ABSTRACT
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