Dept.

of Anatomical Pathology
Medical Faculty
Brawijaya University
TOPICS :
1. Glomerular diseases
2. Diseases affecting tubules and interstitium
* Acute tubular necrosis
* Pyelonephritis
3. Obstructive uropathy
4. Tumor
* Tumor of the kidney :
- Wilm’s tumor, Grawitz tumor
* Tumor of the bladder :
- Urothelial Tumor
5. Prostate
* BPH
* Ca of the Prostate
Glomerular Diseases
• Some of the major problems encountered in nephrology
• Chronic glomerulonephritis (GN) is one of the most common
causes of chronic kidney disease (CKD)

• Glomerulus consists of 4 major element : endothelial cells,

glomerular basement membrane (GBM), visceral epithelial cells
(podocytes), and mesangial cells
Schematic diagram of a lobe of a normal glomerulus
Kumar et al, 2007
CLINICAL MANIFESTATION OF GLOMERULAR
DISEASES
1. Acute nephritic syndrome
2. Nephrotic syndrome
3. Rapidly progressive GN (Acute nephritis, proteinuria,
ARF)
4. Chronic renal failure
5. Asymptomatic hematuria or proteinuria

HISTOLOGIC ALTERATION in GLOMERULUS

1. Proliferation of epithelial, endothelial & mesangial cells
2. Neutrophils & monocytes infiltrates
3. GBM thickening
4. Hyalinization / sclerosis
BMG THICKENING
1. Thickening of GBM itself
* diabetic glomerulosclerosis
2. Thickening of GBM caused by immune complex
deposits

THE HISTOLOGIC CHANGES CAN BE DIVIDED

INTO :
1. Diffuse : involving all glomeruli
2. Focal : involving only a proportion of the glomeruli
3. Segmental : affecting a part of each glomerulus
4. Global : involving the entire glomerulus
5. Mesangial : affecting predominantly the mesangial
region
PATOGENESIS of GLOMERULAR DISEASES
1. Immunologic mechanism :
a. Trapped of circulating Ag – Ab complexes within glomerulus
b. In situ, as react of Ab with :
* intrinsic antigens (GBM  Anti GBM nephritis)
* extrinsic antigens that planted within glomerulus
2. Non immunologic mechanism :
Any renal disease that destroys functioning nephrons 
GFR↓ to ± 30 – 50% of N 
capillary hypertrophy & hypertension (+systemic) 
* epithelial & endothelial damage  proteinuria
* proliferation of mesangial cells & increased
accumulation of extracellular matrix 
glomerulosclerosis
 INJURY GLOMERULAR DISEASE
immune/autoimmune
I. Microscopic :
1. Inflammatory infiltrate
Clinical manifestation
2. Proliferation of Epithel
•Nephritic Syndrome
Endothel
Mesangial • RPGN
Glomerular 3. GBM thickening •Nephrotic Syndrome
alteration 4. Hyalinization / Sclerosis • CGN

II. Terms of histologic changes :

* Diffuse
* Focal
* Segmental
* Global
* Mesangial
Membranous nephropathy. A, Diffuse thickening of the glomerular
basement membrane. B, Schematic diagram illustrating subepithelial
deposits,effacement of foot processes, and the presence of "spikes" of
basement membrane material between the immune deposits.
CHRONIC GLOMERULONEPHRITIS
* A pool of end-stage glomerular disease
- Post Streptococcal GN 1 – 2%
- RPGN 90%
- Membranous Gpathy 30 – 50%
- Focal Segmental GS 50 – 80%
- Membranoproliferative GN 50%
- Ig A Nephropathy 30 – 50%
* Morphology :
- The Kidneys are symmetrically contracted
- Diffuse granular of the cortical surfaces
- On section : the cortex is thinned
- Boundary between cortex & medulla unclear
- Microscopic : depend on underlying diseases
Diseases Affecting Tubules and Interstitium
1. Acute Tubular Necrosis (ATN)
1. Nephrotoxic ATN
2. Ischemic / Tubulorrhectic ATN

2. Tubulointerstitial Nephritis
1. Acute Pyelonephritis
2. Chronic Pyelonephritis
ATN :
* The most common cause of ARF (± 50%)
* Reversible

