Tumors of the urinary tract
& kidney
Outline
• Renal cell carcinoma (RCC)
• Wilms tumor (Nephroblastoma)
• Urothelial (transitional cell) neoplasms
Renal cell carcinoma (RCC)
(hypernephroma, Grawitz tumor)
• 85% malignant renal tumors in adults
• Average age at diagnosis 55–60yrs, 2/3 male
• Risk factors: tobacco, hypertension, obesity,
dialysis & acquired renal cystic disease, petroleum,
asbestos, heavy metals, etc
• Most sporadic, 4% familial
• Familial: 3 types; Von Hippel-Lindau syndrome
(VHL), hereditary clear cell or papillary carcinomas
Classification of RCC
Based on cytogenetics, genetic, & histologic
studies
1. Clear cell RCC
• 70-80%, from proximal convoluted tubule
• Loss of sequences on the short arm of
chromosome 3: 3p-(harbors VHL gene) in 98% of
cases
• Loss VHL (tumor suppressor gene) => increase in
VEGF, ILGF & TGF-ß1=> stimulate cell growth &
angiogenesis
• Metastasizes by the bloodstream
Clear cell RCC
Gross: clear cell RCC
• well circumscribed and variegated, with a
combination of cystic, solid, and hemorrhagic areas,
and has a bright yellow color
Gross: clear cell RCC
Clear cell RCC invading renal vein
• ~50% of clear cell RCC's invade and grow up in renal
vein
Mic: Clear cell RCC
• Cells with clear cytoplasm (from glycogen/lipid),
distinct but delicate cell boundaries
Clear cell RCC
RCC cont.
2. Papillary (chromophil) renal cell carcinoma
• 10-20%, from proximal/distal convoluted tubule
• 75% male, early stage, multifocal in 80%
• Dialysis related carcinomas are usually papillary
• Occurs in sporadic (Trisomies 7, 16, 17 & loss of Y)
or familial forms (Trisomy 7)
• Mutations in MET protooncogene (#7)
• 5 year survival is 82-90%
Papillary (chromophil) RCC
RCC cont.
3. Chromophobe renal cell carcinoma
• 5%, from intercalated cell of cortical collecting
duct
• Multiple chromosomal losses & hypodiploidy
• Excellent prognosis compared with above two
carcinomas
Chromophobe RCC
• The tumor is well circumscribed and has a light
brown color
Chromophobe RCC
• cells with well-defined cell membrane, faintly
granular cytoplasm, and perinuclear clear halo &
solid pattern of growth
RCC cont.
4. Collecting duct or Bellini duct carcinoma
• 1-2%, from distal collecting (Bellini’s) ducts, 2/3
male
• Centered in the medulla
• Chromosome losses & deletions
• Poorest prognosis of common subtypes with death
in months to a few yrs
Collecting duct carcinoma
RCC ctd
5. Sarcomatoid renal cell carcinoma
Arise infrequently in all types of renal cell
carcinomas
median survival of 19 months; 5 yr survival is 22%
Sarcomatoid renal cell carcinoma arising from a
clear cell renal cell carcinoma (lower left)
• Clear cell areas are golden in color due to cellular lipid accumulation
while sarcomatoid foci are white. Note tumor extension along the
renal vein.
Sarcomatoid RCC
Clinical feature of RCC
• "great mimic" due to associated paraneoplastic
syndromes (hypercalcemia, hypertension,
gynecomastia, cushing’s syndrome, leukemoid
reaction, polycythemia, etc)
• Hematuria, flank pain & abdominal mass (diagnostic
triad of RCC): in only 10% of patients, late
manifestation & poor prognosis
• 25% presents with metastases (lung, bones, lymph
nodes, etc)
Prognostic factors of RCC
1.Staging: 60-80% stage I Vs <5% stage IV
2.Distant metastases
3.Microscopic nuclear grading
4.Microscopic variants: favorable for papillary and
chromophobe RCC
Overall 5-year survival rate 45-70% without
metastases; 15-20% with renal vein involvement &
extension into the perinephric fat
Wilms tumor (Nephroblastoma)
• Constitute ~85% of childhood renal cancers
• 90% aged <6yrs, 5-10% bilateral
• Apparently derives from nephrogenic blastema cells
• Most sporadic
Nephrogenic Rests
Risk factors: Wilms' Tumor
• Nephroblastomatosis
– premalignant lesion; immature nephrogenic elements within
otherwise normal kidney
• 10% syndromic with congenital malformation
(chromosome 11: WT1 &WT2)
– WAGR & Beckwith-Wiedemann syndromes
Genetics of Wilms' Tumor
Type Name Comment
gene WT1 Deletion of this zinc finger
transcription factor located on
11p13
chromosome 11 11p13 and 11p15.5
