RENAL PATHOLOGY

CHUKWUEGBO CC MBBS(UNN), MWACP, FMCPath

Anatomy
Anatomy : An overview
► The kidneys are two bean shape organs within peritoneum
located between12th thoracic rib to 3rd lumbar vertebrae.
► Posterior abdomen on either side of vertebral column, in
retroperitoneum
► Surrounded by fat and loose areolar tissue
► Superior border is at T12, inferior border is at L3
► 11cm long x 5-8cm x 3cm
► Weighs 125-170g in males, 115-155g in females
► Capsule: covers kidney, is surrounded by perirenal fat
► Cortex: outer 1.2 cm of kidney, surrounds inner medulla
containing pyramids and lacking glomeruli
► Renal sinus: fatty compartment within confines of
kidney not delineated from renal cortex by a
fibrous capsule
► Gerota’s fascia: fibromembranous tissue
surrounding the kidney that separates it from
adjacent musculature
► Ureter ascends into renal pelvis, divides into
calyces (2-3 major, 12 minor total)
► Related to a calyx are renal pyramids with apices
called papillae
► Vasculature: receives 25% of cardiac output, 90% goes
to cortex, via interlobar, arcuate, interlobular, afferent
arterioles, then into glomeruli, efferent arterioles and
peritubular vascular network
► Deeper juxtamedullary glomeruli give rise to vasa recta,
which supply outer and inner medulla
► Since arteries are end vessels, their occlusion causes
infarction
► Glomerular disease causes tubular disease, since
efferent arterioles supply tubules
► Regional lymph nodes: renal hilar, paracaval, aortic and
retroperitoneal
Glomerulus
► Tuft-like vascular structure composed of lobules of
specialized capillaries that arise from an afferent arteriole
and eventually coalesce to drain into an efferent arteriole
► 200 microns in diameter, 20% larger in juxtamedullary area
► Layers (inner to outer) are: fenestrated endothelium, then
glomerular basement membrane (lamina rare interna,
lamina densa and lamina rare externa), then podocytes
(visceral epithelium with foot processes); also parietal
epithelium which lines Bowman’s space (which contains the
ultrafiltrate of plasma)
Glomerulus
►Glomerular basement membrane (GBM): normally
250-380nm, composed of type IV collagen, laminin,
polyanionic proteoglycans (mostly heparan sulfate),
fibronectin and entactin
►Type IV collagen forms suprastructure to which
other glycoproteins attach; composed of 3 alpha
chains
►Each alpha chain has amino 7S domain, middle
triple helical domain and a carboxyl non-collagenous
(NC1) domain; NC1 domain is site of anti-GBM
nephritis and dimer formation
Glomerulus
► Mesangial cells:
► type of myofibroblast that supports glomerular tuft,
regulates capillary width and blood flow;
► are phagocytic and can proliferate; the mesangium
on the capillary side is covered by endothelial cell
► Podocytes (visceral epithelium):
► their foot processes embed in lamina rare externa of
glomerular basement membrane;
► the distal diffusion barrier to filtration of proteins is a
filtration slit diaphragm between foot processes
► Glomeruli are highly permeable to water and solutes through
fenestrated endothelium, but impermeable to large proteins
like albumin (proteins are more permeable if smaller and more
cationic)
► Hypercellularity: the presence of more than 3 cells in an
individual glomerular mesangial region away from the vascular
pole
► Special stains:
● PAS stain allows assessment of glomerular basement membranes,
mesangial matrix and tubular basement membranes
● Jones methenamine silver (JMS) highlights these better than PAS
● Masson trichrome stain highlights hyalinosis, scarring, immune
deposits and fibrinoid deposits
Nephron
Tubules and Interstitium
► Juxtaglomerular apparatus:
► close to glomerulus where afferent arteriole enters it;
► consists of juxtaglomerular cells (modified smooth
muscle cells) plus macula densa (region of distal tubule
as it returns to vascular pole of parent glomeruli) plus
