3 Urinary System
GROSSING TECHNIQUES
KIDNEY
Renal biopsy is useful in diagnosing primary renal
disease, assessing the nature and severity of renal
involvement in various systemic disorders and some-
times in establishing the diagnosis of certain systemic
diseases, e.g. amyloidosis.
The different types of specimens received are:
a. Needle biopsy
b. Nephrectomywhole or part of the kidney
depending upon the underlying pathology which
may be tumor or nontumor.
Needle Biopsy
1. In most cases, biopsy of the kidney for diagnostic
purposes is performed percutaneously under
local anesthesia under ultrasound guidance.
Fresh kidney specimens are sent for microscopic
analysis preferably in three containersfor light
microscopy (LM), immunofluorescence (IF) and
electron microscopy (EM).
2. Try to determine whether the cortex is visible.
The core can be examined in a fresh state on
a slide under 10x objective to identify glomeruli
which can be seen as rounded structures.
Alternatively a linear piece of the sample may
also be cut at both its ends and taken for EM to
ensure presence of cortex, when only a single core
is sent.
3. Description:
Number of fragments received
Color and size
Homogeneous or not
Bits
1. Entire bit is given for processing.
2. Ideally 6-7 sections, the first and second for
Haematoxylin and Eosin stain, 2 may be taken for
periodic acid Schiff stain, 2 for periodic acid silver
methenamine (PASM) or Jones silver stain and one
for Massons trichrome stain.
3. Additional stains if required would be Congo red
for amyloidosis, if indicated.
Nephrectomy
}
1. Partial
2. Subcapsular for nontumoral conditions
3. Simple
Partial Nephrectomy
A part of the kidney is removed in case of calculi in a
chronically infected calyx, bleeding from an arteriov-
enous malformation, severe trauma to either upper or
lower pole of the kidney, etc.
Simple Nephrectomy
It is removal of kidney with its capsule, done in chronic
(end stage) pyelonephritis and other nonfunctional
states of the kidney.
Radical nephrectomy (for tumoral conditions)
This includes resection of the kidney, ipsilateral ad-
renal gland, perinephric tissue within the confines
of the Gerotas fascia and the regional lymph nodes
(these include para-aortic on the left and para-caval
on the right).
Nephroureterectomy (for tumoral conditions)
For transitional cell carcinoma in the upper ureter.
Nontumoral Conditions
1. Examine the entire specimen and observe the
positions of the renal artery, renal vein and ureteric
stump.
 80 FUNDAMENTALS OF SURGICAL PATHOLOGY

2. Identify the side of the kidney with the help of the

position of blood vessels and ureter at the hilum-
anterior to posterior are renal artery, ureter and
vein.
3. Overnight fixation after injecting formalin through
the ureter is ideal but not a must.
4. Weigh the organ, if fat is adherent then weigh with
the fat.
5. Measurements: Kidney from pole to pole; length of
ureter; length of renal vessels; pelvisextrarenal
or intrarenal.
6. Make a section through the kidney, calyces, pelvis
and ureter (from outer to inner)
7. Take one bit for processing from the cortex
including the capsule, then strip the capsule.
8. Description:
a. Capsulethickness of the capsule, adherence,
scars: Number, size, shape, location.
b. Cortex and medulla width of cortex (normally
8 mm to 1.2 cm), color-cysts: size, location and
content. Fig. 3.1
c. Pelvissize and shape, dilatation, hemorrhage
and calculi. Tumoral Conditions
d. Ureterlength, diameter, dilatation, strictures 1. Cut the kidney, calyces, pelvis and ureter from
if any particularly at the pelviureteric junction. outer to inner aspect. Open the ureter.
e. Renal artery and veinthrombi, stenosis, etc. 2. Identify the renal vessels.
3. Description:
Bits (Fig. 3.1) a. Weight and dimensions as per nontumoral
A and B Two bits cortex, medulla and pyramid with conditions
capsule (to be taken at the upper and lower b. Tumor characteristicslocation, size, shape,
poles as changes of reflux nephropathy are extent, invasion of capsule (intact or not),
most obvious here) involvement of perirenal tissue, calyces, pelvis,
C One bit perinephric fat if adherent renal vein
D Two bits pelvis c. Uninvolved portioncortex and medulla
E One bit ureter d. Pelvisdilated, involved, other features like
F and G Two bits, tips of pyramids (in diabetes for stones, etc.
evidenc of papillary necrosis) e. Perirenal lymph nodesnumber, size and cut
H Renal vessels: cross-section of renal vessels surface
with contents should be taken in allograft f. Adrenal glandinvolved or not.
kidney (transplanted kidney) to ascertain
any fungal infection as a cause of rejection Bits (Fig. 3.2)
(mucormycosis is known to lodge in vas- A,B and C Three bits tumor, one of them with ad-
cular channels in immunocompromised jacent kidney and one preferably from
cases). the periphery. In pediatric cases (Wilms
tumor) one bit from each centimeter of

Fig. 3.2
tumor in its greatest dimension should
be taken.
D and E Two bits uninvolved kidney (preferably
from upper and lower poles)
F One bit pelvis
G Renal artery and vein: surgical margins
H Surgical margin of ureter
J Perihilar lymph nodesone or more
blocks depending on the number of
lymph nodes.
K Perinephric fat.
L If capsule is adherent one bit from that.
One or two bits from adrenal gland if
present
Extra bits from regional lymph nodes if
sent.
URETER
The ureter could be resected for:
Congenital anomalies like megaureter, stricture,
diverticulae.
Traumatic conditions neoplasia
i. with tumor
ii. as surgical margin
Along with pelvis: As pelviureteric junction specimen
(PUJ)
URINARY SYSTEM 81
Long segment of ureter: Measure the length and
open it longitudinally. Examine for strictures, mucosal
irregularities, tumors, etc.
Bits
Two bits are sufficient in the absence of any gross ab-
normality. In case of stricture, 2-3 bits longitudinal to
include the stricture. In case of tumor bit generously
to include surgical margins in separate blocks.
Pelviuretic Junction (PUJ)
Measure the length and open longitudinally. Examine
for strictures, tumors and thickening of the wall.
Bits
Give longtitudinal sections at representative areas.
Transverse sections to be taken only if the probe can-
not be passed through the junction.
URINARY BLADDER
The types of specimens received are: Cystoscopic bi-
opsies and Cystectomies.
Cystoscopic Biopsies
Punch biopsies with mucosa for cystitis.
Measure along three dimensions and block all tis-
sues; mucosa should be on one aspect.
Transurethral resection specimens for grade I carci-
noma.
Weigh if bits are small. For large bits give measure-
ments in addition to weight.
Bits
On a routine, if the specimen is < 10 g, block all to a
maximum of 5 blocks. Apart from this for every 10 g,
one additional block. If muscle is identified then it is
to be blocked separately.
Cystectomy
Fixation
a. Either open with a scissors in a Y-shaped manner
or through the junction of the antero-posterior wall
and fix it flat on a corkboard either overnight or
for a minimum period of 5 hours.
b. Alternatively, fill it with formalin through the
urethra. Fix overnight, open it at the junction of the
antero-posterior wall as shown in the Figure 3.3.
 82 FUNDAMENTALS OF SURGICAL PATHOLOGY
Fig. 3.3: Foleys catheter
Description
a. Size of the bladderthree dimensions (antero-
posterior, superoinferior and right to left)
b. Length of the ureter and urethra (if measureable)
c. Tumor characteristicssize, location, extent of
invasion, shape and appearance of the neoplastic
mucosa.
d. Appearance of the non-neoplastic mucosa
e. Thickness of the bladder wall at the tumor and
away from the tumor.
f. Seminal vesicles to examined, measured and
sectioned.
g. Section through the prostate if present. Record
involvement of these organs grossly.
Bits (Fig 3.4)
A, B and C tumor three bitsto include the full
thickness of the wall.
D and E Trigonetwo bitsto include uretero-
vesicle junctions
Fig. 3.4
F One bit anterior wall
G One bit posterior wall
H One bit dome
J One bit any other abnormal area
K and L Ureter-surgical margins separate blocks
M One bit urethral surgical margin
N Regional lymph nodes; more bits if neces-
sary.
Additional bits in males to include seminal vesicles
and prostate.
GROSS PEARLS
Kidney
Capsule adherent: Chronic pyelonephritis, surface
of infarcts.
Flea bitten kidney: Petechial hemorrhages on the
surfacesubacute bacterial endocarditis (rare these
days), malignant hypertension, some cases of acute
poststreptoccocal glomerulonephritis, crescentic
glomerulonephritis. Can be seen in any condition that
causes marked hematuria.
V-shaped scars: Vascular scarsin infarcts and
hypertensive renal disease
U-shaped scars: Broad based depressed scars
predominantly at the upper and lower poles in re-
flux nephropathy, may be seen elsewhere in chronic
pyelonephritis due to causes other than reflux.
Large kidney, edematous: Acute pyelonephritis
Large kidney, yellowish: Fatty change C/S bulges,
greasy to touch
Small contracted kidney: Seen characteristically in
three conditions:
i. Benign nephrosclerosis: Bilateral contraction, largest
of the small contracted kidney (weighs 110-130 g);
symmetric contraction; fine granular surface, may
have V-shaped scars.
ii. Chronic glomerulonephritis: Bilateral symmetric
contraction, (weighs 90-100 g) with a coarse
granular surface.
iii. Chronic pyelonephritis: Smallest of the small
contracted kidneys (80-90 g) generally unilateral,
asymmetric contraction with irregular scarring.
Cut surface: Cortex pale and well-demarcated from
medulla: Cortical necrosis
 URINARY SYSTEM 83

Cysts Autosomal recessive childhood polycystic kidney

i. Bilateral large cysts and bosselated surface: Adult disease (Potter type I cystic disease) (Figs 3.6A
polycystic kidney disease (each kidney can weigh and B).
2 to 4 kg) (Potters type III cystic disease) (Figs 3.5A
and B).

Enlarged kidneySurface view: smooth

Fig. 3.6A
Surface view: Bosselated and cystic
Fig. 3.5A

Cut surface: Radiating cylindrical cysts,

Cut surface: Cysts of varying sizes a few round cysts in the medulla
Fig. 3.5B Fig. 3.6B

ii. Bilateral Large kidneys with smooth external iii. Occasional cysts in cortex: Simple cysts
surface; C/S shows cylindric cysts arranged per- iv. Cysts in the medulla: Medullary sponge kidney
pendicular to the surface (radiating cylinders). (Fig. 3.7)
 84 FUNDAMENTALS OF SURGICAL PATHOLOGY

Two gross examples are given below diagram-

matically (for more detail see section on assembled
pearls):
a. Multicystic renal dysplasia: Usually unilateral,
enlarged kidneys with cysts of varying sizes, not
associated with other congenital abnormalities.
(Potter type II cystic disease) (Fig. 3.9)

Cysts confined to medullary papillary tips

Fig. 3.7

v. Normal sized or small contracted kidneys with

cysts measuring 1-15 mm in the corticomedullary
junction: Nephronophthisis-medullary cystic
disease complex (Fig. 3.8).
Surface view Cut surface
Fig. 3.9
b. Diffuse cystic dysplasia: Bilateral symmetric
involvement, maintains reniform shape and
associated with other abnormalities (Fig. 3.10).

Variably sized cysts in the corticomedullary junction

Fig. 3.8
vi. Reniform mass of cysts of varying sizes obscures
renal parenchyma, unilateral or bilateralNormal
sized, contracted or sometimes enlarged: Renal Surface view Cut surface
cystic dysplasia. Fig. 3.10

Dilated kidney, unilateral with dilated pelvis and
calyces: Advanced hydonephrosis
Cyst with thick laminated membrane: Hydatid cyst
Cyst with thick walls, variegated cut surface and
necrosis: Cystic change in tumor (RCC)
Tumors
Small cortical nodule upto 5 mm in size: Papillary
adenoma
Tumor at one pole, C/S variegated-solid, cystic,
yellowish and hemorrhagic areas: Renal cell carcinoma
(RCC).
Tumor located either pole or center, C/S homoge-
neous, pale pink, soft or cystic: Wilms tumor
Medullary location of tumor: Medullary carcinoma;
collecting duct carcinoma.
Mahogany brown/tan, localized tumor with cen-
tral scarOncocytoma (in contrast with bright yellow
color of RCC.
(Two other lesions with central scars are: Complex
scars breast; focal nodular hyperplasia liver)
Lipoma like tumorPossibility of angiomyolipoma
URINARY BLADDER
1. Red hyperemic mucosa: Acute cystitis, erosive
cystitis.
2. Single papillary lesion, pedunculated, or multiple
papillae seen as a cluster: Papilloma/well-
differentiated papillary carcinoma/papillary or
polypoid cystitis.
3. Solitary polypoid lesion smooth or lobulated:
Inverted papilloma/transitional cell carcinoma/
von Brunns cell nests/malakoplakia (in the latter
the lesions are yellowish with central umbilication)
4. Confluent papillary tissue with cauliflower
like appearance, may have multiple lesions in
surrounding mucosa: Papillary transitional cell
carcinoma.
5. Bulky polypoid tumors, nodular appearance
with full thickness involvement of the wall:
Poorly differentiated carcinoma, e.g. sarcomatoid
carcinoma/adenocarcinoma/squamous cell
carcinomas/poorly differentiated transitional cell
carcinoma.
6. A cluster of edematous smooth surfaced polypoid
fronds protrude into the bladder lumen: Sarcoma
URINARY SYSTEM 85
botryoides/hamartoma (in particular in bladders
of children).
7. Black nodular mass: Malignant melanoma
8. Cystic neoplasm dark blue in color: Hemangioma
9. Black and hemorrhagic mucosa: Hemorrhagic
cystitis due to administration of chemotheurapeutic
drugs like cyclophosphamide.
MICROSCOPY PEARLS: AIDS IN DIAGNOSIS
Renal Biopsy
Indications for performing a renal biopsy are not
universally agreed upon and opinions vary widely
among different nephrologists. However, broad and
well-accepted indications can be classed as:
Idiopathic nephrotic syndrome in the adult prior
to glucocorticoid therapy.
Non-nephrotic range proteinuria (1-2 g/day) of
unknown cause accompanied by an abnormal
urinary sediment
Proteinuria with glomerular hematuria (exclude
urinary tract infections and neoplasms)
Acute renal failure of unknown cause (when
obstruction has been ruled out)
Suspected cases of rapidly progressive glomeru-
lonephritis (RPGN) or the acute nephritic syndrome
Hematuria (> 6 RBCs/hpf), proteinuria (other
than suspected cases of active lupus nephritis,
characterized by 200 mg/day) and elevated serum
creatinine.
Suspected cases of renal vasculitis, particularly
polyarteritis nodosa and Wegeners granulomatosis
(which often require aggressive combination
therapy)
Evaluation of renal allograft patient with possible
graft rejection, acute tubular necrosis (ATN),
drug induced interstitial nephritis, infarction or
recurrence of original disease in the graft.
Possible Useful Indications
Persistant glomerular hematuria without prote-
inuria
Proteinuria of more than 1 g/day with normal
urinary sediment
Evaluation of suspected inherited glomerular
disease such as Alports or Fabrys disease
 86 FUNDAMENTALS OF SURGICAL PATHOLOGY
Evaluation of the known diabetic with rapid
unexpected deterioration of renal function, sudden
development of nephritic syndrome or early
development of azotemia in the absence of diabetic
retinopathy.
Renal Biopsy is not Useful in Evaluating
Malignant hypertension
Polycystic disease of the kidney
Hepatorenal syndrome
Pyelonephritis
Chronic renal failure with shrunken kidneys
Routine cases of diabetic nephropathy
Clinically silent lupus nephritis (controversial).
Contraindications: Absolute
Uncorrectable and clinically severe bleeding
diathesis
Patient refusal.
Relative Contraindications
Severe thrombocytopenia, <50,000/mm3 (usually
correctable by platelet infusion)
Solitary kidney (except with renal allograft)
Renal artery aneurysm
Active pyelonephritis or perinephric abscess
Hydronephrosis
Uncontrolled severe hypertension
High-risk Situations/Not Contraindications
Moderate thrombocytopenia (100,000 50,000/
mm3)
Moderate hypertension
BUN > 100 mg/dl
TechniquesLight microscopy: Thin sections
with Hematoxylin and Eosin and special stains (PAS,
Jones Methenamine silver stain and Massons tri-
chrome)
Immunofluorescence microscopy: Antibodies
tagged with a fluorchrome dye used to localize im-
munoreactants in the glomerulus. A standard panel
includes IgG. Ig A, IgM, C3, C1q, fibrinogen kappa
lambda light chains.
Electron microscopy: Ultrastructural studies of
the glomerulus to show features such as position of
immunocomplexes, basement membrance reaction
and epithelial cell changes.
Salient Anatomical Features
Normal Glomerulus
1. Anastomosing network of capillaries invested by
two layers of epithelium. The parietal epithelium
lines the Bowmans space and the visceral epithelium
forms an integral part of the capillary wall.
2. The glomerular capillary wall is the filtering
membrane and consists of:
a. A thin layer of fenestrated endothelial cells with
fenestrations measuring 75-100 nm in diameter.
b. The glomerular basement membrane (GBM).
A central thick electron dense with thinner
electronlucent peripheral layers, the lamina
rara interna and the lamina rara externa. It is
composed mainly of type IV collagen. The GBM
is 250-350 nm thick in adults, increased from
approximately 150 nm from birth.
c. Visceral epithelial cells or podocytes which
possess interdigitating processes embedded
in and adherent to the lamina rara externa of
the GBM. The foot processes are separated by
20-30 nm wide filtration slits.
3. Mesangial cells: Support the glomerular tuft and lie
between the capillaries. They are mesenchymal in
origin and possess myofibroblast-like contractile
properties. They also have phagocytic and
proliferative capabilities in laying down matrix
and collagen and secreting biologically active
mediators of inflammation. The basement
membrane like mesangial matrix forms a network
through which mesangial cells are scattered.
4. Juxtaglomerular apparatus: Located at the
vascular pole of the glomerulus. Composed of:
(1) Specialized cells of the distal convoluted
tubule called macula densa with reversed polarity;
(2) terminal portion of the afferent arteriole and
initial portion of the efferent arteriole (3) lacis cells
or Goormaghtigh cellsmodified smooth muscle
cells which are continuous with the mesangial cells
of the glomerulus.
Vasculature: Main renal artery segmental arteries
(5-6 in number) interlobar arteries (between lobes)
arcuate arteries (run along the base of pyramids)