Pathogenesis of ARF in ATN :

1. Persistent preglomerular vasoconstriction
2. Tubular obstruction, caused by interstitial edema /
intratubular cast
3. Tubular damage  tubular back-leak
 interstitial edema
4. Alterations of intrinsic glomerular function
 glomerular filtration 
 ISCHEMIC TUBULAR
ATN DAMAGE
NEPHROTOXIC

(1) (2)
VASO CONSTRICTION OBSTRUCTION (3)
BY CAST S TUBULAR
BACK-LEAK

INTRA TUBULAR
Tubular Fluid
PRESSURE  Flow 

(4)
DIRECT GLOMERU GFR  OLIGURIA
LAR - EFFECT

PATHOGENESIS Of ARF in ATN

1. Nephrotoxic ATN
* Caused by nephrotoxic substance :
- Poisons including heavy metals (eg:Hg)
- organic solvents (e.g., CCl4)
- antibiotics
- radiographic contrast agents
* Morphology :
- Necrosis of tubular cells most obvious in
proximal convoluted tubuli,
- tubular BM intact
- distal convoluted tubuli intact
2. Ischemic ATN
(Shock kidney; Hemoglobinuric Nephrosis)
* Caused by persistent and severe disturbances
in blood flow / shock :
- Severe bacterial Infection
- Severe burns
- Conditions that cause peripheral circulation
insuffisiency
- Massive bleeding caused by rupture of
large arteries / aneurysm
- Mismatched blood transfusion and other hemolytic
crisis causing hemoglobinuria
Morphology :
- Focal tubular epithelial necrosis at multiple point along the
nephron accompanied by rupture of BM (tubulorrhexis) and
occlusion of tubular lumen by cast.
- Others : in distal tub. & collect. ducts

- eosinophilic hyalin cast

- pigmented granular cast
PYELONEPHRITIS
* Renal disorder affecting the tubule, interstitium
and renal pelvis
* One of the most common diseases of the kidney
* Etiology and pathogenesis :
# > 85 % : Gram-negative bacilli
(normal inhabitants of the intestinal tract)
- E. Coli (the most common)
- Proteus
- Klebsiella
- Enterobacter
Route of Infection :
1. Hematogen
- septicaemia; inf. endocarditis pyelonephritis
- the most common etiology : Staphylococci and
E. coli
2. Ascending
- urethritis  cystitis  ureteritis  pyelonephritis
3. Vesicoureteral reflux
Most often caused by :
- Children : congenital anomalies
- Adults : bladder tumor, stones, BPH, persistent
bladder atony
ACUTE PYELONEPHRITIS
* An acute suppurative inflammation
of the kidney caused by bacterial,
sometimes viral infection, whether
hematogenous or ascending and
associated with vesicoureteral
reflux.
* Morphology :
- The Kidneys are enlarged / N (depend on
severity of infection)
- Patchy interstitial suppurative inflammation,
intratubular aggregates of neutrophils
and tubular necrosis
- Focal / diffuse; unilateral / bilateral
- Abscesses can extend through the renal
capsule  perirenal tissue
(perinephric abscess)
Complication :
1. Papillary necrosis
- Coagulation necrosis at 2/3 distal pyramids
- Mainly in diabetics / urinary obstruction
2. Pyonephrosis
- In total / almost complete obstruction
Pus is unable to drain  fills the renal pelvis,
calyces and ureter
3. Perinephric Abscess
- Abscesses can extend through the renal
capsule  perinephric tissue
Predisposing conditions :
1. Urinary tract obstruction
2. Instrumentation of the urinary tract
3. Vesicoureteral reflux
4. Pregnancy
5. Patient’s sex and age
6. Preexisting renal lesion, causing intrarenal
scarring and obstruction
7. Diabetes mellitus
8. Immunosupression and immunodeficiency
* Clinical course :
- Pain at the costovertebral angle
- Fever, malaise
- Dysuria, frequency and urgency
- Lab. : urine  leuco >> (pyuria),
leuco cast (+)
* Diagnosis of infection : by urine culture
CHRONIC PYELONEPHRITIS
* Chronic tubulointerstitial renal disorder
in which chronic tubulointerstitial
inflammation and renal scarring are
associated with pathologic involvement
of the calyces and pelvis.

