BLOCK 3.

3 SESI 3

Pathology of Urinary Tract

By Asdos 2011: Vetta Awe Eric Lily Fiko Ghana Ikal Linda May Fahmi
Reno Bram Tim Yana Yosua Yugata
PATHOLOGY OF
THE KIDNEY
 Glomerular
Disease

Dis. Affecting
Tubules n Pyelonephritis
Interstitium

Dis. Involving
blood vessels
Renal Disease
Chronic Kidney
Dis

Urine outflow
obstruction

Renal Cell
Tumor
Carcinoma
Chronic Pyelonephritis
 TUBULOINTERSTITIAL NEPHRITIS (TIN):
Inflammation of Introduction
tubulus and
interstitium
Bacterial
Infection
Pyelonephritis
Affecting the
pelvis

Affecting the
pelvis
!!!No infection  interstitial nephritis
 Infection, Toxin,
Metabolic Stress

Acute Inflammation

Cured

Chronic Inflammation

Scar
Atrophy
Fibrosis
 CHRONIC PYELONEPHRITIS:
THE DEFINITION

Morphologic entity in which predominantly Interstitial

Inflammation and Scarring of the renal parenchyma,
visible sccarring and deformity (blunting) of the Pelvicalyceal
system.
 THE EPIDEMIOLOGY

Three peaks of incidence:

Infancy and childhood
Childbearing aged women
Older than 60 y.o.
 THE ETIOLOGY

Persistent renal infection

Vesicoureteral Reflux (VUR)
Urinary track obstruction
 THE TYPES

Chronic Obstructive Pyelonephritis

Chronic Reflux-associated Pyelonephritis (Reflux
Nephropathy)
Chronic Obstructive Pyelonephritis
– Reccurent infection on obstructive lesion
– Bilateral (congenital anomaly) or unilateral (obstructive stones)
Chronic Reflux-associated Pyelonephritis (Reflux
Nephropathy)
– Superimposed of UTI on VUR
– Bilateral or unilateral
– More common
 THE CLINICAL FEATURES

Initiated by hypertension  late diagnosis

Flank pain, fever, nausea & vomitting, lethargy
Poliuria & nocturia  tubulus dysfunction
 DIAGNOSIS

Laboratory examination
Urinalysis, blood exam
Radiology
USG, plain abdomen, IVP, cystoscopy, CT, MRI, BNO
Histology
Biopsy
 THE MACROSCOPY

Irregular Scar
Irregular granular surface (polus superior & inferior)
Athropy & scarring of the parenchym
Dilatation of the calyx  blunted papilla
 THE MICROSCOPY
Interstitial fibrosis
Periglomerular fibrosis
Atrophic or dilated tubule
Infiltration of chronic inflammatory cells
Thyroidization (colloid cast)
Atherosclerosis
 THE COMPLICATION

Hypertension
Pyonephrosis
Proteinuria
Progressive scarring  Chronic renal failure
End-stage renal disease  dialysis
Clear Cell Carcinoma
of the Kidney

Synonym:
Grawitz Tumor
Hypernephroma
 TUMOR OF THE KIDNEY:
Introduction
2% of total human Ca
190.000 new case/year, mostly in developed countries
Etiology: smoking, obesity
Can be completely removed, but metastasized early
Familial  von Hippel Lindau disease
 WHO Histological Classification

Renal cell tumour

Metanephric tumor
Nephroblastic tumor
Mesenchymal tumor
Mixed mesenchymal and epithelial tumor
Neuroendocrine tumor
Hematopoetic and lymphoid tumor
Germ cell tumor
Metastatic tumor
 RENAL CELL CARCINOMA:
THE DEFINITION

Group of malignancies
From tubulus renalis epithelium
 THE EPIDEMIOLOGY

90% of all kidney cancers

Ranking: 6th in developed countries, 16th in developing
countries
The highest mortality in 80’s
Increase risk after 40 y.o. then decline after 75 y.o.
Male:Female = 3:1
 THE ETIOLOGY
Major causes:
smoking (39%)
arsenic exposure (industrial, water) (30%)
Estrogen-induced in overweight/obesity (25%)
Parities  estrogen, overweight
Others (unclear):
History of cancer, ant-hypertension drugs, birth weight, low
fruit/veggie intake
 THE CLINICAL FEATURES
Classic triad
hematuria, flank mass, pain (60%)
Systemic symptoms: weight loss, anorexia, fever, abdominal pain (40%)
Increased ESR (50%), normocytic anemia (33%), amyloidosis
(3%)
Hepatosplenomegally, coagulopathy, increased SAP &
transaminase  normal after resection
Paraneoplastic syndrome:
hypercalcemia (pseudohyperparathyroidism), erythrocytosis,
hypertension, ginecomastia
 THE IMAGING
Well developed  well managed
Diagnosed by USG
Can’t conclude  CT with IV contrast
Plain CT for benign mass
 THE CLASSIFICATION
Clear cell renal cell carcinoma
Multilocular clear cell renal cell carcinoma
Papillary renal cell carcinoma
Chromophobe renal cell carcinoma
Carcinoma of the collecting ducts of Bellini
Renal medullary carcinoma
Xp11 translocation carcinomas
Carcinoma associated with neuroblastoma
Mucinous tubular and spindle cell carcinoma
Renal cell carcinoma, unclassified
Papillary adenoma
Oncocytoma
 CLEAR CELL RENAL CELL CARCINOMA:
THE DEFINITION