interlobular arteries (run in a direction perpendicular
to the base of the pyramids and have a less well-
developed external elastic lamina as compared to the
previous; have 3-5 layers of smooth muscles in the
tunica media and give rise to afferent arterioles
glomerular tuft efferent arteriole cortical
peritubular capillaries and in medulla multiple vasa
recta which form a plexus around the tubules form
vascular bundles which supply blood to the medullary
region blood from these capillaries drains into
the interlobular/arcuate/interlobar veins which run
parallel to the arteries and merge to leave the kidney
as the renal vein.
Terms used in the Evaluation of Glomerular Diseases
1. Diffuse > 50% glomeruli affected
2. Focal < 50% of glomeruli affected
3. Global > 50% of glomerular lobules to entire
glomerulus is involved
4. Segmental < 50% of segments (glomerular lobules)
involved
5. Peripheral mesangial area: Mesangium at the
periphery of the glomerulus with 2-3 mesangial
nuclei.
6. Mesangial hypercellularity: Three and more
than 3 mono-nuclear cells or nuclei in atleast one
mesangial area in a section 3 in thickness.
7. Crescentic glomerulonephritis > 50% of glomeruli
show crescents.
8. Extracapillary proliferation or cellular crescent:
Extracapillary cell proliferation of two or more
than 2 cell layers of parietal/visceral epithelial cells
occupying one fourth or more of the glomerular
capsular circumference.
9. Endocapillary proliferation: Proliferative glomeru-
lonephritis with a complex mixture of different
cell types including mesangial cells, endothelial
cells and infiltrating leukocytes-neutrophils,
monocytes, macrophages and lymphocytes.
Clinical Patterns of Glomerular Diseases
Nephrotic Syndrome
1. Characterized by heavy proteinuria (> 3.5 g/
24 hours), consequent hypoalbuminemia (serum
albumin <3.5 g/dl, generalized edema, hyper-
lipidemia and hyperlipiduria.
URINARY SYSTEM 87
2. Protein reabsorption droplets in the proximal
tubular epithelial cells.
3. Lipid within tubular epithelial cells and peritubular
macrophages appears in urine as free fat or oval
fat bodies.
4. The structural/charge barrier of the GBM is lost.
Effacement of epithelial cell foot processes and
swelling of podocytes.
5. Patients may develop renal vein thrombosis due to
loss of coagulation factors (proteinuria). Patients
are vulnerable to infections with staphylococci and
pneumococci.
6. Nephrotic syndrome in children: Protein excretion
of more than 40 mg/m2/hour body surface area in
an overnight collection of urine (as compared to
adults of > 3.5 g/1.73 m2/day body surface area.
Nephritic syndrome
1. Characterized by hematuria, variable proteinuria
(non-nephrotic), diminished GFR, with some
degree of oliguria, azotemia ( BUN and creat-
inine) and hypertension.
2. Caused by diseases that evoke an inflammatory
proliferative response within the glomeruli.
3. Proliferation may involve endothelial, mesangial
or epithelial cells. Exudation of neutrophils may
be present.
Uremia refers to clinical manifestations of azotemia.
Classification of Glomerular Diseases
Primary Glomerular Diseases
Disease process is confined to the kidney and does not
involve other organs.
Those which cause nephritic syndrome: Postinfectious
glomerulonephritis, Rapidly proliferative glomeru-
lonephritis (RPGN), IgA nephropathy/Henoch-
Schnlein purpura, membranoproliferative glomerulo-
nephritis (20% of cases).
Those which cause nephrotic syndrome: Minimal
change disease, Focal segmental glomerulosclerosis,
membranous glomerulonephritis, membranoprolifera-
tive glomerulonephritis (50% of cases).
Secondary Diseases
Renal involvement is part of a systemic disease.
Those which cause nephritic syndrome: Systemic lupus
erythematosus, vasculitis.
 88 FUNDAMENTALS OF SURGICAL PATHOLOGY
Those which cause nephrotic syndrome: Diabetes mel-
litus, amyloidosis.
Acute Postinfectious Glomerulonephritis
Occurs in association with a wide variety of microbial
agents but the classic form is the poststreptococcal
glomerulonephritis.
Clinical Features
1. Age group: 6-10 years of age
2. Occurs after an infection by streptococci
[group A haemolytic streptococci (in > 90% of
cases)subtypes 12, 4, 1 are nephritogenic]
3. Typically develops in a child 1-4 weeks following
group A streptococcal infection. In northern
latitudes respiratory infections predominate, while
in the Southern regions skin infections are the more
common route of infection.
4. Patients present with abrupt onset of hematuria,
proteinuria, edema, hypertension and renal
insuffiency. Serum complement levels are low and
serum anti-streptolysin O titres are elevated. In
the acute phase > 90% of patients have serum
C3 levels and total hemolytic complement CH
(50) and less than 10% have reduced C4 levels.
C3 typically returns to normal within 2 months
(differentiating feature from MPGN where it is
persistently low).
5. Other infections include staphylococcal (2nd most
common cause), gram-negative bacteria and even
viruses, etc.
Pathogenesis
1. Antibody mediated, circulating or planted antigen
(in situ formation of immunocomplexes) or in situ
localization of cationic bacterial molecules that
directly injure glomeruli or activate complement
in the absence of immunoglobulins. A variety of
streptococcal antigens may be seen in the affected
glomerulusendostreptocin, streptokinase and
streptococcal erythrogenic toxin type B (ETB).
GBM products may be altered by streptococcal
enzymes and present as antigens.
Pathology
1. Light Microscopy: Diffuse global hypercellularity of
glomeruli with partial obliteration of the capillary
lumina due to proliferation of endocapillary cells;
and infiltration by neutrophils (exudative change).
Mild interstitial edema and mild periglomerular
interstitial infiltrate by mononuclear cells. Crescent
formation is seen in only the most severe cases.
With a well done Massons trichrome stain
large subepithelial deposits are identified as
fuschinophilic red granules on the outer aspect of
the capillaries.
Resolving phase: Only mesangial hypercellularity
is seen.
2. Immunofluorescence: Coarsely granular, peripheral
capillary wall and/or mesangial deposits of IgG,
C3, IgM
3. Electron Microscopy: Immunocomplexes may be
formed at all sites, but typically there are large
humps in the subepithelial location.
Prognosis
1. Two factors are importantage of the patient and
whether the disease is sporadic or epidemic.
2. Complete recovery occurs in most children with
epidemic cases.
3. Very few children (2-3%) develop RPGN/chronic
renal disease.
4. In adults 15-50% of cases progress to irreversible
renal damage.
Rapidly Progressive Glomerulonephritis
(Crescentic glomerulonephritis)
Crescentic glomerulonephritis is a morphologic
manifestation of severe glomerular injury that can be
caused by many different etiologies and pathogenic
mechanisms. The percentage of glomeruli that should
have crescents to warrant a diagnosis of crescentic
glomerulonephritis as per the WHO is 50% or more.
Lesser degree of crescent formation however should
be indicated in the diagnosis as the percentage of
glomeruli showing crescents.
Clinical
1. Characterized by rapid and progressive loss of
renal function, associated with severe oliguria and
death from renal failure within weeks to months.
2. Proteinuria, hematuria, azotemia and anemia are
constant findings. Nephrotic syndrome is rare.
3. Three subcategories exist:

a. Idiopathic RPGN (anti-GBM antibody glomeru-
lonephritis)Type I
b. Immunocomplex RPGNPostinfectious (post-
streptococcal) RPGN or other immunocomplex
disease (SLE)Type II
c. Pauci-immune RPGN, e.g. vasculitis associated
RPGNType III
Pauci-immune crescentic glomerulonephritis is the
most common category where > 50% of glomeruli are
involved by crescents. More than 80% of patients with
pauci-immune crescentic glomerulonephritis have cir-
culating anti-neutrophil cytoplasmic antibodies (ANCA).
ANCA crescentic glomerulonephritis is the most com-
mon category of crescentic glomerulonephritis in the
older patients whereas immunocomplex glomerulone-
phritis with crescents is more common in younger pa-
tients (IgA nephropathy, Henoch Schnlein purpura,
lupus nephritis, post-streptococcal glomerulonephritis
and membranoproliferative glomerulonephritis).
Anti-GBM disease is a special form of immuno-
complex disease caused by in situ binding of anti-GBM
antibodies to GBM antigens and the frequency of this
type of crescentic glomerulonephritis is less as com-
pared to the other two categories.
In general anti-GBM glomerulonephritis and
ANCA glomerulonephritis have a higher frequency
and severity of crescent formation than immunocom-
plex glomerulonephritis.
Type I: Anti-GBM Glomerulonephritis: Is due to
vascular injury mediated by anti-GBM antibodies.
1. Bimodal age distribution: Young men 18-35 years and
older men and women 50- 60 years. May follow
exposure to drugs, viral infections, etc.
2. Most common clinical presentation is good
pastures syndrome, a combination of glomerulo-
nephritis and pulmonary hemorrhage of varying
severity due to antibodies to glomerular and
alveolar basement membranes. Most patients have
severe renal failure at the time of presentation.
Hemoptysis usually precedes clinical evidence of
renal disease by several months.
3. Many patients appear to benefit from plasma-
pheresis usually combined with immuno-suppres-
sive drugs to suppress underlying immune response.
Type II: Immunocomplex RPGN: May be idi-
opathic or post infectious in nature, SLE associated,
URINARY SYSTEM 89
or even due to Henoch Schnlein prupura. Treatment
is aimed at the etiologic cause.
Type III: Pauci-immune RPGN: Characterized by
crescent formation and paucity/absence of glomerular
immunoglobulins.
1. May beidiopathic
a. ANCA associated due to Wegeners granulo-
matosis
b. Due to microscopic polyarteritis nodosa/
microscopic polyangiitis
c. or Churg-Strauss syndrome .
2. Most cases are a manifestation of small vessel
vasculitis.
3. > 90% of cases are ANCA +ve either perinuclear
(p ANCA) or Cytoplasmic (c ANCA).
Pathogenesis
Formation of crescent: The presence of fibrin in the
Bowmans space due to a breach in the capillary wall
stimulates formation of crescents. A breach of the
capillary integrity allows plasma proteins including
coagulation proteins to enter Bowmans space. Due
to inflammation the coagulation proteins contact pro-
coagulant or thrombogenic surfaces and molecules
such as those generated by tissue necrosis and activat-
ed cells (epithelial cells, monocytes and macrophages).
These activated molecular and cellular mediator sys-
tems generate factors (thrombin generated by coagula-
tion, growth factor cytokines released by monocytes
and platelets, cytokines such as epidermal growth
factor, interleukin -1, etc.). The procoagulant fac-
tors result in fibrin polymerization in the Bowmans
space and participates in crescent formation. The cell
types participating in crescent formation are epithe-
lial cells, monocytes and macrophages. Immunologic
studies have confirmed in the humans the epithelial
phenotype of most cells in many mature cellular cres-
cents with a few cells being macrophages and other
leukocytes. Crescents in patients with anti-GBM and
ANCA glomerulonephritis have a higher proportion
of macrophages than crescents in patients with im-
munocomplex glomerulonephritis which usually has
little or no disruption of Bowmans capsule. Electron
microscopy has demonstrated that crescentic glomeru-
lonephritis has holes in the GBMs. These allow mo-
lecular and cellular inflammatory mediators to enter
 90 FUNDAMENTALS OF SURGICAL PATHOLOGY
Bowmans space resulting in stimulation of epithelial
proliferation.
Pathology
Light Microscopy:
1. Glomerular fibrinoid necrosis and crescent
formation are the histologic hallmarksthese
lesions range from focal and segmental to diffuse
and global.
2. Orderly crescents with chiefly epithelial proli-
feration to very disorderly crescents containing
mainly macrophages, monocytes and occasionally
multinucleated giant cells. Periglomerular inflam-
mation may be seen with a granulomatous response.
Anti-GBM crescentic glomerulonephritis and
ANCA crescentic glomerulonephritis often have
necrotizing glomerular lesions, with disorderly
crescents, disruption of Bowmans capsule and
periglomerular inflammation which differs from
the more orderly crescents and intact Bowmans
capsule usually observed in immunocomplex
crescentic glomerulonephritis. GBM thickening
may be seen in type II.
3. Foci of glomerular fibrinoid necrosis contain
scattered karyorrhectic debris.
4. Tubules show mild tubular atrophy
5. Variable degree of interstitial inflammation and
fibrosis which parallel the severity and activity of
the glomerular disease.
6. Hilar arterioles show fibrinoid necrosis.
Immunofluorescence: Generalized and diffuse depos-
its of IgG and C3 along the glomerular basement mem-
branes (Type I shows linear deposits, Type II shows
granular deposits and Type III shows no deposits).
Electron Microscopy: Lucent expansion of suben-
dothelial zone (Type I), frequently no deposits (Type
III). Capillary walls often show breaks particularly in
the region of crescents.
IgA Nephropathy/ Henoch-Schnlein Purpura
IgA is the most common form of primary glomeru-
lonephritis in the world.
Clinical
1. Patients usually present with recurrent gross or
microscopic hematuria with or without proteinuria.
2. More common in young adults, mostly males.
3. Onset follows an upper respiratory, urinary or GI
tract infection.
4. Most cases are idiopathic. However, may be a
component of Henoch-Schnlein purpura or
associated with a variety of extrarenal diseases
liver disease, ankylosing spondylitis, psoriasis,
Reiters disease, celiac disease, Inflammatory
bowel disease, dermatitis herpetiformis, etc.
5. Serum IgA levels are increased in about 50% of
cases, while serum complement component levels
remain normal.
Henoch-Schnlein Purpura (HSP)
This is a small vessel ie capillaries, venules and arte-
rioles vasculitis with vessel wall IgA dominant im-
munocomplex deposits.
1. Clinical syndrome consists of characteristic skin
rash, abdominal manifestation, non-migratory
arthalgia and renal abnormalities. Not all com-
ponents of the syndrome need be present, any one
component may be the dominant feature.
2. Renal manifestations include gross or microscopic
hematuria and proteinuria. Patients may present
with nephrotic syndrome. A few patients mostly
adults develop RPGN.
3. Presence of systemic manifestations distinguishes
this entity from IgA nephropathy.
4. Most common in children 3-8 years old but also
occurs in adults.
5. Onset often follows an upper respiratory tract
infection.
Pathology (Similar for IgA and Henoch-Schnlein Purpura)
1. Picture varies from normal at LM to focal or
diffuse mesangioproliferative glomerulonephritis
(widening of the mesangial area, often associated
with variable degree of mesangial cell proliferation,
frequently focal); focal/diffuse endocapillary
proliferative glomerulonephritis; crescentic glome-
rulonephritis; Type I MPGN (rare); focal /diffuse
sclerosing glomerulonephritis. Focal proliferative
GN is most frequent.
2. Immunofluorescence: Predominantly mesangial
deposits of IgA and C3. IgG and/or IgM may be
present in similar distribution but with less intensity.

