Kathryna Lesley T.

Ayro, MD, FPSP | August 1, 2015 | ADVANCED PATHOLOGY

PATHOLOGY OF THE KIDNEY AND URINARY TRACT

Introduction o Obtain critical information on the

Kidney has limited reactions to various injuries evolution and prognosis of a disease
The kidney being the excretory organ is usually subjected process
to all various injuries affecting the body. Most systemic o Develop a rational approach to the
diseases usually involve the kidney in general and the treatment of renal diseases
most common cause of morbidity and mortality of all Disease recurrence in renal transplant
systemic and metabolic diseases include the kidney to be Presence of cellular or humoral rejection
one of the causes Methods:
o Percutaneous route more common
Factors:
o Open biopsy
o Location of a particular type injury
o Host response or stability of the immune Handling:
system o Light microscopy (H&E Stain)
o Type of injury - presence or absence of o Immunofluorescence
other comorbid problems o Electron microscopy
Classification of renal diseases 2 cores ideally
o Clinical o Cold solution of 2% glutaraldehyde in
They are classified if pre-renal, post-renal and renal phosphate for IF (Immunofluorescence)
o Saline then fixative for LM (10% buffered
causes
formalin) but mercuric solution gives the
o Etiologic
best detail
o Immunologic
o Snap frozen in liquid nitrogen or
They could be primary or secondary to systemic diseases
isopentane cooled on dry ice for IF
o Morphologic
(Immunofluorescence)
They are classified based on what is observed under the
Percutaneous route of renal biopsy is also used in
microscope
prostatic biopsy
Can also be classified into syndromes
Interpretation
Most of the syndromes usually overlap in the later stages
o Evaluate the four renal components
of the renal disease. It is difficult to identify the initial insult The four renal components are: glomeruli, tubules, blood
of that causes the renal disease. vessels, interstitial spaces
o Nephritic syndrome o Hypercellularity
o Nephrotic syndrome
In hypercellularity, there is increase in the number of
o Non-nephrotic proteinuria
cells. You should identify if there is increase in the (1)
o Microscopic hematuria
endothelial cells, (2) epithelial cells, (3) mesangial cells or
o Acute and chronic renal injury
(4) inflammatory cell infiltrates
o RPGN
o Asymptomatic renal insufficiency Primary or secondary
WHO definition of
normocellularity
Renal Biopsy
No more than 3 cells in
Evaluation of patients with renal diseases
an individual glomerular
Purposes:
mesangial region
o Establish an accurate diagnosis
2-3 micrometer section
Page 1 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 o Basement membrane
Glomeruli EM
Light microscopy (LM) o Cellular changes
o Size and cellularity o Inclusions
o Mesangium o Basement membrane
o Presence of leucocytes o Deposits: type and location
o Capillary walls IF
o Necrosis o Reactions and pattern
o Deposits: type and location o Intensity
o Crescents: type and percentage LM:
o Sclerosis: distribution and percentage We also evaluate the tubules for the presence of tubular
o Adhesion to bowmans capsule necrosis. There are different stages of tubular injury from
o Thrombi (1) simple swelling or cloudy swelling, (2) reduction of the
Electron microscopy (EM) cytoplasmic vacuoles and eventually (3) coagulative
o Basement membrane necrosis.
Thickness, contours, density This will determine if the stage of injury is reversible or
o Cellular changes not. Cloudy swelling indicates reversible damage and
o Mesangium
irreversible for necrosis.
o Deposits: type and location
o Inclusions
Blood Vessels
Immunofluoresence (IF)
LM
o Positive or negative reaction
o Intimal thickening: type (sclerosis)
o Immunoglobulins, complements, fibrin
o Elastic changes
o Pattern: linear or granular
o Medial hypertrophy (decrease in vascular
o Intensity
lumen)
EM:
o Hyalinosis
There is basement membrane thickening as seen in
o Thrombosis and embolism
membranous glomerulonephritis
o Necrosis
Identify the deposits if they are in the glomerular o Inflammation
basement membrane, endothelial cells or in the epithelial o Juxtaglomerular apparatus
cells or if there is increase in mesangial cells EM
IF: o Intimal and medial changes
Identify the pattern of complements, if linear, it is similar o Deposits
to anti-GBM diseases, good pasture syndrome, or RPGN. IF
If granular, it means that there are patchy deposits in the o Reaction and distribution
glomerular basement membrane as seen in post-strep Remember that kidneys are highly vascularized organ
glomerulonephritis. and they display evident increase in vascular pressure.
They undergo hyalinization and sclerosis and they are
Tubules usually consistent with chronic hypertension
LM Benign hypertension hyalinization, tunica medial
o Necrosis hypertrophy, and sclerosis
o Reparative changes Malignant hypertension hyperplastic arteriolitis
o Dilation
o Casts: type Interstitium
o Crystals LM
o Cellular inclusions o Edema
