lec 8 - 11 RENAL SYSTEM PATHOLOGY pdf - د. مصطفى

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RENAL SYSTEM PATHOLOGY

Lectures objectives:

1. Know the pathological changes of different renal diseases

2. Know the pathogenesis of renal disease

3. Correlate clinical features with disease process

4. Know the morphological changes that the renal diseases do.

Normal

 Adult kidney weighs (150 gm), representing 0.5% of body wt.

receives 25% Cardiac out put ;

 The kidneys function to:

1. Excrete the waste products of metabolism.
2. Regulate the body's concentration of water and salts.
3. Maintain the appropriate acid balance of plasma.
4. Serve as an endocrine organ secreting such hormones as
erythropoietin, renin and prostaglandins.

 The ureter forms the pelvis which is divided into 2 or 3 major

calyces, each one giving 3 or 4 minor calyces.

 The kidney is divided into the cortex 1.2-1.5 cm and medulla.

 The medulla consists of renal pyramids, the apices of which are

called papillae, each related to a calyx.

Congenital Anomalies

 About 10% of all people are born with potentially significant

malformations of the urinary system.

 Congenital renal disease can be:

 Hereditary

 Acquired developmental defect (most often) that arises

during fetal development.

Congenital anomalies-cont

Agenesis of the kidney:

 Bilateral agenesis is incompatible with life, seen in stillborn.

 Unilateral type is uncommon.

 The opposite kidney is usually enlarged as a result of

compensatory hypertrophy.

Hypoplasia:

 Is failure of the kidney to develop to a normal size.

 If bilateral > results in early renal failure.

 Unilateral cases are more common.

Congenital anomalies-cont

Ectopic Kidneys:

 These kidneys lie either just above the pelvic brim or within the

pelvis.

 They are usually normal or slightly small in size.

 Because of their abnormal location, kinking or tortuoisity of the

ureters may cause some obstruction to urinary outflow.

Horseshoe kidneys:

 Fusion of upper or lower poles of the kidneys that is continuous

across the midline anterior to the great vessels.

 This anomaly is common and is found in about 1:500 to 1000

autopsies.

 90% of the kidneys are fused at the lower poles.

Cystic diseases of the kidney

 They are heterogeneous group comprising hereditary,

developmental and acquired disorders.

 They are important because:

 1. They are reasonably common and often represent

diagnostic problems for clinicians, radiologists and
pathologists.

 2. Some forms are major causes of chronic renal failure.

 3. They can occasionally be confused with malignant

tumors.

Cystic diseases of the kidney

Classification;

1. Cystic renal dysplasia.

2. Polycystic kidney disease

a. Autosomal dominant (adult) type.

b. Autosomal recessive (childhood) type.

3. Medullary cystic disease.

a. Medullary sponge kidney.

b. Nephronophthisis.

4. Acquired (dialysis-associated) cystic disease.

5. Simple renal cyst.

6. Renal cysts in hereditary malformation syndromes (e.g. Tuberous
sclerosis).
7. Glomerulocystic disease.
8. Parasitic cysts (e.g. hydatid cyst).

Cystic Renal Dysplasia

 This sporadic disorder is due to an abnormality in metanephric

differentiation.

 Most cases are associated with ureteropelvic obstruction,

ureteral agenesis or atresia , ….etc.

 Dysplasia can be unilateral or bilateral and is almost always cystic.

 When unilateral, the dysplasia is discovered by the presence of

flank mass. The function of the opposite kidney is normal, and
such patients have an excellent prognosis after surgical removal of
the affected kidney.

Histologically:

• Persistence in the kidney of abnormal structures,

cartilage, undifferentiated mesenchyme and immature
collecting ductules.

• Abnormal lobar organization.

• Variable size cysts, lined by flattened epithelium.

Autosomal Dominant (Adult) Polycystic Kidney Disease

 It is characterized by multiple expanding cysts of both kidneys that

ultimately destroy the renal parenchyma and cause renal failure.

 It affects roughly 1 of every 400 to 1000 live births and accounting

for about 5-10% of cases of chronic renal failure requiring
transplantation or dialysis.

 The mode of inheritance is autosomal dominance with high

penetrance.

 The disease is universally bilateral.

Autosomal Dominant (Adult) Polycystic Kidney Disease

 The cysts initially involve only portions of the nephrones, so renal

function is retained until about the 4th or 5th decade of life.

 The condition is genetically heterogeneous, family studies show

gene mutation located on chromosome 16p13.3 (PKD1) and 4q21
(PKD2).

 Mutation of PKD1 accounts for about 85% of the cases and are

associated with a more severe disease.

Morphologically

 Grossly both kidneys are enlarged, weighs up to 4 kg.

 The external surface appears to be composed solely of a mass of

cysts, up to 3 to 4 cm in diameter, with no intervening parenchyma.

 The cysts may be filled with clear serous fluid or more usually

with turbid red to brown, sometimes hemorrhagic fluid.

 Microscopically:

 The cysts arise from the tubules throughout the nephron and

therefore have variable lining epithelia.

 Bowman capsules are occasionally involved

Clinically

 Most remain asymptomatic until renal insufficiency occurs.

 The larger masses, usually palpable, may induce a dragging

sensation.

 In about 40% of cases, one to several cysts in the liver are present,

which are usually asymptomatic and are derived from biliary
epithelium.

