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Multilocular Cystic Renal Tumor

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5.1Introduction

•Multicystic dysplastic kidney (MCDK), a variant of renal dysplasia results from the malformation of the kidney during fetal development.

•Other terms used to describe this condition include multicystic kidney and multicystic renal dysplasia.

•Renal dysplasia results from an abnormal metanephric differentiation.

•Renal dysplasia is the leading cause of endstage renal disease in children.

•It consists of a spectrum of renal conditions, including:

–Renal hypoplasia

–Multicystic dysplastic kidney

–Renal aplasia

•Multicystic dysplastic kidney is characterized by the presence of multiple, noncommunicating cysts of varying size separated by dysplastic parenchyma and the absence of a normal pelvicaliceal system (Fig. 5.1).

•The condition is associated with ureteral or ureteropelvic atresia, and the affected kidney is nonfunctional.

•Multicystic dysplastic kidney is the most common cause of an abdominal mass in the newborn period and is the most common cystic malformation of the kidney in infancy.

•Multicystic dysplastic kidney can be unilateral or bilateral.

•Those with bilateral disease often have other severe malformation syndromes.

•In bilateral cases, the newborn has the classic characteristic of Potter’s syndrome.

•Bilateral multicystic dysplastic kidney is incompatible with survival.

•In those with unilateral multicystic dysplastic kidney:

–Contralateral ureteropelvic junction obstruction is found in 3–12 % of infants.

–Contralateral vesicoureteral reflux is seen in 18–43 % of infants.

–A voiding cystourethrography should be part of the work up of these patients.

•The incidence of unilateral multicystic dysplastic kidney is reported to be 1 in 4,300 live births.

•The combined incidence of unilateral and bilateral multicystic dysplastic kidney is 1 in 3,600 live births.

•Bilateral multicystic dysplastic kidney occurs in about 20 % of prenatally diagnosed cases of multicystic dysplastic kidney.

•Unilateral multicystic dysplastic kidney is more common in males with a male-to-female ratio of 1.48:1.

•The left kidney is involved in 55 % of cases, and the right kidney is involved in 45 %.

•Diagnosed multicystic dysplastic kidney and on follow-up:

–May persist without any change

–May increase in size

–May undergo spontaneous involution

Fig. 5.1 A clinical photograph showing multicystic dysplastic kidney showing multiple noncommunicating cysts of varying sizes. These cysts are separated by dysplastic renal parenchyma and absence of pelvicaliceal system

•Most cases of unilateral multicystic dysplastic kidney undergo spontaneous involution.

•Calcification may develop in persistent multicystic dysplastic kidney.

•Multicystic dysplastic kidney is usually asymptomatic but can be complicated by:

–Urinary tract infection (UTI)

–Hypertension

–Neoplasia

5.2Embryology

•The urogenital system is predominantly derived from the intermediate mesoderm of the embryo.

•This intermediate mesoderm undergoes epithelial transformation to form the nephric duct.

•The nephric duct extends adjacent to another tract called the nephrogenic cord which is also derived from mesoderm.

•The nephric duct induces the adjacent nephrogenic cord mesenchyme to aggregate and transform into epithelial tubules.

•During its caudal migration, the nephric duct induces three embryonic kidneys in the nephrogenic cord:

–The pronephros

–The mesonephros

–The metanephros

•Normal renal development is dependent upon the interaction of the metanephric bud and the metanephric blastema.

•The nephric duct gives rise to a caudal diverticulum called the ureteric bud.

•This invades the metanephric mesenchyme which becomes the ultimate kidney.

•The interactions between the metanephric mesenchyme and the ureteric bud leads to the development of the future kidney.

•This interaction results in the formation of calyces, tubules and nephrons.

•Complete obstruction or atresia impairs ureteral branching and results in decreased division of collecting tubules and inhibition of induction and maturation of nephrons.

•The collecting tubules enlarge and develop cysts in their terminal portions.

•These cysts of various sizes are distributed randomly throughout the abnormal kidney and are held together by connective tissue, without macroscopic evidence of intercommunication of cysts.

•In muticystic renal dysplasia the renal pelvis and or ureter are usually atretic.

