DISEASES OF THE
FEMALE GENITAL
TRACT
Objectives
At the end of the lecture you have to
1-Know the disease involving vulva and cervix.
2-Learn about tumors affecting them.
3-describe the role of viruses in pathogenesis
of the above diseases.
4-Know the macroscopical and microscopical
features of the above disease
DISEASES OF THE VULVA
VULVITIS
The most important infectious agents are
1
. Human
papillomavirus (HPV), producing
condylomata acuminata and vulvar intraepithelial
neoplasia.
2. Herpes simplex genitalis (HSV 1 or 2), causing a
vesicular eruption.
3. Gonococci producing suppurative infection of the
vulvovaginal glands
Contact Dermatitis
is one of the most common causes of
vulvar pruritus. It presents as erythematous weeping and
crusting papules and plaques. Causes include
urine, soaps,
detergents, deodorants, etc.
TUMORS
1. Condylomas and Low-Grade Vulvar
Intraepithelial Neoplasia (VIN)
There are two biologic forms of
anogenital warts
(condylomas)
a. Condylomata lata
:
are manifestations of
secondary syphilis & are
flat, and slightly
elevated.
b.
Condylomata accuminata:
are viral (HPV) warts
and appear as elevated warty or flat & wrinkled
localized lesions. They are often multiple, red-pink
lesions that measure up to several centimeters in
diameter.
Condylomata accuminata of the vulva
These appear as
elevated
warty
localized lesions.
They are often
multiple
, red-
pink lesions that
measure up to
several
centimeters in
diameter
Microscopically
There is acanthosis and
hyper/parakeratosis, with
koilocytosis.
Koilocytes are squamous cells with
perinuclear cytoplasmic vacuoles and
nuclear angulation.
The koilocytes are characteristic of
HPV infection.
There is thickening of the
epidermis (acanthosis),
hyper/parakeratosis, and
cytoplasmic vacuolation
(koilocytosis, center).
Condyloma acuminatum
2. High-Grade VIN and Carcinoma of the
Vulva
Carcinoma of the vulva is used to be seen
mostly in
elderly women.
The vast majority of vulvar carcinomas are
of squamous type.
The cancer was treated by radical vulvectomy. Squamous cell
carcinoma of the vulva usually occurs in older women, or as
a complication of HPV infection in younger women.
Exophytic Squamous Cell Carcinoma arising from Rt. labium minus
Variably sized, invasive, squamous nests some with central keratinization.
Well-differentiated SCC of vulva
DISEASES OF
THE VAGINA
Vaginitis
relatively a common problem
that produces a vaginal discharge
(leukorrhea).
Many of the offenders are commensals
that become pathogenic in conditions
such as
diabetes, antibiotic abuse,
after abortion or pregnancy, or in
AIDS.
Gonorrheal vaginitis
may be
transmitted to the newborn of the
infected mother.
Nonspecific atrophic vaginitis
common cause of postmenopausal
bleeding.
It is associated with thinning (atrophy)
of the squamous vaginal mucosa.
It is due to lack of estrogenic support
of the vaginal epithelium.
Malignant Tumors of Vagina
1. Squamous cell carcinoma
is rare & usually occurs
in
elderly women
, with risk factors similar to those for
cervical carcinoma.
Vaginal intraepithelial neoplasia is a
precursor lesion associated with HPV infection.
2. Sarcoma botryoides (embryonal
rhabdomyosarcoma),
produces soft polypoid
masses and is usually seen in
infants and children
younger 5 years of age.
Sarcoma botrryoides (embryonal rhabdomyosarcoma) of the
vagina: Note the grape like configuration of the tumor
DISEASES OF THE CERVIX UTERI
Transition zone of uterine
cervix between exocervical
squamous cells and
endocervical mucin-
producing glandular
epithelium.Normal histology
Cervicitis
is a very common condition.
Cytologic examination of the associated
mucopurulent
discharge
reveals inflammatory cells admixed with
cervical epithelial cells, and possible microorganisms.