o Vascularization o Inflammation (acute or chronic)
Page 2 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 o Fibrosis: type and percentage
EM
o Cellular infiltration
o Deposits
IF
o Reaction and distribution
Renal biopsy unlike any other biopsy does not directly
conclude a diagnosis in one core biopsy but it needs to
evaluate the four renal components before it can
conclude a medically accurate renal disease.
Review of Glomerular Diseases
Classification of Glomerular Disease by Distribution
A. Classification of disease distribution when many
glomeruli are considered
1. FOCAL disease affects only some of glomeruli
2. DIFFUSE disease affects almost or all glomeruli
B. Classification of disease distribution when single
glomerulus is considered
1. SEGMENTAL - a lesion involving only a part of the
glomerulus
2. GLOBAL - a lesion involving the entire glomerulus
3
of
15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016
The most common encountered are focal segmental
glomerulosclerosis/glomerulonephritis
Review of Glomerular Diseases (Refer to table)
Glomerular diseases are studied based on the clinical
presentation of the patient. Classifying such diseases
focus on the presentation of the initial stages because in
the later stages, the syndromes usually overlap.
NEPHROTIC SYNDROMES
-the most common clinical presentation is gross
proteinuria (>3.5g/day)
Note that Diabetic Focal glomerulonephritis is a metabolic
disease while SLE Secondary Glomerular disease is an
autoimmune disease, both are systemic diseases but
presents a wide range off renal involvement
(nephropathy) presenting with nephrotic syndromes.
Primary Glomerulonephritis
1. Minimal change disease
-minimal
-normal LM findings
-no deposits
-negative immunofluorescence
-elimination or flattening of podocytes in EM
-very common in children (80%)
-very responsive to corticosteroid therapy
-also called lipoid nephrosis due to the luminal histiocytes
containing lipids (foamy histiocytes) in the tubules
-presents with selective albuminuria, very common in
children
-global fat bodies is sometimes seen in urine
2. Diffuse membranous glomerulonephritis
-more common in adults
-very distinct glomerular basement membrane specially in
silver stain
-sometimes associated with viral infections but can also
be primary
-also responsive to corticosteroid therapy but more
resistant than minimal change disease
Secondary Glomerulonephritis
1. Diabetic focal glomerulonephritis
-KW lesion (microscopic finding)
Page
-usually present as nephrotic syndrome NEPHROTIC/NEPHRITIC SYNDROMES
-pathogenesis: there is glycosylation of the glomerular -presents both gross hematuria and proteinuria
basement membrane -> increasing the permeability of the
protein -> presenting as nephrotic syndrome 1. Focal segmental glomerulosclerosis
-seen for patients positive/reactive in HIV
2. Amyloidosis -seen in patients in chronic renal failure showing
-secondary disease because of amyloid deposition (1)sclerosis more extensive to KW lesion and forms
-sometimes associated with multiple myeloma, having nodules and (2) hyalinization
similar presentations 2. MPGN Type 1
-present with lobular deposits in IF
3. SLE secondary glomerular disease 3. MPGN Type 2
-pathogenesis: immune complex deposited in the --present with linear deposits in IF
glomerular basement membrane - tram-tracking or reduplication of the basement
-there is also accompanied proliferation of cells in the membrane
glomeruli usually focal and segmental involvement
-EM: presence of subendothelial and mesangial deposits All will progress to chronic glomerulonephritis or end
but depends on the stage stage renal disease where most of the glomeruli have:
-Hyalinization
NEPHRITIC SYNDROMES -Sclerosis
-the most common clinical presentation is gross -Extensive tubular atrophy
hematuria with RBC casts -Extensive stromal fibrosis and inflammation
-expected RBC casts in the urine
PEDIATRIC RENAL TUMORS
1. Post-infectious/post-streptococcal glomerulonephritis WILMS TUMOR
-most common MESOBLASTIC NEPHROMA
-formation of immune complex produced by the infection NEPHROGENIC RESTS
deposited in the glomerular basement membrane NEPHROBLASTOMATOSIS
-IF: lumpy bumby appearance granular IgG deposits INTRARENAL NEUROBLASTOMA
-EM: subepithelial humps prominence of the epithelial RHABDOID TUMOR
lining
WILMS TUMOR
2. IgA nephropathy (Bergers disease) Nephroblastoma
-pathogenesis: activation of the alternate complement Most common renal malignancy of early
pathway childhood
2-4 years of age
RPGN SYNDROMES Originates from primitive metanephric tissue
-the clinical presentation is hematuria Deletions of short arm of chromosome 11
o WT1 and WT2
1. Good pastures syndrome Genetics
-linear IF pattern Risk is increased in the following:
-LM: presence of crescents o WAGR- 33%
2. Crescentic nephritis Wilms tumor, Aniridia, Genital
-linear IF pattern anomalies, retardation
-LM: presence of crescents Deletions of 11p13
o Denys Drash Syndrome 90%

