MALE GENITAL SYSTEM AND LOWER URINARY TRACT
PENIS
● 2 types of Malformations
● Hypospadias
- More common
● Epyspadias
● Inflammatory lesions
● Balanitis and balanoposthitis
- Local inflammation of the glans
penis
● Candida albicans, anaerobic
bacteria, Gardnerella, and
pyogenic bacteria – common
agents
● Neoplasms
● More than 95% arise on
squamous epithelium.
● Factors:
- Poor hygiene
- Smoking
- HPV Infection
● Bowen disease
- Older circumcised
males.
● Invasive squamous cell
carcinoma
- Gray, crusted, popular
lesion, most commonly
on the glans penis or
prepuce.
SCROTUM, TESTIS, AND
EPIDIDYMIS
● The skin of the scrotum may be affected
by several inflammatory processes,
including local fungal infections and
systemic dermatoses.
● Hydrocele – most common cause of
scrotal enlargement.
● Hematoceles – Accumulation of blood
within the tunica vaginalis.
● Chyloceles – Accumulation of
lymphatic fluid within the tunica
vaginalis
● Elephantiasis – Enlargement to
grotesque size.
● Cryptorchidism and Testicular Atrophy
- Chryptorchidism - failure of
testicular descent into the
scrotum.
- Only affects 1% of the male
population.
- 3 to 5-fold increased risk of
testicular cancer.
● Inflammatory lesions
- Are more common in the
epididymis than in the testis
proper.
- Some of the more important
inflammatory disorders are
sexually transmitted.
- Nonspecific epididymis and
orchitis – other causes of
testicular inflammation.
● Vascular Disturbances
- Torsion typically results in
obstruction of testicular venous
drainage.
- 2 types of testicular torsion
▪ Neonatal torsion
▪ Adult torsion
● Testicular Neoplasms
- Occurs roughly 6 per 100,000
males.
- 15 – 34-year old age group
- In postpubertal males, 95% of
testicular tumors arise.
- Cause of testicular neoplasms
remains unknown.
- Most testicular tumors in
postpubertal males arise from
the in situ lesion – intratubular
germ cell neoplasia.
● Clinical Features
- Patients with testicular germ
cell neoplasms present most
frequently with a painless
testicular mass.
- Seminomas often remain
confined to the testis for long
intervals.
- Nonseminomas germ cell
neoplasms tend to metastasize
earlier, by lymphatic as well as
hematogenous routes.
Prostate
 - Can be divided into several biologically
distinct regions, the most important are the
peripheral and transition zones.
- The normal prostate contains glands with
two cell layers, a flat basal cell layer and an
overlying columnar secretory cell layer.
- Surrounding the prostatic stroma contains a
mixture of smooth muscle and fibrous
tissue.
Prostatitis
- Is divided into four categories
*acute bacterial prostatitis – caused by the same
case organisim associated with other acute
urinary tract infections
*chronic bacterial prostatitis – also caused by
common uropathogens
*chronic nonbacterial prostatitis – in which no
uropathogen is identified despite the
presence of local symptoms
*asymptomatic inflammatory prostatitis –
associated with incidental indetification of
leukocytes in prostatic secretions without
uropathogens
Bacerial Prostatitis
- May be acute or chronic: the responsible
organism usually is E.coli or another gram
negative rods
Chronic nonbacterial prostatitis
- Despite sharing symptomatology with
chronic bacterial prostatitis, is of unknown
etiology and does not respond to antibiotics
Granulomatous prostatitis
- Has a multifunctional etiology with both
infection and non infectious elements.
Benign Prostatic Hyperplasia
● Is characterized by proliferation of benign
stromal and glandular elements.
● Most commonly affects the inner
periuretheral zone of the prostate, producing
nodules that compress the prostatic urethra
● Symptoms are reported by 10% of affected
patients and include hesistancy, urgency,
nocturia, and poor urinary stream
Carcinoma of Prostate
● Carcinoma of the prostate is a common
cancer of older men between 65-75yrs old
● Range from indolent lesions that will never
cause patient to harm aggressive fatal
tumors
● Most common: TPRSS2-ETS fusion genes
Ureter
Ureteropelvic Junction obstruction
– a congenital disorder, results in
hydronephrosis.
– It is usually manifests in infancy or
childhood, much more commonly in
boys.
- It is the most frequent cause of
hydronephrosis in infants and
children.
Retroperitoneal fibrosis
- Is an uncommon cause of ureteral
narrowing or obstruction
characterized by a fibrous
proliferation
Urinary Bladder
Non-neoplastic Conditions
Bladder/Vesical Diverticulum
- Consists of a pouchlike evagination
of the bladder wall.
Diverticula
- May be congenital but more
commonly are acquired lesions that
arise as a consequence of persistent
urethral obstruction.
Cystitis are defined by either morphologic
appearance or causation
*Interstitial cystitis – is a persistent, painful
form of chronic cystitis occurring most
frequently in women
* Malakoplakia – most commonly occurs in the
bladder and results from defects in phagocytic or
degradative function of macrophages, such that
phagosomes become overloaded with undigested
bacterial products.
*Polypoid cystitis – is an inflammatory
condition resulting from a irritation to the
bladder mucosa in which the urothelium is
thrown into broad bulbous polypoid projections
as a result of marked submucosal edema.
SEXUALLY TRANSMITTED
DISEASES
Syphilis
-aka. Lues
-chronic venereal infection caused by the
spirochete Treponema pallidum.
-First recognized in epidemic form in 16th-
century Europe as the Great Pox
T. pallidum
-fastidious organism whose only natural host is
man.
- The usual source of infection is contact with a
cutaneous or mucosal lesion in a sexual partner
in the early (primary or secondary) stages of
syphilis.
- In congenital cases, T. pallidum is transmitted
across the placenta from mother to fetus,
particularly during the early stages of maternal
infection.
Primary Syphilis
-Between 9 and 90 days (mean, 21 days) after
infection
-Two types of antibodies are formed:
● antibodies that cross-react with host
constituents (nontreponemal antibodies)
● antibodies to specific treponemal
antigens.
hard chancre-The chancre of syphilis is
characteristically indurated
soft chancre-caused by Haemophilus ducreyi
-The chancre begins as a small, firm papule,
which gradually enlarges to produce a painless
ulcer with well-defined, indurated margins and a
“clean,” moist base
-Regional lymph nodes often are slightly
enlarged and firm but painless.
-Histologic examination of the ulcer reveals the
usual lymphocytic and plasmacytic
inflammatory infiltrate and proliferative vascular
changes
Secondary Syphilis
-approximately 2 months of resolution of the
chancre, the lesions of secondary syphilis
appear.
-Skin lesions usually are symmetrically
distributed and may be maculopapular, scaly, or
pustular. -Involvement of the palms of the hands
and soles of the feet is common.
-In moist skin areas, such as the anogenital
region, inner thighs, and axillae, broad-based,
elevated lesions termed condylomata lata may
appear.