3. Electron Microscopy: Electron dense deposits in
the mesangium, subepithelial and subendothelial
deposits can occur.
Prognosis
1. In general IgA nephropathy tends to progress
slowly. About 50 % develop end stage renal failure
in 25 years from the time of diagnosis.
2. Most children with HSP recover completely but
in some children and in adults progressive renal
failure develops.
3. IgA nephropathy recurs in 50% of allografts.
Membranoproliferative Glomerulonephritis
(Mesangiocapillary Glomerulonephritis)
A form of glomerulonephritis characterized by base-
ment membrane thickening and proliferation of en-
dothelial and mesangial cells.
Clinical Features
1. Majority of the patients are between the ages of
5-30.
2. The usual presentation is the nephrotic syndrome
(50%); MPGN begins more insidiously as asympto-
matic proteinuria (30%), or as acute nephritis
(20%).
a. Usually, there is hypocomplementemia, caused
in part by excessive consumption of C3.
b. Three types are recognized Type I, Type II and
Type III and their differences outlined in the
table below: Type I is commonest, the other 2
Types are rare; Type 3 is however more common
than Type 2.
Systemic Lupus Erythematosus (SLE)
Systemic lupus erythematosus is a chronic inflam-
matory autoimmune disease affecting multiple organ
system with involvement of the skin, joints, heart,
lung, kidneys, central nervous system and serous
membranes.
Clinical
Renal involvement poses a great threat to the prog-
nosis of the disease. Lupus nephritis as it is called
can manifest with protean clinical and morphological
appearances. Clinically, renal involvement can occur
URINARY SYSTEM 91
at any time during the course of the disease starting
from early onset of clinical disease to years after its
diagnosis. Clinical features range from asymptomatic
hematuria and proteinuria to full blown nephrotic
syndrome or even rapidly progressive renal failure.
Renal biopsy plays an important role in the manage-
ment of patients with SLE. In some a diagnosis of SLE is
made on the renal biopsy alone even before the clinical
picture unfolds itself. This is particularly seen in cases
of morphological variants like mesangial proliferative
and membranoproliferative patterns of glomerular
disease. Renal biopsy provides information about the
class, severity, activity and chronicity of renal disease
that cannot be predicted on the basis of clinical disease.
Pathogenesis
The etiology and pathogenesis of SLE is incompletely
understood. Autoantibodies may lead to cell and tissue
injury by Fc-receptor mediated inflammations as well
as by direct cytotoxicity which is complement depend-
ent. In the kidney intrinsic antigens such as extracel-
lular matrix components or cell surface glycoproteins
may serve as targets for autoantibody binding. In
addition, renal injury may occur from autoantibodies
that bind to circulating antigens, forming circulating
preformed immunocomplexes; or autoantibodies
that bind to antigens deposited from the circulation
in glomerular and vessel walls, causing in situ immu-
nocomplex formation as has been shown for nucleo-
somes and antidouble stranded DNA autoantibodies.
Subsequent Fc-receptor and complement binding then
initiates an inflammatory and cytotoxic reaction. Such
cytotoxicity may be directed towards podocytes in
the setting of membrane nephropathy where in situ
immunocomplex formation occurs along the subepi-
thelial aspect of the glomerular basement membrane;
or towards endocapillary cells in the case of endo-
capillary proliferative; and exudative inflammatory
reaction that follows subendothelial immunocomplex
formation. In addition to this direct immunocom-
plex mediated cell and tissue injury, autoantibodies
with antiphospholipids or cryoglobulin activity may
also promote thrombotic and inflammatory vascular
lesions in SLE. Antineutrophili cytoplasmic antigen
antibodies (ANCA) have been described in a subgroup
of patients with lupus nephritis and may initiate
 92 FUNDAMENTALS OF SURGICAL PATHOLOGY

Heading MPGN Type I (classic type) MPGN Type II MPGN Type III (Burkholders type*
(Dense deposit disease) and Strife and Anders type)
Age 6 years and above Children and young adults Same as type I
Clinical features Nephrotic (common), nephritic, asymp- Nephritic, gross hematuria, proteinu- Onset insidious, remains subclinical
tomatic proteinuria ria including nephrotic range for a while, proteinuria (nephrotic)
Serum components C3 80 % of cases or normal;C1q, C3 persistently low 100% of C3 in 50% of cases; C5, properdin,
C4, C2, factor B, properdin ; C3NeF cases,C1q, C4 normal (classic C1q, C4 normal,C3NeF often absent
present in < 50% cases pathway); Factor B, properdin,
C3NeF often present
Light microscopy Glomerular hypercellularity;Lobular Variable histology; Glomerular Similar to type I with varying degrees
accentuation; mesangial matrix; hypercellularity not pronounced; of hypercellulrity; more diffuse cap
Mesangial expansion may be nodular. ribbon-like thickening of GBM PAS wall thickening; Double contours
Double contours of GBM seen as tram +ve but JMS ve; double contours and in addition spikes on silver stain
track due to mesangial interposition of GBM less well developed. Lobular
accentuation+/ Varying degrees of
in mesan matrix
Immunofluorescence Prominent granular C3 peripheral C3 ++ intense in irregular foci in GBM C3 + fine granular
deposits. IgG, C1q, C4 often present; and as rail road;C3 ++ as mesangial Along GBM amd in mesangium;
Properdin + rings; IgG, C1q, C4 absent p roperdin similar to C3
Electron Microscopy Mesangial interposition within GBM; Ribbon like zone of electron dense Subendothelial and subepithelial
predominantly subendothelial, material located centrally within the deposits connected through lamina
mesangial and some subepithelial thickened basement membrane densa (Strife and Anders); washed
deposits out deposits.Subendothelial and
subepithelial in Burkholders type*
Prognosis Poor: Chronic and slowly progressive, Worse than in Type I; more Similar to Type I
end stage in due course aggressive course
Associated diseases Partial lipodystrophy
Primary diseases in Hepatitis C, B, liver disorders, SLE, Malignant melanoma Sjgrens syndrome, cirrhosis, HIV
secondary MPGN sickle cell disease, Cryoglobulinemia infection
schistosomiasis,malignancies

vasculitis and glomerulonephritis by pauci-immune
neutrophil dependent mechanisms similar to those
described for microscopic polyangiitis or Wegeners
granulomatosis.
Pathology
The pathologic manifestations of lupus nephritis are
diverse and the morphologic spectrum was classified
according to the WHO classification in 1974. In 1982
this original WHO classification was expanded and
refined by the International Study of Kidney Disease
in Children. These two classifications are based pre-
dominantly on light microscopic appearances with
some correlation with immunofluorescence and elec-
tron microscopy. The concept of active and chronic
renal lesions was first introduced by Pirani Pollack
and Schwartz (1964) and subsequently refined by
Morel-Maroger et al in 1976. Austin et al in 1984 de-
vised a system of applying semiquantitative scores
for activity and chronicity by grading and adding
the individual morphologic components in a given
biopsy and this proved to be of use in treatment and
prognosis.. Activity and chronicity scores were then
used as an adjunct to the WHO classification of lupus
nephritis. In 1995, attention was again drawn to the
significance of glomerular capillary wall necrosis seen
in class III lesions.
Currently the widely accepted Classification put
forth by the International Society of Nephrology/Renal
Pathology Society 2004, given below is in use.
Explanatory terms: as applied in SLE: in addition
to those outlined at the beginning of the chapter
Karyorrhexis: Presence of apoptotic, pyknotic and
fragmented nuclei.
Necrosis: A lesion characterized by fragmentation
of nuclei or disruption of glomerular basement mem-
brane, often associated with the presence of fibrin rich
material.

Hyaline thrombi: Intracapillary eosinophilic
material of a homogeneous consistency which by
immunoflurescence has been shown to consist of im-
munodeposits. These hyaline thrombi are seen to be
actually in continuity with the subendothelial deposits
(which give rise to the wireloop appearance).
Proportion of involved glomeruli: Intended to
indicate the percentage of total glomeruli affected by
lupus nephritis, including the glomeruli that are scle-
rosed due to lupus nephritis, but excluding ischemic
glomeruli with inadequate perfusion due to vascular
pathology separate from lupus nephritis.
Wireloops: When subendothelial deposits com-
pletely involve the peripheral circumference of the
glomerular capillary they are referred to as the classic
wireloops which produce a rigid, refractile thicken-
ing of the glomerular capillary wall in the hematoxy-
lineosin stained section.
Hematoxyphil bodies: Rare finding in lupus ne-
phritis. Consists of rounded, smudgy iliac-stained
structures that are generally smaller than normal
nuclei. Their smudgy borders and lilac coloration
enables them to be distinguished from the more darkly
basophilic, smaller and more punctuate nuclear frag-
ments.
Original WHO classification of Lupus Nephritis 1974
Class I Normal glomeruli by LM, IF, EM
Class II Purely mesangial disease:
a. Normocellular mesangium by LM, but me-
sangial deposits by IF, and/or EM
b. Mesangial hypercellularity, with mesangial
deposits by IF and/or EM
Class III Focal proliferative glomerulonephritis (<50%
glomeruli)
Class IV Diffuse proliferative glomerulonephritis (>
or = 50% glomeruli)
Class V Membranous glomerulonephritis
Modified WHO classification of Lupus Nephritis 1982
Class I Normal glomeruli:
a. Nil by all techniques
b. Normal by LM but deposits seen by IF and
/or EM
Class II Purely mesangial alterations (mesangiopathy):
a. Mesangial widening and/or moderate me
sangial alterations
b. Moderate hypercellularity
URINARY SYSTEM 93
Class III Focal segmental glomerulonephritis (as-
sociated with mild or moderate mesangial
alterations):
a. With active necrotizing lesions
b. With active and sclerosing lesions
c. With sclerosing lesions
Class IV Diffuse glomerulonephritis (severe me-
sangial, endocapillary, or mesangiocapillary
proliferation and/or extensive subendothe-
lial deposits). Mesangial deposits are present
invariably and subepithelial deposits often,
and may be numerous:
a. Without segmental lesions
b. With active necrotizing lesions
c. With active and sclerosing lesions
d. With sclerosing lesions
Class V Membranous glomerulonephritis:
a. Pure membranous glomerulonephritis
b. Associated with lesions of category II (a or b)
c. Associated with lesions of category III (a, b
or c)
d. Associated with lesions of category IV (a, b, c,
or d)
Class VI Advanced sclerosing glomerulonephritis
(Class V c and d are deleted from the 1995
modified WHO classification)
Categories of lupus nephritis based on the current
Classification put forth by the International Society
of Nephrology (ISN/Renal Pathology Society 2004:
Class I: Defined as minimal mesangial lupus ne-
phritis. Appearances are normal by light microscopy
but mesangial accumulation of immunocomplexes are
identified by immunoflurescence or by immunoflures-
cence and electron microscopy.
Class II: Mesangial proliferative lupus nephritis:
characterized by any degree of mesangial hypercel-
lularity (defined as 3 or more mesangial cells per me-
sangial area in a 3 micron thick section) in association
with mesangial immunodeposits. IF or EM may show
a few small rare deposits of immunocomplexes in the
peripheral capillary walls but not by light microscopy.
Identification by light microscopy of any peripheral
deposits should shift the category to Class III or Class
IV depending on the degree and distribution of sub-
endothelial deposits.
 94 FUNDAMENTALS OF SURGICAL PATHOLOGY

International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Classification of Lupus Nephritis (2004)*
Class I Minimal Mesangial Lupus Nephritis
Normal glomeruli by LM, but mesangial immunodeposits by IP.
Class II Mesangial Proliferative Lupus Nephritis
Purely mesangial hypercellularity of any degree and/or mesangial matrix expansion by LM, with mesangial by LM, with mesangial
immunodeposits. A rare isolated subepithelial or subendothelial deposit may be visible by IF or EM, but not by LM.
Class III Focal Lupus Nephritis
Active or inactive focal, segmental, or global endo- or extracapillay glomerulonephritis involving < 50% of glomeruli, typically with
focal subendothelial immunodeposits, with or without mesangial alterations.
III (A) Active lesions (focal proliferative lupus nephritis)
III(A/C) Active and chronic lesions (focal proliferative sclerosing lupus nephritis)
III(C) Chronic inactive lesions with scars (focal sclerosing lupus nephritis)
* Indicate the proportion of glomeruli with active and with sclerotic lesions
* Indicate the proportion of glomeruli with fibrinoid necrosis and with cellular crescents
* Indicate and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis, arteriosclerosis or other
vascular disease
Class IV Diffuse Lupus Nephritis
Active or inactive diffuse, segmental, or global endo- and/or extracapillary glomerulonephritis involving 50% all glomeruli, typically
with diffuse subendothelial immunodeposits, with or without mesangial alterations. This class is divided into diffuse segmental (IV-
S) when > 50% of the involved glomeruli have segmental lesion, and diffuse global (IV-G) when 50% of the involved glomeruli
have global lesions.
Segmental is defined as a glomerular lesion that involves less than half of the glomerular tuft. This class includes cases with
diffuse wire-loop deposits, but with little or no glomerular proliferation.
IV-S (A) or IV-G (A) Active lesions (diffuse segmental or global proliferative lupus nephritis)
IV-S (A/C) or IV-G (A/C) Active and chronic lesions (diffuse segmental or global proliferative and sclerosing lupus nephritis)
IV-S (C) or IV-G (C) Chronic inactive lesions with scars (diffuse segmental or global sclerosing lupus nephritis)
* Indicate the proportion of glomeruli with active and with sclertic lesions
* Indicate the proportion of glomeruli with fibrinoid necrosis and with cellular cresents
* Indicate and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis, arteriosclerosis or other
vasular disease
Class V Membranous Lupus Nephritis
Global or segmental subepithelial immunodeposits or their morphologic sequelae by LM and by IF or EM, with or without mesangial
alterations.
* May occur in combination with III or IV, in which case both will be diagnosed.
* May show advanced sclerosis.
Class VI Advanced Sclerosing Lupus Nephritis
90% of glomeruli globally sclerosed without residual activity

Class III: Defined as focal lupus nephritis involv-
ing less than 50% of all glomeruli. Affected glomeruli
may display segmental endocapillary proliferation
or inactive glomerulate scars, with or without capil-
lary wall necrosis and crescents with subendothelial
deposits (usually in a segmental distribution). Both
active and sclerotic glomeruli are taken into account
as these may co-exist especially in chronic cases with
recent clinical reactivation. Focal and diffuse mesangial
lesions including mesangial deposits may accompany
the focal glomerular lesions. IF shows global and dif-
fuse mesangial deposition in all glomeruli with more
focal and segmental subendothelial capillary wall
deposition. The latter may be comma shaped with an
outer smooth contour due to the peripheral limiting
capillary wall.
Class II lesions often display focal tubulointersti-
tial disease with interstitial edema, inflammation and
tubular atrophy. In chronic lesions fibrosis is more
evident.
In the body of the report parameters of activity
and chronicity should be described. The proportion of
glomeruli affected by active and chronic lesions and by
fibrinoid necrosis and crescents should be indicated.
Presence of any tubulointerstitial and vascular pathol-
ogy should be reported.
A specific diagnosis of combined class III and class V
requires membranous involvement of atleast 50% of the
glomerular capillary surface area of atleast 50% of the
glomeruli by light microscopy or Immunofluorescence.
Class IV: It is defined as diffuse lupus nephritis
involving 50% or more of the glomeruli in the biopsy.