gene WT2 This gene located on 11p15.5 is
deleted
syndrome WAGR Wilms tumor, iridia,
genitourinary malformation and
mental retardation
syndrome Beckwith-Wiedemann Hemihypertrophy,
syndrome macroglossia, omphalocele and
visceromegaly
Wilms' Tumor
large with solid soft gray tan cut surface
and seemingly well-circumscribed borders
Micro: Wilms' Tumor
• Triphasic tumor (3 distinct elements)
– blastema, stroma & epithelial
Clinical features of Wilms' Tumor
• Presents as an abdominal mass felt by the mother
when handling the child
• Rarely hematuria, pain, intestinal obstruction,
hypertension
Spread of Wilms' Tumor
Local in perirenal soft tissues
May involve adrenal, bowel, liver, etc
Commonly invasion of the renal vein
Metastasizes to regional lymph nodes (15%), lung,
liver, peritoneum; rarely bone
Prognostic factors
1. Age
2. Stage
3. Anaplasia
4. Extensive tubular & skeletal muscle differentiation
Overall cure rate for unilateral tumor 80–90%
A small percentage develop second neoplasms
(sarcomas, leukemia, lymphoma, etc) due to a
genetic predisposition to neoplasia & secondary to
therapy
Unfavorable histology: Anaplasia
predicts resistance to chemotherapy
1. Enlarged nuclei >3X the
size of typical blastema
cell
2. Hyperchromasia
3. Multipolar mitotic figures
• RCC Wilms tumor
Urothelial (transitional cell) neoplasms
• From renal pelvis to distal urethra (most bladder)
• Many multifocal, M > F, urban, age 50+
• Non invasive papillary or invasive
• Noninvasive papillary tumors & carcinoma in situ are
precursor lesions to invasive urothelial carcinoma
• Invasive urothelial neoplasms: invasion into lamina
propria & muscularis propria
• Low grade tumors may begin with 9p-/9q-, some
acquire p53 and become invasive
• High grade tumors may begin with p53 alterations
Causes
Cigarette smoking (50-80% of cancers)
Industrial exposure to arylamines
Radiation, cyclophosphamide
Schistosoma haematobium
Squamous metaplasia => dysplasia => squamous
cell carcinomas
WHO classification of papillary
urothelial tumor
Papillary urothelial tumors
Papilloma: <1% of bladder tumors, benign, usually
solitary
Inverted urothelial papilloma: 1-2% of bladder
tumors
Papillary urothelial neoplasm of low malignant
potential: 1/3 recur, 5% as higher grade; 10 year
survival >95%
Low grade papillary urothelial carcinoma
10% are invasive, 50-65% recur
Papillary urothelial tumor
High grade papillary urothelial carcinoma
Usually aneuploid, 80% invasive
Clinical course of papillary urothelial tumors
Painless hematuria, infection, obstruction if near
ureteral orifices
Tumors tend to recur (50% of low grade tumors Vs
80% of high grade), often at higher grade and
different site
Invasion to adjacent structures & metastasis to
regional l. nodes
Hematogenous spread is late
Invasive urothelial carcinoma
Bladder urothelial carcinoma
Radical cystectomy specimen showing a single large hemorrhagic tumor attached
to the bladder wall with a narrow base. It was invasive high-grade papillary
urothelial carcinoma (Stage pT2; invasion of Detrusor muscle) with glandular
differentiation. Extensive urothelial carcinoma-in-situ was also seen.
Radical cystectomy specimen showing extensive papillary
tumors throughout the bladder
Bladder urothelial carcinoma
Bladder urothelial carcinoma
Renal pelvis urothelial
carcinoma
• normal cortex and medulla, but the calyces
show focal papillary tumor masses of
urothelial carcinoma
Papilloma
Papillary urothelial neoplasm of low
malignant potential
Low grade papillary urothelial
carcinoma
High grade papillary urothelial
carcinoma
Prognostic factors
• Grading; 10yr survival 98% for low grade Vs 40% for
high grade
• Stage (5 year survival is 75% if T1, 50% for T2 and
20% for T3)
Other kidney tumors
Angiomyolipoma
Oncocytoma
Fibroma
Adenoma
Congenital mesoblastic nephroma
Clear cell sarcoma
Metastases to kidney
Angiomyolipoma
A benign neoplasm of adipose tissue (lipoma) in which
muscle cells and vascular structures are fairly
conspicuous; most commonly a renal tumor containing
smooth muscle, often associated with tuberous
sclerosis.
Oncocytoma
Metastases of carcinoma to the kidneys