Histologic examination of mucocutaneous
lesions reveals the characteristic proliferative
endarteritis, accompanied by a
lymphoplasmacytic inflammatory infiltrate.
-Lymph node enlargement is most common in
the neck and inguinal areas. Histologic
examination of enlarged nodes demonstrates
hyperplasia of germinal centers accompanied by
increased numbers of plasma cells or, less
commonly, granulomas or neutrophils.
-Less common manifestations include
➢ Hepatitis
➢ renal disease
➢ eye disease (iritis)
➢ gastrointestinal abnormalities.
Tertiary Syphilis
-usually after a latent period of 5 years or more.
Complications are divided into three major
categories:
➢ cardiovascular syphilis(syphilitic aortitis
)
➢ Neurosyphilis
➢ benign tertiary syphilis(gummas)
○ uncommon form marked by the
development of gummas in
various sites.
○ Gummas occur most commonly
in bone, skin, and the mucous
membranes of the upper airway
and mouth
○ Spirochetes are rarely
demonstrable within gummas.
Congenital Syphilis
- transmitted across the placenta from an
infected mother to the fetus at any time during
pregnancy.
- likelihood of transmission is greatest during
the early (primary and secondary) stages of
disease, when spirochetes are most numerous.
-the stigmata of congenital syphilis typically do
not develop until after the fourth month of
pregnancy.
Manifestations of congenital syphilis:
➢ Stillbirth
○ Hepatomegaly-shows
extramedullary hematopoiesis
and portal tract inflammation.
○ bone abnormalities-
inflammation and disruption of
the osteochondral junction in
long bones and, on occasion,
bone resorption and fibrosis of
the flat bones of the skull.
○ pancreatic fibrosis
 ○ pneumonitis-firm and pale as a
result of the presence of
inflammatory cells and fibrosis
in the alveolar septa (pneumonia
alba)
➢ Infantile syphilis-congenital syphilis in
liveborn infants that is clinically
manifest at birth or within the first few
months of life.
○ Rash
○ Osteochondritis
○ Periostitis
○ Liver and lung fibrosis
➢ late (tardive) congenital syphilis-cases
of untreated congenital syphilis of more
than 2 years’ duration.
○ Hutchinson triad:
■ notched central incisors
■ interstitial keratitis with
blindness
■ deafness from eighth
cranial nerve injury.
❏ Aso-called saber shin deformity
caused by chronic inflammation
of the periosteum of the tibia
❏ deformed molar teeth
(“mulberry molars”)
❏ chronic meningitis
❏ Chorioretinitis
❏ gummas of the nasal bone and
cartilage with a resultant
“saddlenose” deformity.
-In cases of congenital syphilis, the placenta is
enlarged, pale, and edematous.
-Microscopy reveals proliferative endarteritis
involving the fetal vessels, a mononuclear
inflammatory reaction (villitis), and villous
immaturity.
Serologic Tests for Syphilis
-polymerase chain reaction (PCR)–based testing
for syphilis
-Serologic tests for syphilis include:
➢ nontreponemal antibody tests
○ Measure antibody to cardiolipin
○ These antibodies are detected by
the rapid plasma reagin (RPR)
and Venereal Disease Research
Laboratory (VDRL) tests.
○ positive by 4 to 6 weeks of
infection
○ Two additional points regarding
nontreponemal antibody tests
deserve emphasis:
■ Nontreponemal
antibody test results
often are negative
during the early stages
of disease
■ As many as 15% of
positive VDRL test
results are unrelated to
syphilis.
➢ antitreponemal antibody tests
○ positive within 4 to 6 weeks
after an infection
○ usually remain positive
indefinitely, even after
successful treatment.
Serologic response may be delayed, exaggerated
(falsepositive results), or absent in patients with
syphilis and coexistent HIV infection.
Gonorrhea
-sexually transmitted infection of the lower
genitourinary tract
-caused by Neisseria gonorrhoeae.
➢ Humans are the only natural reservoir
➢ The organism is highly fastidious
➢ The bacteria initially attach to mucosal
epithelium, particularly of the columnar
or transitional type.
➢ The organism then penetrates through
the epithelial cells to invade the deeper
tissues of the host.
Clinical Features
In infected males it is manifested by
➢ the presence of dysuria
➢ urinary frequency
➢ mucopurulent urethral exudate within 2
to 7 days of the time of initial infection.
female patients manifest
➢ acquired by vaginal intercourse may be
asymptomatic
➢ Dysuria
➢ lower pelvic pain
➢ vaginal discharge.
Gonococcal infection of the upper genital tract
may spread to the peritoneal cavity, where the
exudate may extend up the right paracolic gutter
to the dome of the liver, resulting in gonococcal
perihepatitis. Disseminated infection- more ➢ perihepatic inflammation
common in females than in males. ➢ proctitis
➢ Manifestations include Morphologic and Clinical Features
○ Tenosynovitis -The primary infection is characterized by a
○ Arthritis mucopurulent discharge containing a
○ pustular or hemorrhagic skin predominance of neutrophils.
lesions -diagnosis is by nucleic acid amplification tests
○ Endocarditis on voided urine.
○ Meningitis -culture can be done from genital swabs, it is not
Gonococcal infection- may be transmitted to possible from urine. Molecular tests also are
infants during passage through the birth canal. more sensitive than culture.
➢ affected neonates develop purulent -reactive arthritis (formerly known as Reiter
infection of the eyes (ophthalmia syndrome), predominantly in patients who are
neonatorum), an important cause of HLA-B27–positive. This condition typically
blindness in the past. manifests as a combination of urethritis,
-Diagnosis can be made by culture of the conjunctivitis, arthritis, and generalized
exudates as well as by nucleic acid amplification mucocutaneous lesions.
techniques.
Lymphogranuloma Venereum
Nongonococcal Urethritis and Cervicitis -chronic, ulcerative disease caused by certain
-most common forms of STD. strains of C. trachomatis.
-caused by C. trachomatis,and the rest of -sporadic cases of LGV are seen most often
Trichomonas vaginalis, U. urealyticum, and among persons with multiple sexual partners.
Mycoplasma genitalium. MORPHOLOGY
C. trachomatis ➢ nonspecific urethritis
➢ small gram-negative bacterium that is an ➢ papular or ulcerative lesions involving
obligate intracellular pathogen. the lower genitalia
➢ It exists in two forms ➢ tender inguinal and/or femoral
○ elementary body lymphadenopathy that typically is
■ capable of at least unilateral
limited survival in the ➢ proctocolitis.
extracellular -lesions contain a mixed granulomatous and
environment. neutrophilic inflammatory response
■ taken up by host cells, -Regional lymphadenopathy is common, usually
primarily through a appearing within 30 days of the time of
process of receptor- infection.
mediated endocytosis. -Lymph node involvement is characterized by a
○ the reticulate body granulomatous inflammatory reaction associated
■ replicates and with irregularly shaped foci of necrosis and
ultimately forms new neutrophilic infiltration (stellate abscesses).
elementary bodies -Rectal strictures also occur
capable of infecting -In active lesions, the diagnosis made by
additional cells demonstration of the organism in biopsy
■ preferentially infect sections or smears of exudate.
columnar epithelial -Nucleic acid amplification tests
cells.