It is often due to
vaginal flora, streptococci,
staphylococci, and
E. coli.
Much more important are
Chlamydia trachomatis,
Ureaplasma, Trich. vaginalis, Candida spp., Neisseria
gonorrhoeae, herpes simplex II (genitalis), and HPV.
Many of these microorganisms are
transmitted sexually
.
Herpetic infections
of the cervix may be transmitted to the
infant during its passage through the birth canal, resulting
sometimes in a serious fatal systemic infection.
Cervical Tumors
Despite dramatic improvements in early diagnosis and
treatment, cervical carcinoma continues to be one of the
major causes of cancer-related deaths in women in the
developing world.
Cervical Intraepithelial Neoplasia (CIN)
Nearly all invasive cervical squamous cell carcinomas
arise from precursor epithelial changes referred to as
cervical intraepithelial neoplasia (CIN).
The Pap smear, introduced 50 years ago by
Papanicolaou,
remains the most successful cancer
screening test ever developed.
Cytological examination can detect CIN long
before any abnormality can be seen grossly
.
Detection of CIN by the Pap smear at an early
stage permits curative treatment.
In populations that are screened
regularly, cervical cancer mortality is
reduced by up to 99%
.
CIN begins as low-grade lesion that may
progress to higher grade CIN, or it is a high-
grade lesions from the outset.
This depends on the location of the HPV
infection in the transformation zone, the type
of HPV infection , and other host factors.
On the basis of histology, precancerous
changes are graded as:
•
CIN I: Mild dysplasia
•
CIN II: Moderate dysplasia
•
CIN III: Severe dysplasia/carcinoma in situ
The current
Bethesda system
divides the
precancerous lesions into only two groups:
1. Low-grade SIL
(SIL for squamous intraepithelial
lesions), equivalent to CIN I
2. High-grade SIL
. Equivalent to CIN II & III
• Progression from low- to high-grade SIL may or may not
occur.
• The higher the grade of CIN the greater the likelihood of
progression to invasive carcinoma,
this reaches to
70% with CIN III.
nuclear hyperchromasia
koilocytotic changes (
is characterized by
CIN I
and angulation with perinuclear vacuolization produced by cytopathic
effect of HPV
) in the superficial layers of the epithelium.
The dysplastic epithelium is limited to the lower third of the mucosa.
thirds of the
-
, involving the lower two
more severe
the dysplasia is
:
CIN II
mucosa. The superficial layer in some cases shows the koilocytotic
changes.
shows dysplastic changes that affect virtually all layers of the
CIN III
epithelium.
Koilocytotic changes are usually absent.
Microscopic features CIN & Carcinoma in situ
.
Koilocytotic changes in
cervical squamous
epithelium. These are
diagnostic of HPV infection
Epidemiology and Pathogenesis
The peak age of CIN incidence is about 30 years.
whereas that of invasive carcinoma is about 45 years
i.e. precancerous changes usually take many years to
evolve into overt carcinomas.
Important risk factors for the development of CIN
and invasive carcinoma are:
1. Early age at first intercourse
2. Multiple sexual partners
3. Persistent infection by "high-risk" papilloma viruses
4. Low socio-economic status
(All of the above favor a sexually transmitted causative
agent HPV).
Indeed,
HPV
can be detected by
molecular techniques
in nearly all
precancerous and cancerous lesions
.
Specifically
,
high-risk HPV types
including 16 & 18,
account for the
majority of cervic
al carcinomas.
By contrast, condylomas, which are
benign lesions, are caused by
low-risk
HPV
types (i.e., 6 & 11).
In these benign
lesions the viral DNA does not integrate
into the host genome.
1.A cervical biopsy is performed after an abnormal
Pap smear result is obtained on a 42-year-old
female. The biopsy shows that dysplastic cells
occupy the full thickness of the epithelium above
the basement membrane. A cervical conization is
performed because
1.She has a high risk for invasive carcinoma.
2.HPV infection cannot be treated.
3.She is perimenopausal
4.CIN I is present.
5.She has invasive cancer.
In time, dysplastic changes become more
atypical and may extend into the endocervical
glands, but the alterations are confined to the
epithelial layer and its glands.
These changes
constitute
carcinoma in situ
.
The next stage is
invasive canrcinoma.