In the affected glomeruli the lesions may be segmental
(i.e. sparing atleast half of the glomerular tuft). Many
investigators consider Class III and Class IV lupus ne-
phritis as ends of a pathologic continuum such that the
two classes differ from each other quantitatively but
not qualitatively. All lesions described for class III may
be seen in class IV with the latter showing 50 % or more
of glomerular involvement. Class IV is further subdi-
vided into diffuse segmental lupus nephritis (class IV-S
when > 50% of the glomeruli have segmental lesions
and diffuse global lupus nephritis (class IV-G) when
> 50% of the glomeruli have global lesions. Class IV-S
typically shows segmental endocapillary proliferation
enchroaching upon capillary lumina with or without
necrosis and may be superimposed upon similarly dis-
tributed glomerular scars. Class IV-G is characterized
by diffuse and global endocapillary, extracapillary or
mesangiocapillary proliferation or widespread capil-
lary loops. Any active lesion may be seen with Class
IV-G including karyorrhexis, capillary loop necrosis
and crescent formation. Rare examples of extensive
diffuse and global subendothelial glomerular deposits
with little or no proliferation should also be included
in this category. This new subdivision for segmental
and global lesions is based on the evidence suggesting
that diffuse segmental lupus nephritis may have a dif-
ferent outcome than diffuse global lupus nephritis (an
outcome between classic focal segmental, i.e. class III
and diffuse globalie class IV proliferative groups). It
is in class IV that all histologic features of active lupus
nephritis reach their most florid expression, in severe
examples there may be abundant wireloop deposits
and necrosis and it is in class IV that Hematoxyphil
bodies are most likely to be encountered.
Parameters of activity and chronicity should be
stated in the report as for the previous category. The
proportion of glomeruli affected by active and chronic
lesions and by fibrinoid necrosis and crescents should
be indicated.
Scattered subepithelial deposits are commonly seen in
class IV biopsies. Therefore a diagnosis of combined class
IV and class V is to be made only if subepithelial deposits
involve at least 50% of the glomerular capillary surface
area in atleast 50% of the glomeruli by light microscopy
or IF. Again in assessing the extent of lesions both active
and sclerotic lesions are to be taken into account.
URINARY SYSTEM 95
In the membranoproliferative subgroup of class IV
there is widespread circumferential proliferation or
partial mesangial interposition with double contoured
capillary loops owing to subendothelial neomembrane
formation
Class V: It is defined as membranous lupus nephri-
tis and is characterized by widespread subepithelial
immunodeposits, often associated with mesangial
immunodeposits and variable mesangial hypercellu-
larity. Scattered subendothelial immunodeposits may
be identified by immunofluorescense or electron mi-
croscopy. If present by light microscopy subendothe-
lial deposits warrant a combined diagnosis of lupus
nephritis class III and V, or class IV and V, depending
on their distribution. When a membranous change
involving > 50% of the glomerular tuft in > 50% of the
glomeruli by light microscopy or immunofluorescense
is associated with an active lesion of class III or IV
both diagnosis are to be given in the final impression.
This is because endocapillary proliferation constitutes
an ominous lesion, emphasis should be placed on its
presence as treatment should be directed towards this
proliferative change.
As class V evolves to chronicity, there is typically
the development of segmental or global glomerulo-
sclerosis without the superimposition of proliferative
lupus nephritis. Patients with the membranous form
of lupus nephritis differ significantly from those with
class III and class IV with regard to presenting sero-
logic findings and multisystem disease manifestation.
Patients with class V change are more likely to present
with renal limited disease before other systemic fea-
tures of lupus nephritis are present. They are more
likely to be ANA negative and may have normocom-
plementemia. In a significant group of patients the
renal disease may precede by months or years a clinical
diagnosis of SLE.
The features which differentiate the two and favor
SLE are mesangial hypercellularity, mesangial immu-
nodeposits, focal small subendothelial deposits, tissue
ANA, strong staining for C1q and tubulointerstitial
disease.
Class VI: Advanced stage lupus nephritis shows
90 or >90% global glomerulosclerosis with clinical
or pathologic evidence of SLE. There should be no
evidence of ongoing active glomerular disease. It
 96 FUNDAMENTALS OF SURGICAL PATHOLOGY
represents the advanced stage of classes III, IV and V.
Without the aid of sequential biopsies it is impossible
to determine from which class the sclerotic glomerular
lesions evolved.
Immunofluorescence: Features common to all classes
IgG is found in all cases. Co-deposits of IgM and IgA in
most specimens. When all three immunoglobulins are
identified it is referred to as full house staining. C3
is the most frequent complement component followed
by C1q which usually stains most intensely, sometimes
in the absence of C3 and C4. C4 stains least frequently.
(C1q and C4- activation of complement by the classic
pathway).
Properdin can be identified in the glomerular de-
posits ( complement activation by the alternate path-
way) as also membrane attack complex (C5 through
C9).
Fibrin-related antigens are commonly intensely posi-
tive in areas corresponding to necrotizing lesions and
in the urinary space in association to cellular crescents.
Recommendations for reporting a renal biopsy in
a patient with lupus nephritis:
1. A detailed description (quantitative and qualitative)
of all the findings at light microscopy, electron
microscopy and immunofluorescence.
2. Followed by a diagnostic segment summarizing
and including the class of lupus nephritis (at times
more than one class), percentage of glomeruli
with severe active lesions (fibrinoid necrosis and
crescents), percentage of glomeruli with other
active and chronic lesions should be indicated.
3. The extent, severity, and type of tubulointerstitial
disease (tubular atrophy, interstitial inflammation
and fibrosis) should be stated.
4. Vascular lesions (vascular deposits, thrombi,
vasculitis and sclerosis) should also be documented
and graded as mild, moderate and severe in the
final impression.
5. Austin et al (1984) score of activity and chronicity
should be scored.
6. Similar guidelines should be applied to repeat
biopsies in any patient. A comparison with previous
biopsies should be made and important changes
in class, activity and chronicity highlighted.
7. Renal biopsy findings per se cannot be used
to establish a diagnosis of SLE. They should
be interpreted in the context of the patients
entire clinical presentation including serologic
findings.
Activity and Chronicity Indices (Austin et al, 1984)
Index of activity (0-24)
Endocapillary hypercellularity (0-3+)
Leukocyte infiltration (0-3+)
Subendothelial hyaline deposits (0-3+)
Fibrinoid necrosis/karyorrhexis (0-3+) x 2
Cellular crescents (0-3+) x 2
Interstitial inflammation (0-3+)
Index of chronicity (0-12)
Glomerular sclerosis (0-3+)
Fibrous crescents (0-3+)
Tubular atropy (0-3+)
Interstitial fibrosis (0-3+)
Vascular Lesions in Lupus Nephritis
Arteriosclerosis and arteriolosclerosis
Uncomplicated vascular immunodeposits
Noninflammatory necrotizing vasculopathy (so
called lupus vasculopathy)
Thrombotic microangiopathy
Associated with HUS/TTP syndromes
Associated with antiphospholipid antibodies
Associated with scleroderma/mixed connective
tissue disease
Necrotizing vasculitis (PAN type)
Lupus anticoagulant or antiphospholipid syn-
drome: Patients with this syndrome have antibodies to
a family of naturally occurring phospholipids, includ-
ing cardiolipin, phosphatidylcholine, phosphatidylser-
ine, phosphatidylionositol, etc. It has varied clinical
manifestations with diverse organ system involvement
and may be seen in pregnant women. Lab diagnosis
is made by the demonstration of a positive lupus
anticoagulant or demonstration of APL antibodies by
the Enzyme linked immunosorbent assay (ELISA).
Patients with this syndrome may have SLE, a lupus
like condition that fails to fulfil ARA criteria for SLE.
The kidney is commonly affected in this condition
and shows variable degrees of microthrombosis of
glomerular capillaries and arterioles to thrombosis of
the main renal artery and vein with secondary cortical
necrosis and infarction.

Prognosis: Survival rates for diffuse proliferative
lupus nephritis are approximately 25% at 5 years, 65%
for patients with focal proliferative glomerulonephri-
tis for the same period of time, and 85% for patients
with membranous nephritis. Clinical predictors of
poor outcome in class IV nephritis are black race,
higher serum creatine levels and lower hematocrit
values. Mesangial lupus nephritis has an excellent
prognosis with a five year renal survival rate of
> 90%.
Hereditary Nephritis: Alports Syndrome
Clinical
1. Nephritis is accompanied by nerve deafness
and various eye disorders, including lens
dislocation, posterior cataracts and corneal
dystrophy.
2. Incidence is more in males and males are more
likely to progress to renal failure.
3. Gross and microscopic hematuria, RBC casts
4. Symptoms appear at age 5-20 years. Overt renal
failure in males between 20-50 years of age.
5. Inheritance is heterogeneous either X-linked or
autosomal
Pathogenesis
Defective GBM synthesis: In patients with X-linked
disease, there is a mutation in the gene encoding the
chain of the type IV collagen.
Pathology
1. Light microscopy: The glomeruli are always
involved. There is focal proliferation or sclerosis
or both. There is an increase in mesangial matrix.
The tubular epithelial cells contain neutral fat and
mucopolysaccharides (foam cells). Glomerulo-
sclerosis, vascular narrowing, tubular atrophy and
interstitial fibrosis.
2. Immunofluorescence: GBM does not stain with
anti-GBM antibodies. Differential diagnosis from
patients with Good pastures syndrome
3. Electron microscopy: The basement membrane
shows irregular foci of attenuation or thickening,
with pronounced splitting and lamination of the
lamina densa (moth eaten). Similar changes are
found in the tubular basement membrane.
URINARY SYSTEM 97
Minimal Change Disease (MCD): Lipoid Nephrosis
Glomerular disease with minimal or no glomerular
alterations.
Clinical Features
1. Most frequent cause of nephrotic syndrome in
children. Peak age 2-6 years. There is no hypertension
and renal function is preserved in most cases.
2. Etiology and pathogenesis are unknown. Several
features point to an immunologic basis:
a. Clinical association with respiratory infections
b. Response to steroids
c. Association with atopic diseases like eczyma,
rhinitis
d. Increased prevalence of HLA haplotypes in
these patients associated with atopy
e. Increased association with Hodgkins disease
(pointing to T cell defects).
Release of cytokine-like circulating substance
damages the visceral epithelial cells causing
proteinuria. Protein loss is typically confined to
smaller serum proteins chiefly albumin (selective
proteinuria). The tubular epithelial cells resorb lipid
and protein (therefore the name lipoid nephrosis).
3. A secondary form of minimal change disease may
result as a complication of certain forms of drug
therapy in association with NSAID and rarely with
lithium therapy. In both instances achievement of
remission is achieved within weeks of stoppage of
the offending drug.
Pathology
1. Light Microscopy: Normal glomeruli. Mild mesangial
prominence with slight increase in mesangial
cellularity/matrix. Cells of proximal tubules are
filled with lipids secondary to tubular reabsorption of
lipoproteins passing through the diseased glomeruli.
2. Immunofluorescence: No staining
3. Electron microscopy: Uniform and diffuse effacement
of foot processes of the visceral epithelial cells and
microvilli formation. These changes are completely
reversible after remission of the proteinuria.
Prognosis
1. Most adults and children show complete remission
of proteinuria within 8 weeks of initiation of
corticosteroid therapy.
 98 FUNDAMENTALS OF SURGICAL PATHOLOGY
2. There is no tendency to progress to chronic renal
disease.
Histologic Variants of Minimal Change Disease
1. Diffuse Mesangial Hypercellularity:
Definition: More than 4 mesangial cells per
mesangial area affecting atleast 80% of glomeruli
in tissue sections 2-3 thick
Clinical features: Accounts for 3% of pediatric cases
of idiopathic nephrotic syndrome. Patients more
likely to have hematuria and hypertension.
Pathology: Glomerular hypercellularity confined
to mesangium without occlusion of capillary
lumina and varies from mild-to-severe (3-5 nuclei/
mesangial cells)
Immunoflouresence: Negative, some show mesangial
positivity for IgM and C3
Electron microscopy: Diffuse effacement of foot
processes of the podocytes.
2. IgM nephropathy: Characterized by diffuse and
global deposits of IgM 2+ or greater in intensity
by IF. Glomeruli show no or mild mesangial
hypercellularity by LM.
3. Minimal change disease with IgA nephropathy:
Mesangial IgA deposits in patients presenting
with nephrotic syndrome and shows effacement
of foot processes typical of MCD. No capillary
wall deposits. LM shows little or no mesangial
hypercellularity.
Focal Segmental Glomerulosclerosis (FSGS)
Characterized by nephrotic range proteinuria, focal
and segmental glomerulosclerosis and foot process
effacement without glomerular immunocomplex
deposits. Most investigators consider MCD and
FSGS to be related entities that lie along a clinico-
pathologic continuum. MCD is on the mild end of
the spectrum with steroid responsitivity whereas
FSGS lies at the severe end of the spectrum manifest-
ing steroid resistance and progress to end stage renal
failure.
Clinical Features
1. Accounts for 10% of the nephrotic syndrome in
children and 10-20% in adults. Many patients have
hypertension and/or hematuria.
2. Etiology and pathogenesis are unknown. Majority
of the patients have idiopathic FSGS which
progresses to renal failure over 10 years.
3. Genetic basis: NPHS2 gene encodes podocin
a protein present in the foot processes of the
podocytes and mutations in this may contribute
to the development of the disease.
4. Secondary FSGS is seen in several conditions and
FSGS in association with AIDS, heroin abuse and
vesicoureteric reflux has been observed.
Pathology
The lesion initially affects the juxtamedullary glomeruli
and may be missed in a biopsy in the initial stages. A
repeat biopsy is therefore necessary in patients reported
as MCD and not responding to corticosteroid therapy.
1. Light microscopy: Sclerosis and hyalinosis of some
of the tufts within a glomerulus, sparing others.
Hyalinosis is plasmatic insudation beneath the
GBM and appears as amorphous glassy material
on the H and E stain. It is PAS +ve, nonargyrophilic
and trichrome red.
The classic lesion of segmental sclerosis is
seen close to the hilar region.
A tip lesion is seen at the periphery opposite
the hilar pole.
An occasional glomerulus completely sclerosed.*
Foam cells in involved glomeruli.
In AIDS a collapsing variant of FSGS is described
with segmental/global obliteration due to
wrinkling and collapse of the GBM associated
with overlying podocyte hypertrophy and
hyperplasia.
A cellular variant of FSGS is also seen with
focal and segmental endocapillary prolife-
ration occluding lumens with foam cells
and karyorrhexis, also showing podocyte
hypertrophy and hyperplasia.
The interstitium has infiltrates of lymphocytes
and plasma cells.
Cystic dilatation of tubules and Bowmans
space containing proteinaceous material.
2. Immunofluorescence: Mesangial deposits of IgM and
C3 in the affected segments
3. Electron microscopy: Diffuse effacement of foot
processes of podocytes. Folding and thickening