 Cysts occur less frequently in the spleen, pancreas and lungs.

 Intracranial Berry aneurysms may be present and can cause death

in about 4-10% of patients due to subarachnoid hemorrhage.

 Mitral valve prolapse and the other cardiac valvular anomalies

occur in 20-25% of patients, but most are asymptomatic.

Autosomal Recessive (Childhood) Polycystic Kidney Disease

 Is rare anomaly.

 Perinatal, neonatal, infantile, and juvenile subcategories have

been defined, depending on the time of presentation and presence
of associated liver disease.

 The first 2 are the most common;

 The disease appears to be genetically homogeneous, being

associated with a gene, PKHD1, that maps to chromosome region
6p21-23.

Morphology

 The kidneys are enlarged and have a smooth external surface. On

cut section, numerous small cysts in the cortex and medulla give
the kidney a sponge-like appearance.

 The cysts are perpendicular to the cortico-medullary junction.

 Microscopically, the cysts have a uniform lining of cuboidal cells,

reflecting their origin from the collecting tubules.

 The disease is invariably bilateral. In almost all cases, the liver has

cysts with portal fibrosis as well as proliferation of portal bile
ducts.

 Clinical Features;

 Neonetaes & young infant progress rapidly to renal failure.

Patients, who survive infancy, may develop congenital hepatic
fibrosis. In older children, the hepatic picture predominates, in
form of portal hypertension

Cystic Disease Of Renal Medulla:
1/ Medullary Sponge Kidney

 Multiple cystic dilations of the collecting ducts in the medulla;

with unknown pathogenesis.

 The condition occurs in adults

 Discovered radiologically, either as an incidental finding or

sometimes in relation to secondary complications such as
calcifications within the dilated ducts, hematuria, infection and
urinary calculi.

 Renal function is usually normal.

 The cysts are lined by cuboidal epithelium or occasionally by

transitional epithelium.

Cystic Disease Of Renal Medulla:
2/ Nephronophthsis-Medullary Cystic Disease Complex

 Usually have their onset in childhood.

 The cysts are usually concentrated at the cortico- medullary

junction.

 There is injury of the distal tubules with tubular basement

membrane disruption, followed by chronic and progressive tubular
atrophy involving both medulla and cortex and interstitial fibrosis.

 The cortical tubulointerstitial damage is the cause of the eventual

renal insufficiency.

Acquired (Dialysis-Associated) Cystic Disease

 The kidneys of patients on chronic dialysis, sometimes exhibit

numerous cortical and medullary cysts.

 The cysts measure 0.5-2cm, contain clear fluid, are lined by either

hyperplastic or flattened tubular epithelium and often contain
calcium oxalate crystals.

 They probably form as a result of tubular obstruction due to

interstitial fibrosis or by oxalate crystals.

Acquired (Dialysis-Associated) Cystic Disease

 Most are asymptomatic, but sometimes the bleeding inside the

cysts cause hematuria.

 Complication; development of renal cell carcinoma in the walls of

these cysts in about 7% of patients during 10 years period.

Simple Cysts

 Single or multiple, usually cortical.

 The size range from 1-10cm or more.

 They are translucent and filled with clear fluid.

 They are lined by a single layer of cuboidal or flattened epithelium.

 They are common postmortem findings. On occasion, hemorrhage

into them may cause sudden pain, and calcification may be visible
radiologically.

 The main importance of these cysts lies in their differentiation

from kidney tumors.

Glomerular Diseases:

 They constitute some of the major problems in nephrology; in fact

they are the most common causes of chronic renal failure in
humans.

 Clinical manifestations; they are clustered into 5 major syndromes.

 1. Acute nephritic syndrome.

 2. Nephrotic syndrome

 3. Asymptomatic hematuria or proteinuria, or combination

 4. Acute renal failure.

 5. Chronic renal failure.

Schematic Representation of a Glomerular Lobe

Histologic alterations

 There are 5 basic tissue reactions

 1. Increased glomerular cellularity

 a. Proliferation of mesangial or endothelial cells.

 b. Leukocyte infiltration, including neutrophils, monocytes,

and, in some diseases, lymphocytes.

 c. Formation of crescents.

 2. Basement membrane thickening, best seen with (PAS) stain.

By EM, it can be resolved as one of 2 alteration;

 a. Deposition of amorphous electron dense material, most

often immune complexes, on the endothelial or epithelial side
of basement membrane, or within the GBM itself.

 b. Thickening of the BM proper, as occurs in diabetic

glomerulosclerosis.

3. Hyalinization and sclerosis, made up of plasma proteins and

collagen material deposited exracellularly.

4. Additional alterations include; accumulation of lipids, fibrin or

other metabolic materials.

5. Intraglomerular vascular thrombosis

 The histologic changes can be further subdivided into;

1. Diffuse 2. Focal. 3. Global. 4. Segmental. 5. Mesangial

Localization of immune complexes in the Glomerulus

1. Subepithelial humps, as in acute glomerulonephritis;

2. Epimembranous deposits, as in membranous nephropathy and
Heymann glomerulonephritis;

3. Subendothelial deposits, as in lupus nephritis and
membranoproliferative glomerulonephritis;

4. Mesangial deposits, as in IgA nephropathy;

5. Basement membrane.

 EN, endothelium; EP, epithelium; LD, lamina densa; LRE, lamina

rara externa; LRI, lamina rara interna; MC, mesangial cell; MM,
mesangial matrix.

