Pathology of the Kidney

4 basic morphologic components of the Kidney

1. Glomeruli
2. Tubules
3. Interstitium
4. Blood vessels
Pathology of the Kidney
1. Glomerular diseases are mostly immun-mediated
2. Tubular and interstitial disorders are frequently
caused by toxic or infectious agents
3. Damage to one component almost always
secondarily affects the others
4. Primary disorders of the blood vessels affect all
the structures
Pathology of the Kidney
 The basic structural and functional unit of the
kidney is called the nephron.
 A nephron consist of :
– a glomerulus (filtering part)
– a tubule (reclaiming part)
Figure 20.4 Structure of a nephron.
Structure of the glomerulus

 Invagination of the blind end of the proximal tubule 

Bowman’s capsule (contain parietal epithelial cells )
 Capillary tuft  fed by the afferent arteriole and
drained by efferent arteriole  arranged in lobules
(up to 8 in number)
 Capillary tuft (loop) :
– Lined by discontinuous endothelial cells
– covered by visceral epithelial cells (podocytes)
 Supported mesangium  mesangial cells
Juxtaglomerular apparatus

Situated at the vascular pole of the glomerulus and is

made up of 3 parts :
1. Juxtaglomerular cells  modified granular smooth
muscle cells in the media of the afferent arteriole
and contain the hormone (renin & angiotensin II).
2. Macula densa is comprised by specialised region of
the distal tubule.
3. Lacis cells or non-granular cells occupy the space
between the macula densa and the arterioles and
merge with the glomerular mesangium.
Glomerular filtration barrier
Glomerular filtration barrier
Pathologic Responses of the Glomerulus
to Injury
Four basic tissue reactions :
1. Hypercellularity : Acute response
2. Basement Membrane Thickening
3. Hyalinosis
4. Sclerosis
Pathologic Responses of the Glomerulus
to Injury
1. Hypercellularity :
– Proliferation of mesangial or endothelial cells.
– Infiltration of leukocytes
– Formation of crescents : accumulations of cells
composed of proliferating glomerular epithelial
cells (parietal & visceral cells) and infiltrating
leukocytes.
Pathologic Responses of the Glomerulus
to Injury
2. Basement Membrane Thickening
Three forms:
– Deposition of amorphous material, most often
immune complexes
– Increased synthesis of the protein components of
the basement membrane  in diabetic
glomerulosclerosis
– Formation of additional layers of basement
membrane  membranaproliferative
glomerulonephritis
Pathologic Responses of the Glomerulus
to Injury
3. Hyalinosis
– Accumulation of homogeneous and eosinophilic
material (hyalin) composed of plasma proteins
– When extensive, these deposits may obliterate the
capillary lumens of the glomerular tuft
– Usually a consequence of endothelial or capillary
wall injury
– The end result of various forms of glomerular
damage.
Pathologic Responses of the Glomerulus
to Injury
4. Sclerosis
– Deposition of extracellular collagenous matrix
– It may be confined to mesangial areas, or involve
the capillary loops, or both.
– May also result in obliteration of the capillary
lumens in affected glomeruli.
KEY CONCEPTS

 The glomerular basement membrane is composted of

type IV collagen molecules and other matrix proteins.
– These proteins can be the target of antibodies in some types
of glomerulonephritis;
– genetic abnormalities in their composition are the basis for
some forms of hereditary nephritis.

 Visceral epithelial cells (podocytes) are a critical

component of the glomerular filtration barrier, and
injury to these cells leads to leakage of proteins into
the urinary space, clinically manifest as proteinuria.
KEY CONCEPTS

 The acute glomerular response to injury includes

hypercellularity with proliferation of mesangial and/or
endothelial cells, influx of leukocytes, and, in severe
injuries, formation of crescents.