* An important cause of “End-Stage Kidney”

(up to 10-20% of patients in renal
transplants or dialysis units).
* Diagnostic criterion of
Chronic Pyelonephritis :
- Irregular scarr formation
- Inflammation
- Calyceal deformity
Morphology :
- The Kidneys usually are irregularly scarred
If bilateral, the involvement is asymmetric
- Deformity of the calyces and renal pelvis
- The tubules show atrophy in some areas, and
hypertrophy and dilation in others
- Dilated tubules may filled with colloid cast
(thyroidization)
- Chronic interstitial inflammation
 fibrosis in the cortex & medulla
- Periglomerular fibrosis
Types of Chronic Pyelonephritis

1. Chronic Obstructive PN
- Obstruction predisposes to infection
- Recurrent infections superimposed on diffuse
or localized obstructive lesion  scarring 
picture of CPN
- Obstruction  parenchymal atrophy
- Bilateral / unilateral
2. Refluks Nephropathy
- Infection from VU  reflux  the kidney
- Bilateral / unilateral.
Clinical course :
- Insidious in onset / acute recurrent with back
pain, fever, pyuria and bacteriuria
- Loss of tubular function  polyuria & nocturia
- CPN is a result of superimposed bacterial
infection in obstructive urine or vesicoureteral
reflux (CPN rarely caused by
bacterial infection alone)

Tx. and prevention :

* to correct reflux & obsrtuctive lesion,
and eliminate infection
 OBSTRUCTIVE UROPATHY
* Obstruction :
- increases susceptibility to infection
- increases susceptibility to stone
formation
- unrelieved  permanent renal
atrophy
(hydronephrosis / obstructive
uropathy)
* The common causes :
1. Congenital anomalies
2. Urinary calculi
3. BPH
4. Tumor
5. Inflammation
6. Sloughed papillae / blood clots
7. Normal pregnancy
8. Uterine prolapse & cystocele
9. Functional disorders (spinal cord damage,
DM)
HYDRONEPHROSIS
Dilation of the renal pelvis and calyces
associated with progressive atrophy of
the kidney due to obstruction to the
outflow of urine.
MACROS: - The kidney slight to massive
enlargement
- The earlier feature : dilation of the
pelvis and calyces
- In far advanced cases : thin walled
cystic structure, up to Ø 15-20 cm
- Parenchymal atrophy
 total obliteration of pyramids
& thinning of the cortex

MICROS: - Dilation of tubules  pressure atrophy

of tubules and glomeruli  disappear
- Interstitial fibrosis
TUMORS OF THE KIDNEY :
Malignant tumors : 1. Wilm’s tumor
2. Renal Cell Ca

1. WILM’S TUMOR (Nephroblastoma)

* Incidence : - Most often in children,
1-4 years old
- Rarely in adults
* Origin : - Mesonephric (mesodermal)

* Clinical course :
- Pain (-)
- Hematuria
- Dysuria
MACROS :
- Solitary mass, well circumscribe
- 10 % bilateral or multicentric
- Soft, homogen, greyish, sometimes with
hemorrhage foci, necrosis and cyst
formation
MICROS :
* There are 3 types of cells :
blastema, epithelial and stromal
- Epithelial differentiation : tubuli &
glomeruli abortive
- Stromal cells : fibrocytic / myxoid, often
with skeletal muscle differentiation
- Rarely : squamous cells, mucinous
epithelium, smooth muscle,
lipid, cartilage, osteoid,
nerve tissue
* 5% : foci of anaplastic cells
2. RENAL CELL CA
(Grawitz tumor / Hypernephroma / Renal Adeno Ca)
- Represent ± 1-3 % of all visceral cancer
- Account for 85-90 % of renal cancer in adult
- Arise from tubular epithelium
* Etiology / Pathogenesis :
- Tobacco incidence in smokers 2x non
smokers
- Viral and chemical carcinogen
- Genetic  translocation of Cr 3 & 8  cancer
- Renal adenoma  carcinoma
MACROS :
- Commonly affects the poles, particularly
the upper one
- Spherical masses  3 – 15 cm
- Bright yellow-gray-white,
foci of hemorrhage, cystic
- Sometimes : satelite nodule (+)
MICROS :
* 3 types :
# Clear Cell Ca (70-80%)
# Papillary Ca (10-15%)
# Chromophobe Ca (5%)