The above progression sequences do not occur
in all the cases.
Cervical cytology and cervical
colposcopy remain the basis of
cervical cancer prevention.
Invasive Carcinoma of the Cervix
The most common cervical carcinomas are (in descending order)
1. Squamous cell carcinomas (75%)
2. Adenocarcinomas and adenosquamous carcinomas
(20%)
3. Small-cell neuroendocrine carcinomas (<5%).
• The squamous cell carcinomas are increasingly
appearing in younger women, (peak incidence at about
45 years); 10 to 15 years after detection of their
precursors (CIN).
• Invasive carcinomas of the cervix develop in the region
of the transformation zone (the squamo-columnar
junction) and range from invisible microscopic foci of
early stromal invasion to grossly visible exophytic
ulcerating masses or deeply infiltrative cancer that
encircle the os.
A fungating ulcerative tumor that involves the cervix circumferentially
Advanced Carcinoma of the cervix
a large, polypoid lesion present within the ectocervix. The mass appears
hemorrhagic.
Squamous cell carcinoma of the cervix uteri
A large cervical squamous cell
Ca which spread to the vagina.
Advanced Cervical Carcinoma
Pelvic exenteration done for stage IV cervical Ca.
The tumor has involved the cervix (centre),
extended into the vagina and the UB anteriorlu.
The vulva (below) and rectum and anus
(posteriorly) can be seen.
JJ
Three microscopic variants of cervical SCC
squamous cell carcinoma exist, although
admixtures and intermediate forms occur:
1. Large cell nonkeratinizing
2. Keratinizing
3. Small cell;
this should be distinguished from
small cell neuroendocrine carcinoma
•
nests of neoplastic squamous cells are invaded through a chronically inflamed stroma. This
cancer is well- differentiated, as evidenced by keratin pearls. However, most cervical squamous
carcinomas are non-Keratinizing.
Squamous cell ca WD keratinizing
Distant metastases
,
including
• para-aortic nodal involvement,
• remote organ involvement,
• or invasion of adjacent structures such as bladder or
rectum, occur late in the course of disease.
Spread to pelvic lymph nodes and organs correlates
with tumor depth of invasion, ranging from 1-4
Ideally cervical carcinomas should be
diagnosed in the preinvasive phase;
these appear as white areas on
colposcopic examination after
application of dilute acetic acid
(
Schiller test
).
Such tumors call to attention by
unexpected vaginal bleeding,
leukorrhea, painful coitus
(dyspareunia), and dysuria.
BODY OF UTERUS
Endometritis
This may be associated with retained products of
conception subsequent to miscarriage or delivery, or
a foreign body such as an intrauterine device.
Retained tissues or foreign bodies act as a
nidus for
infection,
frequently by flora ascending from the
vaginal or anal region.
All forms of endometritis may present with
menstrual abnormalities, infertility and ectopic
pregnancy due to extension of the damaging
inflammation to the fallopian tubes.
Acute endometritis is frequently due to N.
gonorrhoeae or C. trachomatis.
;
Generally the diagnosis of chronic endometritis show the
presence of plasma cells
A 19-year-old female whose Pap smear demonstrates
many neutrophils but no dysplastic cells.
A cervical culture grows
N. gonorrhoeoe
. If this infection
is not adequately treated, the patient will be at increased
risk for
1.Ectopic pregnancy
2.Dysfunctional uterine bleeding
3.Cervical carcinoma
4.Endometrial hyperplasia
5.Endometriosis
Adenomyosis
This refers to the “
invagination of the stratum
basalis of endometrium down into the myometrium
.”
Nests of endometrial stroma, glands, or both, are
found well down in the myometrium between the
muscle bundles. The latter become hypertrophied.
uterus is enlarged and globular.
Because these glands derive from the stratum
basalis, they do not undergo cyclical bleeding.
Nevertheless, marked adenomyosis may produce
menorrhagia
,
dysmenorrhea
, and
pelvic pain
before
the onset of menstruation.
Adenomyosis uterus
Gross appearance of
uterus involved by
adenomyosis. The wall is
irregularly thickened and
contains small
hemorrhagic foci (arrow).