Page 4 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 Gonadal dysgenesis (male
pseudohermaphroditism) and early
onset nephropathy
P13 of chromosome 11
Dominant genetic missense
mutation affecting DNA binding
properties
o Beckwith-Wiedmann Syndrome
Organomegaly: macroglossia,
hemihypertrophy, renal medullary
cysts, omphalocoele and adrenal
cytomegaly
P15.5 of chromosome 11, WT2
Cells with attempts to recapitulate the different
stages of nephrogenesis
Classic tri-phasic combination
o Blastema (dark, undifferentiated cells)
o Stroma
o Epithelial (some are differentiated cells)
Clinical features:
o Commonly presents as large abdominal
mass
Sometimes patients are asymptomatic until you palpate
an abdominal mass at the age of 2.
o Hematuria, abdominal pain after a
traumatic incident
Slight injury in the abdomen will cause hemorrhage that
will initiate the symptoms
o Prognosis is good with surgery,
radiotherapy and chemotherapy
diagnosis before age 2
MESOBLASTIC NEPHROMA
Also called:
o Fetal hamartoma
o Mesenchymal hamartoma
o Leiomyomatous hamartoma
Most common renal tumor of infancy
Congenital tumor
May present in utero causing non-immune fetal
hydrops and polyhydramnios
Gross:
o Classic
variably circumscribed
white/yellow, whorled mass
mean 5 cm, near hilum
o Cellular
necrosis
large cystic areas and
hemorrhage
mean 9 cm. in diameter
Microscopic
o Classic, cellular and mixed types; usually no
necrosis or hemorrhage, not well circumscribed
o Classic
resembles infantile fibromatosis or
leiomyoma with fascicles and whorls of
bland spindled myofibroblasts and thin
collagen fibers
tumor surrounds tubules and glomeruli
metaplastic and dysplastic elements
common, usually cartilage, also
extramedullary hematopoiesis and cuboidal
metaplasia
usually few mitotic figures (resemble
sarcomatous lesion)
no desmoplasia
o Cellular
resembles infantile fibrosarcoma with
densely packed plump atypical spindle cells
with abundant cytoplasm, vesicular nuclei
and nucleoli
frequent mitotic figures (25-30/10 HPF) and
necrosis

Note: It is important to identify if the tumor is of renal

origin or a tumor from the adrenal gland

Page 5 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 DD: Wilms tumor (particularly for extrarenal
rests)