Clear Cell Ca :
- Tumor cells : rounded / polygonal
- Abundant clear / granular cytoplasm
- Tubular / solid / trabecular
- Most tumor : well differentiated
- Some tumors show marked nuclear atypia,
bizzare nuclei and giant cells
Clinical course :
* Classic diagnostic features :
- Costovertebral pain, palpable mass & hematuria (10%)
* Others :
- Fever, malaise, weight loss
- Paraneoplastic syndrome (abN hormone
production)
- polycytemia, hypercalcemia, hypertension,
feminization/masculinization, Cushing syndrome,
eosinophilia, leukemoid reactions, amyloidosis.
- Tendency to metastasize widely before giving rise
to any local symptoms or signs.
* The most common locations of metastasis :
- lung (50%), bone (23%), lmn, adrenal,
liver, brain

* Prognosis : 5 ysr ± 45%

 TUMOR OF THE BLADDER :
Exophitic papilloma
Inverted papilloma
Papillary urothelial neoplasm of low malignant
potential
Low grade and high grade papillary urothelial ca
Ca in situ (flat non invasive urothelial ca)
Mixed ca
Adeno ca
Small-cell ca
Sarcoma
Etiology and Pathogenesis :
* Cigarette smoking (risk : 3-7x)
* Carcinogen (industrial)
- 2 Naphtylamine 15-40th dr pajanan.
* Schistosoma Hematobium
- inflammation / local irritation
 mucosal squamous metaplasia
 dysplasia  neoplastic changes
* Long-term use of analgesics
* Heavy long-term use of cyclophosphamide→
hemorrhagic cystitis
* Irradiation
X familial
MALIGNANT TUMORS

• Worldwide IARC 2003

• Urothelial carcinoma 84%( males), 79% (females)
• Squamous cell carsinoma 1.2% (males), 2.8% (females)
• Adenocarcinoma 1,5% (males), 1.9% (females)

80

80
81
82
MACROS :
- solitary / multiple
- papillary / nodular / flat / mixed papillary-nodular
- red elevated

MICROS :
* Grade I : - close resemble N transitional cells
- mitosis ±, number of layer >, slight loss of
polarity
* Grade II : - mitosis >, layers >>, greater loss of polarity
* Grade III :- mitosis>>, layers >>>, polarity (-)
- anaplastic, giant cells (+)
 GRADE I II III
DIFFERENTIATION well moderately poorly
NUMBER of
LAYER
>7 >10 >>10

POLARITY slight loss greater loss disarray

MITOSIS + > >>

SUPERF. LAYER
CELLS + - -

CELLULAR
VARIATION + ++ +++
(size, shape,
chromatin)
 PROSTATE
• Retroperitoneal organ
• Encircling the neck of the bladder & urethra
• Pear-shaped
• Weight (normal adult male) : ± 20 gr
• The prostate disorder usually found in older men
(> 50 yrs old).
• 2 component :
- tubuloalveolar gland
- fibromuscular stroma
Anatomy of the Prostate
Anatomical lobes:
• Anterior, posterior and 2 lateral lobes.
Anatomical zone ( Mc Neal ):
• Peripheral zone
• Central zone
• Periurethral zone and transitional zone.
• Anterior fibromuscular stroma.
Normal prostate, nodular hyperplasia and
adenocarcinoma.
In prostatic hyperplasia, which involves predominantly
the periurethral part of the gland, the nodules compress and distort
the urethra. The expansion of the central prostatic glands leads to
compression of the peripheral parts and fibrosis, resulting in the
formation of a so-called surgical capsule. Prostatic carcinoma
usually arises from the peripheral glands, and compression of the
urethra is a late clinical event.
 Prostatic disorders
Only 3 pathological processes affect the prostate gland:
= Non – neoplastic:
• 1. inflammation.
• 2. benign nodular enlargement.
= Neoplastic
• 3. tumors/neoplasm.
Benign enlargements are the most common and occur so often
in advanced age.
 Prostatic Hyperplasia
• Weight : 60- 100 grams.
• Incidence : 20 % of men 40 – 45 years.
70 % by the age 60.
90% by the age of 70.
• No correlation between histologik changes with clinical
symptom.
• Morphology : proliferation of acini and fibromuscular
tissue.
• Hyperplasia : stromal & epithelial
 discrete nodule in the periurethral region
 compress & narrow the urethral canal
 obstruction (partial / complete)
Pathogenesis Testosteron
Stromal Cell Epithelial Cell
Sromal Cell