➢ Epididymitis Chancroid (Soft Chancre)
➢ Prostatitis -“third” venereal disease
➢ pelvic inflammatory disease -acute, ulcerative infection caused by
➢ Pharyngitis Haemophilus ducreyi, a small, gram-negative
➢ Conjunctivitis coccobacillus.
-serves as an important cofactor in the
transmission of HIV infection.
MORPHOLOGY
-4 to 7 days after inoculation, a tender,
erythematous papule develops on the external
genitalia.
-the ulcer of chancroid is not indurated, and
multiple lesions may be present
-base of the ulcer is covered by shaggy, yellow-
gray exudate.
-the regional lymph nodes, particularly in the
inguinal region, become enlarged and tender
-In untreated cases, the inflamed and enlarged
nodes (buboes) may erode the overlying skin to
produce chronic, draining ulcers.
-On microscopic examination:
➢ the ulcer of chancroid contains a
superficial zone of neutrophilic debris
and fibrin, with an underlying zone of
granulation tissue containing areas of
necrosis and thrombosed vessels.
➢ A dense, lymphoplasmacytic
inflammatory infiltrate is present
beneath the layer of granulation tissue.
➢ Coccobacillary organisms sometimes
are demonstrable in Gram- or silver-
stained preparations,
➢ A definitive diagnosis of chancroid
requires the identification of H. ducreyi
on special culture media.
Granuloma Inguinale
-chronic inflammatory disease caused by
Calymmatobacterium granulomatis
➢ a minute, encapsulated
coccobacillus related to the
Klebsiella genus.
-associated with a history of multiple sexual
partners.
-Untreated cases are characterized by
➢ extensive scarring
➢ lymphatic obstruction
➢ lymphedema (elephantiasis) of the
external genitalia.
MORPHOLOGY
-begins as a raised, papular lesion involving the
moist, stratified squamous epithelium of the
genitalia.
-As the lesion enlarges, its borders become
raised and indurated. Disfiguring scars may
develop in untreated cases, sometimes
associated with formation of urethral, vulvar, or
anal strictures.
-Regional lymph nodes typically are spared or
show only nonspecific reactive changes, in
contrast with chancroid.
-Microscopic examination of active lesions
reveals marked epithelial hyperplasia at the
borders of the ulcer, sometimes mimicking
carcinoma (pseudoepitheliomatous hyperplasia).
-demonstrable in Giemsa-stained smears of the
exudate as minute coccobacilli within vacuoles
in macrophages (Donovan bodies). Silver stains
(e.g., the Warthin-Starry stain) also may be used
to demonstrate the organism.
Trichomoniasis
-Caused by a sexually transmitted protozoan T.
vaginalis
➢ adheres to the mucosa, where it causes
superficial lesions.
➢ In females-associated with loss of acid-
producing Döderlein bacilli.
○ asymptomatic or associated with
pruritus and a profuse, frothy,
yellow vaginal discharge.
○ Urethral colonization may cause
urinary frequency and dysuria.
○ demonstrable in smears of
vaginal scrapings.
➢ in males
○ asymptomatic
○ may manifest as NGU. The
organism usually is
Genital Herpes Simplex
-herpes genitalis
- Genital HSV infection occur in any sexually
active population.
-Up to 95% of HIV-positive men who have sex
with men are seropositive for HSV-1 and/or
HSV-2.
-transmitted when the virus comes into contact
with a mucosal surface or broken skin of a
susceptible host.
-transmission requires direct contact with an
infected person, because the virus is readily
inactivated at room temperature, particularly if
dried.
MORPHOLOGY
initial lesions:
➢ Painful
 ➢ erythematous vesicles on the mucosa or
skin of the lower genitalia adjacent
extragenital sites.
- anorectal area- particularly common site of
primary infection among men who have sex
with men.
-histologic examination the vesicles of HSV
infection contain necrotic cells and fused
multinucleate giant cells with intranuclear
inclusions (Cowdry type A) that stain with
antibodies to the virus.
-classic Cowdry type A inclusion appears as a
light purple, homogeneous intranuclear structure
surrounded by a clear halo.
Clinical Features
The manifestations of HSV infection vary
considerably, depending on whether the
infection is primary or recurrent.
Primary infection with HSV-2 often is mildly
symptomatic.
In persons experiencing their first
episode,locally painful vesicular lesions are
often accompanied by
➢ Dysuria
➢ urethral discharge
➢ local lymph node enlargement and
tenderness
➢ Fever
➢ muscle aches
➢ headache.
Recurrences are much more common with HSV-
1 than with HSV-2
➢ typically are milder and of shorter
duration than in the primary episode.
FEMALE GENITAL SYSTEM AND BREAST
VULVA
The vulva is the external female genitalia and
includes the moist hair-bearing skin and mucosa
in that region.
VULVITIS
One of the most common causes of vulvitis is
reactive inflammation in response to an
exogenous stimulus, whether an irritant (contact
irritant dermatitis) or an allergen (contact
allergic dermatitis) Scratching-induced trauma
secondary to associated intense “itching”
-HSV pose a major threat to immunosuppressed
patients, in whom fatal, disseminated disease
may develop.
-Neonatal herpes can be life-threatening and
occurs in children born to mothers with genital
herpes. -Affected infants have generalized
herpes, often associated with encephalitis and
consequent high mortality
-The laboratory diagnosis of genital herpes relies
on viral culture.
Human Papillomavirus Infection
-HPV causes many proliferative lesions of the
genital mucosa, including condyloma
acuminatum, precancerous lesions, and invasive
cancers.
-Condylomata acuminata, also known as
venereal warts, are caused by HPV types 6 and
11.
➢ These lesions occur on the penis as well
as on the female genitalia.
-Genital HPV infection may be transmitted to
neonates during vaginal delivery.
MORPHOLOGY
In males
● condylomata acuminata usually occur
on the coronal sulcus or inner surface of
the prepuce, where they range in size
from small, sessile lesions to large,
papillary proliferations measuring
several centimeters in diameter.
In females
● commonly occur on the vulva.
(pruritus) often exacerbates the primary
condition.
NON-NEOPLASTIC EPITHELIAL
DISORDERS
The epithelium of the vulvar mucosa may
undergo both atrophic thinning and hyperplastic
thickening, often in the form of lichen sclerosus
and lichen simplex chronicus, respectively.
Lichen sclerosus is characterized by thinning of
the epider- mis, disappearance of rete pegs,
hydropic degeneration of the basal cells, dermal
fibrosis, and a scant perivascular, mononuclear
inflammatory cell infiltrate occurs in all age
groups but most com- monly affects
postmenopausal women
● Lichen sclerosus is benign
● Lichen sclerosus is characterized by
atrophic epithelium, usually with
dermal fibrosis.