lacis or Goormaghtigh cells (nongranular cells near
afferent arteriole, macula densa and glomerulus and
resemble mesangial cells);
► produces renin;
► Interstitium: contains fibroblast like cells and peritubular
capillaries; expands due to edema and inflammation
Tubules and Interstitium
► Medullary rays: in cortex, contain cortical collecting
tubules and loops of Henle of superficial nephrons
► Proximal tubules: long microvilli, numerous
mitochondria and extensive intercellular
interdigitations assist in reabsorption of sodium,
water, proteins, glucose, potassium, phosphate and
amino acids; vulnerable to toxins and ischemic
damage
► Renal columns of Bertin: cortical tissue extending
into spaces between pyramids
Glomerular lesions
► Focal: less than 50% of glomeruli
► Diffuse: more than 50% of glomeruli
► Segmental: part of a glomerulus
► Global: all of a glomerulus
► Mesangial hypercellularity: 4 or more nuclei in mesangial region
► Endocapillary hypercellularity: increased cellularity internal to the
GBM composed of leukocytes, endothelial cells or mesangial
cells.
► Extracapillary hypercellularity: increased cellularity in Bowman`s
space (more than one layer of parietal or visceral epithelial cells
or monocyte/machrophage)
► Crescent: extracapillary hypercellularity other than the epithelial
hyperplasia of collapsing variants of FSGS
Glomerular lesions
► Fibrinoid necrosis: lytic destruction of cells and matrix with
deposition of acidophilic fibrin-rich material
► Sclerosis: increased collagenous extracellular matrix that is
expanding the mesangium,
► obliterating capillary lumens or forming adhesions to
Bowman`s capsule
► Hyaline: glassy acidophilic extracellular material
► Membranoprolifrative: combined capillary wall thickening
and mesangial or endocapillary hypercellularity
► Lobular (hypersegmented): expansion of segments that are
demarcated by intervening urinary space
► Mesangiolysis: detachment of the paramesangial GBM from
the mesangial matrix or lysis of mesangial matrix
► Focal glomerulonephritis: is includes inflammatory
lesions in less than 50% of glomeruli. the
differential diagnoses are noted based on the age
and are as follow:
► <15 years:
● mild postinfectious glomerulonephritis
● IgA nephropathy
● thin basement membrane disease
● hereditary nephritis
● Henoch Schoenlein purpura
► Mesangial prolifrative glomerulonephritis 15-40
years:
● IgA nephropathy
● thin basement membrane disease
● systemic lupus erythematous
● hereditary nephritis
► Mesangial prolifrative glomerulonephritis >40 years:
● IgA nephropathy
► Diffuse glomerulonephritis: affects most or all of the
glomeruli and differential diagnoses according to
age are:
► <15 years:
● postinfectious glomerulonephritis
● membranoprolifrative glomerulonephritis
► 15-40 years:
● postinfectious glomerulonephritis
● systemic lupus erythematous
● rapid progressive glomerulonephritis
● fibrillary glomerulonephritis
► membranoprolifrative glomerulonephritis >40
years:
● rapid progressive glomerulonephritis
● fibrillary glomerulonephritis
● vasculitis
● postinfectious glomerulonephritis
► Nephrotic syndrome: is associated with proteinuria and
lipiduria and its differential diagnoses according to age
include:
► <15 years:
● minimal change disease
● focal segmental glomerulosclerosis
► Mesangioprolifrative glomerulonephritis 15-40 years:
● focal segmental glomerulosclerosis
● minimal change disease
● membranous nephropathy
● diabetic nephropathy
● preeclampsia
► post infectious glomerulonephritis >40 years:
● focal segmental glomerulosclerosis
● membranous nephropathy
● diabetic nephropathy
● minimal change disease
● IgA nephropathy
● amyloidosis
● light chain deposition disease
● benign nephrosclerosis
● postinfectious glomerulonephritis
Tubular lesions
Acute tubular cell injury
► acute tubular necrosis (often coagulation necrosis/
usually secondary to toxins or ischemia.