NEUROBLASTOMA
Primary renal tumors or secondary spread from
adrenal or other retroperitoneal site
Metastases to bone and orbit
Poor prognosis if N-myc amplification (30%) or
1p-
Laboratory: catecholamines in serum and urine
Microscopic: small blue cell tumor with Homer-
Wright rosettes
Positive stains: catecholamines (90%), NSE
(neuron specific enolase), S100
DD: Wilms tumor (rosettes resemble Wilms
tubules)
NEPHROGENIC RESTS
congenital, not neoplastic
ADULT RENAL TUMORS
may originate from persistent nephrogenic
Renal Cell Carcinoma
blastema
single or multiple, unilateral or bilateral; rarely Adenomas
occur in ectopic sites Oncocytoma
considered precursor lesion of Wilms tumor, Angiomyolipoma
found in 30-44% of kidneys resected for Wilms Metastatic Tumors
tumor
o Intralobar rests (compared to perilobar rests): RENAL CELL CARCINOMA TRIAD: hematuria, flank
may progress to Wilms tumor at higher pain, abdominal mass
General Features:
rate o Adult 5th to 6th decade
more commonly associated with WT1 o Male to female ratio is 2:1
mutations, Denys-Drash syndrome and o Increased risk cigarette smoking and
WAGR syndrome HPN
o Perilobar rests: o Associated with the following:
rarely progress to malignancy Von Hippel Lindau 50%
may be associated with loss of imprinting at Acquired cystic disease
11p, are associated with idiopathic Tuberous sclerosis
hemihypertrophy and Beckwith-Wiedemann Neuroblastoma
syndrome o Peculiarities
Microscopic: Occasional regression
o aggregates of primitive metanephric tissue, Common recipient of metastasis
either perilobar or intralobar of a cancer into another cancer
Perilobar: It can also have another primaries with renal cell
o Peripheral with sharply demarcated carcinoma. And like your melanoma, it has the greatest
margins,composed of blastema and tubules mimic in medicine. It can mimic any other tumor even
with scanty or sclerotic stroma, often solitary mesangial tumor when it is not classic, and can
Intralobar: metastasize widely even with a small tumor.
o randomly distributed throughout cortex and Clinical Features
medulla with irregular margins, more stroma o Triad
than blastema or tubules, usually multifocal Hematuria
Page 6 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 Flank pain
Abdominal mass
o Weight loss, anemia, fever, metastatic
foci
o Hepatomegaly due to hepatic dysfunction
and renal cell carcinoma = Stauffer
syndrome
o Hypercalcemia, hypertension,
polycythemia (presented as a
paraneoplastic syndrome)

Morphology
o Gross
Well delineated o IM and HIS
Usually in the cortex Keratin
Solid golden yellow on cut EMA
sections CEA
With hemorrhages, necrosis, o Co-expression of keratins and vimentins
calcifications and cystic change is the rule- not found in renal tubular cells
o Microscopic: clear cells o To determine whether renal cell ca or not
o EM - keratin, vimentin and CD10
Abundant glycogen, some fat, o Cytogenetics - terminal deletion of the
numerous cell junction, scanty short arm of chromosome 3 (beginning at
organelles, long microvilli 3p13); absent in oncocytic and papillary
It usually have benign features but it is also infiltrative and types
one important feature of RCC is that it invades your renal
vein and inferior vena cava. Other histologic types

Papillary renal cell carcinoma

Chronic dialysis
Hereditary c-met oncogene
Multicentric and bilateral
No loss of 3p13
Consistent expression of keratin 7
Trisomy of chromosome 3q, 7, 8, 12, 16, 17, 20

Collecting duct carcinoma

Arise from or differentiate towards collecting duct
(Bellini) - more common in the medullary area than
in the cortical region