● Lichen sclerosus carries a slightly
increased risk for devel- opment of
squamous cell carcinoma.
Lichen simplex chronicus is marked by
epithelial thicken- ing (particularly of the
stratum granulosum) and hyper- keratosis.
Increased mitotic activity is seen in the basal and
suprabasal layers
● Lichen simplex chronicus is
characterized by thickened epithelium
(hyperplasia), usually with an
inflammatory infiltrate.
● The lesions of lichen sclerosus and
lichen simplex chroni- cus must be
biopsied to definitively distinguish them
from other causes of leukoplakia,
such as squamous cell carci- noma of
the vulva.
TUMOR
➢ Condyloma is the name given to any
warty lesion of the vulva. Most such
lesions can be assigned to one of two
distinctive forms
➢ Condylomata lata, not commonly seen
today, are flat, moist, minimally
elevated lesions that occur in secondary
syphilis
➢ Condylomata acuminata may be
papillary and distinctly elevated or
somewhat flat and rugose.
Carcinoma of the vulva represents about 3% of
all female genital tract cancers, occurring mostly
in women older than age 60. Approximately
90% of carcinomas are squamous cell
carcinomas; the other tumors are mainly
adenocarcino- mas or basal cell carcinomas.
➢ HPV-related vulvar squamous cell
carcinomas usually are poorly
differentiated lesions and sometimes are
multifocal. They often evolve from
vulvar intraepithelial neoplasia (VIN)
➢ Non–HPV-related vulvar squamous cell
carcinomas occur in older women,
usually are well differentiated and unifo-
cal, and often are associated with lichen
sclerosus or other inflammatory
conditions.
Extramammary Paget Disease
➢ Paget disease is an intraepidermal
proliferation of malig- nant epithelial
cells that can occur in the skin of the
vulva or nipple of the breast. It
manifests as a red, scaly, crusted plaque
that may mimic the appearance of an
inflammatory dermatitis.
● Vulvar Paget disease is characterized by
a red, scaly plaque caused by
proliferation of malignant epithelial
cells within the epidermis; usually,
there is no underlying carcinoma,
unlike Paget disease of nipple.
● Positive staining for PAS
distinguishes Paget disease cells from
melanoma.
VAGINA
In adult fernales, the vagina is seldom a site of
primary disease. More often, it is involved
secondarily by cancer or infections arising in
adjacent organs (e.g., cervix, vulva, bladder,
rectum)
➢ Vaginitis is a relatively common
condition that is usually transient and of
no clinical consequence. It is associated
with production of a vaginal discharge
(leukorrhea) vaginitis is characterized
by a curdy white discharge. This
organism is part of the normal vaginal
flora in about 5% of women
Cervix
Anatomically the cervix consists of the:
1. External vaginal portio (ectocervix) - is
visible on vaginal examination and is
covered by a mature squamous epithelium
that is continuous with the vaginal wall.
 2. Endocervical canal - The endocervix is
lined by columnar, mucus-secreting
epithelium.
3. Squamocolumnar junction - The point
where the squamous and columnar
epithelium meet
4. Transformation Zone - Columnar cells are
constantly changing into squamous cells in
this area of cervix
Inflammations
Settings that altered vaginal environment promotes
the overgrowth of other microorganisms, which may
result in cervicitis or vaginitis:
● Antibiotic therapy that suppress lactobacilli
can also cause the pH to rise
● Bleeding
● Sexual intercourse
● Vaginal douching
May produce significant acute or chronic cervicitis
and are important to identify due to their association
with upper genital tract disease
● Gonococci
● Chlamydiae
● Mycoplasmas
● HSV
Endocervical Polyps
They vary from small, sessile “bumps” to large
polypoid masses that may protrude through the
cervical os.
Endocervical polyps are common benign exophytic
growths that arise within the endocervical canal.
Their main significance:
● the source of irregular vaginal
“spotting”
● or bleeding that arouses suspicion
of some more ominous lesion
● Simple curettage or surgical
excision is curative.
Premalignant and Malignant Neoplasms
of the Cervix
Worldwide, cervical carcinoma is the third
most common cancer in women.
No form of cancer better documents the
remarkable benefits of effective screening, early
diagnosis, and curative therapy than does cancer of
the cervix.
These dramatic gains belongs to the
effectiveness of the Pap test in detecting cervical
precursor lesions, some of which would have
progressed to cancer if not treated; in addition, the
Pap test can also detect low-stage, highly curable
cancers.
The accessibility of the cervix to Pap testing
and visual exam (colposcopy) as well as the slow
progression from precursor lesions to invasive
carcinoma (typically over the course of years)
provides ample time for screening, detection, and
preventive treatment.
Pathogenesis
High-risk HPVs are by far the most important
factor in the development of cervical cancer
There are 15 high risk HPVs that are currently
identified, but HPV-16 alone accounts for
almost 60% of cervical cancer cases, and
HPV18 accounts for another 10% of cases; other
HPV types contribute to less than 5% of cases,
individually.
High risk HPVs are also implicated in squamous
cell carcinomas arising at many other sites,
including:
● the vagina
● vulva
● penis
● anus
● tonsil
● other oropharyngeal locations.
Genital HPV infections are extremely common;
most of them are asymptomatic, do not cause
any tissue changes, and therefore are not
detected on Pap test.
The duration of the infection is related to HPV
type; on average, infections with high-risk HPVs
last longer than infections with low oncogenic
risk HPVs (13 months versus 8 months,
respectively).
The ability of HPV to act as a carcinogen
depends on the viral proteins E6 and E7, which
interfere with the activity of tumor suppressor
proteins that regulate cell growth and survival
Another factor that contributes to malignant
transformation by HPV is the physical state of
the virus
Cervical Intraepithelial Neoplasia (Squamous
Intraepithelial Lesions)
The oldest classification system grouped lesions
as having mild dysplasia on one end and severe
dysplasia/carcinoma in situ on the other.
This was followed by the cervical intraepithelial
neoplasia (CIN) classification, with:
● mild dysplasia (CIN I)
● moderate dysplasia (CIN II)
● severe dysplasia termed (CIN III)
CIN I renamed low-grade squamous
intraepithelial lesion (LSI L) and CIN II and
CIN III combined into one category referred to
as high-grade squamous intraepithelial lesion
(HSIL)
LSIL
- LSI L is associated with a productive
HPV infection
- There is a high level of viral replication
and only mild alterations in the growth
of host cells
- Does not progress directly to invasive
carcinoma and in fact most cases regress
spontaneously; only a small percentage
progress to HSIL
- is not treated like a pre-malignant lesion
- ten times more common than HSILs
HSIL
- there is a progressive deregulation of the
cell cycle by HPV which results in
o increased cellular proliferation
o decreased or arrested epithelial
maturation
o lower rate of viral replication, as
compared with LSIL
- Are considered to be at high risk for
progression to carcinoma
More than 80% of LSILs and 100% of HSILs
are associated with high-risk HPVs, with
HPV16 being the most common HPV type in
both categories of lesions
Cervical Carcinoma
The average age of patients with invasive
cervical carcinoma is 45 years.