► hyaline droplet formation (small to large droplets in
lysosomes of tubular epithelium because of altered
permeability and absorption of proteins.)
► vacuolar change (fine and diffuse appearance)
► fatty change (cytoplasm with fine small vacuoles in base
of epithelial cells in severe proteinuria or nephrotic
syndrome with hyperlipidemia, Reyes` syndrome,
poisoning with phosphorus or carbon tetrachloride. In non
nephrotic syndrome, it is in favour of Alport’s syndrome)
► Tubular casts (principal histologic feature of
light chain disease, myoglubolnuria,
hemoglubolinuria, oxalate nephropathy, urate
nephropathy, nephrocalcinosis and drug induced
tubular lesions)
● hyaline: renal failure or low urine output
● WBC: tubulointerstitial inflammation
● epithelial cell or granular: acute tubular injury
● RBC: glomerular bleeding
 ● large hyaline fractured: light chain casts (often accompanied
by giant cells and neutrophils)
● coarse granular acidophilic: myoglobulin or hemoglobulin
► Tubular atrophy (simplified epithelial cells with thickening
of basement membrane)
► Tubulitis (infiltration of inflammatory cells indicative of
active tubulointerstitial inflammation or nephritis or
allograft rejection)
► Tubular basement membrane changes (in tubular atrophy,
hereditary nephritis, diabetic nephropathy, monoclonal
immunoglobulin deposit, dense deposit disease)
Interstitial lesions
► No pathologic changes -
● normal kidney
● no changes in the portion
● early disease
► Acute and chronic interstitium nephritis
● Acute shows reversible infiltration of inflammatory
cells accompanied with edema
● Chronic displays irreversible fibrosis and atrophy of
other compartments.
► Acute phase can heal or result in chronic phase and
scarring.
Interstitial lesions
► Expansion and edema (due to increased permeability of
vessels)
● acute tubular necrosis
● thrombosis of renal vein
● nephrotic syndrome
● acute glomerulonephritis
● thrombotic microangiopathy
► Expansion with eosinophilic material
● fibrosis (chronic disease)
● sickle cell anemia
● radiation
● amyloidosis
► Expansion with leukocyte infiltration
● interstitial nephritis with polymorphonuclear cells (infections, drug
induced, sepsis)
● lymphoplasmacytic (chronic nephritis, vasculitis, lupus nephritis,
infections, rejection, drug induced)
● eosinophils (vasculitis, drug induced, lupus nephritis)
● epithelioid cells/granuloma (tuberculosis, sarcoidosis, drug induced,
malakoplakia) Foam cells
● Alport`s syndrome
● prolonged nephrotic syndrome
► Hemorrhagia
● acute rejection
● vasculitis
● severe glomerulonephritis
● malignant hypertension
► Expansion with neoplastic cells
● lymphoma/leukemia
● primary or secondary tumors
► Crystals
● calcium carbonate
● calcium oxalate
● uric acid
● cholesterol
► Fibrosis
● chronic phase of inflammation
● secondary to chronic lesions of other parts
Vascular lesions
► The main injuries of vascular elements are
► Vasculitis
● in systemic injury of vessels
● in local injuries of vessels due to toxins or infection or inflammation
► Deposition of materials
● amyloidosis
● immune complexes
● arteriosclerosis
► Hypertension induced injuries
● hypertrophy of media
● intimal thickening
● fibrinoid necrosis
● thrombotic microangiopathy
● fibrointimal hyperplasia
► Endothelitis
● drug induced
● toxins
► Thrombus
● secondary lesion to endothelitis; may cause anemia and
thrombocytopenia Emboli
● small parts of coagulated blood, fat or tumor cells usually in
larger arterioles of the kidney In summary, the importance of
clinical characteristics and laboratory results in pathologic
assessment of renal biopsies should be stressed. Proper
diagnoses can be achieved using light microscopy, electron
microscopy and immunofluorescence study of biopsies, in
addition to integration of all clinical, laboratory and pathologic
data.
Acute Nephritic Syndrome
Introduction

