Kidney and Lower Urinary Tract

AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE (ARPKD)

(PKHD1) ●● Fibrocystin and polyductin proteins

involved ●● Cystic dilatation of collecting ducts ●● Massively enlarged symmetric reniform

kidneys ●● Radially arranged collecting duct cysts

(1-2 mm) under the capsule in cortex ●● Rounded cysts in medulla ●● Normal glomeruli and tubules seen

between cysts ●● Oliguria, oligohydramnios ●● Associated congenital hepatic fibrosis (duc-

tal plate malformation)

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)

infancy ●● Enlarged/normal-sized kidneys ●● Cysts vary in size (up to 3 cm), both cortex

and medulla ●● Any part of nephron may become cystic

MEDULLARY CYSTIC DISEASE

Medullary sponge kidney

ducts in renal medulla ●● Bouquet of flowers on intravenous

pyelography ●● Symptomatic if complicated by renal

stones/infection/hematuria

dren and autosomal recessive ●● MCKD = adult onset and autosomal

dominant ●● Chronic sclerosing tubulointerstitial dis-

ease, cysts at corticomedullary junction (1-15 mm diameter), secondary glomerular sclerosis

CORTICAL CYSTS

Glomerulocystic kidney disease (GCKD)

phy of glomerular tufts ●● Cysts <1 cm in size, located in cortex

Simple cysts

CYSTS ASSOCIATED WITH SYNDROMES

Tuberous sclerosis

plastic epithelium, eosinophilic granular cytoplasm

Von Hippel-Lindau disease

Meckel-Gruber syndrome

●● Examination of gross specimen of renal biopsy with dissecting microscope to assess specimen adequacy

●● In the medulla, vasa recta appear as linear striations

GLOMERULAR LESIONS TERMINOLOGY

●● Focal: Involvement of only some of the glomeruli, by the lesion

●● Diffuse: Involvement of almost all of the glomeruli, by the lesion

●● Segmental: Involvement of part of a glomerulus, by the lesion

●● Global: Involvement of almost the entire glomerulus, by the lesion

●● Mesangial proliferation: More than three mesangial cells per peripheral mesangial area

●● Crescent: Proliferation of glomerular epithelial cells and inflammatory cells that fill part (segmental) or all (circumferential) of Bowman space. May be cellular/ fibrocellular/fibrous

NEPHROTIC SYNDROME

●● Conditions causing mainly heavy proteinuria

Minimal change disease

●● Hematoxylin and eosin (H&E) and immunofluorescent (IF) findings are normal

●● EM: Foot process effacement, microvillous transformation of epithelial cells

Focal segmental glomerulosclerosis

mesangial sclerosis ●● African American boys

Membranous glomerulonephritis (GN)

short spikes extending from outer surface of capillary (silver stain positive)

●● IF: Granular staining for IgG and C3 along capillary walls

●● EM: Subepithelial deposits, foot process retraction

Other causes

●● Nail patella syndrome, collagen type III glomerulopathy, Pierson syndrome

GLOMERULOPATHY WITH MAINLY HEMATURIA WITH/ WITHOUT PROTEINURIA

IgA nephropathy

Berger disease

●● Nephropathy after upper respiratory/gastrointestinal infection

●● Focal segmental/global mesangial hypercellularity

●● IF: Confluent mesangial granular deposits of IgA

Henoch-Schönlein purpura nephritis

●● Similar morphological and IF findings as Berger disease

●● More severe glomerular disease (including crescents)

Basement membrane nephropathy

Alport syndrome

●● Family history of hematuria progressing to end-stage renal disease

nephritis ●● Defect in type IV collagen involved in BM

structure ●● E/M: Thick/thin/irregular basement mem-

brane, splitting of lamina-densa (basketweave pattern), thinning of BM (less than 150 nm)

Thin basement membrane nephropathy

function

●● Family history of hematuria with AD inheritance

●● EM: Diffuse thinning/attenuation of glomerular basement membrane (<250 nm)

GLOMERULOPATHIES WITH NEPHRITIC SYNDROME

●● Hypertension, impaired renal function, hypocomplementemia

Postinfectious GN

●● Acute GN following skin/throat infection with Group A streptococcus

●● Glomerular hypercellularity, accentuation of lobular architecture, thick capillary walls