 Chronic glomerular responses to injury include

basement membrane thickening, hyalinosis, and
sclerosis.
 Pathogenetic mechanisms in glomerular diseases
MECHANISM
I IMMUNOLOGIC MECHANISMS
A Antibody-mediated glomerular injury
1. Immune-complex disease
2. Anti-glomerular basement
membrane (Anti-GBM) disease
3. Alternate pathway disease
4. Other mechanisms (anti-neutrophil
cytoplasmic antibodies or
ANCA, anti-endothelial cell antibodies
or AECA)
RELATED GLOMERULAR DISEASE
Immune-complex mediated GN (Acute
diff use proliferative GN,
membranous GN,
membranoproliferative GN, IgA
nephropathy;
secondary glomerular disease in SLE,
malaria etc.)
Goodpasture’s disease
Membranoproliferative GN type II
Vasculitis
 Pathogenetic mechanisms in glomerular diseases
MECHANISM RELATED GLOMERULAR DISEASE

I IMMUNOLOGIC MECHANISMS

B Cell-mediated glomerular injury Pauci-immune GN (type III RPGN)

C Secondary pathogenetic mechanisms
II NON-IMMUNOLOGIC MECHANISMS
1. Metabolic
Various primary and secondary
glomerular diseases
Diabetic nephropathy, Fabry’s disease

2. Haemodynamic Hypertensive nephrosclerosis, FSGS

3. Deposition Amyloid nephropathy

HIV-nephropathy, immune-complex
4. Infectious
GN in SABE
NSAIDs-associated minimal change
5. Drugs
disease
Alport’s syndrome, nail-patella
6. Inherited
syndrome
Immune Mechanisms of Glomerular Injury

1. Injury by antibodies reacting in situ within the

glomerulus
– binding to insoluble fixed (intrinsic) glomerular
antigens
– extrinsic molecules planted within the glomerulus

2. injury resulting from deposition of circulating

antigen-antibody complexes in the glomerulus.
 Immune Mechanisms of Glomerular Injury
Antibody-Mediated Injury

In Situ Immune Complex Deposition

Fixed intrinsic tissue antigens
NC1 domain of type IV collagen antigen (anti-GBM nephritis)
PLA2R antigen (membranous glomerulopathy)
Mesangial antigens
Others
Planted antigens
Exogenous (infectious agents, drugs)
Endogenous (DNA, nuclear proteins, immunoglobulins, immune complexes, lgA)
Circulating Immune Complex Deposition
Endogenous antigens (e.g., DNA, tumor antigens)
Exogenous antigens (e.g., infectious products)
Cell-Mediated Immune Injury

Activation of Alternative Complement Pathway

Antibody-mediated glomerular injury can result either from the
deposition of circulating immune complexes (A) or, more commonly,
from in situ formation of complexes exemplified by anti-GBM
disease (B) or Heymann nephritis (C).
Diseases Caused by In Situ Formation
of Immune Complexes
 Antigen-antibody complexes are formed locally
 Antibodies react with antigens (intrinsic or extrinsic
antigens)
 Intrinsic antigens :
– Megalin that is present in epithelial cell foot processes  Heymann
glomerulonephritis (in rats)
– Phospholipase A2 receptor (PLA2R)  membranous nephropathy
in human
 Extrinsic (planted) antigens :
– nuclear proteins  DNA, nucleosomes
– large aggregated proteins (e.g., aggregated immunoglobulins)
– viral, bacterial, and parasitic products
– drugs
Disease Caused by Anti-GBM antibodies

 The GBM antigen is a component of the

noncollagenous domain (NC1) of type IV collagen
 Anti-GBM antibodies may cross-react with other
basement membranes, especially those in the lung
alveoli  lung and kidney lesions (Goodpasture
syndrome)
 Anti GBM glomerulonephritis only < 5% of human
glomerulonephritis, however it causes severe
necrotizing and crescentic glomerular damage and
the clinical syndrome of rapidly progressive
glomerulonephritis.
Glomerulonephritis Resulting from Deposition
of Circulating Immune Complexes

 Glomerular injury is caused by the trapping of

circulating antigen-antibody complexes within
glomeruli.
 Antigens may be :
– Endogenous  as in the glomerulonephritis associated with
SLE or in IgA nephropathy
– Exogenous  glomerulonephritis post infections :
streptococcal proteins, hepatitis B virus antigens, hepatitis C
virus antigens, and antigens of Treponema pallidum,
Plasmodium falciparum, and several viruses and some
tumor antigens
Glomerular Injury Following Immune
Complex Formation

