Tumors of kidney & urinary tract 2012

To discuss

Cystic Lesions of Kidney

Common Tumors of kidney and

Urinary bladder

Learning OutcomesClassify cystic diseases of kidney

Explain pathogenesis of adult

&childhood polycystic kidney diseases

Describe Morphology of adult

&childhood polycystic kidney diseases

Learning Outcomes Classify tumors of kidney and bladder

Compare and discuss

age and sex prdeominance & incidence, genetic, clinical presentation & clinical course, morphology, prognosis of

Renal cell carcinoma

Wilms Tumor

Transitional cell carcinoma

Cystic Diseases of the KidneyCystic diseases of the kidney are

heterogeneous, comprising

Hereditary

Developmental

acquired disorders

Classification of renal cysts 1. Multicystic renal dysplasia

2. Polycystic kidney disease

a. Autosomal-dominant (adult) polycystic

disease

b. Autosomal-recessive (childhood)

polycystic disease

Classification of renal cysts 3. Medullary cystic disease

a.Medullary sponge kidney

b. Nephronophthisis

4. Acquired (dialysis-associated)

cystic disease

5. Localized (simple) renal cysts

Classification of renal cysts 6. Renal cysts in hereditary

malformation syndromes (e.g.,

tuberous sclerosis)

7. Glomerulocystic disease

8. Extraparenchymal renal cysts

(pyelocalyceal cysts, hilar

lymphangitic cysts)

Adult polycystic kidney diseaseInheritance

Autosomal dominant

Pathologic Features

Large multicystic kidneys, liver

cysts, berry aneurysms

Adult polycystic kidney diseaseClinical Features or Complications

Hematuria, flank pain, urinary tract

infection, renal stones, hypertension

Chronic renal failure beginning at

age 40–60 years

Adult polycystic kidney disease

A hereditary disorder

characterized by multiple

expanding cysts of both kidneys

that ultimately destroy the renal

parenchyma and cause renal

failure


Despite the autosomal dominant

inheritance

the manifestation of the disease

requires

mutation of both alleles of either

PKD gene

mutations in genes located on

chromosome

16p13.3 (PKD1) & 4q21 (PKD2)


Genetics and Pathogenesis

The PKD1 gene encodes

a large integral membrane protein

named polycystin-1 which has

a large extracellular region, multiple

transmembrane domains, and a short

cytoplasmic tail

Adult polycystic kidney diseaseGenetics and Pathogenesis

The PKD2 gene product polycystin-2 is an integral membrane protein

It has been localized to all segments of the renal tubules and is also expressed in many extrarenal tissues

Polycystin-2 functions as a Ca2+-permeable cation channel, and a basic defect in ADPKD is a disruption in the regulation of intracellular Ca2+ levels


The epithelial cells of the kidney each contain

a single nonmotile primary cilium, a 2–3 μm

long hairlike organelle that projects into the

tubular lumen from the apical surface of

tubular cells

Function of cilium in tubular cells-

sense mechanical signals (mechanosensor)

to monitor changes in fluid flow and shear

stress



In response to external signals, these

sensors regulate ion flux (cilia can

induce Ca2+ flux in cultured kidney

epithelial cells) and cellular behavior,

including cell polarity and proliferation

The hypothesis that defects in

mechanosensing, Ca2+ flux, and signal

transduction underlie cyst formation



Both polycystin-1 and polycystin-2 are

localized to the primary cilium

Polycystin-1 and polycystin-2 may form a

protein complex that acts to regulate

intracellular Ca2+ in response to fluid flow,

perhaps because fluid moving through the

kidney tubules causes ciliary bending that

opens Ca2+ channels



Mutation of either of the PKD genes

lead to

loss of the polycystin complex or the

formation of an aberrant complex

changes in intracellular Ca2+ level


Genetics and Pathogenesi

second-messenger effects of Ca2+ lead to

changes in cellular proliferation

basal levels of apoptosis

interactions with the ECM

secretory function of the epithelia

that together result in the characteristic feature of ADPKD



Progressive enlargement of cyst result from increase in the number of cells caused by abnormal

proliferationexpanding volume of intraluminal fluid caused by

abnormal secretion from epithelial cells lining the cysts

mediators in cyst fluids enhance fluid secretion and induce inflammation

These abnormalities contribute to further enlargement of cysts and the interstitial fibrosis characteristic of progressive polycystic kidney disease.