of the GBM and capillary collapse. Advanced
lesions show extensive deposition of electron dense
material throughout the affected segments.
Tubuloreticular inclusions in the endothelial cells are
seen in AIDS, not seen in heroin or idiopathic FSGS.
Prognosis
1. About 50% of cases suffer a decline in renal
function over a period of 10 years, about 20% of
cases progress to endstage disease in 3 years time.
2. The disease recurs frequently in transplanted
kidneys25-50% of transplanted allografts.
3. In children, it is important to differentiate FSGS as
a cause of nephrotic syndrome from that of MCD
as the clinical course is markedly different.
(* Normally by age 40 years upto 10% of glomeruli
may be obsolete/sclerosed due to aging and should
be differentiated from sclerosis due to FSGS)
Membranous Glomerulonephritis
Clinical
1. Most frequent cause of nephrotic syndrome in
adults (30-40%)
2. Most patients have the primary idiopathic form
but a number of conditions are associated with
the development of secondary membranous
nephropathy.
3. Pathogenesis: Involves the deposition of immuno-
complexes on the epithelial side of the GBM.
In most cases, the inciting cannot be identified
(idiopathic). MHC locus influences the ability
to produce antibodies, the idiopathic type is
considered to be an autoimmune disease.
4. Known antigens (secondary form) include tumor
antigens (solid tumors like lung, Ca colon and
melanoma), HBsAg, DNA antigen-antibody
complexes in patients with SLE (10%) and a number
of drugs (gold, penicillamine, captopril), infections
like malaria, syphilis and schistosomiasis, etc.
(secondary form). Most antigens are planted
antigens.
5. The site of origin of immunocomplexes is
unclear. Circulating immunocomplexes cannot be
identified in more than half the cases, they may be
formed and deposited in situ (on the GBM).
6. C3 levels are normal. Urinary excretion of C5b-C9
terminal complement complex is elevated in some
patients-correlated with disease activity. Direct
URINARY SYSTEM 99
action of C5bC9 on the glomerular epithelial cells
and mesangial cells results in the release of proteases,
capillary wall damage, leakage and proteinuria.
Pathology
1. Light microscopy: Glomeruli are slightly enlarged
but normocellular. Capillary walls are normal or
thickened depending on the stage of the disease.
Open capillary lumina are typically seen. Spikes
are noted on the silver stain which later in the
disease give rise to chain formation. Late in the
disease the glomeruli become sclerotic and totally
hyalinized.
2. Immunofluorescence: Granular deposits of IgG and
C3 along the GBM. In secondary MGN there may
be mild mesangial hypercellularity and mesangial
deposits.
3. Electron microscopy: Subepithelial deposits that
initially rest on the GBM. With time there are spike-
like protrusuions of the GBM around the deposits.
As disease progresses these spikes close over the
deposits incorporating them into the GBM. Late in
the disease the incorporated deposits are resorbed
and eventually disappear leaving lucent defects in
the GBM.
Prognosis
1. Usual course in the adults is chronic proteinuria
and slow deterioration into renal failure within
10-15 years in 50%, spontaneous remission in 25%
and a slow indolent course in 25%.
2. Rapidity of deterioration is variable and cannot be
accurately predicted at the time of diagnosis.
Congenital Nephrotic Syndrome
Congenital nephrotic syndrome is the term applied
to the development of nephrotic syndrome at birth
or within 3 months of development of life. Caused
by a variety of different pathological conditions. Two
types of the genetic variants unique to this age group
are: (1) Congenital nephrotic syndrome of the Finnish
type (CNF) and (2) Diffuse mesangial sclerosis (DMS).
Congenital nephrotic syndrome of the Finnish
type (CNF): Inherited disorder of autosomal recessive
transmission that manifests as severe unremitting
nephrotic syndrome within first 3 months of life.
Frequency of genetic carriers in Finland is 1 in 200 and
therefore the name.
 100 FUNDAMENTALS OF SURGICAL PATHOLOGY
Clinical
1. Affected fetuses are often born prematurely with
postural deformities such as contractures of knee
and elbows. A high placental/fetal weight ratio is
a heralding feature of the disease.
2. Infant is small for gestational age, may have edema
at birth and ascites often produces breathing
difficulties.
3. Level of proteinuria is very high 1-6 g/day.
4. Few infants survive to an age where end-stage
renal failure develops.
Pathology
1. Focal cystic dilation of the proximal tubules first
observed in inner cortex and corticomedullary
junction.
2. Epithelium of the proximal convoluted tubules
contain intracytoplasmic protein resorption
droplets which are PAS +ve and trichrome red as
well as lipid droplets.
3. Glomeruli may be normal, microglomeruli may be
seen and sometimes mild mesangial cellularity and
matrix. As the disease progresses, there is FSGS
and total sclerosis.
Prognosis: poor
Diffuse Mesangial Sclerosis (DMS)
Also known as French type congenital nephrotic
syndrome. Both familial and sporadic forms are seen.
Clinical
1. In majority of cases the onset of nephrotic
syndrome tends to be later than in CNF, i.e. around
3-9 months of age.
2. Unlike CNF, DMS is not associated with an enlarged
placenta, low infant weight or premature birth.
3. Presence of hypertension and more accelerated
course of renal failure, within 1-3 months.
4. Most cases are renal limited, sometimes associated
with renal and extrarenal abnormalities. The
combination of DMS, Wilms tumor and male
pseudohermaphroditism is known as Denys-Drash
syndrome.
Pathology
1. Characteristic finding is increased mesangial
matrix in a diffuse and global distribution. May
have associated mesangial hypercellularity.
2. FSGS or global glomerular sclerosis may be seen.
Capping of podocytes oversclerotic tufts may be
seen.
3. Tubular interstitial changes to include tubular
ectasia, focal microcyst formation and presence of
hyaline casts. Resorption droplets seen.
Prognosis: Poor
Diabetic Nephropathy
Clinical
1. Patients usually have a history of 10 or more years
of diabetes mellitus.
2. Proteinuria is the earliest and invariable feature.
Edema usually presents as the first symptom and
may be severe.
3. Diabetic retinopathy is regularly present. Hyper-
tension occurs commonly though it may appear
late in the course of disease.
Pathogenesis
1. Basement membrane though thickened is abnormal
biochemically irreversible glycosylation
2. Increased collagen IV and fibronectin synthesis
possibly due to high glucose
3. Hemodynamic factors: glomerular filtration early
in course of disease (glomerular hyperfiltration
may be due to reduced mesangial contractility
secondary to hyperglycemic state) glomerular
protein deposits (hyaline deposits) resulting in
glomerular sclerosis.
Pathology
Light Microscopy
1. Enlarged glomeruli ( corresponding to supernormal
GFR).
2. Diffuse glomerulosclerosisdiffuse thickening
of GBM and diffuse increase in the amount of
mesangial matrix. Mild proliferation of mesangial
cells.
3. Nodular diabetic glomerulosclerosismay be
superimposed on the earlier change. Characterized
by occurence of the Kimmelsteil-Wilson nodules-
rounded, ovoid or spherical intercapillary lesion
composed of increased mesangial matrix material
with few mesangial cells. May be layered or
laminated by the JMS stain.
4. Exudative lesions: Capsular drops (homogeneous
eosinophilic and acellular hyaline mass between

parietal epithelium and Bowmans capsule and
represents insudation of plasma proteins) and
fibrin caps (similar material within capillary
lumina between BM and endothelioma.
5. Hyaline arteriolosclerosis: Affects both the afferent
and efferent arterioles.
6. Armanni-Ebstein anomaly: glycogen in tubules of
uncontrolled diabetes.
7. Thickening of tubular basement membrane.
Immunofluorescence: Frequently, there is low inten-
sity diffuse linear staining by IgG in the glomerular
and tubular basement membranes. This represents a
nonimmunologic accumulation of IgG in the thickened
GBMs.
Electron microscopy: The lamina densa of the GBM is
uniformly and diffusely thickened. (6-10 times normal).
Prognosis
1. About 40% of Type I diabetics (juvenile insulin
dependent DM) and 20% of Type II (adult onset
insulin independent or dependent) develop renal
failure usually 20-30 years after the onset of diabetes.
The ratio of Type II to Type I diabetics is 10:1,
therefore the number of patients with chronic renal
failure from Type 2 diabetics exceeds Type I diabetics.
2. Normalization of blood glucose with diet, insulin
or oral agents, dietary protein restriction and blood
pressure control certainly delays the progression
of diabetic nephropathy.
Amyloidosis
Clinical
Defined as extracellular accumulation of proteins in a
characteristic form that results in positive staining by
the Congo red stain as detected by LM and the forma-
tion of 10 nm randomly oriented nonbranching fibrils
that can be seen by standard transmission electron
microscopy.
1. Renal disease is most common in secondary
amyloidosis (AA amyloidosis) due to chronic
infections, degenerative diseases or malignancies.
It also occurs in amyloidosis associated with
familial mediterranean fever (FMF) (AA).
2. Amyloidosis (AL) is much more common in
patients with light chain myeloma than in those of
other types and is preferentially present in patients
with lambda type myeloma. It also occurs in other
B-cell dyscrasias.
URINARY SYSTEM 101
3. The main clinical feature is proteinuria associated
with nephrotic syndrome. Renal failure develops
at a variable rate, sometimes rapidly. It is the
most common cause of death in patients with
amyloidosis.
Pathology
1. Amyloid deposits (both AA and AL): Are
amorphous and acidophilic, the acidophilia
being less dense than that of the mesangial matrix
or zones of sclerosisinvolves the glomeruli,
blood vessels, interstitium and tubular basement
membranes.
2. Light microscopy: Deposits of amyloid in capillary
wall and mesangium stainable with thioflavin
T, crystal violet and Congo-red (apple green
birefringence under polarized light). They are non
argyrophilic ie do not stain by the JMS stain.
Potassium permanganate treatment prior to Congo
red staining can be used to discriminate between AA
and AL amyloidafter this treatment birefringent
Congo red staining is lost by AA amyloid but retained
by AL amyloid.
3. The intrarenal vasculature frequently contains
similar deposits of amyloid.
4. Immunofluorescence: Typically negative except for
occasional staining by monoclonal light chains
kappa and lambda in AL amyloid.
5. Electron microscopy: Characteristic fibrillar deposits.
These are non-branching fibrils of indefinite length
and measuring 7-10 nm in diameter. They are
first detected in the mesangial areas, replacing
the normal extracellular matrix. Later seen in the
peripheral vascular walls.
Prognosis
1. Therapy for primary amyloidosis is generally
ineffective.
2. Colchicine seems to limit the advance of AA
amyloidosis in patients with FMF.
Thrombotic Microangiopathy
The term thrombotic microangiopathy is used to
describe the vascular lesions in hemolytic uremic syn-
drome (HUS), thrombotic thrombocytopenic purpura
(TTP), disseminated intravascular coagulation and
related conditions like scleroderma renal crisis, malig-
nant hypertension, eclampsia and pre-eclampsia and
 102 FUNDAMENTALS OF SURGICAL PATHOLOGY
postpartum renal failure. The term microangiopathic
hemolytic anemia is used to describe the forms of
anemia seen in HUS and TTP.
Relationship between HUS and TTP: Morphologic
lesions of both conditions are virtually identical but
certain clinical differences are observedTTP occurs
among older persons, affects the CNS more commonly,
exhibits less severe and less frequent involvement of
the kidney, involves multiple organs and has a poorer
prognosis. The differences are not absolute as for
example, HUS can be seen in adults as well and TTP
can also be seen in children. To several authors HUS
and TTP represent varied clinical expressions of
the same disease and the generic term thrombotic
microangiopathy is recommended. As clinical renal
involvement is predominant in HUS it will be dis-
cussed separately.
Hemolytic Uremic SyndromeForms of Clinical
Presentation
Classic form: Also known as diarrhea-positive (D+)
or epidemic HUS. Occurs mainly in young children
and may be seen as an epidemic. Sporadic cases have
also been reported. This form is associated with infec-
tion with verotoxin producing Escherichia coli (VTEC).
Patients present with watery or bloody diarrhea and
hemorrhagic colitis. The natural course of colitis may
be favorable but sometimes fatal. Renal manifestations
include oliguria or anuria, hematuria hemoglobinuria,
proteinuria, various types of casts in the urine and el-
evated blood urea nitrogen and creatinine levels. Throm-
botic microangiopathy is confined to the glomeruli in the
kidney with a consequently good prognosis.
Atypical form: This form presents without prodromal
diarrhea in children as well as adults and accounts for
about 5-12% of all cases. The onset is insidious and
marked proteinuria and hypertension are characteristic
features. These are considered to be D-ve cases and
may have varied etiologic factorsextrinsic toxins
(pneumococcal neuraminidase), intrinsic causes such
as hypocomplementemia or of unknown etiology.
Some cases may be hereditary with an autosomal
recessive or dominant pattern of inheritance. In D-ve
cases, the renal arterial involvement is more severe
than in D+cases and explains the poorer prognosis
seen in D-ve cases.
HUS may occur in renal transplant recipients ei-
ther as a recurrent disorder or as a de novo disease.
The diagnosis of post-transplant HUS which can oc-
cur as recurrent disease or as cyclosporine or FK-506
nephrotoxicity is difficult to differentiate as the
features can be similar to humoral allograft rejection.
The clinical signs of microangiopathic hemolytic
anemia and thrombocytopenia when present helps
in diagnosis as these are not present in acute allograft
rejection.
PathologyGross: Renal cortical necrosis is a frequent
finding in patients who die of HUS. More often the
necrosis is patchy. The swollen kidney has a reddish
mottled appearance. Sometimes only petechial hemor-
rhages may be seen.
Light Microscopy
1. Glomeruli: The percentage of glomeruli involved
may vary according to the severity of the disease.
In early stages, the glomeruli show thickening
of the capillary walls caused by expansion
(swelling) of a thin layer between the endothelial
cells and the underlying basement membrane.
Acellular fibrillar material may be seen in
the subendothelial areas of swelling and is
particularly apparent on electron microscopy.
Separation of the endothelium from the
underlying basement membrane due to the
production of new basement like material by
the endothelial and interposed mesangial cells
results in the occasional double contours of the
glomerular capillary walls best seen with the
silver or periodic acidSchiff stain. Severe
swelling of the endothelial and mesangial cells
may result in the occlusion of the capillary
lumina. The term bloodless glomeruli is used
to describe these.
a. Glomerular capillary lumina may also
show fragmented red cells, fibrin and platelet
thrombi.
b. Fibrin may be seen below the endothelial cells,
in the glomerular capillary tufts particularly
in continuity of fibrin thrombi in the afferent
arteriole as it enters the glomerulus.
c. Glomeruli may sometimes contain red cells
in dilated capillary loops particularly in cases
with severe vascular involvement. This is called
glomerular paralysis and is typical of cases
with early cortical necrosis.
d. Early crescents may be observed and the
mesangium may show a characteristic