 Antigen-antibody complexes formed or deposited in

the glomeruli may elicit a local inflammatory reaction
that produces injury
 Deposition of immune complexes may in the form :
1. Subepithelial deposits, as in acute glomerulonephritis;
2. Epimembranous deposits, as in membranous
nephropathy and Heymann nephritis;
3. Subendothelial deposits, as in lupus nephritis and
membranoproliferative glomerulonephritis
4. Mesangial deposits, as in lgA nephropathy
Localization of immune complexes in the
glomerulus

(1) Subepithelial deposits

(2) epimembranous
deposits
(3) Subendothelial deposits
(4) Mesangial deposits
Mechanisms of Progression in
Glomerular Diseases
 Once any renal disease, glomerular or otherwise,
destroys functioning nephrons and reduces the GFR
to about 30% to 50% of normal, progression to end-
stage renal failure proceeds at a steady rate,
independent of the original stimulus or activity of the
underlying disease.
 Progressive glomerular injury can be the result of
either primary or secondary glomerular injuries, of
diseases that are either renal limited or systemic, and
of diseases that initially involve renal structures other
than glomeruli.
 The principal glomerular manifestation of progressive
injury is focal segmental glomerulosclerosis,
eventually leading to global glomerular involvement
and glomerular obsolescence.
 Progressive injury ensues from a cycle of glomerular
and nephron loss, compensatory changes that lead
to further glomerular injury and glomerulosclerosis,
and eventually end-stage renal disease.
 Progressive glomerular injury is accompanied by
chronic injuries to other renal structures, typically
manifest as tubulointerstitial fibrosis
Nephritic Syndrome

 Glomerular diseases presenting with a nephritic

syndrome are often characterized by inflammation in
the glomeruli.
 Clinic :
– hematuria, red cell casts in the urine,
– azotemia,
– oliguria,
– mild to moderate hypertension
– Proteinuria and edema are common (not as
severe as those in the nephrotic syndrome)
Nephritic Syndrome
1. Acute Proliferative (Poststreptococcal,
Postinfectious) Glomerulonephritis
2. Rapidly Progressive (Crescentic)
Glomerulonephritis
Acute Proliferative (Poststreptococcal,
Postinfectious) Glomerulonephritis
 Characterized histologically by diffuse
proliferation of glomerular cells associated
with influx (exudation) of leukocytes.
 These lesions are typically caused by
immune complexes caused by:
a. Poststreptococcal Glomerulonephritis
b. Nonstreptococcal Acute Glomerulonephritis
(Postinfectious Glomerulonephritis)
Poststreptococcal Glomerulonephritis

 Children 6 to 10 years of age

 Etiology : group A β-hemolytic streptococci
 Pathogenesis:
– immune complexes (containing streptococcal
antigens and specific antibodies)  glomerular
capillary walls  in situ formation of immune
complexes  inflammatory response
A, Normal glomerulus.
B, Glomerular hypercellularity is due to intracapillary leukocytes
and proliferation of intrinsic glomerular cells.
Nonstreptococcal Acute Glomerulonephritis
(Postinfectious Glomerulonephritis)
 Other infections, including :
– Bacterial (staphylococcal endocarditis,
pneumococcal pneumonia, meningococcemia)
– viral ( hepatitis B, hepatitis C, mumps, HIV
infection, varicella, infectious mononucleosis),
– parasitic (malaria, toxoplasmosis)
 Postinfectious glomerulonephritis due to
staphylococcal infections differs by sometimes
producing immune deposits containing IgA rather
than IgG.
Rapidly Progressive (Crescentic)
Glomerulonephritis
 A syndrome associated with severe glomerular injury,
but does not denote a specific etiologic form of
glomerulonephritis.
 characterized by rapid and progressive loss of renal
function associated with severe oliguria and signs of
nephritic syndrome;
 if untreated, death from renal failure occurs within
weeks to months
Rapidly Progressive (Crescentic)
Glomerulonephritis
 The most common histologic picture is the presence
of crescents in most of the glomeruli (crescentic
glomerulonephritis)
 in most cases the glomerular injury is
immunologically mediated
Rapidly Progressive (Crescentic)
Glomerulonephritis
 A practical classification divides RPGN into three
groups on the basis of immunologic findings :
– Anti-GBM antibody-mediated disease, characterized by
linear deposits of IgG and, in many cases, C3 in the
GBM.
– Diseases caused by immune complex deposition
RPGN can be a complication of any of the immune
complex nephritides, including postinfectious
glomerulonephritis, lupus nephritis, IgA nephropathy,
and Henoch-Schonlein purpura
– Pauci-immune RPGN
 Normal glomerulus