Pathogenesis

 Although little is known about etiologic agents and triggering

events, it is clear that immune mechanisms underlie most forms of
primary glomerulopathies, and many of the secondary forms.

I.  Immune-mediated mechanisms;
  1. Ab-mediated;
  a. In situ immune complex deposition

 Fixed intrinsic antigens

 Planted antigens (exogenous as infectious agent

or drug and endogenous as DNA,
immunoglobulins)

b. Circulating immune complex deposition

 Endogenous Ag (DNA, tumor)

 Exogenous Ag (infectious products)

c. Cytotoxic Ab

Pathogenesis-cont

2. Cell-mediated.

3. Activation of alternative complement pathway.

II. Non-immune mechanism (adaptive changes secondary to renal
ablation)

 The 2 major histologic characteristics of such changes are;

1. Focal segmental Glomerulosclerosis.
2. Tubulointerstitial fibrosis

Epithelial cell injury and destruction of the basement membrane
as a result of immune complex in the glomerulus. Normally, the basement
cell membrane does not filter large molecules such as albumin (70,000
kD), which is present in urine if the membrane is damaged.

Clinical Presentations of GN

Acute Glomerulonephropathy:
This group is characterized by inflammatory alterations in the glomeruli
and clinically by acute nephritic syndrome
Postsreptococcal type

 Typically occurs 1-4 weeks after a streptococcal infection of the

pharynx or skin.

 It affects most frequently children aging 6-10 years, but adults of

any age can be involved.

 Only certain strains of group A, Beta-hemolytic streptococci are

nephrogenic.

 Several streptococcal Ag such as endostreptosin and several

cationic Ag are found in the glomeruli.

Postsreptococcal GN

 It is not known if these represent planted Ag, part of circulating

immune complexes, or both.

 GBM proteins altered by streptococcal enzymes have also been

implicated as an Ag.

 The classic diagnostic morphologic change is enlarged,

hypercellular glomeruli, due to;

 1. Infiltration by leukocytes, both neutrophils and

monocytes.

 2. Proliferation of endothelial and mesangial cells.

 3. Crescent formation, in severe cases.

Postsreptococcal GN

 The changes are both diffuse and global.

 By immunofluoresence microscopy, there are granular deposits of

IgG, IgM and C3 in the mesangium and along the basement
membrane.

 In the classic case, a young child abruptly develops fever, malaise,

oliguria and hematuria, 1-2 weeks after recovery from a sore
throat.

 The patient exhibits red cell cast in the urine, mild proteinuria,

periorbital edema and mild to moderate hypertension.

 In adults, the onset is more likely to be atypical, with sudden

appearance of hypertension or edema, frequently with elevation of
BUN.

Postsreptococcal GN

 > 95% of affected children eventually recover completely with

conservative therapy.

 <1% do not improve, and develop a rapidly progressive form of

glomerulonephropathy.

 Some undergo slow progression to chronic

glomerulonephropathy.

 In adults, the disease is less benign, as only 60% of patients do

recover promptly

Rapidly Progressive (Crescentic) Glomerulonephropathy

 It is a syndrome associated with severe glomerular injury and is

characterized clinically by rapid and progressive loss of renal
function, and if untreated, death from renal failure within weeks or
months.

 Regardless of the cause, the classic histologic picture is the

presence of crescents in most of the glomeruli

Classification and pathogenesis

 In most of the cases, immunologic injury of the glomeruli is

present. Accordingly 3 groups are identified:

1. Type I RPGN (Anti-GBM AB-Mediated)

Idiopathic

Goodpasture Syndrome

2. Type II RPGN (Immunecomplex-Mediated)

Idiopathic

Postinfectious

Systemic lupus erythemotosus

Henoch-Schonlein purpura (IgA)

Others

3. Type III RPGN (Pauci-Immune)

ANCA associated

Idiopathic

Wegener granulomatosis

Microscopic polyarteritis nodosa

Morphology,

 The kidneys are enlarged and pale, often with petechial

hemorrhages on the cortical surfaces.

 Histologic picture: formation of crescents.

 Electron microscopy: distinct rupture in the basement membrane.

 In time, most crescents undergo sclerosis.

 By immunofluorescence microscopy:

 Postinfectious cases exhibit granular immune deposits.

 Good pasture syndrome show linear deposits.

 Pauci-immune cases have little or no deposits.

Nephrotic Syndrome

 Certain glomerular diseases virtually always produce the nephrotic

syndrome. The manifestations include;

1. Massive proteinuria.
2. Hypoalbuminemia.
3. Generalized edema.
4. Hyperlipidemia and lipiduria.

 These patients are particularly vulnerable to infection especially

with staphylococci and pneumococci.

 Thrombotic and thromboembolic complications are also common.

Nephrotic Syndrome

Membranous Glomerulonephropathy

 It is common cause of nephrotic syndrome in adults.

 It is characterized by diffuse thickening of the glomerular

capillary wall and the accumulation of electron-dense
immunoglobin-containing deposits along the subepithelial side of
the basement membrane.

Membranous Glomerulonephropathy

 Etiology and pathogenesis: it is a form of chronic immune-

complex-mediated disease.