Squamous cell carcinoma is the most common
histologic subtype, accounting for approximately
80% of cases.
The second most common tumor type is
adenocarcinoma, which constitutes about 15%
of cervical cancer cases and develops from a
precursor lesion called adenocarcinoma in situ.
Adenosquamous and neuroendocrine
carcinomas are rare cervical tumors that
account for the remaining 5% of cases
All of the aforementioned tumor types are
caused by high-risk HPVs.
Cervical cancer is staged as follows:
Stage 0—Carcinoma in situ (CIN III, HSIL)
Stage I—Carcinoma confined to the cervix
● Ia—Preclinical carcinoma, that is,
diagnosed only by microscopy
● Ia1—Stromal invasion no deeper than 3
mm and no wider than 7 mm (so-called
microinvasive carcinoma)
● Ia2—Maximum depth of invasion of
stroma deeper than 3 mm and no deeper
than 5 mm taken from base of
epithelium; horizontal invasion not more
than 7 mm
● Ib—Histologically invasive carcinoma
confined to the cervix and greater than
stage Ia2
Stage II—Carcinoma extends beyond the cervix
but not to the pelvic wall. Carcinoma
Stage III—Carcinoma has extended to the
pelvic wall. On rectal examination there is no
cancer-free space between the tumor and the
pelvic wall. The tumor involves the lower third
of the vagina.
Stage IV—Carcinoma has extended beyond the
true pelvis or has involved the mucosa of the
bladder or rectum. This stage also includes
cancers with metastatic dissemination
Clinical Features
While early invasive cancers of the cervix
(microinvasive carcinomas) may be treated by
cervical cone excision, most invasive cancers
are managed by hysterectomy with lymph node
dissection for advanced lesions, radiation and
chemotherapy.
The prognosis and survival for invasive
carcinomas depend on the stage of the cancer at
diagnosis and to some degree on histologic
subtype, with small-cell neuroendocrine tumors
having a very poor prognosis
With current treatments the 5-year survival rate
is 100% for microinvasive carcinomas and less
than 50% for tumors extending beyond pelvis
Most patients with advanced cervical cancer die
of the consequences of local tumor invasion
(ureteral obstruction, pyelonephritis, and
uremia) rather than distant metastases.
Cervical Cancer Screening and Prevention
Cytologic cancer screening has significantly
reduced mortality from cervical cancer
The reason that cytologic screening is so
effective in preventing cervical cancer is that
most cancers arise from precursor lesions over
the course of years. These lesions shed abnormal
cells that can be detected on cytologic
examination.
a. Using a spatula or brush, the
transformation zone of the cervix is
circumferentially scraped
b. And the cells are smeared or spun down
onto a slide
c. Following fixation and staining with the
Papanicolaou method, the smears are
screened microscopically by eye or
(increasingly) with automated image
analysis systems
d. The cellular changes seen on the Pap
test, illustrating the spectrum from LSIL
to HSIL
Cervical Cancer Screening and Prevention
First smear should be at age 21 years or
within 3 years of onset of sexual activity, and
thereafter every 3 years.
After age 30, women who have had
normal cytology results and are negative for
HPV may be screened every 5 years
Women with a normal cytology result,
but test positive for high-risk HPV DNA, should
have cervical cytology repeated every 6 to 12
months.
When the result of a Pap test is
abnormal, a colposcopic examination of the
cervix and vagina is performed to identify the
lesion.
a. application of acetic acid
b. mucosa is examined with a
magnifying glass
c. Abnormal appearing areas are
biopsied
d. Women with biopsy confirmed
LSIL can be followed in a
conservative fashion.
e. Some gynecologists will perform
local ablation (e.g., cryotherapy) of
LSIL.
A new aspect of cervical cancer prevention is
vaccination against high-risk oncogenic HPVs,
which is now recommended for all girls and
boys by age 11 to 12 years, as well as young
men and women up to age 26 years.
The vaccines offer protection for up to 10 years
BODY OF UTERUS
● Composed of endometrial mucosa and
the underlying smooth muscle
myometrium.
● ENDOMETRITIS
- Acute – neutrophilic response
- Chronic – lymphoplasmacytic
response
- Often a consequence of pelvic
inflammatory disease due to N.
gonorrhoeae or C. trachomatis.
● ADENOMYOSIS
- Refers to the growth of the basal
layer of the endometrium down
into the myometrium.
-
- The aberrant presence of
endometrial tissue induces
reactive hypertrophy of the
myometrium.
- May produce menorrhagia,
dysmenorrhea, and pelvic pain
before onset of menstruation.
● ENDOMETRIOSIS
- Defined by the presence of
endometrial glands and stroma
 in a location outside the
endomyometrium.
- Occurs in 10% of women on
their reproductive years.
● ABNORMAL UTERINE BLEEDING
- 2 types of bleeding
▪ Menorrhagia – profuse
or prolonged bleeding at
the time of the period.
▪ Metrorrhagia – irregular
bleeding between the
periods.
- Common causes
▪ Endometrial polyps
▪ Leiomyomas
▪ Endometrial hyperplasia
▪ Endometrial carcinoma
▪ Endometritis
-4 groups that cause abnormal
uterine bleeding
▪ Failure of ovulation
▪ Inadequate luteal phase
▪ Contraceptive-induced
bleeding
▪ Endomyometrial
disorders
● PROLIFERATIVE LESIONS OF THE
ENDOMETRIUM AND
MYOMETRIUM
- The most common proliferative
lesions of the uterine corpus:
▪ Endometrial hyperplasia
▪ Endometrial carcinomas
▪ Endometrial polyps
▪ Smooth muscle tumors.
● Endometrial Hyperplasia
-Excess of estrogen relative to
progestin, if sufficiently
prolonged or marked, can
induce exaggerated endometrial
proliferation.
- Potential causes of estrogen
excess:
▪ Failure of ovulation
▪ Prolonged
administration of
estrogenic steroids
without
counterbalancing
progestin
▪ Estrogen producing
ovarian lesions
▪ Obesity – common
cause of estrogen
excess.
● Endometrial Carcinoma
- Most frequent occurring cancer
in the western countries.
- 2 distinct cancers:
▪ Endometrioid
▪ Arise in association
with estrogen excess
and endometrial
hyperplasia in
perimenopausal women.
▪ Serous
▪ Arise in the setting of
endometrial atrophy in
older postmenopausal
women
- Clinical course:
 ▪ Usually manifests with
leukorrhea and irregular
bleeding.
▪ Slow to metastasize.