Malignant neoplasm composed of cells with clear

(eosinophilic) cytoplasm within delicate vascular network
SYNONYM
Granular renal cell carcinoma, Grawitz tumor,
Hypernephroma
 THE MACROSCOPY
Solitary, randomly distributed, from the cortex
Bilaterality/multicentricity <5% (hereditary syndrome)
Rounded well demarcated mass with pseudocapsule
Increasing size, increasing metastases
Golden yellow  lipid content
Others: cyst, necrosis, hemorrhage, calcification within
necrotic zones
 THE MICROSCOPY

Patterns: solid, alveolar, acinar, tubular, pseudopapillary

Regular network of small thin-walled blood vessels (sinusoidal pattern) 

chicken wire vasculature

The cell: lipid & glycogen in cytoplasm, round uniform nuclei,
sometimes huge nuclei without nucleoli (bizarre nuclei)
Sarcomatoid changes  worse prognosis

Inflammatory response  neutrophil or lymphocyte infiltrate

 THE STAINING

Positively stain IHC : CK8, CK18, PAX2, MUC1, MUC3

Negatively stain IHC : CK7, C-Kit
Simple stain : PAS (for glycogen),
Oil red O (for lipid)
 THE GRADING
Fuhrman Nuclear Grade
Grade 1 :
round/uniform nuclei, nucleoli not discernible or absent
Grade 2 :
slightly irregular nuclear contours, nucleoli visible at 400x
Grade 3 :
moderately irregular nuclear contours, nuclei visible at 100x
Grade 4 :
multilobular/bizarre nuclei, large prominent nucleoli
 Grade 1: round or uniform nuclei; nucleoli not Grade 2: slightly irregular nuclear contours;
discernible or absent nucleoli visible at 400x

Grade 3: moderately to markedly irregular nuclear

contours; nucleoli visible at 100x Grade 4: multilobular nuclei or bizarre nuclei and
large and prominent nucleoli
 THE PROGNOSIS

Widely metastized in early stage

5-year survival rate  45%, 70%
with no metastasis METASTASES LOCATION

Others
17%

Lungs
50%
Bones
33%
PATHOLOGY OF
THE BLADDER
Urothelial Bladder Cancer
Synonym:
Transitional Cell Carcinoma Of The Bladder
Infiltrating Urothelial Carcinoma of the Bladder
 BLADDER CANCER:
THE EPIDEMIOLOGY
• 7th most common cancer worldwide (3.2%)
• Males (84%) > females (79%)
• North America, European Union
• Developed countries: 6-times higher
• Mostly common: urothelial carcinoma
• Other types: squamous cell carcinoma, adenocarcinoma
 THE ETIOLOGY
• Most important:
• Cigarette smoking, aromatic amine exposure
• Others:
• Analgesic : phenacetin
• Drug : cyclophosphamide, chlornaphazine
• Chronic infection : chronic cystitis (S. haematobium)
• Arsenic, caffeine, saccharin
 UROTHELIAL CELL CARCINOMA:
THE DEFINITION
• Urothelial carcinoma
• Invades beyond basement membrane
 UROTHELIAL CELL CARCINOMA:
THE CLINICAL FEATURES
• Mostly common: • Advanced:

microscopic hematuria,
– weight loss, bone/abdominal

painless hematuria pain (metastatic)

• Complication:
• Extensive tumor:
– hydronephrosis (poor
dysuria, urgency, frequency
prognosis)
• Rarely:
palpable mass, lower extremity
oedema
 UROTHELIAL CELL CARCINOMA:
THE DIAGNOSIS

• Imaging: detection, staging

USG, CT Scan, MRI, cystoscopy

• Histopathology:
TURBT -transurethral resection of bladder
tumor- (diagnosis, treatment)
 TURBT
trans-urethral resection of bladder tumor
UROTHELIAL CELL CARCINOMA:
THE STAGING
 UROTHELIAL CELL CARCINOMA:
THE MACROSCOPY

• Papillary, polypoid, nodular, solid, ulcerative,

transmural diffuse

• Solitary, multifocal
• Mucosa: normal, erythematous
 Picture 1

Picture 2
 UROTHELIAL CELL CARCINOMA:
THE MICROSCOPY

• Variable, not specific • Early:

papillary core invasion
• Mostly common (nest/single cell)
Papillary : low/high grade, T1
desmoplastic reaction
non-papillary : high grade, T4
inflammatory infiltrate
• Mitotic figures
• Squamous/glandular differentiation
 UROTHELIAL CELL CARCINOMA:
THE HISTOLOGIC VARIANT

• with squamous differentiation • Lymphoepithelioma-like

• with glandular differentiation • Lymphoma-like

• Plasmacytoid
• with trophoblastic differentiation
• Sarcomatoid
• Nested
• Giant cell
• Microcystic
• Undifferentiated
• Micropapillary
 UROTHELIAL CELL CARCINOMA:
SQUAMOUS DIFFERENTIATION

• Intercellular bridges, keratinization

• Poor prognosis
• Poor response to radiation/chemo therapy
• Increases with stage & grade
• IHC
• CK14, L1 Antigen (+)
• Uroplakins (-), (+) for urothelial cell carcinoma
 UROTHELIAL CELL CARCINOMA:
GLANDULAR DIFFERENTIATION

• True glandular spaces within the tumor, mucin

secretion
• IHC
• MUC5AC-apomucin (+)
• Clinical significance
• uncertain
 UROTHELIAL CELL CARCINOMA:
MICROPAPILARY DIFFERENTIATION

• Fine papillary, filiform processes, vascular cores

• Glomeruloid apperances, vascular/lymphatic invasion,
high grade, high stage
• Highly metastasized
• IHC:
• EMA, CK7, CK20, LeuM1, CEA (+)
• Others: CA-125 Antigen, B72.3, BerEp4
 UROTHELIAL CELL CARCINOMA:
THE PROGNOSIS

• Can be reccurent after cystectomy