Crescentic glomerulonephritis
(PAS stain).
Note the collapsed glomerular
tufts and the crescent-shaped
mass of proliferating parietal
epithelial cells and leukocytes
internal to Bowman capsule.
Nephrotic Syndrome

 Nephrotic syndrome is caused by a

derangement in glomerular capillary walls
resulting in increased permeability to plasma
proteins.
 The manifestations of the syndrome include:
– Massive proteinuria, with the daily loss of 3.5 gm
or more of protein (less in children)
– Hypoalbuminemia, with plasma albumin levels
less than 3 gm/dL
– Generalized edema
– Hyperlipidemia and lipiduria
Membranous nephropathy

 Is caused by an autoimmune response, most

often directed against the phospholipase A2
receptor on podocytes;
 It is characterized by granular subepithelial
deposits of antibodies with GBM thickening
and loss of foot processes but little or no
inflammation;
 The disease is often resistant to steroid
therapy.
Membranous nephropathy. A. Silver methenamine stain. Note the marked
diffuse thickening of the capillary walls without an increase in the number of cells.
There are prominent "spikes" of silver-staining matrix (arrow) projecting from the
basement membrane lamina densa toward the urinary space, which separate and
surround deposited immune complexes that lack affinity for the silver stain. B.
Electron micrograph showing electron-dense deposits (arrow) along the epithelial
side of the basement membrane (B). Note the effacement of foot processes
overlying deposits. CL, Capillary lumen; End, endothelium; Ep, epithelium; US,
Minimal-Change Disease

 Relatively benign disorder

 Is characterized by diffuse effacement of foot
processes of visceral epithelial cells
(podocytes), detectable only by electron
microscopy, in glomeruli that appear virtually
normal by light microscopy.
 Most frequent cause of nephrotic syndrome in
children
Minimal-Change Disease

 Clinical Features:
– massive proteinuria (mostly albumin)
– Renal function remains good
– no hypertension
– no hematuria
 Shows dramatic response to corticosteroid
therapy
 Excellent prognosis
Minimal-change disease.
A, Glomerulus stained with PAS. Note normal basement membranes and absence of
proliferation.
B, Ultrastructural characteristics of minimal-change disease include effacement of
foot processes (arrows) and absence of deposits. CL, Capillary lumen; M,
mesangium; P, podocyte cell body.
Focal and segmental glomerulosclerosis
(FSGS)
 May be primary (podocyte injury by unknown
mechanisms) or secondary (e.g ., as a consequence
of prior glomerulonephritis, hypertension or infection
such as HIV);
 As the name implies, this lesion is characterized by
sclerosis of some, but not all, glomeruli (thus, it is
focal); and in the affected glomeruli, only a portion of
the capillary tuft is involved (thus, it is segmental),
and loss of foot processes;
Focal and segmental glomerulosclerosis
(FSGS)
 The disease is often resistant to therapy and
may progress to end-stage renal disease.
 Clinical Course:
– little tendency for spontaneous remission in
idiopathic FSGS,
– responses to corticosteroid therapy are variable.
– In general, children have a better prognosis than
adults do.
– Progression to renal failure occurs at variable
rates
Focal segmental glomerulosclerosis, PAS stain.
A, Low-power view showing segmental sclerosis in one of three glomeruli (at 3
o'clock).
B, High-power view showing hyaline insudation (arrow) and lipid (small vacuoles) in
sclerotic area.
Membranoproliferative
glomerulonephritis (MPGN)
 Synonym : mesangiocapillary glomerulonephritis.
 Best considered a pattern of immune-mediated injury
rather than a specific disease
 In most cases is the result of immune complex
deposition in both mesangial regions and capillary
walls.
 It may be associated with systemic infections.
Membranoproliferative
glomerulonephritis (MPGN)
 MPGN divided into two groups:
– type I: characterized by deposition of immune
complexes containing IgG and complement