Page 7 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 More common in males and centered in the
medulla, with tubulopapillary architecture with
desmoplastic stroma
Aggressive behavior
Monosomies of chromosome 1, 6, 15, 22
Renal medullary carcinoma
Rare
Young black patients with sickle cell disease
Also called the seventh sickle cell nephropathy
Arises from collecting duct system; may be due to
regenerating renal papillary epithelium
All patients have been black; average age 21-24
years, 75% male; 75% right kidney
Aggressive, death in 4-6 months, resistant to
chemotherapy
May be related to collective duct carcinoma since
similar histologic and immunoreactive features
Clinical:
gross hematuria
flank pain
weight loss
usually advanced disease at presentation
with metastases to lymph nodes, adrenal
gland, peritoneum, perinodal
retroperitoneal tissue, liver, lungs or inferior
vena cava
Cytogenetics:
sickle cell trait or hemoglobin SC disease in
almost all cases; associated with monosomy 11
(beta globin gene is at end of 11p)
Gross:
ill-defined firm, rubbery, tan-gray tumor in renal
medulla and adjacent soft tissues
mean 7 cm; satellite nodules in cortex;
hemorrhage and necrosis common
Microscopic:
tubular, solid, reticular, adenoid cystic, yolk sac
like patterns
not tubulopapillary; infiltrative
contains mucin; tumor cells have
hyperchromatic nuclei, prominent nucleoli,
rhabdoid features
vascular invasion common
desmoplastic stroma
neutrophils common within tumor, lymphocytes
at rim; angiolymphatic invasion, hemorrhagic
and geographic necrosis common; frequent
mitotic figures
Positive stains: high molecular weight cytokeratin,
variable vimentin and mucicarmine, occasional
EMA (epithelial membrane antigen) and CEA
(carcinoma epmbryonic antigen)
It is difficult to differentiate it with collecting duct of Bellini
so it is evaluated with immunostaining to consider it if it is
epithelial in origin
Negative stains: colloidal iron, PAS, desmin (used
for sarcomatous lesion)
DD: collecting duct carcinoma (irregular glands
within desmoplastic stroma with neutrophils), high
grade urothelial carcinoma, rhabdoid tumor
Chromophobe renal cell carcinoma
Just like clear cell carcinoma but the cytoplasmic
membrane is very distinct morphologically

Page 8 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 Well circumscribed, solitary (it can grossly mimic a
benign tumor)
Usually with absent necrosis and hemorrhage
Sharply defined borders and abundant cytoplasm
often with PERI-NUCLEAR REGION
Positive Hales colloidal iron acidic mucins
Positive for EMA, keratin, CD9, E-cahedrin
Negative for vimentin
Loss of chromosome 1, 2, 6, 10, 13, 17, 21
Can undergo sarcomatoid transformation
Close relationship to oncocytoma
More favorable prognosis

Spread and metastasis

o Peri-nephric fat and regional LN
o Renal sinus
o Distant metastases (same as prostatic
carcinoma metastasizing in the lungs and
bones)
Lung
Bones pelvis, femur
o Notorious to unusual places
Prognosis
o Staging
Characterisitically yellow and cells with prominent I kidney
cytoplasmic membrane showing a cobblestone II peri-renal fat but within
appearance. The nucleus is pleomorphic and Gerotas fascia
hyperchromatic compared to RCC. III renal vein, IVF, or regional
LN
IV other than adrenal
Sarcomatoid renal cell carcinoma
metastasis
Hardest type of RCC to find and usually asked for
o Distant metastasis: single most important
immunostaining to rule out sarcoma or markers of
prognostic parameter
mesenchymal tumors like vimentin, two tracts were o Tumor size: 5.0 5.5 cm
always used, those that will identify it as mesenchymal o Renal vein invasion
and those that identify it as epithelial Gross invasion: important for
Spindle cell carcinoma, anaplastic carcinoma, high grade tumors
carcinosarcoma Microscopic invasion: important
High nuclear grade predictor of relapse
Strong reactivity to vimentin o Microscopic grade: important predictor of
Extremely aggressive survival (strongly correlated with staging)
o P53 overexpression: metastatic disease
and poor survival in early stage disease
Staging is important before doing a radical nephrectomy.