● Endometrial Polyps
- Hemispheric lesions that range
from 0.5 to 3cm in diameter.
- They are composed of
endometrium resembling the
basalis, frequently with small
muscular arteries.
- May occur at any age, most
commonly detected around time
of menopause.
● Leiomyoma
- Benign tumors that arise from
the smooth muscle cells in the
myometrium.
- Clinically referred to as fibroids.
- Most common benign tumors in
females. More frequent in
blacks than in whites.
- Leiomyomas in the uterus often
are asymptomatic, most
frequent sign is menorrhagia,
with or without metrorrhagia
● Leiomyosarcoma
- Arise de novo from the
mesenchymal cells of the
myometrium.
- Almost always solitary and
most often occur in
postmenopausal women.
FALLOPIAN TUBES
Salpingitis – The most common disorder of the
fallopian tubes is inflammation, almost
invariably occurring as a component of pelvic
inflammatory disease
- All forms of salpingitis can
produce fever, lower abdominal
or pelvic pain and pelvic masses
which are a result of distention of
the tubes with exudate or
inflammatory debris
● Adherance of the inflamed tube to the
ovary and adjacent ligamentous tissues
may result in a tubovarian absess,
referred to as a tubovarian complex
when infection subsides.
Primay adenocarcinoma of the fallopian tubes
may be of serous or endometrioid histologic type
OVARIES
Cyst are often multiple and and develop to the
serosal covering in the ovaries
● They are typically small (1-1.5cm in
diameter) and aare filled with clear
serous fluids
● They can occasionally become large (4-
5cm) to produce palpable masses and
pelvic pain
Polycystic Ovarian Disease (formerly Stein-
Leventhal syndrome)
- Is a disorder in which multiple
cystic follicles in the ovaries
produce excess androgens and
estrogens.
TUMORS OF THE OVARY
● Ovarian cancer is the eight most
common cancer in U.S
● It is also the fifth leading contributor to
cancer mortality in women.
● Tumors of the ovary are amazingly
varied. This diversity is attributable to
the presence of three cell types: the
multipotent surface epithelium, the
totipotent germ cells, and the sex
cordstromal cells.
Serous Tumors
– are the most common of the ovarian
epithelial tumors. About 60% are benign, 15%
are low of malignant potential, and about 25%
are malignant.
Benign tumors: 30 – 40 yrs old
Malignant Tumors: 45 – 65 yrs old
Two types of Serous Carcinoma:
Low grade – are associated with KRAS, BRAF,
or ERBB2 mutations
High grade – 96% of these tumors have
mutations in TP53
Mucinous Tumors
- are, in most respects, similar to
serous tumors, the essential
difference bein that the neoplastic
epithelium consists of mucin-
secreting cells.
Brenner Tumors
- is an uncommon, solid, usually
unilateral ovarian tumor
consisting of abundant stroma
containing nest of transitional-
type epithelium resembling that of
the urinary tract
- genrally are are smoothly
encapsulated and gray white on
cut section, ranging from a few
centimeters to 20cm in diameter.
- These tumors may arise from the
surface epithelium or from
urogenital epithelium or from the
urogenital epithelium trapped
within the the germinal ridge.
Endometroid Tumors
- These tumors may be solid or
cystic: they sometimes develop in
association with endometriosis.
- On microscopic examination, they
are distinguished by the formation
of tubular glands, similar to those
of the endometrium, within the
lining of the cystic spaces.
● Germ cell tumors are the most common
ovarian tumors in young woman: a
majority are benign
o Germ cell tumors may
differentiate toward oogonia,
primitive embryonal tissue, yolk
sac, placental tissue, or multiple
fecal tissues.
Gestational and Placental Disorders
Diseases of pregnancy and pathologic
conditions of the placenta are important
causes of
 fetal intrauterine or perinatal death,
 congenital malformations,
 intrauterine growth retardation,
 maternal death,
 morbidity for both mother and child.
 Ectopic Pregnancy
Disorders of Early Pregnancy
Spontaneous Abortion “miscarriage”
- is defined as pregnancy loss before
20 weeks of gestation.
- Most of these occur before 12 weeks.
In most individual instances, the
mechanisms leading to early loss of
pregnancy are unknown. However, multiple
fetal and maternal causes of spontaneous
abortion have been identified. Among the
most important are the following:
Fetal chromosomal anomalies
 Aneuploidy
 Polyploidy
 Translocations
Maternal endocrine factors
 luteal-phase defect
 poorly controlled diabetes
 other uncorrected endocrine
disorders
Physical defects of the uterus
 submucosal leiomyomas
 uterine polyps
 uterine
Systemic disorders affecting the maternal
vasculature
 antiphospholipid antibody syndrome
 coagulopathies
 hypertension
Infections
 Protozoa
 Bacteria
 A number of viruses
- refers to implantation of the fetus in
a site other than the normal
intrauterine location
 - the most common site is the
extrauterine fallopian tube
(approximately 90% of cases)
- . Other sites include the:
Ovary pregnancy results from the
fertilization and trapping of the ovum within
the follicle just at the time of its rupture
Abdominal cavity/abdominal pregnancy
occur when the fertilized ovum fails to enter
or drops out of the fimbriated end of the
tube
Intrauterine portion of the fallopian tube
Ectopic pregnancies account for 2% of
confirmed pregnancies
Clinical Features
The clinical course of ectopic tubal
pregnancy is characterized by the onset of
moderate to severe abdominal pain and
vaginal bleeding 6 to 8 weeks after last
menstrual period
Diagnosis is based on determination of:
 chorionic gonadotropin titers
 pelvic sonography
 endometrial biopsy
 laparoscopy
Disorders of Late Pregnancy
Disorders that occur in the third trimester of
pregnancy are related to the complex
anatomy of the maturing placenta
Twin Placentas
- arise from fertilization of two ova
(dizygotic) or from division of one
fertilized ovum (monozygotic)
There are three basic types of twin
placentas:
 diamnionic dichorionic (which may
be fused)
 diamnionic monochorionic
 monoamnionic monochorionic
Abnormalities of Placental Implantation
Placenta previa
- a condition in which the placenta
implants in the lower uterine segment
or cervix, often leading to serious
third-trimester bleeding
- . Common predisposing factors are
placenta previa (in up to 60% of
cases) and history of previous
cesarean section
.
Placenta accrete
- caused by partial or complete absence
of the decidua, such that the placental
villous tissue adheres directly to the
myometrium, which leads to a failure
of placental separation at birth
Placental Infections
Infections in the placenta develop by two
pathways:
(1) ascending infection through the birth
canal
- most common and are virtually
always bacterial
(2) hematogenous (transplacental)
infection
Preeclampsia and Eclampsia
- a systemic syndrome characterized by
widespread maternal endothelial
dysfunction that presents during
pregnancy with:
 hypertension
 edema
 proteinuria
- more severe form of the disorder is
termed eclampsia
Pathogenesis
The principal pathophysiologic aberrations
appear to be the following:
 Abnormal placental vasculature
 Endothelial dysfunction and
imbalance of angiogenic and
antiangiogenic factors
 Coagulation abnormalities
Clinical Features
Preeclampsia most commonly starts after
34 weeks of gestation but begins earlier in
women with:
 hydatidiform mole or preexisting
kidney disease
 hypertension
 coagulopathies
Eclampsia is heralded by central nervous
system involvement, including convulsions
and eventual coma.