Acute nephritic syndromes classically present

with the following:
• Hypertension
• Hematuria
• Red blood cell casts
• Pyuria
• Mild to moderate proteinuria
Introduction

Extensive inflammatory damage to glomeruli can

cause a fall in GFR and eventually produce
uremic symptoms with salt and water retention,
leading to edema and hypertension.
Acute Nephritic Syndromes

Poststreptococcal Glomerulonephritis
Subacute Bacterial Endocarditis
Lupus Nephritis
Antiglomerular Basement Membrane Disease
IgA Nephropathy
ANCA Small Vessel Vasculitis
Membranoproliferative Glomerulonephritis
Mesangioproliferative Glomerulonephritis
Poststreptococcal Glomerulonephritis

Poststreptococcal glomerulonephritis is an
immune-mediated disease involving:

Streptococcal antigens
Circulating immune complexes
Activation of complement in association with
cell-mediated injury.
Poststreptococcal Glomerulonephritis

Poststreptococcal glomerulonephritis is
prototypical for acute endocapillary proliferative
glomerulonephritis.

Acute poststreptococcal GN
• 90% of cases affect children between the ages of 2
and 14 years
• 10% of cases are patients older than 40
Poststreptococcal Glomerulonephritis

The classic presentation is an acute nephritic

picture with hematuria, pyuria, red blood cell
casts, edema, hypertension, and oliguric renal
failure, which may be severe enough to appear
as RPGN.

Systemic symptoms of headache, malaise,

anorexia, and flank pain (due to swelling of the
renal capsule) are reported in as many as 50% of
cases.
Poststreptococcal Glomerulonephritis

Poststreptococcal glomerulonephritis caused by

impetigo and streptococcal pharyngitis:

• Impetigo: 2–6 weeks after skin infection

• Streptococcal pharyngitis: 1–3 weeks after infection
Poststreptococcal Glomerulonephritis

Overall, the prognosis is good, with permanent

renal failure being very uncommon (1–3%), and
even less so in children.

Complete resolution of the hematuria and

proteinuria in children occurs within 3–6 weeks
of the onset of nephritis.
Poststreptococcal Glomerulonephritis

The renal biopsy in poststreptococcal

glomerulonephritis demonstrates:
• Hypercellularity of mesangial and endothelial cells
• Glomerular infiltrates of polymorphonuclear
leukocytes
• Granular subendothelial immune deposits of IgG, IgM,
C3, C4, and C5-9
• Subepithelial deposits (which appear as "humps")
Subacute Bacterial Endocarditis

Endocarditis-associated glomerulonephritis is
typically a complication of subacute bacterial
endocarditis.

Particularly in patients who:

• Remain untreated for an extended period of time
• Have negative blood cultures
• Have right-sided endocarditis (IVDU)
Subacute Bacterial Endocarditis

Grossly, the kidneys in subacute bacterial

endocarditis have subcapsular hemorrhages
with a "flea-bitten" appearance.

Microscopy on renal biopsy reveals a focal

proliferation around foci of necrosis associated
with abundant mesangial, subendothelial, and
subepithelial immune deposits of IgG, IgM, and
C3.
Subacute Bacterial Endocarditis

The pathogenesis hinges on the renal deposition

of circulating immune complexes in the kidney
with complement activation.
Subacute Bacterial Endocarditis

Patients present with:

• Gross hematuria
• Microscopic hematuria
• Pyuria
• Mild proteinuria
• RPGN with rapid loss of renal function (less common)
Subacute Bacterial Endocarditis

Primary treatment is eradication of the infection

with 4–6 weeks of antibiotics, and if
accomplished expeditiously, the prognosis for
renal recovery is good.
Lupus Nephritis

Lupus nephritis is a common and serious

complication of systemic lupus erythematosus
(SLE) and most severe in African-American
female adolescents.
Lupus Nephritis

Thirty to fifty percent of patients will have clinical

manifestations of renal disease at the time of
diagnosis.

Sixty percent of adults and eighty percent of

children develop renal abnormalities at some
point in the course of their disease.
Lupus Nephritis

Lupus nephritis results from the deposition of

circulating immune complexes:
• Which activate the complement cascade
• Leads to complement-mediated damage
• Leukocyte infiltration
• Activation of procoagulant factors
• Release of various cytokines
Lupus Nephritis

The most common clinical sign of renal disease is

proteinuria, but hematuria, hypertension, varying
degrees of renal failure, and an active urine
sediment with red blood cell casts can all be
present.
Lupus Nephritis

Hypocomplementemia is common in patients with

acute lupus nephritis (70–90%) and declining
complement levels may herald a flare.

Renal biopsy, however, is the only reliable method

of identifying the morphologic variants of lupus
nephritis.
Lupus Nephritis

Patients with crescents on biopsy may have a

rapidly progressive decline in renal function.

