulopelvis MCDK - Imaging Large mass with cysts of varying sizes scattered throughout Cysts do not communicate Hydronephrotic type large central cyst but no identifiable parenchyma No identifiable cortex or medulla Nonreniform shape Nuclear renogram no significant excretion VCUG 25% VUR MCDK - DDx Multilocular cystic kidney A tumor Cysts within the intervening septa Severe hydronephrosis UPJO Nuclear renogram Contralateral kidney also affected MCDK - Histopathology Histologic hallmark presence of immature dysplastic-appearing tubules surrounded by collarettes of PAS-staining condensed mesenchyme Cysts of varying size formed by dilated, dysplastic tubules Cysts can occur in any part of the nephron High nuclear to cytoplasmic ratio dysplasia MCDK Course and Prognosis Natural history of a true MCDK is to resolve Formerly these were all removed due to rare reports of nephroblastoma1 Now followed to resolution If they do not resolve, surgical removal is indicated to prevent complications of infection and neoplasm 1 Strife JL, Souza AS, Kirks DR, Strife CF, Gelfand MJ, Wacksman J. Multicystic dysplastic kidney in children: US follow-up. Radiology. 1993 Mar;186(3):785-8. ARP 101
ARPKD Pathology - Kidneys Large kidneys Cysts are dilated collecting tubules predominantly in the medulla Dilated (1-2mm) tubules arranged in a fan-shape Cortex relatively spared No dysplasia On cut section, cortex and medulla unrecognizable Few coalescent macrocysts Autosomal Recessive Polycystic Kidney Disease (ARPKD) Kidneys and liver ectasia and fibrosis Kidneys ectasia of the collecting tubules Liver biliary duct ectasia and periportal fibrosis Latter develops in early childhood Degrees of renal and liver involvement are inversely proportional and determine age of presentation and prognosis ARPKD Pathology- Liver All associated with congenital hepatic fibrosis = ductal plate malformation Dilation of interlobular bile ducts associated with a variable amount of portal fibrosis (Caroli syndrome) All portal areas are expanded and contain dilated ducts at the periphery with blood vessels in the middle Sinusoidal portal hypertension ARPKD Spectrum of Presentation Blyth and Ockenden Clinical Classification 1 Perinatal bilateral nephromegaly, Potter syndrome, death in first week Neonatal present in first month, death by 1 year Infantile present at 3-6 mo Juvenile - presentation in first decade Portal hypertension Incidental finding on US Presentation in second decade with renal failure 1 Blyth H, Ockenden BG. Polycystic disease of kidney and liver presenting in childhood. J Med Genet. 1971 Sep;8(3):257-84. 102 ARP
ARPKD - Ultrasound Large kidneys with increased echogenicity in the medulla due to multiple accoustic interfaces of dilated, ectatic ducts May mimic nephrocalcinosis Compressed, spared cortex may form relatively dark rim Poor delineation of cortex, medulla, sinus ARPKD Plain Film Bilateral flank masses in newborns Small, bell-shaped thorax Pneumothorax Older children may have slightly enlarged kidneys, hepatosplenomegaly, and/or ascites ARPKD - Ultrasound High frequency linear transducer may resolve tubular structures in fan-like array or tiny cysts Occasional macrocysts Those who present as children have milder renal findings normal or mild nephromegaly, +/- increased echogenicity of medulla, loss of corticomedullary differentiation Ultrasound - Liver Increased echogenicity +/- ductal ectasia in older children Portal radicals surrounded by bile ducts Splenomegaly, varices, and ascites may also be seen in older children ARP 103
ARPKD - Other Imaging Imaging beyond US is rarely necessary Spoke-wheel or striated appearance of nephrogram Prolonged nephrographic phase Calyces compressed, separated and distorted In older children, mild tubular ectasia similar to medullary sponge kidney MR - few cysts in about half of patients ARPKD - Prognosis Infantile poor prognosis due to renal insufficiency and pulmonary hypoplasia Outcome in childhood is better than previously thought Early recognition and management are important Differential Diagnosis Large Echogenic Kidneys in Neonate ARPKD ARPKD ARPKD Glomerulocystic disease ADPKD Glomerulocystic Disease Rare, sporadic or heritable (AD) May be found in some patients with malformative syndromes Occasionally found in children with family history of ADPKD 104 ARP
Glomerulocystic Disease Clinical Features Present early with renal failure and palpable abdominal masses Renal function normal but deteriorates with age Glomerulocystic Disease Pathology Cystic dilation of Bowman capsule and proximal convoluted tubule Periportal fibrosis, bile duct hyperplasia and hepatic cysts may also be found Autosomal Dominant Polycystic Kidney Disease (ADPKD) Much more common than AR, BUT NOT IN CHILDREN Three genetic loci PKD1-3 Family screening routine Spontaneous mutations frequent Cysts become larger and more numerous with age Autosomal Dominant Polycystic Kidney Disease (ADPKD) Cysts not usually seen in 1st and 2nd decades but can be seen in neonates screened for positive family history Affects multiple organs kidneys, liver, pancreas, spleen, seminal vesicles, ovaries Association with occult intracranial aneurysms screen in adulthood Glomerulocystic Disease Ultrasound Echogenic normal-sized to enlarged kidneys Poor corticomedullary differentiation Tiny cysts may be seen in cortex (vs. ARPKD) ADPKD - Presentation Present in 4th-5th decade with hypertension and renal failure Does not present in childhood but may be found incidentally or secondary to flank pain due to bleeding into cyst Rarely presents in infancy minimal cysts in enlarged, echogenic kidneys ARP 105
ADPKD - Pathology Enlarged but reniform kidneys Cysts of varying size scattered throughout the kidney (cortex and medulla) Usually bilateral but may be asymmetric or even unilateral Abnormality of the ampullary and interstitial portions of the collecting tubules and nephrons Hepatic fibrosis is rare Medullary Cystic Disease Complex Juvenile nephronophthisis AR, presents in first decade Medullary cystic disease AD, presents in 3rd decade Polydypsia, polyuria, salt wasting, severe anemia Progressive renal failure Growth retardation ADPKD - Ultrasound Infantile presentation small, spherical cysts on high resolution US (vs. fan-like, tubular appearance in AR) Older children - cysts of varying size in cortex and medulla Can be unilateral at presentation Normal size or slightly enlarged Look for cysts in liver and pancreas Medullary Cystic Disease Complex Pathology <1.5 cm cysts that increase in size and number with age Cysts in medulla or subcortical region - 70% of patients Secondary glomerulosclerosis small, fibrotic kidneys Associated retinitis pigmentosa, hepatic fibrosis, skeletal defects and CNS abnormalities in familial juvenile form ADPKD - Prognosis Most develop renal failure in 4th-5th decade Presentation in infancy more severe renal cystic disease, more hypertension, more rapid progression to renal failure than adult relatives Medullary Cystic Disease Complex Imaging Small echogenic kidneys Multiple small medullary or corticomedullary cysts may not be present when very young 106 ARP
Cysts Associated with Syndromes Zellweger - cerebrohepatorenal syndrome AR, lethal peroxisomal deficiency Meckel-Gruber AR, posterior encephalocele, polydactyly, cystic kidneys, congenital hepatic fibrosis Beckwith-Wiedemann syndrome macroglossia, visceromegaly and omphalocele, Wilms tumor, also medullary cysts in 13-19% Cysts Associated with Syndromes Turner Down s Orofaciodigital Jeune, short rib polydactyly TS cortical cysts 33-50% VHL multifocal cystic adenocarcinomas in 45% after 3rd decade ARP 107