Tumors of kidney & urinary tract 2012

To discuss
Cystic Lesions of Kidney
Common Tumors of kidney and Urinary
bladder

Learning Outcomes
Classify 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 Kidney
Cystic 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

3. Medullary cystic disease
a.Medullary sponge kidney
b. Nephronophthisis
4. Acquired (dialysis-associated) cystic
disease
5. Localized (simple) 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 disease
Inheritance
Autosomal dominant
Pathologic Features
 Large multicystic kidneys, liver cysts,
berry aneurysms

Clinical Features or Complications
Hematuria, flank pain, urinary tract
infection, renal stones, hypertension
Chronic renal failure beginning at age 40–
60 years

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

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
proliferation
 expanding 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

Morphology (Gross)

Microscopic 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
disease
Inheritance
Autosomal recessive
Pathologic Features
 Enlarged, cystic kidneys at birth

Chidhood polycystic kidney
disease
Clinical Features or Complications
Hepatic fibrosis
Variable, death in infancy or childhood

disease
Subcategories
depending on the time of presentation and
presence of associated hepatic lesions
1. Perinatal
2. Neonatal
3. Infantile
4. juvenile

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

Chidhood polycystic kidney disease
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

disease
Morphology
The 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

Chidhood polycystic kidney disease
Morphology

disease
Morphology
On 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.

TUMORS
BENIGN
Papillary Adenoma
Fibroma/Hamartoma
Angiomyolipoma
Oncocytoma
Juxtaglomerular apparatus tumor

MALIGNANT
Renal cell CA(Adenoca.)
Wilm’s tumor
T.C.C.
Primary 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

Clear cell carcinoma
Most 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 poles
solitary unilateral lesions, spherical
masses
composed of bright yellow-gray-
white tissue that distorts the renal
outline
large areas of ischemic, opaque, gray-
white necrosis, and foci of
hemorrhagic discoloration
The margins are usually sharply
defined and confined within the renal
capsule

Clear cell carcinoma
solid 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 RCC
arise 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

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

Clinical features of RCC
Three 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

Paraneoplastic syndromes
Polycythemia 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.

Renal cell Carcinoma
Prognosis: 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
Renal Cell Carcinoma
Total nephrectomy

(gross)

(Most common renal tumor in adults)

Renal Cell Carcinoma, Clear Cell, Type
(microscopic)

Wilms Tumor
1 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

Wilms Tumor
Congenital anomalies related:
WAGR syndrome: WT1 (11p13)
DENYS-DRASH syndrome: similar path.
BECKWITH-WIEDEMANN syndrome: WT2
WT3

Wilms Tumor
Clinical
• 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 carcinoma
Transitional & 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 Carcinoma
Gross

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
Things you must know

Derived from transitional epithelium
Present with painless hematuria
Prognosis depends on grade and depth of
invasion
Overall 5y survival = 50%

Bladder Carcinoma
Morphology
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 Carcinoma
Grading of Urothelial (Transitional Cell Ca)
WHO/ISUP Grades
Urothelial pappiloma
Urothelial neoplasm of low malignant
potential
Papillary urothelial carcinoma low grade
Papillary 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

Tumors of kidney & urinary tract 2012

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