Without treatment, this aggressive lesion has the

worst renal prognosis.
Antiglomerular Basement Membrane
Disease
Patients who develop autoantibodies directed
against glomerular basement antigens
frequently develop a glomerulonephritis termed
antiglomerular basement membrane (anti-GBM)
disease.
Antiglomerular Basement Membrane
Disease
When they present with lung hemorrhage and
glomerulonephritis, they have a pulmonary-renal
syndrome called Goodpasture's syndrome.
Antiglomerular Basement Membrane
Disease
Goodpasture's syndrome appears in two age groups:
• Young men in their late 20s
• Men and women in their 60–70s

Disease in the younger age group is usually explosive:

• Hemoptysis
• Sudden fall in hemoglobin
• Fever
• Dyspnea
• Hematuria
Antiglomerular Basement Membrane
Disease
The performance of an urgent kidney biopsy is
important in suspected cases of Goodpasture's
syndrome to confirm the diagnosis and assess
prognosis.

Renal biopsies typically show focal or segmental

necrosis that later, with aggressive destruction
of the capillaries by cellular proliferation, leads
to crescent formation in Bowman's space
Antiglomerular Basement Membrane
Disease
The presence of anti-GBM antibodies and
complement is recognized on biopsy by linear
immunofluorescent staining for IgG (rarely IgA).
Antiglomerular Basement Membrane
Disease
Prognosis at presentation is worse if the following
• >50% crescents on renal biopsy with advanced
fibrosis
• Serum creatinine is >5–6 mg/dL
• Oliguria is present
• Need for acute dialysis
Antiglomerular Basement Membrane
Disease
Patients with advanced renal failure who present
with hemoptysis should still be treated for their
lung hemorrhage, as it responds to
plasmapheresis and can be lifesaving.

Treated patients with less severe disease typically

respond to 8–10 treatments of plasmapheresis
accompanied by oral prednisone and
cyclophosphamide in the first 2 weeks.
IgA Nephropathy

IgA nephropathy is an immune complex-mediated

glomerulonephritis defined by the presence of
diffuse mesangial IgA deposits often associated
with mesangial hypercellularity.
IgA Nephropathy

IgA nephropathy is one of the most common

forms of glomerulonephritis worldwide.

There is a male preponderance, a peak incidence

in the second and third decades of life, and rare
familial clustering.
IgA Nephropathy
Deposits of IgA are also found in the glomerular
mesangium in a variety of systemic diseases, including:
• Chronic liver disease
• Crohn's disease
• Gastrointestinal adenocarcinoma
• Chronic obstructive bronchiectasis
• Idiopathic interstitial pneumonia
• Dermatitis herpetiformis
• Mycosis fungoides
• Leprosy
• Ankylosing spondylitis
IgA Nephropathy

The two most common presentations of IgA

nephropathy are recurrent episodes of
macroscopic hematuria during or immediately
following an upper respiratory infection in
children (Henoch-Schönlein purpura) or
asymptomatic microscopic hematuria most
often seen in adults.
IgA Nephropathy

Rarely, patients can present with acute renal

failure and a rapidly progressive clinical picture.

Risk factors for the loss of renal function include

the presence of hypertension or proteinuria, the
absence of episodes of macroscopic hematuria,
male, older age of onset, and more severe
changes on renal biopsy.
ANCA Small Vessel Vasculitis

A group of patients with small-vessel vasculitis

(arterioles, capillaries, and venules; rarely small
arteries) and glomerulonephritis who have
serum ANCA positivity.

The antibodies are of two types:

• Anti-proteinase 3 (PR3)
• Anti-myeloperoxidase (MPO)
ANCA Small Vessel Vasculitis

Wegener's granulomatosis (PR3)

Microscopic polyangiitis (MPO)
Churg-Strauss syndrome (MPO)

Belong to this group because they are ANCA-

positive and have a pauci-immune
glomerulonephritis with few immune complexes
in small vessels and glomerular capillaries.
ANCA Small Vessel Vasculitis

Induction therapy usually includes some

combination of plasmapheresis,
methylprednisolone, and cyclophosphamide.

The steroids are tapered soon after acute

inflammation subsides, and patients are
maintained on cyclophosphamide or
azathioprine for up to a year to minimize the risk
of relapse.
Membranoproliferative Glomerulonephritis

MPGN is sometimes called mesangiocapillary

glomerulonephritis or lobar glomerulonephritis.