Gestational Trophoblastic Disease
- encompasses a spectrum of tumors
and tumor-like conditions
characterized by proliferation of
placental tissue, either villous or
trophoblastic
The major disorders of this type:
 hydatidiform mole (complete and
partial
 invasive mole
 choriocarcinoma
 placental site trophoblastic tumor
(PSTT)
Hydatidiform Mole
- are important to recognize because
they are associated with an increased
risk of persistent trophoblastic
disease (invasive mole) or
choriocarcinoma.
- Moles are characterized histologically
by cystic swelling of the chorionic
villi, accompanied by variable
trophoblastic proliferation.
- Two types of benign, noninvasive
moles—complete and partial—can be
identified by cytogenetic and
histologic studies.
Complete Mole
- results from fertilization of an egg
that has lost its female chromosomes,
and as a result the genetic material is
completely paternally derived
- the embryo dies very early in
development and therefore is usually
not identified
Partial Mole
- Partial moles result from fertilization
of an egg with two sperm . I n these
moles the karyotype is triploid (or
occasionally tetraploid )
- Fetal tissues are typically present
- increased risk of persistent molar
disease, but are not associated with
choriocarcinoma.
Clinical Features
In complete moles, human chorionic
gonadotropin (HCG) levels greatly
exceed those of a normal pregnancy of
similar gestational age.
Most moles are successfully removed
by cureĴage
Continuous elevation of HCG may be
indicative of persistent or invasive mole
Invasive Mole
- defined as a mole that penetrates or
even perforates the uterine wall
- The tumor is locally destructive and
may invade parametrial tissue and
blood vessels
 - The tumor is manifested clinically by
vaginal bleeding and irregular uterine
enlargement
- It is always associated with a
persistently elevated serum HCG
- The tumor responds well to
chemotherapy but may result in
uterine rupture and necessitate
hysterectomy
Choriocarcinoma
Gestational choriocarcinoma is a malignant
neoplasm of trophoblastic cells derived from
a previously normal or abnormal pregnancy,
such as an extrauterine ectopic pregnancy.
Choriocarcinoma is rapidly invasive and
metastasizes widely, but once identified
responds well to chemotherapy.
Clinical Features
Uterine choriocarcinoma usually manifests
as irregular vaginal spotting of a bloody,
brown fluid.
This tumor has high propensity for
hematogenous spread
The treatment of gestational
choriocarcinoma depends on the stage of
the tumor and usually consists of
evacuation of the contents of the uterus and
chemotherapy
Placental Site Trophoblastic Tumor
(PSTT)
- They are neoplastic proliferations of
extravillous trophoblasts, also called
intermediate trophoblasts.
- I n normal pregnancy, extravillous
(intermediate) trophoblasts are found
in nonvillous sites such as:
 the implantation site
 in islands of cells within the placental
parenchyma
 in the placental membranes
- PSTT presents as a uterine mass,
accompanied by either abnormal
uterine bleeding or amenorrhea and
moderately elevated HCG
- Histologically, PSTT is composed of
malignant trophoblastic cells diffusely
infiltrating the endomyometrium
- It may follow a normal pregnancy
(half of the cases), spontaneous
abortion, or hydatidiform mole
BREAST 
● Supernumerary nipples or breast tissue -
found anywhere along the embryonic
ridge (milk line).
● Congenital inversion of the nipple is of
clinical significance because similar
changes may be produced by an
underlying cancer. 
● Galactocele arises during lactation from
cystic dilation of an obstructed duct.
FIBROCYSTIC CHANGES 
● most common breast abnormality seen
in premenopausal women.
● This range of changes is the
consequence of an exaggeration and
distortion of the cyclic breast changes
that occur normally in the menstrual
cycle.
● Estrogenic therapy and oral
contraceptives do not seem to increase
the incidence of these alterations.
Nonproliferative Changes
Cysts and Fibrosis 
● most common type of fibrocystic lesions
● increase in fibrous stroma associated
with dilation of ducts and formation of
variably sized cysts. 
MORPHOLOGY 
● A single, large cyst may form within
one breast
● Changes usually are multifocal and
often bilateral
● cysts: <1cm – 5cm in diameter
● Unopened, they are brown to blue (blue
dome cysts) and are filled with watery,
turbid fluid 
 ● the secretions within the cysts may ● atypical ductal and lobular hyperplasia
calcify, producing microcalcifications are associated with an increased risk of
on mammograms. invasive carcinoma.
Histologic examination  Sclerosing Adenosis 
● reveals an epithelial lining that in larger ● contain marked intralobular fibrosis and
cysts may be flattened or even totally proliferation of small ductules and acini.
atrophic.  MORPHOLOGY 
● lining cells are large and polygonal with ● lesion: has a hard, rubbery consistency,
abundant granular, eosinophilic similar to that of breast cancer. 
cytoplasm and small, round, deeply Histologic examination 
chromatic nuclei. (apocrine metaplasia) ● shows a characteristic proliferation of
and virtually always is benign.  luminal spaces (adenosis) lined by
● the stroma surrounding all types of cysts epithelial cells and myoepithelial cells,
usually consists of compressed fibrous yielding masses of small glands within a
tissue that has lost the delicate, fibrous stroma 
myxomatous appearance of normal Relationship of Fibrocystic Changes to Breast
breast stroma. Carcinoma 
-the only certain way of making this distinction
Proliferative Change  is through biopsy and histologic examination.
Epithelial Hyperplasia  -Although fibrocystic changes are benign, some
● normal ducts and lobules of the breast features may confer an increased risk for
are lined by two layers of cells: development of cancer: 
o luminal cells • Minimal or no increased risk of breast
o myoepithelial cells.  carcinoma: fibrosis, cystic changes, apocrine
● recognized by the presence of more than metaplasia, mild hyperplasia 
two cell layers.  • Slightly increased risk (1.5- to 2-fold):
● the spectrum ranges from mild and moderate to florid hyperplasia (without atypia),
orderly to atypical hyperplasias with ductal papillomatosis, sclerosing adenosis 
features that resemble those of in situ • Significantly increased risk (5-fold): atypical
carcinoma.  hyperplasia, whether ductular or lobular
Morphology  -Proliferative fibrocystic changes usually are
● The gross appearance is not distinctive bilateral and multifocal and are associated with
● dominated by coexisting fibrous or increased risk of subsequent carcinoma in both
cystic changes.  breasts.