●● IF: Coarse capillary granular staining for IgG and C3

MPGN-I

nent lobulation ●● Mesangial hypercellularity, increased matrix ●● Diffuse marked thickening of glomerular

capillary walls ●● Silver stain: Florid double contour (tram-

tracks) of capillary walls ●● IF: Coarse granular C3 staining along capil-

lary loops/periphery of mesangium ●● EM: Subendothelial deposits

MPGN-II

ular capillary basement membrane ●● IF: Linear global ribbon-like C3 deposits in

capillary walls/hollow rings in mesangium of C3

Lupus nephritis

glomeruli/tubules/interstitium/blood

and C1q deposits

●● EM: Fingerprint deposits/tubuloreticular aggregates within endothelial cells

Crescentic glomerulonephritis

●● Etiology: idiopathic, immune complex diseases, post-infectious GN, various vasculitis, Goodpasture syndrome

●● Crescents are initially cellular and later organize into fibrocellular forms; project into the glomerular space and may compress the glomerular tufts

●● Bad prognosis and patients usually progress to end-stage renal disease

Goodpasture syndrome

●● Pulmonary-renal syndrome caused by antiGBM antibody = Goodpasture syndrome

●● These antibodies attack alpha-3 subunit of type III collagen

patchy linear staining for C3

CONGENITAL NEPHROPATHIES

first year of life

Finnish type (CNF)

●● Nephrotic syndrome within first 3 months of life

protein nephrin/podocin) ●● Autosomal recessive, steroid resistant ●● Infants small for gestational age, enlarged

placenta, massive proteinuria in utero, polyhydramnios, elevated AFP, placentomegaly

●● Tubular ectasia (dilatation of proximal tubules)

●● Interstitial inflammation, mesangial hypercellularity, glomerular sclerosis

Diffuse mesangial sclerosis type

●● Nephrotic syndrome between 3 and 11 months

birth ●● Increased mesangial matrix, secondary

tubulointerstitial changes, diffuse mesangial Denys-Drash syndrome

●● Tubular loss and interstitial fibrosis: Correlates with deteriorating renal function/progressive renal failure

ACUTE TUBULAR NECROSIS

●● Mitotically active and swollen tubular epithelial cells, ectasia of tubular lumina

●● Loss of brush border, necrosis/desquamation

Ischemic

●● Etiology: Renal hypoperfusion (from shock, sepsis, trauma)

Toxic

●● Antibiotics (aminoglycoside, amphotericinB), antineoplastic drugs (cisplatin)

INTERSTITIAL NEPHRITIS

reflux uropathy, immunologically mediated metabolic diseases, hereditary diseases, cellular rejection in renal allograft

Pyelonephritis

●● Hematogenous/ascending bacterial infection

●● Both interstitium and collecting system involved

acute renal failure ●● Escherichia coli O157:H7 serotype, linked to

postdiarrheal HUS ●● Thrombotic microangiopathy (TMA) ●● Fibrin thrombi/fragmented red blood cells

occlude glomerular capillaries/arteriolar lumina

RENAL ARTERY STENOSIS

●● Medial fibromuscular dysplasia with aneurysm formation

RENAL CORTICAL NECROSIS

●● Coagulative necrosis due to sudden loss of renal perfusion

WILMS TUMOR

●● WT1 locus on 11p13 (WAGR and DenysDrash syndrome)

●● WT2 locus on 11p15 (Beckwith-Wiedemann syndrome)

primitive cells), epithelium (primitive/abortive tubules and glomeruli), stroma

●● Heterologous elements (skeletal muscle, cartilage) in stroma

●● Unfavorable histology = nuclear anaplasia and multipolar mitotic figures

●● Unfavorable histology implies resistance to therapy

●● Blastema positive for WT-1, vimentin and negative for synaptophysin ●❑ Refer to Appendix for Children’s Oncology

Group (COG) staging of Wilms tumor

CYSTIC NEPHROMA

benign spindle cell stroma ●● No immature elements

CYSTIC PARTIALLY DIFFERENTIATED WILMS TUMOR

●● Stroma surrounding the cysts has immature tubules/glomeruli/blastemal tissue

NEPHROBLASTOMATOSIS

Perilobar nephroblastomatosis

discrete interface with adjuvant parenchyma ●● Associated with hemihypertrophy and