•In this and other forms of dysplasia, the more proximal the level of obstruction, the more likely the cysts will be large.

•It has been hypothesized by Pathak et al. that these changes are the result of the pressure effects on the kidney from the obstruction.

–Proximal obstruction results in calyces that are markedly distended with cyst formation.

–In those with distal obstruction as in posterior urethral valves, the pressure effects are more generalized and less severe, so that the calyces do not distend as much. The kidneys will become dysplastic with much smaller and less visible cysts.

•During embryonic development the central elements of the kidney form first and the more peripheral elements form later.

•The metanephric mesenchyme forms the proximal components of the nephron from the glomerulus to the distal convoluted tubule.

•The ureteric bud that invades and branches inside the mesenchyme forms the distal components of the nephron, including the collecting ducts, calyces, pelvis, and ureter.

•The ureteric bud theory:

–This was proposed by Mackie and Stephens

–Multicystic dysplastic kidney results from an abnormal induction of the metanephric mesenchyme by the ureteral bud.

–This abnormal induction might be due to:

•A defect in the formation of the mesonephric duct

•Malformation of the ureteric bud

•Degeneration of the ureteric bud at an early stage.

–The final shape of the dysplastic kidney depends on the timing of the defect to the ureteric bud and on the effect of this on the ureteric bud branching.

•Multicystic dysplastic kidney usually develops as a sporadic problem; although, familial cases have been reported.

•Mutations in genes important in ureteric bud development have been identified in syndromes with renal dysplasia, including multicystic dysplastic kidney. These include:

–Mutations in EYA1 or SIX1 genes that lead to branchio-oto-renal (BOR) syndrome.

•Teratogens may also play a role in abnormal renal development. Although, their association with multicystic dysplastic kidney has not been clearly established.

5.3Etiology

and Pathophysiology

•The exact etiology of multicystic dysplastic kidney is not known.

•Genetic factors are important etiological factors for multicystic dysplastic kidney.

•Multicystic dysplastic kidney result from an abnormal induction of metanephric mesenchyme.

–Some mutations in genes associated with renal dysplasia (in syndromes) have been determined.

–These mutations occur at EYA1 or SIX1 genes (branchio-oto-renal syndrome).

–The PAX2 gene is also thought to play a role in the etiology of multicystic dysplastic kidney.

•Multicystic dysplastic kidney can be a consequence of a genetic syndrome, which in turn may affect the digestive tract, nervous system, or other areas of the urinary tract.

•Medications such as antihypertensives taken by the mother during pregnancy may play a role in the pathogenesis of multicystic dysplastic kidney.

5.4Histologic Findings

associated with renal dysplasia.

–Hereditary MCDK was found in three generations of a family that also carried a PAX2 gene mutation.

–PAX2 mutations have also been identified in patients with isolated renal hypoplasia/ dysplasia.

•Exposure to viral infections in utero has been associated with multicystic dysplastic kidney. These include cytomegalovirus (CMV), enterovirus, and adenovirus.

and 5.7):

–The multicystic dysplastic kidney is enlarged, abnormally shaped, and often resembles a bunch of grapes (Figs. 5.2 and 5.3).

–The kidney is composed of numerous and irregularly sized cysts.

–The cysts range in size from less than 1 mm to several centimeters in diameter.

–The number of cysts is also variable ranging from <5 cysts in 34 % of patients to >5 cysts in 66 % of patients.

Figs. 5.6 and 5.7 Clinical photographs showing dysplastic kidneys in kidneys with duplex systems

DYSPLASTIC

KIDNEY

DUPLEX

SYSTEM

DYSPLASTIC

KIDNEY

DUPLEX

SYSTEM

–The cysts contain a clear or yellow fluid and are connected by a fibrous tissue stroma.

–Cysts may be quite large, as in the classic description of multicystic dysplastic kidney, or the kidney may be echogenic and dysplastic or small and involuted.

–It has been suggested that some cases of renal agenesis may be due to involuted cases of multicystic kidney disease.

–There is loss of kidney and pelvocaliceal differentiation.

–Rudimentary renal tissue or lobes are sometimes grossly identifiable.