Histologic examination  INFLAMMATORY PROCESSES 
● shows an almost infinite spectrum of - usually associated with pain and
proliferative alterations.  tenderness in the affected areas.
● The ducts, ductules, or lobules may be Acute mastitis
filled with orderly cuboidal cells within ● develops when bacteria, usually
which small gland patterns Staphylococcus aureus, gain access to
(fenestrations) can be discerned.  the breast tissue through the ducts. 
● hyperplasia produces ● The vast majority of cases arise during
microcalcifications on mammography, the early weeks of nursing, when the
raising concern for cancer.  skin of the nipple is vulnerable to the
● Atypical lobular hyperplasia -used to development of fissures. 
describe hyperplasias that exhibit Mammary duct ectasia (plasma cell mastitis) 
changes that approach but do not meet ● a nonbacterial chronic inflammation of
diagnostic criteria for lobular carcinoma the breast associated with inspissation of
in situ.  breast secretions in the main excretory
ducts. 
 ● Ductal dilation and eventual rupture - A cut section shows a uniform tan-white color,
leads to reactive changes in the punctuated by softer yellow-pink specks
surrounding tissue that may present as a representing the glandular areas. 
poorly defined periareolar mass with Histologic examination shows a loose
nipple retraction, mimicking the fibroblastic stroma containing ductlike,
changes caused by some cancers. epithelium-lined spaces of various shapes and
MORPHOLOGY  sizes.
- confined to an area drained by one or more of - in normal breast tissue, these glandular spaces
the major excretory ducts of the nipple.  are lined by luminal and myoepithelial cells with
Histologic examination a well-defined, intact basement membrane. 
- the most distinguishing features consist of a
prominent lymphoplasmacytic infiltrate and Phyllodes Tumor 
occasional granulomas in the periductal stroma. -biphasic, being composed of neoplastic stromal
cells and epithelium-lined glands.
Fat necrosis -uncommon, innocuous lesion that -stromal element of these tumors is more cellular
is significant only because it often produces a and abundant, often forming epitheliumlined
mass. Most women with this condition report leaflike projections (phyllodes is Greek for
some antecedent trauma to the breast. “leaflike”).
MORPHOLOGY  -tumors are much less common than
-early stage of traumatic fat necrosis fibroadenomas and arise de novo, not from
● lesion is small, often tender,  preexisting fibroadenomas. 
● rarely more than 2 cm in diameter -In the past, they had the tongue-tangling name
● sharply localized.  cystosarcoma phyllodes—an unfortunate term
-It consists of a central focus of necrotic fat cells because these tumors usually are benign. 
surrounded by neutrophils and lipid-laden -Ominous changes suggesting malignancy
macrophages, sometimes with giant cells.  include 
-Calcifications may develop in either the scar or ● increased stromal cellularity
the cyst wall. ● Anaplasia
● high mitotic activity
TUMORS OF THE BREAST  ● rapid increase in size
Most important lesions of the female breast.  ● infiltrative margins. 
● Fibroadenoma Fortunately, most phyllodes tumors remain
- Most common benign neoplasm of the localized and are cured by excision; malignant
female breast. lesions may recur, but they also tend to remain
- A biphasic tumor composed of localized. 
fibroblastic stroma and epithelium-lined
glands
-typically appear in young women with Intraductal Papilloma
a peak incidence in the third decade of ● Benign neoplastic papillary growth
life. They usually manifest as solitary, ● Seen in premenopausal women
discrete, mobile masses.  ● Found within the principal lactiferous
-An absolute or relative increase in ducts or sinuses
estrogen is thought to contribute to their
development.  CLINICAL PRESENTATION:
- In addition, fibroadenomas may
● Serous/bloody nipple discharge
enlarge late in the menstrual cycle and
during pregnancy; after menopause, they ● Presence of small subareolar tumor
may regress and calcify. ● Nipple retraction (rare instances)
MORPHOLOGY CARCINOMA
- The fibroadenomas form discrete masses, 1 cm
to 10 cm in diameter and of firm consistency 
 ● Second to lung cancer (cause of cancer-
related death: women)
EPIDEMIOLOGY AND RISK FACTORS
● AGE: after menopause (80 y/o)
75% (50 y/o)
5% (40 y/o)
● Geographic Variations: varies in
countries
Higher in North America and
northern Europe than Asia and Africa.
● Race/Ethnicity: highest rate in non
B. Invasive (infiltrating)
Hispanic young women
● Other risk factors:
o Prolonged exposure to
exogenous estrogens
o Oral contaceptives
o Ionizing radiation
o Obesity
o Alcohol consumption
o Diet in high fat
MORPHOLOGY
● Most common location of tumors within
the breast:
o Upper quadrant (50%)
o Central portion (20%)
o bilateral primary tumors or
sequential lesions in the same
beast (4%)
MAIN FORMS OF BREAST CARCINOMA:
A. Noninvasive (in situ) carcinoma
● Ductal carcinoma in situ (DCIS)
o Fill and distort ductal spaces
o Architectural patterns: solid,
comedo, cribriform, papillary,
micropapillary and “clinging”
o Necrosis may be present
o Name derived from toothpaste-
like necrotic tissue
LESIONS OF THE MALE BREAST
o Current treatment: surgery and
irradiation
o Paget disease of the nipple
- caused by extention of DCIS
- lactiferous ducts and into the
contigious skin of the nipple
● Lobular carcinoma in situ (LCIS)
o Has uniform appearance
o Monomorphic cells with band,
round nuclei and occur in
loosely cohesive vacuoles are
common
o Current treatment:
- Chemoprevention with
tamoxifen
- Bilateral prophylactic
mastectomy
● Invasive ductal carcinoma
o 70 to 80% of cancers
o Usually associated with DCIS
and rarely LCIS
● Invasive lobular carcinoma
o Concists of cell
morphologically identical to the
cell of LCIS
● Inflammatory carcinoma
o Defined by the clinical
presentation of an enlarged,
swollen, erythematous breast,
usually without palpable mass
● Medullary carcinoma
o Rare subtype of carcinoma
o <1% of breast cancer
● Colloid carcinoma (mucinous
carcinoma)
o Also a rare subtype
o Tumor cells produce abundant
quantities of extracellular
mucin which dissects into the
surrounding stroma
● Tubular carcinoma
o Rarely present as palpable
masses
o 10% invasive carcinomas <1cm
with mammorgraphic screening
1. Gynecomastia
● Enlargement of the male breast (in
response to absolute or relative estrogen
excesses)
● Morphologic features:
 o Increase in connective tissue
and epithelial hyperplasia of
the ducts
o Rare lobule formation
● Clinically, button-like, subareolar
swelling develops, usually both breasts
but occasionally in only one
2. Carcinoma
● Breast cancer is rare in men (1%)
● Typically diagnosed in advanced age
● Because of scant amount of breast tissue
in men, the tumor rapidly infiltrates the
overlying skin and underlying thoracic
wall
● Resembles invasive carcinomas seen in
women