9. Adult polycystic kidney disease
Inheritance
Autosomal dominant
Pathologic Features
Large multicystic kidneys, liver cysts,
berry aneurysms
10. Adult polycystic kidney disease
Clinical Features or Complications
Hematuria, flank pain, urinary tract
infection, renal stones, hypertension
Chronic renal failure beginning at age 40–
60 years
11. 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
12. Adult polycystic kidney disease
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)
13. Adult polycystic kidney disease
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
14. Adult polycystic kidney disease
Genetics 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
15. Adult polycystic kidney disease
Genetics and Pathogenesis
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
16. Adult polycystic kidney disease
Genetics and Pathogenesis
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
17. Adult polycystic kidney disease
Genetics and Pathogenesis
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
18. Adult polycystic kidney disease
Genetics and Pathogenesis
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
19. Adult polycystic kidney disease
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
21. Adult polycystic kidney disease
Genetics and Pathogenesis
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.
22. Adult 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
24. Adult polycystic kidney disease
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
28. 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
29. 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
30. Chidhood polycystic kidney
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
32. Chidhood polycystic kidney
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.
34. 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
35. RENAL CELL CARCINOMA (RCC)
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
36. 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
37. RENAL CELL CARCINOMA (RCC)
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
38. RENAL CELL CARCINOMA (RCC)
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
39. 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
40. 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
43. 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
45. 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
46. Clinical features of RCC
Paraneoplastic syndromes
Polycythemia 5-10%
Hypercalcemia
Cushing’s syndrome
Hypertension
Feminization or masculinization
Eosinophilia, leukemoid reactions, and
amyloidosis
47. Clinical features of RCC
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.
48. 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%
49. Clear Cell
Renal Cell Carcinoma
Total nephrectomy
(gross)
(Most common renal tumor in adults)
53. 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
55. 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
•
56. Wilms Tumor
• less common complaints include
a) fever
b) abdominal pain
c) hematuria
d) intestinal obstruction (uncommon)
57. 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
61. 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
65. 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
66. 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%
67. 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
69. 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
70.
71.
72.
73. Low-grade papillary urothelial carcinoma with an overall
orderly appearance, with a thicker lining than papilloma
and scattered hyperchromatic nuclei and mitotic figures
(arrows)