Morphology (Gross)

kidneys are usually bilaterally

enlarged

external surface appears to be

composed solely of a mass of cysts,

up to 3 to 4 cm in diameter, with no

intervening parenchyma


Adult polycystic kidney diseaseMorphology (Gross)

Adult polycystic kidney diseaseMicroscopic examination reveals

functioning nephrons dispersed between the cysts

The cysts may be filled with a clear, serous fluid or, more usually, with turbid, red to brown, sometimes hemorrhagic fluid

The cysts arise from the tubules throughout the nephron and therefore have variable lining epithelia

On occasion, papillary epithelial formations and polyps project into the lumen

Bowman capsules are occasionally involved in cyst formation, and glomerular tufts may be seen within the cystic space

As these cysts enlarge, they may encroach on the calyces and pelvis to produce pressure defects

Childhood polycystic kidney diseaseInheritance

Autosomal recessive

Pathologic Features

Enlarged, cystic kidneys at birth

Chidhood polycystic kidney diseaseClinical Features or Complications

Hepatic fibrosis

Variable, death in infancy or

childhood

Subcategories

depending on the time of presentation and presence of associated hepatic lesions

1. Perinatal

2. Neonatal

3. Infantile

4. juvenile

Chidhood polycystic kidney disease

Genetic and Pathogenesis

Mutations of the PKHD1 gene, which maps to chromosome region 6p21–p23

PKHD1 gene encodes a large novel protein, fibrocystin

Fibrocystin is an integral membrane protein with a large extracellular region, a single transmembrane component, and a short cytoplasmic tail



Genetic and Pathogenesis

Fibrocystin also has been localized to the

primary cilium of tubular cells

The function of fibrocystin is unknown

its putative conformational structure

indicates it may be a cell surface

receptor with a role in collecting-duct

and biliary differentiation

MorphologyThe kidneys are enlarged and have a

smooth external appearance

On cut section, numerous small cysts in the cortex and medulla give the kidney a spongelike appearance

Dilated elongated channels are present at right angles to the cortical surface, completely replacing the medulla and cortex



Morphology

MorphologyOn microscopic examination, there is cylindrical or, less commonly, saccular dilation of all collecting tubules

The cysts have a uniform lining of cuboidal cells, reflecting their origin from the collecting ducts.


TUMORSBENIGN

Papillary Adenoma

Fibroma/Hamartoma

Angiomyolipoma

Oncocytoma

Juxtaglomerular apparatus tumorJuxtaglomerular apparatus tumor

MALIGNANTRenal cell CA(Adenoca.) Renal cell CA(Adenoca.)

Wilm’s tumorWilm’s tumor

T.C.C.T.C.C.

Primary sarcomasPrimary sarcomas

RENAL CELL CARCINOMA (RCC)1-3% of all visceral cancers, 85% of all renal cancer

Most common 60-70 years ; M:F = 2:1

Risk factors Smoking, obesity, hypertension Unopposed estrogen Rx Asbestos, petroleum products & heavy metals CRF & acquired cystic disease (30 folds ) Familial (4%)

Von Hippel-Lindau (VHL) syndrome

Hereditary clear cell carcinoma

Hereditary papillary carcinoma

Grossly: Mainly polar, spherical yellow

variegated tumor with hemorrhagic,

necrotic & cystic areas. May extend into

renal v.

Microscopically:

Clear cell carcinoma: (70-80%)

Papillary carcinoma: (10-15%)

Chromophobe renal carcinoma (5%)

Sarcomatoid carcinoma

RENAL CELL CARCINOMA (RCC)

Clear cell carcinomaMost common ,70-80% of renal

cancer

Clear cells with clear or granular

cytoplasm

Majority are sporadic

Familial forms : von Hippel-Lindau


Site - any portion of the kidney, but more commonly affects the polessolitary unilateral lesions, spherical massescomposed of bright yellow-gray-white tissue that distorts the renal outlinelarge areas of ischemic, opaque, gray-white necrosis, and foci of hemorrhagic discolorationThe margins are usually sharply defined and confined within the renal capsule


Clear cell carcinomasolid to trabecular

or tubular growth

pattern

rounded or

polygonal shape and

abundant clear or

granular cytoplasm,

which contains

glycogen and lipids

Papillary RCC

10-15% of all renal cancer

Papillary growth pattern

Frequently multifocal &bilateral

Appear as early stage tumor

most common cytogenetic

abnormalities are trisomies 7, 16, and

17

Papillary RCCarise from distal convoluted tubules

multifocal and bilateral

typically hemorrhagic and cystic

especially when large

most common type of renal cancer

in patients who develop dialysis-

associated cystic disease

Papillary RCC

Chromophobe renal carcinoma

5% of all RCC

Arise from cortical collecting ducts or

their intercalated cells

composed of cells with prominent cell

membranes and pale eosinophilic

cytoplasm, usually with a halo around the

nucleus

General good prognosis

Chromophobe renal carcinoma

Clinical features of RCCThree classic diagnostic features of renal cell

carcinoma

Hematuria (50%), costovertebral pain, mass

Asymptomatic/incidental finding

Constitutional symptoms (fever, malaise,

weakness, and weight loss)