 The disease is idiopathic in about 85% of cases, and is

called primary MGN

 Secondary forms, in association with;

1. Drugs (penicillamine, captopril, gold, NSAIDS).

2. Malignant tumors; bronchogenic ca, ca colon & melanoma.

3. SLE.

4. Infections (Chronic hepatitis B and C, syphilis, malaria).

5. Autoimmune diseases such as thyroiditis.

 The idiopathic type is considered as an autoimmune disorder linked

to susceptibility genes and caused by Ab to a renal Ag.

 Experimental studies suggest a direct action of C5b-C9, the

pathway leading to the formation of the membrane attack
complex.

 C5b-C9 causes activation of glomerular epithelial and mesangial

cells, inducing them to liberate proteases and oxidants, which
cause capillary wall injury and increased protein leakage

Morphology,

 Light microscopy:

 diffuse thickening of the glomerular capillary wall.

 Electron microscopy:

 Irregular dense deposits between the basement membrane

and the epithelial cells, with loss of the foot processes.

 Basement membrane material is laid down between these

deposits, appearing as irregular spikes, (seen by silver stains
as black in color). These spikes by time thicken to produce
dome-like protrusions.

 Immunofluorescence microscopy:

 The granular deposits : contain Ig and various amounts of

complement.

Clinical course; membranous GN

 Insidious onset of nephrotic syndrome or in 15% of patients with

non-nephrotic proteinuria.

 Hematuria and mild hypertension are present in 15-35% of cases.

 Prognosis:

 Variable course but generally indolent.

 Presence of glomerular sclerosis by biopsy at the time of

diagnosis is a predictor of worse prognosis.

 Spontaneous remission and a relatively benign course occur more

commonly in women and in those with non-nephrotic
proteinuria.

Minimal Change Disease

 This relatively benign disorder is the most frequent cause of

nephrotic syndrome in children.

 The peak incidence is at 2-6 years of age.

 The disease sometimes follows a respiratory infection or routine

prophylactic immunization.

 Etiology and pathogenesis, the current hypothesis is some

immune dysfunction, resulting in the elaboration of a cytokine that
damages visceral epithelial cells.

Morphology

 The glomeruli are normal by light microscopy and

immunoflurecent study.

 Electron microscopy:

 Basement membrane appears normal;

 Uniform and diffuse effacement of foot processes of the

visceral epithelial cells.

Clinical course; minimal change dis

 Despite massive proteinuria, renal function remains good.

 The proteinuria is highly selective mostly consists of albumin.

 More than 90% of children respond rapidly to corticosteroid

therapy. However, some patients may become steroid dependent or
resistant.

 The long-term prognosis is excellent, and even steroid dependent

disease resolves when children reach puberty.

 Although adults are slower to respond, the long-term prognosis is

also excellent.

 Minimal change disease in adults can be associated with Hodgkin

disease and less frequently lymphomas and leukemias

Focal Segmental Glomerulosclerosis

 It occurs in the following settings;

 1. In association with other conditions (HIV infection, heroin

addiction, sickle cell disease and massive obesity).

 2. Secondary to glomerular disease (e.g. IgA nephropathy).

 3. As a component of the adaptive response to loss of renal tissue

(renal ablation).

 4. In certain inherited forms of nephrotic syndrome.

 5. Idiopathic (primary disease).

Morphology, FSGS

 Light microscopy:

 The lesion may involve few glomeruli and could be missed

on biopsy. In the sclerotic segments, there is collapse of
basement membranes, increase in matrix, and segmental
insudation of plasma proteins along the capillary wall.

 Electron microscopy:

 Both sclerotic and non-sclerotic glomeruli show diffuse loss

of foot processes of visceral epithelial cells and there may be
focal detachment of the epithelial cells.

 Immunofluorescence microscopy:

 IgM and C3 may be present in the sclerotic areas and/or in

the mesangium.

 hyalinized thickening of afferent arterioles.

 In time, total sclerosis of glomeruli, with pronounced

tubular atrophy and interstitial fibrosis may occur

Clinical course

 There is little tendency of spontaeous remission

 Responses to corticosteroid therapy are variable.

 Children have a better prognosis than adults do.

 About 20% of patients follow an unusually rapid course ending in

renal failure within 2 years.

 Recurrences are seen in 25%-50% of patients receiving allografts.



د. مصطفى امراض

0202

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lec: 9+10

RENAL SYSTEM

PATHOLOGY

Diseases Affecting Tubules and Interstitium

Acute tubular injury:

 Clinicopathological entity characterized by:

 Morphologically: destruction of tubular epithelium

 Clinically: acute renal failure.

 It can be caused by;

1. Ischemia.
2. Direct toxic injury of tubules (drugs, radiocontrast dyes,
myoglobin, hemoglobin, radiation).
3. Acute tubulointerstitial nephritis, most commonly as a
hypersensitivity reaction to drugs.
4. DIC
5. Urinary tract obstruction.

Acute Tubular Injury-cont

 ATI accounts for 50% of cases of acute renal failure.

 It is a reversible

 Classified as:

1. Ischemic ATI.

2. Nephrotoxic ATI

1. Drugs: gentamicin

2. Radiographic contrast agents

3. Heavy metals poisoning

4. Organic solvents

Pathophysiologic mechanism of ATI

Morphology

 Ischemic ATI is characterized by focal tubular epithelial necrosis

at multiple points along the nephrone.