fibrillar appearance due to edema. Fibrin and
fragmented red cells may also be seen in the
mesangium. Mesangial hypercellularity occurs
in late stages. Rarely mesangiolysis is seen with
dissolution of mesangial matrix. This is seen at
light microscopy as hazy matrix. Eventually
lack of support leads to dilated capillary
lumina, with cystic capillaries.
In the more advanced stages of HUS mesangial
widening is seen from mesangial sclerosis, thick
capillary walls with occasional double contours
and chronic ischemic glomerular injury with
wrinkling of capillary basement membrane.
2. Arteries and arterioles: In the early stages, the
renal arterioles show swelling of the endothelial
cells and subendothelial space. The arteriolar
lumen may be severely narrowed and fragmented
red cells may be seen in the thickened arteriolar
walls. Infiltration of the arteriolar wall may
occur with fibrin resulting in fibrinoid necrosis.
Fibrinois necrosis tends to occur at the hilum of
the glomerulus, involves the intima more often
than the media. An acute inflammatory cell
infiltrate is rarely seen as the change is due to
increased permeability of the plasma proteins
including fibrinogen. In more advanced stages,
the arterioles become more hyalinized with a
homogeneous eosinophilic refractile appearance.
Aneurysmal dilation of the arterioles may be
seen and glomeruloid structures may form when
thrombosis in dilated segments of the arterioles is
followed by organization and cellular proliferation.
Interlobular arteries show changesswelling of
the intima which may be accompanied by a suffusion
of red blood cells or fibrin. Fibrin may permeate the
intima extensively with resultant fibrinoid necrosis.
The second change is intimal swelling which is
usually sparsely cellular containing mainly lucent
amorphous material with a mucoid appearance. This
change is designated mucoid intimal hyperplasia.
Later in the course of the disease, there may be a
rapid proliferation of the intimal cells. The cellular
intimal proliferation may give rise to the onion skin
lesion which consists of concentric, ring like layers
of myointimal cells and delicate connective tissue
fibrils. Severe vascular changes are associated with a
poor prognosis. Fibrous replacement of the thickened
vessel wall is a late change.
URINARY SYSTEM 103
3. Tubules: Usually contain red cells and hyaline
casts. They may show necrosis and atropy. Cases
of cortical necrosis show calcification later on.
Electron Microscopy
a. Thickening of capillary wall resulting from
widening of subendothelial space. The acellular
subendothelial fluff is pale and rarefied and
contains irregular collections of electron dense
material. It is situated in the lamina rara interna
and is granular and of variable electron density.
It is thought to contain breakdown products of
intravascular coagulation.
b. Signs of endothelial damage with endothelial
swelling, localized areas of detachment of endo-
thelial cytoplasm from the basement membrane
and cytolysis.
c. Intracapillary thrombi composed of amorphous
osmiophilic material admixed with platelets and
deformed red cells.
d. Swollen mesangial matrix filled with a similar
granular material as seen in the subendothelial
space. Mesangiolysis may be seen with resultant
capillary ectasia.
e. Multiple layers of material resembling capillary
basement membrane in the capillary walls.
f. Arterioles and arteries show changes similar to
those seen in the glomeruli-widening of intima
and detachment of endothelium. Intima has a
lucent appearance with granules of greater electron
density.
Immnofluorescence
a. Presence of fibrinogen or fibrin along the capillary
loops in a continuous, broken linear or granular
pattern. Mesangium may show presence of
fibrin.
b. Fibrin deposits along the capillary walls may be
accompanied by IgM, C3, less frequently by IgG
and rarely IgA.
c. Capillaries arterioles and arteries show presence
of fibrin or fibrinogen deposits. IgM and C3 may
also be seen.
Prognosis
a. Pediatric patients with classic D+ HUS are consi-
dered to have a better prognosis and renal outcome
than those with D HUS.
 104 FUNDAMENTALS OF SURGICAL PATHOLOGY
b. Adults fare less well than infants and children due
to irreversible arterial changes and infants fare
better than children.
c. Low C3 levels and a high white cell count identify
a group of patients with a D+ HUS with a more
severe episode.
Nephrosclerosis
Benign nephrosclerosis: Renal injury caused by chronic
mild-to-moderate hypertension is called hypertensive
nephrosclerosis or benign nephrosclerosis. All changes
of hypertensive nephrosclerisis are also associated with
advanced aging, in individuals with no evidence of
long standing hypertension.
Pathogenesis
1. Glomerular and arteriolar lesions of arterione-
phrosclerosis involve not only increased deposition
of collagen and other matrix components but also
intramural insudation of plasma proteins and
migration and proliferation of cells in particular
smooth muscle cells.
3. The hyaline of arteriolar hyalinosis is derived
from plasma constituents (water sodium, calcium,
glycosaminoglycans and collagen) that have
leaked across endothelial cells into intima and
muscularis.
4. Persistent injury to endothelium induces intimal
thickening and smooth muscle migration from the
muscularis and subsequent proliferation (onion
thickening).
5. Glomerular sclerosis involves production of both
type III and IV collagen.
Pathology
1. Light microscopy: Focal global glomerular sclerosis,
arteriolar hyalinosis and sclerosis, arterial fibrotic
intimal thickening. Earliest change occurs in
afferent arteriole (severity correlating with the
severity of hypertension). This is in contrast to the
hyaline change of diabetes mellitus which affects both
afferant and efferent arterioles simultaneously.
The hyaline material of arteriolar hyalinosis is
eosinophilic, very periodic acid Schiff +ve, JMS ve
and fuchsinophilic with the trichrome stain.
Characteristic glomerular lesion is an acellular
wrinkled mass of glomerular basement membrane
contracted to the hilar side of Bowmans capsule.
Thickening, wrinkling and reduplication of
Bowmans capsule also occurs.
2. Immunofluorescence: Generally negative. Foci of
arteriolar or glomerular hyalinosis stain irregularly
for complement and immunoglobulins (IgM)
(similar to other forms of glomerular sclerosis)
3. Electron microscopy: Thickened and wrinkled mass
of glomerular basements and mesangial matrix
material.
Malignant hypertension: A form of thrombotic
microangiopathy and should be differentiated from
other categories of the same. Clinical features may help.
1. Red specks or spotches of hemorrhages over
the surface (flea bitten kidney). May have gross
infarcts if the vessels are occluded due to intimal
proliferation or thrombosis.
2. Microscopy: Fibrinoid necrosis of the afferent
arteriole and adjacent glomerular hilar capillaries.
Focal cortical necrosis. Late phase results in
reduplication of the glomerular BM. Associated
changes of benign nephrosclerosis may be seen.
Pyelonephritis
Inflammation of the renal parenchyma and renal
pelvis caused by bacterial infection. May be acute and
chronic.
Acute Pyelonephritis
a. Modes of infectionascending from the urethra
particularly in females and in infants with struc-
tural defects in the urethra.
Hematogenous, as in infective endocarditis, etc.
b. Causative organismsEscherichia coli, Proteus
mirabilis, Enterobacter and Streptococcus faecalis.
c. Complictionspapillary necrosis, pyonephrosis
d. Predisposing conditionsobstructive lesions
of the lower urinary tract, instrumentation and
diabetes mellitus
e. Gross: Kidneys are enlarged and edematous with
yellowish or whitish microabscesses confined to
the cortex. Areas of supurration
f. Microscopy: Tubules filled with neutrophils, Inter-
stitial neutrophilic infiltrate and microabscesses.
Lymphocytes and plasma cells may be seen.
Chronic Pyelonephritis
May be chronic obstructive pyelonephritis as a
result of repeated infections or reflux nephropathy
 URINARY SYSTEM 105

(nonobstructive form). In the latter vesicoureteric Acute rapidly progressive glomerulonephritis and
(UV) reflux and intrarenal reflux are essential patho- chronic progressive renal disease may culminate in
genetic mechanisms. Severe UV reflux due to struc- ESRD.
tural or functional disorders of the UV valve result in The macroscopic renal findings depend on the un-
permanent scarring. Intrarenal reflux occurs where derlying renal disease. When examined late in course
the compound papillae (2-3 pyramids normally of disease the kidneys are markedly reduced in size
fused together) are situated at the poles of the kidney. and may be very atropic.
Therefore findings of reflux nephropathy are usually ESRD can be subdivided into four categories
polar. hypertensive vascular disease, diabetic nephrosclero-
Gross sis, chronic pyelonephritis and chronic glomerulone-
i. Asymmmetrically involved kidneys, may be uni phritis of some sort.
or bilateral. Microscopy: All compartments of the kidney
ii. Adherent capsule glomeruli, vessels, tubules and interstitium become
iii. Irregular U-shaped scars directly overlying the progressively damaged. Global glomerular sclerosis,
damaged pelvi-calyceal system and therefore tubular atrophy, cystic change, interstitial fibrosis and
more common in the upper and lower poles (reflux thickened blood vessels. Marked separation of tubules
nephropathy) by interstitial fibrosis.
iv. Microscopy: Interstitial inflammationlympho- Extensive oxalate deposition.
cytes and plasma cells, periglomerular fibrosis,
tubular atrophy, thyroidization of tubules and Renal Neoplasms
arteriolosclerosis. The Mainz Classification of Renal Cell Tumors, 1999
Tumor Type Relative frequency
End Stage Renal Disease (ESRD) Renal cell carcinoma
Clear cell 70%
ESRD is defined by the United States Renal Data Chromophil (eosinophil, basophil) 15%
System as renal failure continuing beyond a period Chromophobe (typical eosinophil) 5%
of 90 days that requires extracorporeal renal dialysis Collecting duct carcinoma 2%
to sustain life. Renal oncocytoma 5%

Histologic and Cytogenetic Features of Renal Cell Tumors

Tumor type Histopathology
Clear cell RCC Compact alveolar, tubular and cystic
architecture, clear cytoplasm, low N:C
ratio, Vascular stroma
Chromophil (papillary) RCC Papillary architecture with aggregates
of foamy histiocytes (Type I)-Basophilic
cytoplasm, low N:C ratio or eosinophilic
cytoplasm and high N:C ratio (Type II)
Chromophobe RCC Compact solid architecturesheets of cells
divided by fine septa, clear or eosinophilic
cytoplasm, prominent cell membranes,
great variability in cell size, nuclei 10-5 ,
positive colloidal iron stain, diffusely +ve;
150-300 nm cytoplasmic microvesicles
Collecting duct carcinoma Medullary location, tubular and glandular
architecture, hobnail cells, desmoplastic
stroma
Oncocytoma Rounded organoid cell groups, absence
of papillary architecture and clear cell
changeUniform intensely eosinophilic
cells, round regular nuclei 8-10 , incon-
spicuous nuclei, Neg colloidal iron stain
Cytogenetics Immunohistochemistry
3p losses-3: 8 reciprocal CD10 +ve, membranous;Vimentin +ve;
translocation-5q gains Antimitochondrial +ve (diffuse and
coarse); CK 7 ve
Trisomy and tetrasomy 7 CD10 +ve, membranous; Vimentin
and 17-Loss of Y chromo- +ve; Antimitochondrial +ve (diffuse
some and coarse); CK 7 +ve
Losses of chromosomes CD10 ve; Vimentin ve; Antimitochon-
1, 2, 6, 10, 13, 17 and 21 drial +ve (coarse at periphery);CK 7 +ve
Losses of chromosomes 1, CD10+/, RCC ve
6, 14, 15 and 22
CD10+/ve, cytoplasmic; Vimentin ve;
Antimitochondrial +ve (diffuse fine);
CK7 ve
 106 FUNDAMENTALS OF SURGICAL PATHOLOGY
Other Tumors
Angiomyolipoma: Are almost always benign neo-
plasms of the kidney composed of fat, smooth muscle
and blood vessels in varying proportions. (Classified
by some authors as a malignant neoplasm). Present in
25-50% of patients with tuberous sclerosis (i.e. devel-
opment of hamartomas in the brain and other tissues,
like the lung, and angiofibromas in skin).
1. About half are associated with tuberous sclerosis
and half occur sporadically.
2. Local invasion has been reported and rarely
sarcomatous change.
3. Range in size from < 1 to 20 cm, may be golden
yellow, color varies according to the proportion of
smooth muscle and blood vessels.
4. Cut surface may look like lipoma.
5. Microscopy: Fat, smooth muscle and blood vessels.
A frequent finding is radial arrays of smooth
muscle fibers oriented about blood vessels; found
in bundles and as individual fibers. Smooth muscle
cells occasionally may be epitheliod with abundant
cytoplasm (Differential diagnosis for RCC).
Blood vessels are thick-walled with narrow lumens
Nuclear pleomorphism and mitoses may be seen.
Lipocytic component may also show atypical cells.
Cystic Nephroma: (Syn: multilocular cyst; multilocular
cystic nephroma), uncommon neoplasm which occurs
in adults.
i. More common in women
ii. Diagnostic criteria areadult patient, expansile
mass surrounded by fibrous capsule, interior
entirely composed of cysts and septa with no
solid nodules, cysts lined by flattened, hobnail or
cuboidal epithelium, septa may contain epithelium
resembling mature renal tubules but not cells with
clear cytoplasm, septa should not show skeletal
muscle.
iii. Imporatnce of this neoplasm lies in Differential
diagnosis from cystic Wilms tumor and cystic renal
cell carcinoma.
Classification of Kidney Tumors in Infants and Children
Nephroblastoma (Wilms tumor)
Unfavorable histology
Favorable histology
Cystic partially differentiated nephroblastoma
Mesoblastic nephroma
Clear cell sarcoma
Rhabdoid tumor
Rare tumors
Wilms Tumor
1. Most common primary renal tumor of childhood
2. Between 2-5 years
3. 5-10% involve both kidneys (synchronous/
metachronous)
4. 10% are associated with congenital syndromes:
i. WAGR syn aniridia, genital abnormalities,
mental retardation (30% chance of tumor)-WT1
gene involved
ii. Denys-Drash syn (90% risk)gonadal
dysgenesis (male pseudohermaphroditism),
early onset nephropathy (diffuse mesangial
sclerosis)WT1 germline abnormality
iii. Beckwith-Weidemann syndrome: Organome-
galy, macroglossia, hemihypertrophyspauom-
phalocele WT2 locus involved.
5. Familial predisposition to tumor is rare.
6. Gross: Large, solitary well-circumscribed masses.
C/s soft, homogeneous and tan to gray with
occasional foci of hemorrhage and cyst formation
7. Microscopy: Recapitulates different stages of neph-
rogenesis 3 elements: Blastema, stromal and epi-
thelial components 3% of tumors show anaplastic
histology: Large, hyperchromatic, pleomorphic
nuclei and abnormal mitoses.
8. Based on the NWTS (National Wilms Tumor
Study): Wilms tumors are divided into 2 categories
Favorable and unfavorable histology according to
the absence or presence of anaplasia. Anaplasia is
found in approximately 6% of Wilms tumors, it
is rare in patients less than one year.
Tumor anaplasia has been defined by the National
Wilms tumor study (NWTS) system as: combination
of cells with very large hyperchromatic nuclei and
multipolar mitotic figures. The enlarged nuclei should
be atleast 3 times as large as the typical blastemal nuclei
in both axes and the hyperchromasia should be obvious.
Cystic partially differentiated Wilms tumor:
Grossly resembles cystic nephroma, elements typical of

Wilms are contained in the septa; may be inconspicu-
ous, therefore tumors should be sampled excessively.
Mesoblastic nephroma: Comprises < 3% of pri-
mary renal tumors in children.
1. Occur in first 3 months of life and are uncommon
in children.
2. Associated with polyhydramnious and pre-
maturity.
3. Abdominal mass is the presenting symptom and
vast majority are cured by surgical excision.
4. Incomplete excision results in recurrences as the
tumor is not well-circumscribed.
5. Grossly large with nonencapsulation.
6. Microscopy: Moderately cellular proliferation
of interlacing bundles of spindle-shaped cells.
Entrapment of glomeruli and tubules is common.
7. Cellular mesoblastic nephroma with proliferation
of polygonal cells with mitoses has been reported.
8. Differential diagnosis: Stromal predominant Wilms
tumor.
Cysts of the Kidney
Cystic Diseases of the Kidney (Modified from Ameri-
can Academy of Paediatrics, 1987)
Genetic
1. Autosomal recessive polycystic kidney disease
(infantile) (Potter type I)
2. Autosomal Dominant polycystic kidney disease
(adult) (Potter type III).
3. Juvenile nephronophthisismedullary cystic
disease complex
Juvenile nephronophthisis (autosomal recessive)
Medullary cystic disease (autosomal dominant)
4. Congenital nephrosis (familial nephrotic syndrome)
(autosomal recessive)
5. Familial hypoplastic glomerulocystic disease
(autosomal dominant)
6. Multiple malformation syndrome with renal cysts
(tuberous sclerosis, Von Hippel-Lindau disease)
Nongenetic
1. Multicystic kidney (multicystic dysplastic kidney,
Potter type II)
2. Simple cysts
3. Medullary sponge kidney
4. Sporadic glomerulocystic kidney disease
5. Acquired renal cystic disease
URINARY SYSTEM 107
6. Calyceal diverticulum (pyelogenic)
7. Unilateral partial ADPKD-like kidney disease
8. Glomerular cysts 2 renal obstruction during
nephrosis (Potter type IV).
Neoplastic
1. Cystic nephroma (Multilocular cyst)
2. Cystic partially differentiated nephroblastoma
3. Multilocular cystic renal cell carcinoma
4. Multifocal cystic change in renal cell carcinoma,
Wilms tumor, mesoblastic nephroma, clear cell
sarcoma
Miscellaneous
1. Cystic hamartoma of renal pelvis
2. Endometrisis
3. Teratoma
Renal cystic dysplasia: Due to an anomalous differ-
entiation of the metanephros that does not proceed
beyond the development of undifferentiated tubular
structures surrounded by primitive mesenchyme,
sometimes with accompanying divergent differentia-
tion that results in heterotopic tissue such as cartilage.
Abnormal tubules/ducts develop into cysts of varying
sizes, however these are not a must for the diagnosis
of renal dysplasia.
1. Several distinct patterns of dysplasia exist: Some
are genetic and associated with malformation
syndromes, others are not genetic and develop as
a result of congenital obstruction.
a. Multicystic dysplasia (Potter type II cystic disease):
Unilateral, nongenetic
b. Aplastic dysplasia: Rudimentary dysplastic
kidney, nongenetic
c. Obstructive dysplasia (Potter type IV cystic disease):
Congenital obstruction during nephrogenesis,
nongenetic.
d. Diffuse dysplasia: Genetic, associated with
malformation syndromes, e.g. Meckel-Gruber
syndrome, tuberous sclerosis, Von Hippel-
Lindau, etc.
3. Most common of cystic renal disease in the newborn
period which presents as an abdominal mass.
4. Most are sporadic, a few familial or occur in
syndromes of multiple malformations (diffuse
develops with multiple malformations).
5. Associated with urinary tract abnormalities such
as ureteral agenesis, ureteral atresia, ureteropelvic
 108 FUNDAMENTALS OF SURGICAL PATHOLOGY
junction obstruction and urethral obstruction,
urethral atresia and valves.
6. Gross: Reniform mass of cysts of varying sizes
obscures renal parenchyma. Can be unilateral,
bilateral, segmental or focal. Multicystic dysplasia
is unilateral with cysts of varying sizes. Diffuse
dysplasia is bilateral with symmetric involvement
with maintainance of the reniform shape. Aplastic
dysplasia results in rudimentary dysplastic
kidneys.
7. Microscopy: Cysts are lined by cuboidal epithelium
and surrounded by immature stromal elements.
Primitive tubules and glomerular structures
may be present. Islands of dysplastic mese-
nchyme, including cartilage, adipose and fibro-
muscular tissue are observed. Glomerular cysts
may be seen.
8. Prognosis: Severe bilateral renal dysplasia is
often lethal. Unilateral renal dysplasia may
cause no signs and symptoms during life and
may be detected only at postmortem. Bilateral
hypoplastic dysplasia frequently causes renal
insuffiency as a renal of associated abnormalities
and hydornephrosis and pyelonephritis.
Autosomal Dominant Adult Polycystic
Kidney Disease (ADPKD)
1. Congenital renal disease characterized by nume-
rous cysts within renal parenchyma manifesting
clinically during adulthood (therefore the
previously called adult polycystic renal disease)
(Potters type III cystic disease).
2. Associated with mutations in Chr 16p13.3(PKD
1-85% of cases) and 4q21( PKD2). Autosomal
dominanthigh penetration. Abnormalities in
tubular epithelial cell differentiation, proliferation
and secretion result in cyst formation.
3. Many patients remain asymptomatic until renal
insufficiency develops.
4. Symptoms: Hematuria with proteinuria and
progressive renal failure.
5. Prevalence is 1 in 200 to 1000 population.
Contributes to about 10% end stage renal disease.
6. Gross: Bilateral enlargement of kidneys, each
kidney may weigh from 2 to 4 kg. External surface
shows a mass of cysts 3-5 cm in diameter with no
intervening parenchyma. Both cortex and medulla
are involved. Cysts are filled with fluid, either
serous or hemorrhagic.
7. Microscopy: Cysts arise from tubules throughout
the nephrons and therefore show variable
epithelial lining. Foci of proliferation result
in multilayering and papillary projections
(renal cell carcinoma can arise from such foci).
Intervening compressed renal parenchyma may be
identified. Glomerular cysts are seen in younger
patients.
8. Hepatic cysts are seen in 33% of patients, splenic
cysts in 10% and pancreatic cysts in 5% of cases.
9. Prognosis: Once renal failure sets in, the rate of
deterioration accelerates with time. The residual
renal parenchyma disappears with time giving rise
to fibrosis and chronic inflammation and finally
end stage disease.
Autosomal Recessive Childhood Polycystic Kidney
Disease (Potter Type I Cystic Disease)
1. ARPKD: Rare abnormality, autosomal recessive
inheritance
2. Perinatal, neonatal, infantile and juvenile subtypes
(1st two are common) infant may succumb to renal
failure.
3. PKD1 gene (encodes a protein fibrocystin involved
in collecting duct and biliary differentiation).
Associated with cysts in the liver.
4. Gross: Bilateral, enlarged kidneys with a smooth
external surface.
C/S: Cylindrical cysts at right angles to the cortical
surface resulting in a sponge-like appearance of
cortex and medulla.
5. Microscopy: Saccular dilation of collecting tubules
with uniform cuboidal lining.
6. Older children who survive the infantile stage
develop hepatic fibrosis (congenital HF).
Cystic Disease of Renal Medulla
Medullary Sponge Kidney
1. Common and innoccuous structural change
multiple cystic dilatations of collecting ducts in
the medulla.
2. Occurs in adults and discovered radiologically as
an incidental finding.