T
T
5-reductase tipe 2

DHT
Androgen
receptors

Nukleus

Growth
factor
Growth
factor

Growth factor
receptors
Macros :
• Usual case : 60 – 100 gm  200 gm
• >> : inner aspect ( TZ & PUZ )
• c/s : nodules  fairly readily identified,
pseudo capsules (+)
• Yellow-pink, soft / pale gray, tough

Micros :
• Glandular proliferation / dilatation, lined by 2 layers,
columnar (inner) & cuboidal / flattened (outer) epithel
 papillary buds and infoldings (Σ>N)
• Fibromuscular proliferation
Clinical Course
1. Compression of the urethra
 difficulty in urination
2. Retention of urine in the bladder
 distention, hypertophy, infection
 cystitis & pyelonephritis
3. Frequency, nocturia, difficulty in starting &
stopping the stream of urine, overflow dribbling &
dysuria
4. Acute urinary retention  catheterization
5. Residual urine → infection → pyelonephritis
6. Hydronephrosis, uremia
Treatment
• Trans Urethral Resection (TUR)
• Open Prostatectomy
TUR
BPH
BPH
Prostatic hyperplasia
Prostatic hyperplasia

Dilated acini
CARCINOMA of the PROSTATE
Insidence :
• Disease of men  50 y.o;  50 y.o : 1%
• > 300.000 new cases / yr, 41.000 lethal
• << in Asians, age-adjusted insidence :
- Japanese : 3-4 / 100.000
- Hong Kong : 1 / 100.000
- USA (whites) : 50-60 /100.000
Etiology : ?
Risk Factors :
• age, race, family history, genetics, hormonal
(androgens/testosterone), environmental (fat
intake)
Morphology:
• ± 70% cases : arises in the PZ, classically in posterior lobe
• c/s : gritty & firm

Micros :
• Adenocarcinoma

Histologic Grading
Gleason System :
5 grades, depend on :
- glandular pattern
- degree of differentiation
( good correlation between d of d and prognosis )
Staging
• TNM:
+ Tx Primary tumor can’t be assessed
+ T0 no evidence of primary tumor.
+ T1a histological incidental finding in < 5% of tissue
resected.
+ 1b > 5% tsuue resected.
+ 1c. Tumor identified by needle biopsy.
+ T2 Tumor confined within prostate.
+ T3. Tumor extend beyond the prostate.
+ T4 Tumor invades adjacent structures other than
seminal vesicles.
Clinical Course

• Stage A : asymptomatic, discovered incidentally

at autopsy / tissue remove for BPH
• Difficulty in starting/stopping the stream
• Dysuria, frequency, hematuria
• Pain (late finding)  involvement of capsular
perineural space
• Back pain  vertebral metastasis
(osteoblastic)
Diagnosis :
• Clinical symptoms
• Rectal toucher
• Transrectal USG
• Transrectal / transperineal biopsy
• Biochemical markers :
Prostatic Acid Phosphatase (PAP)
Prostate-spesific Antigen (PSA)
# organ spesific, not cancer specific,
also ↑ in non neoplastic condition
(BPH, prostatitis)
- 25-30% BPH : PSA > 4 ng/ml
- 80% Prostate Ca : PSA > 4 ng/ml
- 20-40% Prostate Ca : PSA ≤ 4 ng/ml
 gray zone 4-10 ng/ml
 Treatment
• Surgery
• Radiotherapy
• Hormonal manipulation
- orchiectomy
- estrogen therapy
- agonist of luteinizing hormon-releasing hormon

Surgery & Radiotherapy :

- Most suited for localized cases
- > 90% : expect to live for 15 years
Endocrine therapy : mainstay for advanced cases
Gleason
score 3+3=6
Adenocarcinoma,
periganglional/neural invasion
THANK YOU