 The straight portion of the proximal tubule and the ascending limb

of Henle’s loop in the medulla, are especially vulnerable.

 Eosinophilic hyaline casts and pigmented granular casts, are

common in DCT and CD.

 Other features: epithelial regeneration, interstitial edema and

leukocytic infiltration.

 Toxic ATI affect mainly proximal convoluted tubules.

Clinical course

 is divided into;

1. Initiation phase:

 Mild oliguria.

 Lasting about 36 hours

 Dominated by features of the cause (medical, surgical, or

obstetric)

2. Maintenance phase:

 Sustained oliguria to 40-400 ml/24 hrs,

 Salt and water retention, rising BUN, hyperkalemia,

metabolic acidosis and uremia.

3. Recovery phase:

 Steady increase in urine output that may reach 3L/24 hrs.

 Lost of large amounts of water, sodium, and potassium

(Hypokalemia )

 Eventually, renal tubular function is restored to normal.

 The prognosis depends on the clinical settings,

 95% : complete recovery.

 Mortality rate can rise to 50% in shock related to sepsis, extensive

burns, or multiorgan failure

Urinary Tract Infections

Pyelonephritis

 It is one of the most common diseases of the kidney.

1. Acute Pyelonephritis, caused by bacterial infection.

2. Chronic Pyelonephritis,

 Bacterial infection plus:

 Other factors (Vesicoureteral reflux, obstruction)

Acute Pyelonephritis,

 Acute suppurative inflammation of the kidney caused mainly by

bacteria

 > 85% of cases caused by gram negative bacilli

 Mostly E.coli, followed by proteus, klebsiella, and Enterobacter.

 In immunocompromised patients, viruses may be the cause.

Pathways of Renal Infection:

There are 2 routes by which the organism can reach the kidneys;

1. Ascending : from the lower urinary tract (much common).

2. Hematogenous: through the blood stream (less common).

 Morphology: patchy interstitial suppurative inflammation, tubular

leukocyte casts and tubular necrosis.

 Complications :

1. Papillary necrosis, particularly in diabetics and those with urinary

tract obstruction.

2. Pyonephrosis, when there is total or almost complete obstruction

3. Perinephric abscess.

 The end-result is healing by scars formation, almost always

associated with deformity of the underlying calyces and pelvis.

Clinical Course

 Predisposing factors;

1. Obstruction.
2. Instrumentation of the urinary tract.
3. Vesicoureteral reflux.
4. Pregnancy.
5. Patient's sex.
6. Pre-existing renal lesion.
7. Diabetes mellitus.
8. Immunodeficiency.

 The onset is sudden with pain at the costovertebral angle, fever and

malaise.

 There is also dysuria, frequency and urgency.

 Urine contains pus cells and leukocyte casts

Chronic Pyelonephritis

 Characterized by chronic tubulointerstitial inflammation and renal

scarring associated with pathologic involvement of the calyces and
pelvis.

 It is an important cause of end-stage kidney disease.

 It can be divided into 2 forms:

1. Reflux nephropathy, which is the more common. It occurs early in

childhood. The reflux may be uni- or bilateral. The reflux
occasionally causes renal damage in the absence of infections
(sterile reflux),

2. Obstructive nephropathy, which could be uni- or bilateral.

Morphology,

 Grossly:

 The kidneys are irregularly scarred; if bilateral, the involvement

is asymmetric.

 The scars overlie dilated, blunted or deformed calyces, mostly in

the upper and lower poles.

Chronic pyelonephritis

 Microscopically, tubules are atrophic in areas and hypertrophic and

dilated in others. There are varying degrees of chronic interstitial
inflammation and fibrosis in the cortex and medulla.

Xanthogranulomatous Pyelonephritis

 Is a relatively rare form of chronic PN, characterized by

accumulation of foamy macrophages, plasma cells, lymphocytes,
neutrophils and occasional giant cells.

 Often associated with Proteus infection and obstruction.

 Grossly, the lesion produces large, yellowish/orange nodules that

may be confused with renal cell carcinoma

Urinary Tract Obstruction (Obstructive Uropathy)

 Importance:

1. Increases susceptibility to infection

2. Increased stone formation

3. If not treated, results in permanent renal atrophy, termed
hydronephrosis.

 The obstruction may be:

 unilateral or bilateral

 sudden or insidious

 partial or complete

 intrinsic or extrinsic

 Pathogenesis, even with complete obstruction, glomerular

filtration persists for sometimes because the filtrate subsequently
diffuses back into the renal interstitium and perirenal spaces, where
it ultimately returns to the lymphatic and venous system. This
continued filtration leads to pelvicalyceal dilation, which leads in
turn to renal atrophy and hydronephrosis

The most common causes of obstruction:

1. Congenital anomalies: posterior urethral valves and urethral
strictures, bladder neck obstruction, etc…

2. Urinary calculi.
3. Prostatic hyperplasia.
4. Tumors.
5. Inflammation.
6. Sloughed papillae or blood clot.
7. Pregnancy.
8. Uterine prolapse and cystocele.
9. Functional disorders, neurogenic bladder.

Morphology

 Sudden and complete obstruction: there is mild hydronephrosis

 If the obstruction is subtotal or intermittent, there is more severe

hydronephrosis.