– type II, (often called dense deposit disease) in

which activation of complement appears to be the
most important factor = C3 glomerulopathies
Schematic representation of patterns in the two types of membranoproliferative
glomerulonephritis. In type I there are subendothelial deposits; type II is
characterized by intramembranous dense deposits (dense-deposit disease). In
both, the basement rnernbranes appear split when viewed in the light microscope.
Glomerular Lesions Associated with
Systemic Diseases
 Lupus Nephritis
 Henoch-Schonlein Purpura
 Glomerulonephritis Associated with Bacterial
Endocarditis and Other Systemic Infections
 Diabetic Nephropathy
 Fibrillary Glomerulonephritis
 Other Systemic Disorders
Acute Tubular Injury/Necrosis
 Acute tubular injury is the most common cause of
acute kidney injury and attributed to ischemia and/or
toxicity from an endogenous or exogenous
substance.
 Tubular epithelial cell injury and altered intrarenal
hemodynamics are the primary contributors to acute
tubular injury.
 The clinical outcome is determined by the magnitude
and duration of acute tubular injury.
Acute Tubular Injury/Necrosis
 ATI is a reversible process that arises in a variety of
clinical settings
 ATI can be caused by:
– Ischemia, due to decreased or interrupted blood
flow
– Direct toxic injury to the tubules by endogenous
(e.g., myoglobin, hemoglobin, monoclonal light
chains, bile/bilirubin) or exogenous agents (e.g.,
drugs, radiocontrastdyes, heavy metals, organic
solvents)
Pathogenesis

 The critical events in both ischemic and

nephrotoxic ATI :
(1) tubular injury
(2) persistent and severe disturbances in blood flow
Acute Tubular Injury/Necrosis
Patterns of tubular damage in ischemic and toxic acute tubular injury. In the ischemic type,
tubular necrosis is patchy, relatively short lengths of tubules are affected, and straight segments
of proximal tubules (PST) and ascending limbs of Henle's loop (HL) are most vulnerable. In toxic
acute tubular injury, extensive necrosis is present along the proximal convoluted tubule
segments (PCT) with many toxins (e.g., mercury), but necrosis of the distal tubule, particularly
ascending HL, also occurs. In both types, lumens of the distal convoluted tubules (DCT) and
collecting ducts (CD) contain casts.
Acute tubular injury. Some of the tubular epithelial cells in the tubules are necrotic,
and many have become detached (from their basement membranes) and been
sloughed into the tubular lumens, whereas others are swollen, vacuolated, and
regenerating.
Neoplasms of the Kidney

Benign Neoplasms
• Renal Papillary Adenoma
• Angiomyolipoma
• Oncocytoma
Malignant Neoplasms
• Renal Cell Carcinoma
• Urothelial Carcinoma of the Renal Pelvis
Renal Papillary Adenoma