The thickened and spongy
appearing myometrial wall of
this sectioned uterus is typical
of adenomyosis. There is also a
small white leiomyoma at the top
Adenomyosis of uterus
endometrial glands and stroma invaginated in myometrium
Endometriosis
This is characterized by
“the presence of
endometrial glands and stroma in a
location outside the endomyometrium.”
It occurs in as many as
10%
of women in
their reproductive years and
in nearly half of
women with infertility.
It may present as a pelvic mass filled with
degenerating blood (
chocolate cyst
).
It is frequently multifocal and may involve
any tissue in the pelvis (ovaries, pouch of
Douglas, uterine ligaments, tubes, and
rectovaginal septum
Endometriosis. A, Endometriosis is present in the
mucosa of the colon. B, Higher magnification
reveals the presence of both endometrial glands and
stroma
Three possibilities have been
suugested to explain the origin of
these lesions:-
1. The regurgitation theory
,
currently the most
accepted, proposes menstrual backflow through
the fallopian tubes with subsequent
implantation.
2. The metaplastic theory
proposes
endometrial differentiation of coelomic
epithelium.
3. The vascular or lymphatic dissemination
theory
has been raised to explain extrapelvic
endometriosis.
Endometriosis usually contains
functioning endometrium, which
undergoes cyclic bleeding, thus
appearing grossly as red-blue to yellow-
brown nodules, due to collected blood.
When the ovaries are involved, the lesions
may form large, blood-filled cysts that are
transformed into so-called
chocolate
cysts as the blood ages
Seepage and organization of the blood
leads to widespread fibrosis, adherence
of pelvic structures, sealing of the tubal
fimbriated ends, and distortion of the
oviducts and ovaries.
Endometriosis ovary
Inner surface of cyst in a case of ovarian endometriosis.
The color is typically brown.
This is a section through an
enlarnged 12 cm ovary to
demonstrate a cystic cavity filled
with old blood typical for
endometriosis with formation of an
endometriotic, or "chocolate", cyst.
Ovarianendometriosis
In this area endometrial tissue faithfully reproduces the appearance of
normal endometrium, in terms of both glands and stroma. Lt., collection of lipofuscin-laden histiocytes
below the endometriotic epithelium.
Endometriosis ovary
Microscopic features
The histologic diagnosis depends on finding two of the
following three features within the lesions:
1. Endometrial glands.
2. Endometrial stroma.
3. Hemosiderin pigment.
Extensive scarring of the oviducts and ovaries often
causes sterility.
Pain on defecation reflects rectal wall involvement,
and
dyspareunia
(painful intercourse) and
dysuria
reflect involvement of the uterine and bladder
serosa, respectively.
In almost all cases, there is severe
dysmenorrhea
and pelvic pain as a result of intrapelvic bleeding
and periuterine adhesions.
Dysfunctional Uterine Bleeding (DUB):
is
an abnormal bleeding in the absence of a
well-defined organic lesion in the uterus
.
Examples of the causes of DUB include :
Anovulatory cycles
are very common at both
ends or reproductive life, and have several
cause including:
Endocrine dysfunctions
e.g. of the
hypothalamic-pituitary axis, adrenal, or
thyroid
Ovarian lesions producing an excess of
estrogen
Malnutrition, obesity, or debilitating disease
Severe physical or emotional stress.
Regardless of the cause, an anovulatory
cycle leads to an excess of estrogen
relative to progesterone; the endometrial
glands may appear crowded with mild
cystic changes with a relative scant
stroma. The poorly supported
endometrium partially collapses, with
rupture of spiral arteries, accounting for
the bleeding.
Endometrial glands appear crowded
with mild cystic changes and a
relative scant stroma.
The poorly supported endometrium
partially collapses, with rupture of
spiral arteries, accounting for the
bleeding.
Anovulatory (persistent proliferative) endometrium with stromal breakdown
Inadequate luteal phase.
The corpus
luteum may fail to mature normally or
may regress prematurely, leading to a
relative lack of progesterone. The
endometrium under these
circumstances shows delay in the
development of the secretory changes
expected at the date of biopsy.