 Depending on the level of urinary block, the ureter and the bladder

may be affected too.

 The size of the kidney is variable, depending on the duration of

obstruction.

 In advanced cases, the kidney may become transformed into a

thin-walled cystic structure having a diameter of up to 15-20 cm
with thinning of the cortex.

Clinical Course

 Acute obstruction : loin pain.

 Unilateral complete or partial hydronephrosis: remain silent for

long periods.

 Complete bilateral obstruction results in anuria.

Urolithiasis:

 Most arise in the kidney.

 Men > women.

 Peak age: 20-30 years.

Cause and pathogenesis

 There are 4 main types of calculi :

1. Calcium containing (70%), composed of pure calcium oxalate or

mixed with calcium phosphate.

2. Triple stones (15%), composed of magnesium ammonium

phosphate (MAP).

3. Uric acid stones (5-10%).

4. Cystine stones (1-2%).

 All calculi have an organic matrix of mucoprotein making up to 1-

5% of the stone.

 Predisposing factors:

1. Increased concentration of stone constituents.

2. Changes in urinary pH.

3. Urinary tract obstruction.

4. Infection of urinary tract.

Morphology,

 Bilateral in about 80%

 The favored sites are: calyces and pelvis, and bladder.

 The stones may have:

- Smooth contours

- Irregular external surface

- Develop branches (stag-horn stones) which take a shape of the
pelvicalyceal system.

Clinical course

 Importance of stones:

 Obstruct urinary flow

 Infection

 Ulceration

 Bleeding.

Tumors of the kidney

 Benign Tumors :

 Renal Papillary Adenoma: small discrete tumors arising

from renal tubular epithelium are found in

7-22% of autopsies.

 Oncocytoma

 Angiomyolipoma

 Malignant Tumors :

Pediatric renal tumors:

 Wilms tumor ( nephroblastoma)

 Mesoblastic nephroma

 Clear cell sarcoma

 Rhabdoid tumor

Pediatric Tumors
Nephroblastoma (Wilm’s Tumor)

 Mainly infants; rarely as congenital tumor.

 Age:

 50% < 3 years,

 90% < 6 years.

 M=F.

 Bilaterality: 5-10%

 Conditions associated with definite increased risk of

nephroblastoma are :

 WAGR syndrome.

 Beckwith-Wiedemann syndrome (omphalocele-

macroglossia, hemihypertrophy).

 Denys-Drash syndrome

Clinical features

 Abdominal mass.

 Hematuria and pain are rare.

 Other features include; hypertension, proteinuria and tumor

rupture.

Morphological features

Grossly:

 Solitary, well circumscribed, rounded mass of soft consistency.

 Cut section : solid and pale gray or tan, with necrosis, and

hemorrhage.

 Multicentric foci are found in 7% of cases.

Microscopically:

 Three major components are identified

 1. Undifferentiated blastema.

 2. Mesenchymal (stromal) tissue.

 3. Epithelial tissue.

Molecular genetic features

 The genetic loci predisposing to nephroblastoma are:

1. WT1 located on 11p13.

2. WT2 located on 11p15.5.

3. Other chromosomal abnormalities include, 1, 7q, 12, & 16.

Prognosis,

 The overall cure rate is 80-90%.

 A small percentage of long-term survivors, develop a second

malignant neoplasm, either because of a genetic predisposition to
neoplasia or secondary to therapy.

 Prognostic factors:

1. Age, patients under 2 years have better prognosis.

2. Stage, capsular invasion, rupture at surgery, extrarenal vein

invasion, tumor implants, lymph node metastasis, distant
metastases, and bilaterality are the main criteria used.

3. Size, (weight).

4. Anaplasia.

5. Extensive tubular differentiation, and also extensive glomerular

differentiation, are good prognostic features.

6. Extensive skeletal muscle differentiation,

7. P53 mutation, correlates with the presence of anaplasia.

Adult Tumors And Tumor-Like Conditions

Renal Cell Carcinoma

 Age: 55-60 years. Rare in childhood.

 M:F ratio is 2:1

 Bilaterality 1%.

 Risk factors;

1. Tobacco is the most significant factor.
2. Obesity, particularly in women.
3. Hypertension.
4. Estrogen therapy.
5. Asbestos, petroleum products, and heavy metals.

 Most renal cancers are sporadic, but unusual forms of autosomal

dominant cancers do occur, usually in younger individuals.

 Conditions that may be complicated by renal cell carcinoma;

1. von-Hippel-Lindau (VHL) disease, RCC occurs >50%.
2. Acquired cystic renal disease.
3. Adult form of polycystic kidney
4. Tuberous sclerosis.
5. Neuroblastoma.
6. Familial cutaneous leiomyomatosis.
7. Lymphoma.

 Occasional regression in the absence of treatment.

Clinical features

 Hematuria, flank pain or abdominal mass. This triad occurs in only

9% of the patients.

 Weight loss, anemia, fever.

 Rarely paraneoplastic manifestations may occur including;

leukomoid reaction, polyneuropathy, hepatosplenomegaly and

hepatic dysfunction, hypercalcemia, hypertension, polycythemia,
gynecomastia, and Cushing syndrome.

 Investigations (IVP, U/S, CT or MRI).

Morphologic features

 Grossly,

 Most are well delineated and cortical in location.