Present with metastasis (lungs and bones )

Paraneoplastic syndromes

Clinical features of RCC

Paraneoplastic syndromesPolycythemia 5-10%

Hypercalcemia

Cushing’s syndrome

Hypertension

Feminization or masculinization

Eosinophilia, leukemoid reactions, and

amyloidosis

Common characteristics of this tumor is

its tendency to metastasize widely

before giving rise to any local

symptoms or signs

locations of metastasis are the lungs

(more than 50%) and bones (33%),

followed in frequency by the regional

lymph nodes, liver, adrenal, and brain.

Clinical features of RCC

Renal cell CarcinomaPrognosis: 5 yr survival is around

70% in the absence of distant

metastases

With renal vein invasion or

extension into the perinephric fat,

the figure is reduced to

approximately 15% to 20%

Clear Cell Clear Cell Renal Cell CarcinomaRenal Cell Carcinoma

Total nephrectomyTotal nephrectomy

(gross)(gross)

(Most common renal tumor in adults)(Most common renal tumor in adults)

Renal cell carcinoma

Renal Cell Carcinoma, Clear Cell, Type(microscopic)

Wilms Tumor1 in every 10,000 children in the

United States

most common primary renal tumor

of childhood

peak incidence for Wilms tumor is

between 2 and 5 years of age

5% to 10% of Wilms tumors involve

both kidneys

Congenital anomalies related:

WAGR syndrome: WT1 (11p13)

DENYS-DRASH syndrome: similar

path.

BECKWITH-WIEDEMANN

syndrome: WT2

WT3

Wilms Tumor

Wilms TumorClinicalClinical

• Good outcome with early diagnosis.

Tumor has

tendency to easily metastasize

major complaint is associated with large

size of the tumor - readily palpable mass

•

Wilms Tumor• less common complaints include

a) fever

b) abdominal pain

c) hematuria

d) intestinal obstruction

(uncommon)

NEPHROBLASTOMA (WILM’S TUMOR)Grossly: Large well-

circumbscribed soft tan-gray

homogenous tumor

MICRO: Blastemal, stromal and

epithelial elements

Prognosis: Currently 90% long

term survival

MICRO: Blastemal, stromal and epithelial elements

Renal pelvis carcinomaTransitional & squamous

carcinomas of renal pelvis

5-10% of renal neoplasms

Often small and present early with

Painless Hematuria

Pain or mass due to

hydronephrosis

May be multifocal

Renal pelvis carcinoma

Prognosis:

variable, depend on stage & grade

Despite removal by

nephrectomy :50% 5 YSR

Transitional Cell CarcinomaGross

Urinary bladder tumors

Exophytic papilloma

Inverted papilloma

Papillary urothelial neoplasms of low malignant potential

Low grade and high grade papillary urothelial cancers

Carcinoma in situ (CIS, or flat non-invasive urothelial

carcinoma)

Mixed carcinoma

Adenocarcinoma

Small-cell carcinoma

Sarcomas

Bladder Carcinoma

Derived from transitional

epithelium

Present with painless hematuria

Prognosis depends on grade and

depth of invasion

Overall 5y survival = 50%

Things you must know

Bladder CarcinomaMorphology

The gross patterns of urothelial tumors vary

from purely papillary to nodular or flat

Papillary lesions appear as red, elevated

excrescences varying in size from less

than 1 cm in diameter to large masses up

to 5 cm in diameter

Multicentric origins

Urinary bladder tumors

large papillary tumor

multifocal smaller papillary neoplasms

Bladder CarcinomaGrading of Urothelial (Transitional Cell Ca)

WHO/ISUP Grades Urothelial pappiloma Urothelial neoplasm of low malignant potential

Papillary urothelial carcinoma low gradePapillary urothelial carcinoma, high grade

Low-grade papillary urothelial carcinoma with an overall orderly appearance, with a thicker lining than papilloma and scattered hyperchromatic nuclei and mitotic figures (arrows)

High-grade papillary urothelial carcinoma

with marked cytologic atypia

Flat carcinoma in situ

Tumors of kidney & urinary tract 2012

Health & Medicine

Transcript of Tumors of kidney & urinary tract 2012