3. Cysts lined by cuboidal or transitional epithelium.
4. Secondary complications such as calcification
within ducts, urinary complications such hematuria
and calculi develop.
5. Pathogenesis unknown and renal function
maintained.
Nephronophthisis: Medullary Cystic Disease Complex
1. Several different clinical syndromes resulting in
renal disease that often have cysts in the cortico-
medullary junction. Nephronophthisis is an
autosomal recessive disease that progresses to early
onset renal failure whereas medullary cystic disease
has an autosomal dominant mode of inheritance
with late onset renal failure. The diseases are
grouped into nephronophthisis: Medullary cystic
disease complex due to overlapping clinical and
pathologic features. Three genesNPH1, NPH2,
NPH3 define the juvenile forms (autosomal
recessive disease).
2. Onset in childhood. Clinical features include
polyuria, polydipsia, anemia and insidious onset
of renal failure.
3. Gross: Normal sized or small contracted kidneys
with cysts measuring 1-15 mm in the cortico-
medullary junction.
4. Microscopy: Tubular basements are thickened
and reduplicated resulting in puff-pastry
appearance in cross-sections. Others are normal
or thinned BMs. Dilated and tortuous tubules are
seen resulting in cysts at the corticomedullary
junction.
Chronic and progressive tubular atrophy and fi-
brosis resulting eventually in renal failure.
Ureter
Primary neoplasia of the uereter is rare. The two most
common benign tumors are fibroepithelial polyp and
leiomyomas. Primary malignant tumors of the ureter
follow patterns similar to those arising in the renal
pelvis, calyces, bladder and the majority of them are
transitional cell carcinomas found in the 6th and 7th
decade of life. They may be multiple and occur con-
currently with similar tumors in the bladder or the
renal pelvis.
URINARY SYSTEM 109
Urinary Bladder
Cystitis
1. Common variants of cystitis areinterstitial
cystitis (Hunners cystitis), eosinophilic cystitis,
emphysematous cystitis and chronic tuberculous
cystitis.
2. Malakoplakia: Multiple nodular thickenings of
the mucosa and submucosa commonly occurring
in the region of the trigone. They are associated
with immunodeficiency states. Microscopy
shows collections of histiocytes with granular
acidophilic cytoplasm. Rounded concentric layered
intracytoplasmic inclusions known as Michalis-
Gutmann bodies or calcospherules are observed.
They are basophilic, stain with Hematoxylin and
Eosin stain; are PAS positive and stain for iron
and calcium. On electron microscopy intracellular
bacteria can be identified.
3. Von Brunns Cell Nests: Most common reactive
proliferative change within the urothelium seen in
the form of invagination of the surface urothelium
into the underlying lamina propria. Sometimes
continuity of the surface mucosa is lost and the
nests are seen lying free in the lamina propria.
Cystic change in them with a lumen formation is
called cystitis cystica. When glandular metaplasia
occurs it is called cystitis glandulariscells become
cuboidal to columnar with mucin secretion.
4. Transitional Cell Carcinoma (TCC):
a. E t i o l o g y : M o s t u r o t h e l i a l c a r c i n o m a s
are transitional cell carcinomas (90%). A
combination of genetic and environmental
factors are implicated in the etiopathogenesis
incidence with cigarette smoking and
arylamines, benzidene and beta napthylamines
(aniline dyes). Schistosoma hematobium
infection is also associated with TCC.
Commonly occurs beyond 50 years of age and
males are more often affected than females.
Common symptom is hematuria.
b. The pathologic features that influence the
progression of the tumors aredepth of
invasion at presentation, multiplicity, tumor
size and grade. Cytologically benign papillary
110 FUNDAMENTALS OF SURGICAL PATHOLOGY
tumors may recur but do not invade. As a
rule only high grade tumors develop regional
lymph node metastasis. Recurrences occur at
different sites as compared to the site of first
presentation.
c. Pathologic stage with depth of invasion is an
important predictor of disease progression. A 5
year survival rate of 75% is expected in patients
with lamina propria invasion and 5 year
survival for patients with muscularis propria
and those with perivesical fat infiltration are
50 and 20% respectively.
d. Evaluating biopsy specimens: The following
features should be indicated:
What components of the bladder wall
are present (i.e. mucosa, lamina propria,
muscularis propria),
The state of epithelial surface (ulcerated
or denuded), in the presence of tumor-
histologic type,
Pattern of growth (papillary or nodular as
papillary tumors tend to be of low grade),
Tumor grade and depth of invasion in
particular invasion into muscle layer,
Presence or absence of small vessel invasion
(lymphovascular) and
The status of adjacent mucosa (dysplastic
or otherwise).
e. The WHO/ISUP Consensus Classification of
Urothelial Transitional Cell Neoplasms 2003
Normal
Hyperplasia
Flat hyperplasia
Papillary hyperplasia
Flat lesions with atypia
Reactive inflammatory atypia
Atypia of unknown significance
Dysplasia (low grade intra-urothelial
neoplasia)
Carcinoma in situ (high grade intraurothe-
lial neoplasia and severe dysplasia)
Papillary neoplasms
Papilloma
Inverted papilloma
Papillary neoplasm of low malignant
potential
Noninvasive papillary carcinoma, low
grade
Noninvasive papillary carcinoma, high
grade
Invasive neoplasms
Lamina propria invasion
Muscularis propria (detruser muscle
invasion)
Explanatory notes on some of the entities listed
above:
Flat hyperplasia: More than 7 layers of cells. In prac-
tice, it may not be possible to count the layers (due to
tangential cuts); so a diagnosis is made on a markedly
thickened mucosa but without atypia. Usually seen
adjacent to low grade papillary neoplasm. It is not a
precursor to malignancy when seen by itself.
Flat lesion with dysplasia (low grade intraurothelial
neoplasm): Has appreciable cytologic and architectural
abnormalities felt to be neoplastic yet falling sjort of a
diagnostic threshold for urothelial carcinoma in situ
(CIS). It is a likely precursor for invasive carcinoma.
Flat lesions with CIS (High grade intraurothelial
neoplasia and dysplasia): It is a documented precursor
for invasive carcinoma. Presence of cells with large,
irregular, hyperchromatic nuclei that may be present
through the entire thickness of the epithelium or only
part of it. Mitotic activity is seen in the middle and
upper urothelium. An important factor to remember
is that atypia need not be full thickness and cells may
be scattered within the urothelium; have a pagetoid
spread or present as isolated cells in a partially de-
nuded surface. Umbrella cells may be identified. It
is associated with papillary or invasive carcinoma in
about 90% of cases.
Papillary urothelial hyperplasia: There are rare reports
as to it being a precursor lesion to low grade papillary
urothelial neoplasm. It is generally seen on follow-up
cystoscopy of papillary neoplasms. Consists of undu-
lating epithelium that is thicker than normal. Absence
of atypia but it has increased vascularity at the base of
the folds.
Papillary neoplasm of low malignant potential (PUN-
LMP): Neoplasm with an orderly arrangement of cells
within papillae with minimal architectural abnormality
and minimal nuclear atypia, irrespective of cell thick-
ness. Mitoses is infrequent and limited to basal layers.

Not associated with invasion or metastasis. Patients
are at a risk of developing new bladder tumors i.e.
recurrences, with similar histology. A close follow-up
is needed as recurrent lesions may lead to carcinoma
(In contrast in a papilloma the papillary epithelium is
of normal thickness and cytology, recurrence is rare).
Noninvasive papillary carcinoma, low grade: Exhib-
its an overall orderly epithelium, but cytologic and
architectural abnormality is easily identified at low
power itself. Variability in polarity, nuclear size, shape
and chromatin texture are minimal but comprise the
hallmarks of the cytologic atypia seen in low grade
papillary urothelial carcinoma. Mitotic figures are
infrequent, may be seen at any level but are not atypi-
cal and limited to the lower half. Fusion of papillae is
noted. They frequently recur and have a low-risk of
progression to invasion carcinoma (<5%).
High grade noninvasive papillary urothelial carcinoma:
marked atchitectural and cytologic abnormalities rec-
ognizable at low power. Moderate to marked cellular
pleomorphism and atypical mitotic figures are seen at
all levels of the urothelium. It is generally associated
with invasive disease at the time of initial presenta-
tion. Progression rate to invasive carcinoma when seen
byitself is 15-40%.
f. Gross features of transitional cell carcinoma: Location
in the urinary bladderlateral wall 37%; posterior
wall 18%; trigone 12%; neck 11%; ureteric orifices
10%; dome 8% and the anterior wall 4%.
Exophytic tumors may be papillary or have a solid
nodular appearance. Endophytic tumors have a
nested pattern in lamina propria and are usually
underdiagnosed as Vonn Bruns cell nests.
g. Microscopy shows a papillary pattern covered
by transitional epithelial cells. Invasive as
well as noninvasive components are identified. The
noninvasive components have been described in
detail above. Invasion may be into lamina propria,
muscle layer or into perivesicular tissue.
About 20-30% of tumors show focal mucin
production (to be differentiated from adeno-
carcinoma in the bladder). Some show foci of
squamous differentiation (to be differentiated from
pure squamous cell carcinoma). A microcpapillary
pattern may be seen which is considered a high
grade neoplasm.
URINARY SYSTEM 111
h. In routine practice Bladder cancers are histologically
graded on a 3 tier system into:
Grade I: Well-differentiated tumors
Grade II: Moderately differentiated tumor
Grade III: Poorly differentiated tumors
i. Immunohistochemistry: Transional cell carcinoma of
the urinary bladder: CK 7+ve/ CK 20+ve CK 8 and
18+ve: at the interface of the tumor and stroma
Other carcinomas: Primary squamous cell carci-
nomas constitute 2-7% of urothelial tumors. Incidence
is high along the Nile Valley due to the prevalence of
Schistosoma infection.
Primary adenocarcinoma of the urinary bladder
is rare (< 2.5%) and an extension from adjacent
organs should be ruled out before a diagnosis of this
is made in the bladder. Small cell neuroendocrine
carcinomas and sarcomatoid carcinomas have also
been reported.
Urethra
1. The most common urethral mass is the caruncle.
Lesions usually occur on the inferior aspect of the
urethral meatus in postmenopausal female. They
are red tender and bleed on touch possibly due
to increased vascularity of the granulation tissue
that compose them. Rarely the stroma may show
atypical cells which are reactive in nature. They
are invariably benign.
2. Fibro-epithelial polyps occur in the urethra but are
less common than in the ureter.
3. Condyloma acuminatum of the urethra occurs in
association with genital and perineal condylomata
and generally the distal urethra is involved.
4. A prostatic type polyp occurs in the prostatic
urethra in young men and is composed of
papillae covered by cuboidal to low columnar
cells similar to those lining the prostatic acini as
confirmed by immunohistochemistry. Prostatic
glands may be present in the stroma. The
differential diagnosis is a prostatic adenocar-
cinoma particularly if the lesion is seen in older
individuals.
5. Urethral carcinomas are more common in women
than in men and majority (60-70%) are squamous
cell carcinomas. Next in frequency are the
transitional cell and then adenocarcinomas.
 112 FUNDAMENTALS OF SURGICAL PATHOLOGY

SYNOPTIC REPORTING AND MINIMUM DATA SETS

Kidney Biopsy Histopathology Reporting Format

Side: Right Left
Type of biopsy: Needle Wedge Other

No of cores
Specimen taken for electron microscopy: Yes No
Specimen taken for immunofluorescence: Yes No
Microscopy:
Biopsy is adequate: Yes No of glomeruli............. No of arteries.............
No No of glomeruli............. No of arteries.............
Glomeruli: Hypercellular Yes Focal Diffuse
Mesangial Mild Moderate Severe
Endocapillary Global Segmental
Mild Moderate Severe
Capsular crescents: Yes ...........% of glomeruli
No
Hyalinosis: Yes No
Membrane thickening: Focal Diffuse
Segmental Global
Mesangial matrix: Increased: Yes Segmental Global
No
K-W lesions: Yes No
Mesangiolysis: Yes No
Foam cells: Yes No
Fibrin thrombi: Present Absent
Fibrinoid necrosis: Present Absent
Capsular drop: Present Absent
Spikes ( JMS): Yes No
Tram track appearance (JMS): Yes No
Amyloid: Yes No
Tubules: Normal:
Casts: Yes No
Lipid droplets: Yes No
Protein droplets: Yes No
Atropy: Yes Mild Moderate Severe
No
Calcification: Yes No
Amyloid: Yes No
Interstitium: Inflammation: Nil Mild Moderate Severe
Lymphocytes Plasma cells Neutrophils
Blood Vessels: Thickening: Mild Moderate Severe Nil
Fibrinoid necrosis: Yes No
Thrombus: Yes No
Amyloid Yes No
 URINARY SYSTEM 113

SLE: Activity score: ........................../24 Chronicity score: ........................../12

Immunofluorescence: IgG + ++ +++ C3 + ++ +++
Along BM Mesangial C1q + ++ +++
IgA + ++ +++ Fibrinogen + ++ +++
Along BM Mesangial Kappa + Lambda +
IgM + ++ +++
Along BM Mesangial
In case of tumor: Benign Malignant Cannot be assessed
Histologic type: Cannot be assessed
Adenoma
Papillary adenoma
Conventional (clear cell) renal carcinoma
Papillary renal cell carcinoma
Chromophobe renal cell carcinoma
Collecting duct carcinoma
Sarcomatoid carcinoma
Oncocytoma
Other.....................................Specify.........................................
Additional Findings............................................................................................................................................................
Comments:..........................................................................................................................................................................
Impression:.........................................................................................................................................................................
Signature .......................................... Date ..........................................