 Multiple tumor nodules (5%) .

 Cut surface is solid golden/yellow in color.

 Areas of hemorrhage, necrosis, calcification, and cystic change are

common findings.

Morphologic features

 Microscopically, the tumor cells are large, with cytoplasm ranging

from granular to clear.

 Pattern of growth: solid & tubular differentiation

 Electron microscopically: contain abundant glycogen, variable

amounts of fat.

 Immunohistochemically:

 Coexpression of keratins and vimentin is the rule.

Microscopic types

 Segregated on the basis of their cytoarchitectural features,

cytogenetic, and behavioral properties.

1. Papillary renal cell carcinoma, (15%).

- Found in patients on chronic hemodialysis.

- Some are hereditary.

- Characteristically hypovascular, localized to the kidney, and more
likely to be multicentric or bilateral.

- Microscopically, complex papillary formations, and psammoma
calcifications.

- Better prognosis than conventional RCC.

Microscopic types

2. Collecting duct carcinoma,(1-2%).

- It is thought that the tumor is arising from or differentiating toward
collecting ducts.

- > males, & centered in the medulla,

- Has tubulopapillary configuration, and is surrounded by desmoplastic
reaction.

- The behavior : aggressive.

3. Renal medullary carcinoma, (very rare),

- Occurring in young blacks with sickle cell disease.

- Behavior is very aggressive

Microscopic types

4. Chromophobe renal cell carcinoma,(5%).

- Grossly: well circumscribed, solitary with a homogeneous gray to
brown.

- Microscopically: nests of cells with abundant, pale acidophilic
cytoplasm.

- Prognosis is better than conventional type.

5. Sarcomatoid renal cell carcinoma (spindle cell carcinoma), (1%).

- Composed of spindle and/or pleomorphic tumor giant cells.

- Extremely aggressive.

6. Renal cell carcinoma with rhabdoid features,

- Contains rhabdoid cells. Very aggressive tumor.

Molecular genetic features

 3p del (most common). Seen in most classical renal cell carcinoma

and is absent in oncocytic and most papillary variant.

 p53 Overexpression is present in 10-35% of tumors.

Spread and metastasis

 1/3 of RCC locally invade perinephric fat and/or regional lymph

nodes at the time of operation.

 1/3 of patients already have distant metastases.

 Renal vein invasion : 10% of cases.

 Sometimes, these metastases develop years or decades after the

removal of the primary tumor.

 Spontaneous regression of these metastases may occur.

 Metastases are extremely rare in tumors that measure 3cm or less.

Prognosis

 The overall 5 years survival is approximately 70%.

 Prognostic parameters;

1. Staging.
2. Distant metastases, most important prognostic parameter.

3. Tumor size, relates to prognosis for the very small (<3cm), and
the very large (> 12cm) tumors.

4. Renal vein invasion, predictor of relapse.
5. Grade.
6. Microscopic variants.
7. Cell proliferation
8. P53 overexpression, is associated with metastatic disease and poor
survival.

Oncocytoma

 Make up 7% of primary epithelial renal neoplasms.

 Gross: solid and mahogany brown, often with central stellate scar

 They can be multicentric and bilateral

 Microscopically: are composed of entirely of cells with abundant

acidophilic granular cytoplasm, arranged in alveolar or tubular
fashion.

 Has been suggested to be originated from the intercalated cells of

the collecting ducts.

 Majority are cured by nephrectomy

Angiomyolipoma

 Adults.

 1/3 of the patients suffer from tuberous sclerosis, the incidence

being higher if the tumors are multiple or bilateral.

 80% of patients with the complete or severe tuberous sclerosis

have renal angiomyolipoma.

 Grossly: admixture of yellow areas and

hemorrhagic areas.

 Capsular invasion (25%)

 The tumors are multiple in 1/3

 Bilateral in about 15% of the cases.

 Microscopically, there is admixture of mature adipose tissue,

tortuous thick-walled blood vessels, and bundles of smooth
muscle.

 The treatment of angiomyolipoma is surgical.

 A potential for malignant behavior should be anticipated for

tumors which are highly pleomorphic, mitotically active, with
necrosis.

د. مصطفى امراض

0202

( عدد االوراق

) م

موصل

lec: 11

RENAL SYSTEM PATHOLOGY

Tumors of Renal Pelvis

 Transitional Cell Carcinoma;

 Most cases occur in adults.

 25% has history of analgesic abuse and/or coexistence of renal

papillary necrosis.

 Cases have been seen following administration of thorotrast for

radiographic purposes, and as a complication of cyclophosphamide
therapy,

 Hematuria is the most common clinical presentation.

 Synchronous or metachronous tumors elsewhere in the urinary

tract: 40%.

 5 year survival is 50%.

 The prognostic factors:

- stage of the tumor.

- DNA ploidy levels,

- vascular invasion.

Tumors of Renal Pelvis

 Adenocarcinoma:

Transitional epithelium >chronic inflammation>glandular
metaplasia > origin of Adenocarcinoma

 Squamous Cell Carcinoma:

Transitional epithelium >chronic irritation> squamous metaplasia
> origin of squamous ca

Usually is high grade

Very poor prognosis.

The Lower Urinary Tract: Ureters:

 Congenital Anomalies: (2-3%)

1. Double ureters.

2. Ureteropelvic junction obstruction

- Most common cause of hydronephrosis in infants and children.