 Small, discrete adenomas arising from the renal

tubular epithelium are found commonly (7% to 22%)
at autopsy.
 They are most frequently papillary and are therefore
called papillary adenomas.
 On microscopic examination, they are composed of
complex, branching, papillomatous structures with
numerous complex fronds. Cells may also grow as
tubules, glands, cords, and sheets of cells. The cells
are cuboidal to polygonal in shape and have regular,
small central nuclei, scanty cytoplasm, and no atypia.
Renal Cell Carcinoma
 Renal cell carcinomas represent about 3% of all
newly diagnosed cancers in the United States and
account for 85% of renal cancers in adults.
 There are approximately 65,000 new cases per year
and 13,000 deaths from the disease.
 The tumors occur most often in older individuals,
usually in the sixth and seventh decades of life, and
show a 2: 1 male preponderance.
Epidemiology:
 Tobacco is the most significant risk factor.
 Cigarette smokers have double the incidence of renal
cell carcinoma, and pipe and cigar smokers are also
more susceptible.
 Additional risk factors: including obesity (particularly in
women); hypertension; unopposed estrogen therapy;
and exposure to asbestos, petroleum products, and
heavy metals.
 There is also an increased risk in patients with endstage
renal disease, chronic kidney disease, acquired cystic
disease (see earlier) and tuberous sclerosis.
Acute and Chronic Cystitis of the bladder

 In acute cystitis there is hyperemia of the mucosa

and neutrophilic infiltrate, sometimes associated with
exudate.
 Patients receiving cytotoxic antitumor drugs, such as
cyclophosphamide, may develop hemorrhagic
cystitis.
 Adenovirus infection also causes a hemorrhagic
cystitis.
 Persistence of the bacterial infection leads to chronic
cystitis associated with mononuclear inflammatory
infiltrates.
Acute and Chronic Cystitis of the bladder

 Other patterns of chronic cystitis :

– Follicular cystitis is characterized by the presence
of lymphoid follicles within the bladder mucosa
and underlying wall.
– Eosinophilic cystitis, manifested by infiltration with
submucosal eosinophils, typically is a nonspecific
subacute inflammation but may also be a
manifestation of a systemic allergic disorder.
Inflammatory disorders and metaplasias
of the bladder
 The bladder can be involved by a number of inflammatory
lesions, many of which manifest with frequency and
dysuria.
 Acute or chronic bacterial cystitis is extremely common,
particularly in women, and results from retrograde spread
of colonic bacteria in most cases.
 Other forms of cystitis have iatrogenic causes, such as
radiation cystitis and hemorrhagic cystitis due to antitumor
chemotherapeutics
 Some inflammatory or metaplastic bladder lesions are
significant in that they may clinically mimic bladder cancer,
including malakoplakia, polypoid cystitis, cystitis cystica et
glandularis and nephrogenic adenoma.
Tumors of the Urinary Bladder

 Urothelial (transitional) tumors

 Exophytic papilloma
 Inverted papilloma
 Papillary urothelial neoplasms of low malignant potential
 Low-grade and high-grade papillary urothelial cancers
 Carcinoma in situ (CIS, or flat noninvasive urothelial
carcinoma)
 Mixed carcinoma
 Adenocarcinoma
 Small-cell carcinoma
 Sarcomas
Papilloma

 These tumors typically arise singly as small (0.5 to 2

cm), delicate structures, superficially attached to the
mucosa by a stalk and are referred to as exophytic
papillomas.
 The individual finger-like papillae have a central core
of loose fibrovascular tissue covered by epithelium
that is histologically identical to normal urothelium.
 Inverted papillomas are completely benign lesions
consisting of inter-anastomosing cords of
cytologically bland urothelium that extend down into
the lamina propria.
Urothelial papilloma, exophytic
Small, short papillae are present. No appreciable urothelial thickening
is seen, and many umbrella cells are present. Note the vacuolation of
some umbrella cells.
Low-grade papillary urothelial carcinoma

 The cells are evenly spaced (i.e., maintain polarity)

and cohesive.
 There is a mild degree of nuclear atypia consisting of
scattered hyperchromatic nuclei, infrequent mitotic
figures predominantly toward the base, and slight
variation in nuclear size and shape.
 These low-grade cancers may recur and although
infrequent, may also invade.
Low-grade papillary urothelial carcinoma with an overall orderly appearance,
with a thicker lining than papilloma and scattered hyperchromatic nuclei and
mitotic figures (arrows).
High-grade papillary urothelial carcinoma