Beckwith-Wiedemann syndrome

Intralobar nephroblastomatosis

●● Blastema/immature tubules blend with surrounding kidney

syndrome

CONGENITAL MESOBLASTIC NEPHROMA

Classic pattern

●● Intersecting bundles of uniform bland spindle cells, minimal atypia

Cellular pattern

aberration as CIFS and secretory carcinoma of breast)

tumor of childhood

separated by capillary network of vessels ●● Nuclei have optically clear appearance

(similar to papillary carcinoma of thyroid) ●● Cytoplasm pale/clear ●● Positive for vimentin, CD99, CD56

MALIGNANT RHABDOID TUMOR

mononuclear cells, prominent nucleolus ●● Intracytoplasmic hyaline inclusions ●● Mutations/deletions of HSNF5/INI1 gene

located on chromosome 22q11 ●● Positive for vimentin, CK, EMA, desmin,

and NF ●● Loss of nuclear staining for INI1 and BAF47 ●● High risk for metastases

RENAL CELL CARCINOMA

●● Associated with Von Hippel-Lindau syndrome

Translocation associated

plasm separated by fibrovascular stroma ●● Tumor cells negative for EMA, CK, CAM5.2,

and vimentin (in contrast to other RCC) ●● Positive nuclear reactivity to TFE3 proteins

OSSIFYING RENAL TUMOR OF KIDNEY

EWING SARCOMA

●● Pseudorosettes; small, blue cell tumor; entrapped tubules

RENAL MEDULLARY CARCINOMA

INI1 ●● Highly malignant tumor, desmoplastic

stroma with marked inflammation

ANGIOMYOLIPOMA

INFLAMMATORY MYOFIBROBLASTIC TUMOR

CONGENITAL MALFORMATIONS OF URETER

Ureteral agenesis

Ureteral duplication

●● Two ureteric buds/branching of ureteric bud

●● Associated duplication of renal pelvis/ duplex kidney

Ureteral ectopia

Ureterocele

●● Congenital cystic dilation of distal intravesical portion of ureter

obstruction ●● Results in hydronephrosis, hydroureter,

multicystic renal dysplasia

Vesicoureteric reflux

formed trigone, ectopic ureteral orifice ●● Results in recurrent infection, hyperten-

sion, and renal failure

CONGENITAL LESIONS

Agenesis

●● Associated with renal agenesis, malformations (sirenomelia, caudal regression syndrome)

Hypoplasia

Duplication

●● VACTERL (vertebral-anorectal-cardiac-tracheal-esophageal-renal-limb)

Bladder exstrophy

●● Associated anomalies: Epispadias (urethral orifice on upper surface of penis), bifid clitoris in girls, cloacal exstrophy (bladder divided in two parts by central exstrophic bowel)

●● Open symphysis pubis (whole posterior wall of bladder may be exposed)

●● Risk of adenocarcinoma/squamous cell carcinoma

Obstructive lesions

●● Posterior urethral valves in boys (most common cause of bladder outlet obstruction)

Prune-belly syndrome

abdominal wall musculature (lax and wrinkled wall), cryptorchidism, urinary tract anomalies

Megacystic microcolon

●● Massive abdominal distension due to largely dilated bladder (non-obstructed)

●● Intestinal hypoperistalsis syndrome with microcolon

Urachal remnants

●● Urachus connects urinary bladder to allantoic duct

●● Normally it should be a solid cord by 4 months’ gestation

●● If fully/partially patent, fistula, sinus, or cysts between bladder and umbilical cord

ACQUIRED LESIONS

Cystitis

●● Uncomplicated cystitis in healthy children; E. coli

tract; coagulase negative staphylococci and Candida

Granulomatous cystitis

●● Etiology; chronic granulomatous disease (congenital anomaly of phagocytic NADPH), tuberculosis, schistosomiasis, fungal infections

Cystitis cystica and glandularis

lium, respectively

bladder mucosa increased → irritation and inflammation

Eosinophilic cystitis

●● Food allergy, parasites, drugs, bronchial asthma

Malakoplakia

calcospherites) ●● Positive with von-Kossa, iron, and PAS stains

Hemorrhagic cystitis

●● BK virus (bone transplant patients), adenovirus (type 11), E. coli, Candida, cyclophosphamide drug

TUMORS OF BLADDER AND URETHRA

Inflammatory myofibroblastic tumor

desmin

Rhabdomyosarcoma

●● Embryonal RMS polypoid, grape like gross appearance

●● Densely packed small primitive tumor cells underneath mucosa = cambium cell layer