It is an immune-mediated glomerulonephritis
characterized by thickening of the GBM with
mesangioproliferative changes; 70% of patients
have hypocomplementemia.
Membranoproliferative Glomerulonephritis

MPGN is subdivided pathologically:

• Type I
• Type II (idiopathic)
• Type III (idiopathic)
Membranoproliferative Glomerulonephritis

Type I MPGN is commonly associated with:

• Persistent hepatitis C infections
• Autoimmune diseases (lupus)
• Cryoglobulinemia
• Neoplastic diseases
Membranoproliferative Glomerulonephritis

Type I MPGN, the most proliferative of the three

types.

Tram-tracking - mesangial proliferation with

lobular segmentation on renal biopsy and
mesangial interposition between the capillary
basement membrane and endothelial cells.
Membranoproliferative Glomerulonephritis

Type I MPGN is secondary to glomerular deposition

of circulating immune complexes

Patients with MPGN present with:

• Proteinuria
• Hematuria
• Pyuria (30%)

Systemic symptoms of fatigue and malaise that are

most common in children with Type I disease.
Membranoproliferative Glomerulonephritis

In the presence of proteinuria, treatment with

inhibitors of the renin-angiotensin system is
prudent.

There is some evidence supporting the efficacy of

treatment of primary MPGN with steroids,
particularly in children.

In secondary MPGN, treating the associated

infection, autoimmune disease, or neoplasms is
of demonstrated benefit.
Mesangioproliferative Glomerulonephritis

Mesangioproliferative glomerulonephritis is
characterized by expansion of the mesangium,
sometimes associated with mesangial
hypercellularity; thin, single contoured capillary
walls; and mesangial immune deposits.
Mesangioproliferative Glomerulonephritis

Clinically, it can present with varying degrees of

proteinuria and, commonly, hematuria.

Mesangioproliferative disease may be seen in:

• IgA nephropathy
• P. falciparum malaria
• Resolving postinfectious glomerulonephritis
• Lupus nephritis
RENAL NEOPLASMS
RENAL CELL CARCINOMA- Adult
 Epidemiology

► Male predominance (M:F 1.5:1).

► Most common in sixth to eighth decades; peak

incidence in sixth decade
► Metastatic disease in 30% at diagnosis, and
eventually in 50% (lung, liver, bone, distant LN,
adrenal, brain, opposite kidney, soft tissue)
► Most sporadic RCCs are unilateral and unifocal
► Stage at diagnosis is the most important prognostic
factor
► Predominant histologic type: adenocarcinoma arising
from tubular epithelium
► Adenocarcinoma subtypes:
● clear cell (75–85%)
● chromophilic/ papillary (10–15%)
● chromophobe (5–10%)
● oncocytic (rare)
● Sarcomatoid (1–6%; poor prognosis)
Papillary (chromophilic) renal cell carcinoma extending into the
collecting system
 Risk factors
► Tobacco , urban environmental toxins (cadmium/ asbestos/ petrols),
obesity, high dietary fat intake, acquired cystic renal disease from
renal failure
► Association with von Hippel-Lindau disease:
● autosomal dominant
● loss of 3p
● >70% chance developing RCC (almost all clear cell histology) risk of
developing multiple other benign and malignant tumors (retinal angiomas,
CNS hemangioblastomas, pheochromocytoma , pancreatic cancer)
Familial Renal Cell Carcinoma Syndromes
Pathology

► Round to ovoid

► Circumscribed by a pseudo capsule of compressed

parenchyma and fibrous tissue

► Nuclear features can be highly variable

Fuhrman's Classification System for Nuclear Grade
Diagnosis

► Common signs and symptoms:

● hematuria (80%)
● flank pain (45%)
● flank mass (15%)
● classic triad of prior three only present in 10%
● normocytic/normochromic anemia, fever, weight loss

► Less common signs and symptoms:

● hepatic dysfunction without mets
● Polycythemia
● hypercalcemia (occurs in 25% of patients with RCC mets)
Paraneoplastic syndromes in 20% of patients with
RCC
CT scan shows right renal tumor with perinephric stranding suggesting invasion
of the perinephric fat
Contrast inferior venacavogram in patient with a right renal tumor shows
involvement of the subdiaphragmatic vena cava
Staging AJCC 7th Edition
Prognostic Factors For RCC
Pediatric Renal Tumors
Renal Cell Carcinoma
► 2-6% of all pediatric renal tumors
● Less than 2% of all cases of RCC occur in children
► Assoc. with von Hippel-Landau syndrome
● Multiple tumors, younger age at diagnosis
● R/o VHL in pediatric pts. Dx with RCC, esp if bilateral disease
► Clinical presentation
● Gross, painless hematuria-more common in RCC than WT
● Palpable mass
● Flank pain
● 20% present with metastasis at time of diagnosis
► Several pediatric renal tumors
● Wilms tumor, RCC, RTK, Clear cell sarcoma of the
kidney
 RCC, RTK and CCSK more rare in children