3. Dverticula

4. Hydroureter, Massive enlargement of the ureter is called megaureter.

 Inflammations:

Occur as part of UTI

Tumors And Tumor-Like Lesions:

 Primary tumors (rare) . The most common are :

1. Fibroepithelial polyps
2. Leiomyoma.
3. Transitional cell carcinoma

Urinary Bladder: Congenital Anomalies

 Diverticula:

- Congenital

- Acquired (> common), results from persistent urethral obstruction,
frequently multiple.

 Most of them are asymptomatic, but may predispose to infection

and stone formation.

 Rarely carcinoma may arise in them.

 Exstrophy:

Implies developmental failure in the anterior wall of the abdomen
and the bladder.

 The exposed bladder mucosa may undergo colonic glandular

metaplasia and is subject to infection, which if becomes chronic,
the bladder mucosa will undergo ulceration and squamous
epithelial metaplasia of the margins.

 There is tendency toward the development of adenocarcinoma.

 Persistent Urachus:

adenocarcinoma may arise in it.

 Vesicoureteral Reflux:

Inflammation:

1. Interstitial cystitis (Hunner Ulcer)

 This is a persistent painful chronic cystitis

 > women

 Inflammation and fibrosis of all layers of bladder wall.

 Etiology: unknown, may be autoimmune.

2. Polypoid cystitis, indwelling catheters are the most common cause

3. Malakoplakia,

 Refers to peculiar inflammation, characterized by soft, yellow,

slightly raised mucosal plagues 3-4cm in diameter

 Histologically : infiltration with foamy macrophages, mixed

occasionally with multinucleated giant cells; with lysosomal and
extracellular deposition of laminated mineralized concretions
known as Michaelis-Gutmann bodies.

 The condition is related to chronic infections mostly by E.coli and

proteus species.

 The pathogenetic proposal, is that there is some defect in

phagocytic or degradative function of macrophages.

Metaplastic Lesions

1. Cystitis Glandularis and Cystitis Cystica, nest of urothelium

(Brunn nests).

2. Squamous Metaplasia, as a response to chronic irritation.

3. Nephrogenic Metaplasia

Transitional Cell Tumors (urothelial)

 90% of all bladder tumors

 Many are multifocal.

 Most are in the bladder, (also seen in the pelvis, ureters, and

urethra).

Morphology

 The gross patterns vary from purely papillary to nodular or flat.

 The tumors may also be invasive or non invasive.

 Papillary lesions range in size between 1-5cm.

 They may be multicentric.

 Overall, the majority of papillary tumors are low grade and most

arise from the lateral or posterior walls at the bladder base

4 morphologic patterns of urothelial tumors

Papillomas

 1 % of all bladder tumors

 Youngs.

 Usually solitary and exophytic, but, sometimes endophytic pattern

is seen (inverted papilloma).

 Rarely recur

 Finger-like papillae have a central core of loose fibrovascular

tissue covered by transitional epithelial cells that are histologically
identical to normal urothelium.

 Urinary bladder, papilloma

Urothelial Neoplasms Of Low Malignant Potential

 Gross: are larger than papillomas

 Histology: thicker than papilloma or show diffuse nuclear

enlargement.

 Mitotic figures are rare.

 They may recur with the same morphology, are not associated with

invasion, and only rarely recur as high tumors

Papillary urothelial carcinoma , low grade

 Minimal nuclear atypia & infrequent mitoses.

 Can recur & can invade (infrequently).

 Has minimal threat to life.

Papillary urothelial carcinoma, high grade

 Marked nuclear atypia, and some cells show frank anaplasia.

 Frequent mitoses.

 Have higher incidence of muscle invasion, progression, local

invasion & metastasis

 80% of high grade cancers are invasive whereas <10% of low

grade cancers invade

 Hematogenous dissemination, generally occur late.

 Papillary TCC, high grade

Carcinoma In Situ

 Any cytologically malignant cells within a flat urothelium.

 It is commonly multifocal and may involve most of the bladder

surface and extend into the ureters and urethra.

 If untreated, 50-75% of CIS cases progress to muscle-invasive

cancers.

Other Types Of Carcinoma

 Squamous Cell Carcinomas,

 3-7% of bladder cancers
 urinary schistosomiasis.

 Adenocarcinomas, are rare, some arise from urachal remnants

Epidemiology and Pathogenesis

  > males (M:F = 3:1).
   Age:  80% : 50 to 80 years.
  Causative factors of bladder cancer:

1. Smoking.
2. Industrial exposure to arylamines.

3. Schistosomiasis.
4. Heavy long-term exposure to cyclophosphamide.
5. Long term use of analgesics.
6. Radiation.
Clinical course

 Painless hematuria, frequency, urgency and dysuria
 When ureteral orifice is involved, pyelonephritis or hydronephrosis

may follow.

Prognosis:

  Tumor size,
   Stage,
  Grade,
   Multifocality,
  Prior recurrence,
  Associated dysplasia and/or carcinoma in situ in the surrounding

mucosa.

Mesenchymal Tumors

 Benign, rare, the most common is leiomyoma.
 Malignant, sarcomas are extremely rare.

 Childhood: embryonal rhabdomyosarcoma.
 Adults: leiomyosarcoma.

 Secondary Tumors