–Sometimes, multicystic dysplastic kidney might be seen in only the upper or lower pole of a duplicated collecting system.

–Ureteral or ureteropelvic atresia is always present (Figs. 5.8, 5.9, and 5.10).

–The atretic portion of the ureter varies in length from 1 to 5 cm.

–The ipsilateral renal artery is absent or hypoplastic.

–The change in size of the cysts in multicystic renal dysplasia are likely related to the number of preserved glomeruli and thus the degree of residual renal function (Fig. 5.11).

–As long as the kidney is able to filter plasma, the overall size of the multicystic dysplastic kidney will increase.

–As the nephrons become fibrotic, the amount of filtrate will diminish and the growth of the kidney will stop and subsequently decrease in size.

–On follow-ups of multicystic dysplastic kidneys, it was shown that:

•70 % decrease in size

•20 % showed no change in size

•10 % increased in size

•Microscopic findings:

–Histopathologic examination reveals abnormal ductal differentiation and only rudimentary corticomedullary differentiation.

–Thick-walled or thin-walled cysts with smooth inner linings are present throughout the kidney.

Fig. 5.11 Clinical intraoperative photograph showing multicystic dysplastic kidney showing multiple cysts of different sizes

sent the principal microscopic criteria for a diagnosis of multicystic dysplastic kidney.

–Although the kidney in multicystic dysplasia is usually described as having no renal function, there is evidence that these kidneys may have some component of residual renal function.

–Microscopic examination of the MCDK has shown that the number of nephrons are reduced but are seldom absent.

–The glomeruli are primitive, and sometimes normal glomeruli may be seen.

demonstrate an initial increase in size followed by involution.

•An involution of prenatally diagnosed multicystic dysplastic kidney has been noted before birth.

•The natural history of multicystic dysplastic kidney is variable:

–They may persist without any change

–They may increase in size

–They may undergo spontaneous involution

–Most cases of unilateral multicystic dysplastic kidney undergo spontaneous involution

•Calcification may develop in persistent multicystic dysplastic kidney.

•The Multicystic Kidney Registry reported 260 patients with multicystic dysplastic kidney whose cases were managed nonoperatively and whose cases were followed for varying periods as long as 5 years.

–Approximately 18 % of these kidneys were undetectable by age 1 year.

–31 % were undetectable by age 3 years

–54 % were undetectable by age 5 years.

5.6Classification

•Multicystic dysplastic kidney (MCDK) was first described as a distinct clinical entity by Spence in 1955.

•In 1986, the Urology Section of the American Academy of Pediatrics established the National Multicystic Kidney Registry, which is a large, multicenter, longitudinal database that has helped clarify the appropriate management of MCDK.

•Multicystic dysplastic kidney (MCDK) is a congenital maldevelopment of the kidney in which the renal cortex is replaced by numerous cysts of multiple sizes.

•A dysplastic parenchyma anchors the cysts, the arrangement of which resembles a bunch of grapes.

•No functional renal tissue can be identified.

•The calyceal drainage system of the affected kidney is absent.

•Typically, MCDK is a unilateral disorder and bilateral MCDK is incompatible with life.

•Several forms of MCDK have been described.

–The classic type

–The less common hydronephrotic type

–A third type known as solid cystic dysplasia

•The classic type has a random configuration of cysts, whereas the hydronephrotic type presents with a discernible, dilated renal pelvis surrounded by cysts.

•The solid cystic dysplasia is composed of smaller cysts with a greater amount of nonfunctional parenchyma.

•MCDK should not be confused with polycystic kidney disease (PCKD) or other renal cystic diseases.

•The multicystic kidney is a dysplastic kidney which has been classified by Potter et al. as type II disease.

•Subsequently, this type has been sub classified into two groups:

–Type IIa

–Type IIb

–The more common type IIa is secondary to pelvoinfundibular atresia.

–Type IIb is the hydronephrotic form.

–The pelvoinfundibular atresia and resulting dysplasia of MCKD is thought to result from a vascular insult.

–MCKD have been reported to be familial in few cases.

–Ipsilateral multicystic dysplastic kidney was also reported in identical twins.

Potter classification of renal dysplasia