 Contain dyscohesive cells with large hyperchromatic

nuclei. Some of the tumor cells are highly anaplastic
 Mitotic figures, including atypical ones, are frequent.
 Architecturally, there is disarray and loss of polarity.
 These tumors have a much higher incidence of
invasion into the muscular layer, a higher risk of
progression, and significant metastatic potential.
High-grade papillary urothelial carcinoma with marked cytologic
atypia.
Condyloma Acuminatum of the penis

 A benign sexually transmitted wart caused by human

papillomavirus (HPV) mostly type 6 and 11
 On the penis these lesions occur most often about the
coronal sulcus and inner surface of the prepuce.
 They consist of single or multiple sessile or pedunculated,
red papillary that may be up to several millimeters in
diameter
 Histologically, a branching, villous, papillary connective
tissue stroma is covered by epithelium that may have
considerable superficial hyperkeratosis and thickening of
the underlying epidermis (acanthosis)
Condyloma Acuminatum of the penis

 The normal orderly maturation of the epithelial cells is

preserved; dysplasia is not evident.
 Cytoplasmic vacuolization of the squamous cells
(koilocytosis), characteristic of HPV infection, is noted
in these lesions.
 Condylomata acuminata tend to recur but only rarely
progress into in situ or invasive cancers.
Condyloma acuminatum of the penis.
The epithelium shows vacuolization (koilocytosis)
characteristic of human papillomavirus infection.
Bowen disease
 This is Carcinoma in Situ (CIS) which occurs in the genital
region of both men and women
 In men it tends to involve the skin of the shaft of the penis
and the scrotum.
 This lesion has strong association with infection by high-
risk HPV, most commonly type 16.
 Grossly it appears as a solitary, thickened, gray-white,
opaque plaque.
 Histologically the epidermis is hyperproliferative,
containing numerous mitoses, some atypical. The cells
are markedly dysplastic with large hyperchromatic nuclei
and lack of orderly maturation
Bowen disease (carcinoma in situ) of the penis.
Note the hyperchromatic, dysplastic dyskeratotic epithelial cells with scattered
mitoses above the basal layer. The intact basement membrane is not readily seen in
this picture.
Squamous cell carcinoma of the penis

 Associated with poor genital hygiene and with high-risk

HPV infection.
 Carcinomas are usually found in patients between 40 - 70
y/o
 Circumcision confers protection  extremely rare among
Jews and Muslims
 Circumcision reduces exposure to carcinogens that may
be concentrated in smegma and decreases the likelihood
of infection with potentially oncogenic types of HPV.
 Low-risk (6,11) and high-risk (16, 18) subtypes of HPV
Squamous cell carcinoma of penis.
The tumor forms a large, broad-based, polypoid mass.
Well-differentiated invasive squamous carcinoma.
Seminoma of the Testis

 The typical seminoma has a homogeneous,

graywhite, lobulated cut surface, usually devoid of
hemorrhage or necrosis.
 Generally the tunica albuginea is not penetrated, but
occasionally extension to the epididymis, spermatic
cord, or scrotal sac occurs.
 Microscopically the typical seminoma is composed of
sheets of uniform cells divided into poorly
demarcated lobules by delicate fibrous septa
containing a lymphocytic infiltrate
Seminoma. A, Low magnification shows clear seminoma cells
divided into poorly demarcated lobules by delicate septa.
B, Microscopic examination reveals large cells with distinct cell
borders, pale nuclei, prominent nucleoli, and a sparse
lymphocytic infiltrate.
Benign Prostatic Hyperplasia

 BPH is characterized by proliferation of benign stromal

and glandular elements. DHT, an androgen derived from
testosterone, is the major hormonal stimulus for
proliferation.
 BPH most commonly affects the inner periurethral zone of
the prostate, producing nodules that compress the
prostatic urethra.
 On microscopic examination, the nodules exhibit variable
proportions of stroma and glands. Hyperplastic glands are
lined by two cell layers, an inner columnar layer and an
outer layer composed of flattened basal cells.
Benign (nodular) prostatic hyperplasia. Low-power view of a
gland-rich hyperplastic nodule.
BPH. Glands appear bland and can have papillary infoldings,
which on cross section appear as fibrovascular cores floating
within the lumen.