 Wilms tumor is most common- accounts for 87% of

pediatric renal masses.
– Occurs 1:10,000 persons
– Peak incidence 3-4 yrs. 80% present< 5 yrs.
– Bilateral tumors in 4-13% of children
► Prognosis influenced by stage at diagnosis
► Overall survival 64% for all stages
Rhabdoid tumor of the kidneys
► Rare, highly aggressive malignancy of early childhood
● 80% occur in pts. <2 yrs. Of age
● Median age of dx- 11 months
► Clinical manifestations
● Hematuria
● Fever
● Anemia
● Symptoms of metastatic disease-most pt. present with
advanced disease
● Associated with synchronus/ metachronus primary
intracranial masses
● Hypercalcemia
Amar, Aneesa M.; Thomlinson, Gail, et al. Clinical Presentation of Rhabdoid Tumors of the Kidney.
Journal of Pediatric Hematology. Vol. 23(2), February 2001, pp 105-108.
Clear Cell Sarcoma
► Uncommon renal neoplasm of childhood-20 new
cases/yr. U.S.
► Aggressive behavior-higher rate of relapse/mortality
than WT
● Long term survival-60-70%
● Survival assoc. with stage at diagnosis
► Usually presents with abd. Mass
► Treatment-nephrectomy/chemotherapy
● Addition of Doxorubicin to VCR/Dactinomycin improved
survival
► Bone metastasis most common
► Can recur long after therapy
Argani, Perlman et al. Clear Cell Sarcoma of the Kidney: A Review of 351 cases from the NWTSG
Pathology Center. The American Journal of Surgical Pathology. Vol. 24(1), January 2000.
Wilms Tumor
► Wilms Tumor (nephroblastoma) predominant
renal tumor in children 3 months -6 yrs.
● 90% overall survival
► Chromosomal abnormalities assoc. with some
WT
● Two locations on chromosome 11
 11p13-WT 1 gene, 11p15-WT 2 gene
 Abnormalities on 1, 12 and 8
► Familial WT 1-2%
● FWT1 at 17Q12-q21
● FTW2 at 19q13.4
► Biallelic BRAC 2 mutations assoc. with multiple
pediatric malignancies include. WT

Ruteshouser,EC, Huff,V. Am J Med Genet C Semin Med Genet. 2004 Aug 15;129
Reid,S et al. Journal of Medical Genetics 2005; 42: 147-151.
Genetic Syndromes
► WAGR-WT, aniridia, genitourinary malformation, mental
retardation; somatic germline deletions of 11p13
► Denys-Drash-pseudohermaphroditism, severe
glomerulopathy, WT; inactivating point mutations in the
WT1 gene, 11p13
► Beckwith-Wiedemann-hemihypertrophy,
macroglossia, omphalocele, visceromegaly; loss of
heterozygosity in 2nd WT locus on 11p15
Clinical Presentation
► Most common asymptomatic abd. mass in
children
► Abdomen pain,distention
► Fever
► Hematuria
► Hypertension
► Anorexia
► Vomiting
Prognostic Factors
► Age- younger age better prognosis
► Anaplasia- worse prognosis, 13% of pts.>5 yrs.
Old
● Focal
● Diffuse
► LOH at chormosomes 1p and 16q-greater risk of
relapse and mortality regardless of stage,
histology
Long term effects
► 4-5% develop kidney failure
► Higher incidence of renal dysfunction
► Reproductive dysfunction
► Pulmonary fibrosis if lung radiation used
► Congestive heart failure-Green et al (2001) cumulative incidence of CHF 4.4% 20 yrs
after initial tx with Doxorubicin
► Scoliosis, asymmetry
► Muscle atrophy
► 2nd primary tumors
► Long-term follow-up guidelines: www.childrensoncologygroup.org

Nelson, MB and Meeske, K. Recognizing Health Risks in Childhood Cancer Survivors. Journal of the American Academy of Nurse
Practitioners. 2005.
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