ADENOMAS
Tubulo-papillary adenoma
o Papillary and tubular pattern

Page 9 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 o Cortical in location
o Rarely exceed 1 cm.
o Cytoplasm is acidophilic
o Common in end stage disease and long
term dialysis
Metanephric adenoma
o Young to middle aged females
o Larger than tubule-papillary adenomas
o Tubules and papillary structures with
scanty stroma
ONCOCYTOMA
It is usually made up of oncytes, similar to the thyroid
namely oncytoma of the thyroid or Hurthle cell adenoma
of the thyroid. A prominent feature of oncocyte is the
extensively eosinophilic cytoplasm due to the abundance
of mitochondria. So when subjected to formalin, the red
feature (eosinophilic cytoplasm) turns into brown creating
a grossly mahogany brown color.
Solid and mahogany brown tumor
Often with stellate scar centrally
Can be multicentric and bilateral
Cells with abundant acidophilic cytoplasm in
tubular or alveolar patterns
Small nuclei and regular
Express mitochondrial markers
Cytogenetics: allelic deletions at 10q
No 3p abnormalities
They are benign lesion but they become malignant once
they invade the renal parenchyma and usually
encapsulated.
ANGIOMYOLIPOMA
Less than 1% of renal tumors
Usually adults
Benign (almost always) neoplasm composed of
thick walled blood vessels, smooth muscle and
fat; includes spindle and epitheloid cells
Usually one large mass; multiple masses
suggests tuberous sclerosis
Risk factors:
o Tuberous sclerosis (50% of AMLs occur in
these patients)
o Tuberous sclerosis:
Autosomal dominant neurocutaneous
disorder
10
of
15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016
With hamartomas/tumors of brain
(subependymal giant cell cell tumor), retina,
skin (cutaneous angiofibroma), heart
(rhabdomyomas), bone, lung
(lymphangioleiomyomatosis, multifocal
micronodular pneumocyte hyperplasia),
kidney (angiomyolipoma in 40-80%, renal
cell carcinoma, some epitheloid tumors
may be misclassified), cysts
Clinically mental retardation and
infantile/childhood seizures
Blood vessels have thick walls appearing as blood
vessels supporting a polyp.
Risk factors:
TSC2/PKD1 contiguous gene syndrome: both kidneys
enlarged and cystic with
classic angiomyolipomas and rare intraglomerular
microlesions
Member of perivascular epithelioid cell (PEC)
tumor family; related to
lymphangioleiomyomatosis (in lung); "sugar"
tumor of lung, clear cell tumors of pancreas and
uterus
Neoplastic, not a hamartoma; many cases have
loss of heterozygosity of TSC2 gene
Adipose tissue and smooth muscle cells are
monoclonal, but may arise independently
Also occurs in liver, where epithelioid smooth
muscle cell component predominates
May coexist with renal cell carcinomas in non
tuberous sclerosis patients, particularly clear cell,
which is HMB45 negative
Gross:
red, gray-white, yellow (for vascular, smooth muscle
and adipose components)
resembles clear cell carcinoma
may invade local lymph nodes and renal vein even
though benign
Microscopic:
triphasic with myoid spindle cells, islands of mature
lipid-distended cells, dysmorphic thick walled blood
vessels without elastic lamina
Page
 smooth muscle component appears to spin off from
vessel walls and may be hypercellular, atypical,
pleomorphic or epithelioid
may resemble a high grade sarcoma if it
metastasizes
The ureter unlike the pelvis is not expandable, so any
tumor growing in this region will present as obstruction
and can lead to hydronephrosis of the kidney. Also, due
to its very thin vascular layer, invasion on the outside of
the ureter can occur early