Renal Allograft Biopsy Interpretation (Transplant Biopsy)

Side: Right Left
Side: Right Left
Type of biopsy: Needle Wedge Other
No of core
Specimen taken for electron microscopy: Yes No
Specimen taken for immunofluorescence: Yes No
Microscopy:
Biopsy is adequate: Yes No of glomeruli............ No of arteries............
No No of glomeruli............ No of arteries............
Tubules: No mononuclear cells in tubules t0
Foci with 1-4 cells/tub cross-section t1
Foci with 5-10 cells/tub cross-section t2
Foci with >10 cells /tub cross-section t3

No tubular atropy ct0

Tubular atropy in 25% of area of cortical tubules ct1
Tubular atropy in 26-50% of area of cortical tubules ct2
Tubular atropy in > 50 % of area of cortical tubules ct3

Interstitium: Trivial interstitial inflammation <10% of unscarred parenchyma i0

10-25% of parenchyma inflammed i1
26-50% of parenchyma inflammed i2
>50% of parenchyma inflammed i3*
 114 FUNDAMENTALS OF SURGICAL PATHOLOGY

Interstitial fibrosis in up to 5% of cortical area ci0

Mild interstitial fibrosis in 6-25% of cortical area ci1
Moderate interstitial fibrosis in 26-50% of cortical area ci2
Severe interstitial fibrosis in > 50 % of cortical area ci3

Glomeruli: No glomerulitis g0
Glomerulitis in <25% glomeruli g1
Glomerulitis in 25-75% of glomeruli g2
Glomerulitis in >75% of glomeruli g3

No glomerulopathy
Double contours in < 10% of peripheral capillary loops in most severely affected
glomerulus cg0
Double contours in upto 25% of peripheral capillary loops in most severely affected
of nonsclerotic glomeruli cg1
Double contours in upto 26-50 % of peripheral capillary loops in most severely affected
of the nonsclerotic glomeruli cg2
Double contours in >50% of peripheral capillary loops in most severely affected of the
nonsclerotic glomeruli cg3
Mesangial matrix:
No mesangial matrix increase mm0
Upto 25% of nonsclerotic glomeruli affected
(by moderate matrix increase**) mm1
26-50% of nonsclerotic glomeruli affected
( by moderate matrix increase) mm2
>50% of nonsclerotic glomeruli affected
(by moderate matrix increase) mm3

Vessels: No arteritis v0
Mild-to-moderate intimal arteritis in atleast 1 arterial cross-section (v1)
Severe intimal arteritis with loss of 25% luminal area in atleast 1 arterial
cross-section (v2)
Transmural arteritis and/or arterial fibrinoid change and
muscle necrosis (v3)
Infarction/interstitial hemorrhage: Yes No

No chronic vascular changes cv0

Narrowing upto 25% by fibrointimal thickening of arteries cv1***
26-50% narrowing of vascular luminal area with increased severity of changes cv2
>50% narrowing of vascular luminal area with severe vascular changes cv3

Arteriolar hyaline thickening (ah):

No PAS positive hyaline thickening ah0
Mild-to-moderate PAS positive hyaline thickening in atleast one arteriole ah1
Moderate to severe hyaline arteriolar thickening in more than one arteriole ah2
Severe PAS positive hyaline thickening in several arterioles ah3
Other finding: Specify................................................
 URINARY SYSTEM 115

Impression:
Within normal limits
Antibody mediated rejection
Type I Type II Type III
Borderline changes for rejection
Acute/Active T-cell mediated rejection :
Type IA Type IB Type IIA Type IIB Type III
Chronic active T-cell mediated rejection
Interstitial fibrosis and tubular atrophy:
Mild Moderate Severe
Other: Changes not considered to be due to rejection Specify........................
Signature: ........................ Date: ........................

* or the presence of atleast 2 areas of basement membrane destruction accompanied by i2/i3 inflammation
and t2 tubulitis elsewhere in the biopsy
** (mod matrix increase: Expanded mesangial interspace between adjacent capillaries. If the width of the
interspace exceeds 2 mesangial cells on the average in atleast 2 glomerular lobules the mm is moder-
ately increased)
*** with or without breach of internal elastic lamina or presence of foam cells or mononuclear cells

Banff 97 diagnostic categories for renal allograft biopsies: 2007 update.

1. Normal
2. Antibody-mediated changes
Due to documentation of circulating antidonor antibody, and C4d1 or allograft pathology C4d deposition
without morphologic evidence of active rejection. C4d+, presence of circulating antidonor antibodies, no
signs of acute or chronic TCMR or ABMR (i.e. g0, cg0, ptc20, no ptc lamination). Cases with simultaneous
borderline changes or ATN are considered as indeterminate.
Acute antibody-mediated rejection3
C4d+, presence of circulating antidonor antibodies, morphologic evidence of acute tissue injury, such as
(Type/Grade):
I. ATN-like minimal inflammation.
II. Capillary and or glomerular inflammation (ptc/g >0) and/or thromboses
III. Arterial v3
Chronic active antibody mediated rejection3
C4d+, presence of circulating antidonor antibodies, morphologic evidence of chronic tissue injury, such
as glomerular double contours and/or peritubular capillary basement membrane multilayering and/or
interstitial fibrosis/tubular atrophy and/or fibrous intimal thickening in arteries.
3. Borderline Changes: Suspicious for acute T-cell mediated rejection (may coincide with categories 2 and
5 and 6)
This category is used when no intimal arteritis is present, but there are foci of tubulitis (t1, t2 or t3 with
minor interstitial infiltration (i0 or i1) or interstitial infiltration (i2, i3) with mild (t1) tubulitis.
4. T-cell mediated rejection (TCMR, may coincide with categories 2 and 5 and 6)
Acute T-cell mediated rejection (Type/Grade: )
IA. Cases with significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of moderate
tubulitis (t2)
IB. Cases with significant interstitial infiltration (>25% of parenchyma affected, i2 or i3) and foci of severe
tubulitis (t3)
 116 FUNDAMENTALS OF SURGICAL PATHOLOGY

IIA. Cases with mild-to-moderate intimal arteritis (v1)

IIB. Cases with severe intimal arteritis comprising more than 25% of luminal area (v2)
III. Cases with transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle
cells with accompanying lymphocytic inflammation (v3)
Chronic active T-cell mediated rejection chronic allograph arteriopathy (arterial intimal fibrosis with
mononuclear cell infiltration in fibrosis, formation of neointima)
5. Interstital fibrosis and tubular atrophy, no evidence of any specific etiology (may include nonspecific
vascular and glomerular sclerosis but severity graded by tubulointerstitial features)
Grade
I. Mild interstitial fibrosis and tubular atrophy (<25% of cortical area)
II. Moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area)
III. Severe interstitial fibrosis and tubular atrophy/loss (more than 50% of cortical area)
6. Other: Changes not considered to be due to rejectionacute and/or chronic; may include isolated g, cg,
or cv lesions and coincide with categories 2, 3, 4 and 5)

1 Scoring of C4d staining (% of biopsy or 5 high-power fields)

C4d0 Negative 0%
C4d1 Minimal C4d stain/detection 1<10%
C4d2 Focal C4d stain/positive 10-50%
C4d3 Diffuse C4d stain/positive >50%
2 Peritubular capillaries

3 Suspicious for antibody mediated rejection if C4d (in the presence of antibody) or alloantibody (C4d+) not

demonstrated in the presence of morphologic evidence of tissue injury.

Adult Renal Tumor ResectionHistopathology Report

Gross
Total nephrectomy Partial Portion of kidney Other
Side: Right Left Not specified
Size of kidney with tumor: ..................(length) .................. ..................cm.
Location of tumor: Upper pole Lower pole Medulla Other Not specified
Multicentric Yes No
Size of tumor: .................. .................. .................. cm (largest dimension if multifocal).
Cannot be determined
Adrenal attached Yes No
Tumor infiltrates the renal capsule
Tumor infiltrates the perirenal tissue/fat
Tumor infiltrates Gerotas fascia
Tumor infiltrates adrenal gland
Tumor in the renal veins Yes No
Cut surface: Variegated Homogeneous Cystic
Microscopy:
Presence of tumor Yes Benign Malignant No
Histological subtype: Renal cell carcinoma
Conventional type
Papillary (Chromophil)
Chromophobe renal cell carcinoma
Small cell carcinoma
 URINARY SYSTEM 117

Oncocytoma
Papillary adenoma
Adenoma
Angiomyolipoma
Fibroma/ interstitial fibrous tumor
Others..................................... Specify.....................................
Histologic grade Gx G1 G2 G3 G4
Tumor: Confined to kidney
Infiltrates renal capsule
Tumor margins: Infiltrates parenchymal cut margin (perinephric fat, in partial nephrectomy)
Infiltrates perirenal fat/renal sinus fat
Infiltarates Gerotas fascia
Infiltrates adrenal gland
Infiltrates renal vascular cut margin
Ureteric cut margin
Lymphovascular invasion: Present Absent
Renal vein invasion Yes No
Regional lymph nodes: No of nodes examined.....................................
No of nodes involved.......................................
Distant metastasis: Cannot be assessed
Known, specify site.....................................

Fuhrman Nuclear Grade

Gx: Cannot be assessed
G1: Nuclei round, uniform, approximately 10 , nucleoli inconspicuous or absent
G2: Nuclei slightly irregular, approximately 15 , nucleoli evident
G3: Nuclei very irregular, approximately 20 , nucleoli large and prominent
G4: Nuclei bizarre and multilobated, 20 or greater, nucleoli prominent, chromatin clumped.

TNM Staging of Renal Carcinomas

Primary tumor (pT)
pTX: Primary tumor cannot be assessed
pT0: No evidence of primary tumor
pT1: Tumor 7 cm or less in greatest dimension (gd), limited to kidney.
pT1a: Tumor 4 cm or less in gd, limited to kidney
pT1b: Tumor > 4 cm but not > 7 cm in gd, limited to kidney
pT2: Tumor > 7 cm in gd, limited to kidney
pT3: Tumor extends into major veins or invades adrenal gland or perinephric tissues but not beyond Gerotas
fascia.
pT3a: Tumor directly invades adrenal or perirenal and/ or renal sinus fat but not beyond Gerotas fascia
pT3b: Tumor grossly extends into the renal veins or its segmental (muscle containing) branches, or vena cava
below the diaphragm
pT3c: Tumor grossly extends into vena cava above the diaphragm or invades the wall of the vena cava
pT4: Tumor invades beyond the Gerotas fascia
Regional lymph nodes (pN)
pNX: Cannot be assessed
pN0: No regional lymph node metastasis
 118 FUNDAMENTALS OF SURGICAL PATHOLOGY

pN1: Metastasis in a single regional lymph node

pN2: Metastasis in > one regional lymph node.
Distant metastasis (pM)
pMX: Cannot be assessed
pM1: Distance metastasis, specify sites, if known

Pathological Tumor Stages Illustrated Diagrammatically

Fig. 3.11 Fig. 3.12

Fig. 3.13
 URINARY SYSTEM 119

Fig. 3.14 Fig. 3.15: Tumor beyond Gerotas fascia

Cystoscopic Biopsy
Site of biopsy.......................................
Measurement ....................................... ....................................... mm

A. Nontumor
Epithelial hyperplasia Yes Flat Papillary No
Inflammation Nonspecific Eosinophilic cystitis
Granulomatous Tuberculous (BCG cystitis) Nontuberculous
Other, specify if possible..................................................
Edema
Malakoplakia

B. Tumor
Components of biopsy identified: Epithelium
Lamina propria
Muscularis propria
State of epithelium: Ulcerated
Denuded
Other Specify......................................................
Neoplasm present: Yes No
Histologic subtype: Transitional cell carcinoma
Papillary
Nodular
Flat
Mixed Specify patterns.............................................................
 120 FUNDAMENTALS OF SURGICAL PATHOLOGY

Grade: PUNLMP
Low grade
High grade
Muscularis propria invaded: Yes No
Lymphovascular invasion: Yes No
Associated CIS: Yes No
Other carcinoma Yes Specify.................................................
Grade: well Mod Poor
Comments ...................................................................................................................................................................

Signature of pathologist........................................ Date........................................

BLADDER RESECTION SPECIMENS

Gross
TURBT Diverticulectomy Partial cystectomy

Radical cystectomy

Site (s) of biopsy or TURBT......................................................................................

Weight of TURBT.................................................................................................(g)
Tumor location.......................................................................................................
Maximum tumor size.....................................................................................(mm)
Number of tumors...................................................................................................

Right obturator nodes Yes No

Left obturator nodes Yes No
Right pelvic nodes Yes No
Left pelvic nodes Yes No

Invasion into perivesical tissue (pT3b) Yes No Cannot assess

Margins N/A Negative Positive Cannot assess
Microscopy:
Nontumor
Epithelial hyperplasia
Inflammation Nonspecific Eosinophilic cystitis
Granulomatous Tuberculous (BCG cystitis) Nontuberculous
Other, specify.........................................................................
Edema
Malakoplakia

Tumor
Tumor subtype(s)
(one or more)
Urothelial carcinoma
Papillary
Nodular
 URINARY SYSTEM 121

Flat
Mixed Specify patterns.................................................................................................................

Squamous cell carcinoma

Adenocarcinoma
Small cell carcinoma
Sarcomatoid carcinoma
Sarcoma
Other Please specify..................................................

For urothelial tumors:

WHO 1975
Papilloma
Grade 1
Grade 2
Grade 3

OR USE

WHO 2003 / IUSP Classification /Grading

Papilloma
PUNLMP
Low grade
High grade

For squamous cell and adenocarcinoma

Well differentiated
Moderate differentiated
Poorly differentiated

Associated CIS Yes No

Vascular invasion Yes No

Muscle invasion (for TURBT only) Yes No

Carcinoma in situ only (pTis) Yes No Cannot assess (pTx)

Noninvasive papillary tumor (pTa) Yes No Cannot assess (pTx)
Invasion into lamina propria (pT1) Yes No Cannot assess (pTx)
Invasion into inner half of muscle (pT2a) Yes No Cannot assess (pTx)
Invasion into outer half of muscle (pT2b) Yes No Cannot assess (pTx)
Microscopic invasion into perivesical tissue (pT3a) Yes No Cannot assess (pTx)
Invasion into perivesical tissue confirmed (pT3b) Yes No Cannot assess (pTx)
Invasion into prostate, uterus or vagina (pT4a) Yes No Cannot assess (pTx)
Invasion into pelvic or abdominal wall (pT4b) Yes No Cannot assess (pTx)
 122 FUNDAMENTALS OF SURGICAL PATHOLOGY

Margins N/A Negative Distance to nearest margin mm

Site ........
Positive

Right nodes Total No pos ECS Left nodes Total No pos ECS
Obturator N/A Obturator N/A
Pelvic Pelvic N/A
Other: N/A Other: N/A
Please specify.................................................... Please specify....................................................

Size of largest lymph node with metastasis...................................

pTNM stage: pT......................pN......................pM...................... SNOMED codes

T........................... M...........................
T........................... M...........................

Comments...................................................................................................................................................................

Signature of pathologist....................................... Date.......................................

TNM Staging of Bladder Tumors

TX: Primary tumor cannot be assessed.
T0: NO evidence of primary tumor
Ta: Noninvasive papillary carcinoma
Tis: Carcinoma in situ flat tumor
T1: Tumor invades subepithelial connective tissue
T2: Tumor invades muscle (muscularis propria)
Invasion into inner half of muscle (pT2a)
Invasion into outer half of muscle (pT2b)
T3: Tumor invades perivesical tissue
T3a: Microscopically
T3b: Macroscopically
T4: Tumor invades any of the followingprostate, uterus, vagina, pelvic wall, abdominal wall
T4a: Tumor invades prostate, uterus, vagina
T4b: Tumor invades pelvic wall, abdominal wall
Regional Lymph nodes (N): Regional lymph nodes (N) are those within the true pelvis, all others are distant
nodes.
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph nodes metastasis
N1: Metastasis in a single lymph node 2 cm or less in greatest dimension
N2: Metastasis in a single lymph node > 2 cm but more > 5 cm in greatest dimension
N3: Metastasis in a lymph node more > 5 cm in greatest dimension
 URINARY SYSTEM 123

Distant Metastasis (M):

MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis.

Jewett-Marshal Staging of Urinary Bladder Cancers:

Stage Tumour description

0 Confined to mucosa
A Infiltration of submucosa
B1 Infiltration of superficial muscle
B2 Infiltration of deep muscle
C Perivesical infiltration
D1 Involvement of adjacent organs and pelvic lymph nodes
D2 Distant metastasis or nodes above aortic bifurcation