UROTHELIAL CARCINOMAS OF THE RENAL PELVIS The urinary bladder has big space so the clinical
AND LOWER URINARY TRACT manifestation if a tumor will arise would be painless
5-10% of renal tumors hematuria. There is a continuous erosion of the tumor.
Benign papillomas to invasive TCCA Obstruction is not a major clinical symptom unless the
Manifests as hematuria tumor is located where the ureters are inserted or near
Never clinically palpable the urethra.
Block urinary flow causing hydronephrosis and
flank pain In the urothelial tumor of the urinary bladder, they get a
Sometimes multiple section of the tumor and get a section of the thick muscle
layer to identify the presence or absence of invasion in
URINARY BLADDER TUMORS deep vascular layer.
Urothelial tumors are graded based on their (1)
morphology if it is flat/ diffuse or papillay and then based Flat lesions usually do not present as an obstructive
on the (2) polarity of the cells from the basement lesion.
membrane to the superficial layer (usually transitional
epithelium has 4-5 layers of cells) and (3) presence of UROTHELIAL TUMORS
nuclear atypia. These features classifies the tumor if they Morphology
are high or low grade. o Papilloma
1% younger patients
Urothelial tumors Finger-like papillae
o Inverted papilloma Histologically identical to normal
o Exophytic papilloma urothelium
o Low malignant potential o Grade I
o Carcinoma-in-situ Low malignant potential
o Carcinoma Grossly similar to papilloma
Squamous cell carcinoma Mild cytologic and architectural
Adenocarcinoma atypia
Small cell carcinoma Increase in the number of layers
Sarcoma of cells (6-8)
Clinical course: o Grade II: greater loss of polarity, more
o Painless hematuria layers of cells, mitoses, atypia, papillary
o Frequency, urgency, dysuria architecture
o Depends on the location of the tumor o Grade III: papillary, flat or both, greater
o Pyelonephritis and hydronephrosis pleomorphism, atypia and mitoses, larger
o Prognosis: in size, more disorganized
Histologic grade Grading
Tumor stage at the time of
diagnosis WHO Grading ISUP consensus
Histologic type Papilloma Urothelial papilloma
TCC Grade I Urothelial neoplasm of
low malignant potential
Page 11 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 TCC Grade II Urothelial carcinoma, low Mesenchymal tumors
grade o Most common is LEIOMYOMA
TCC Grade III Urotelial carcinoma, high o Sarcomas are not common
grade Inflammatory conditions may
mimic sarcomas
Carcinoma-in-situ Sarcomas are fleshy with
High grade, flat lesion confined to the bladder necrosis and hemorrhages
mucosa Secondary tumors
Grossly appears as mucosal hyperemia, o More common than primary tumors
granularity or thickening o Direct extension from cervix, uterus,
May be multifocal ovaries, prostate or rectum
Uremia is the most common cause of death in patients
Tumor Staging with cervical carcinoma
Extent of tumor spread affects the prognosis
AJCC/UICC (American Joint Commission on TUMORS OF URETHRA
Cancer/Union Internationale Contre le Cancer) Urethral caruncle
o Inflammatory lesion, small painful red
PATHOLOGIC STAGING OF BLADDER CA nodule
o Highly vascularized fibroblastic tissue
with inflammation
Depth of Invasion AJCC/UICC
Papilloma (transitional or squamous depending
Non invasive, papillary Ta
Noninvasive, flat T1S Tis on the location)
Lamina propria T1 Carcinoma uncommon
Superficial muscularis T2 o Papillary growth transitional cell ca
propria o Squamous cell ca most common
Deep muscularis propria T3a o More aggressive and invasive
Perivesical fat T3b
Adjacent structures T4
Lymph node metastases N1-3
Distant metastases M1
*N1, regional LN <2 cm; N2, regional LN 2-5 cm; N3
regional LN >5 cm. or other LN

OTHER TUMORS
Squamous cell carcinoma
o 3-7%
o Chronic bladder irritation and infection -
Schistosomiasis
o Mixed with TCC is more common
o More invasive and ulcerative, rare
papillary forms
Adenocarcinoma - rare
Arise from urachal remnants
Small cell carcinoma and signet ring carcinomas
o Very rare, highly malignant (rule out
rectum, cervix, and uterus because they
are more common in that area than in the
urinary bladder)
Page 12 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 Review of Glomerular Diseases

Page 13 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 Page 14 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016

 Page 15 of 15
GELUZ | OLALIA | SUGAY
Property of AUF SOM Batch 2017
V 3.1 s 2015-2016