FEMALE GENITAL TRACT
Benign Exophytic Lesions
INFECTIONS OF THE FEMALE GENITAL TRACT
Herpes Simplex Virus Infection
Common
Involves cervix, vagina, and vulva
HSVs are DNA viruses that include two serotypes, HSV-1 and
HSV-2
Initial lesions typically develop 3 to 7 days after sexual
transmission and consist of red papules that progress to
vesicles and then to painful coalescent ulcers
Molluscum contagiosum
MCV-1 being the most prevalent
MCV-2 being most often sexually transmitted
Infections are common in young children between 2 and 12
years of age and are transmitted through direct contact or
shared articles
Incubation period: 6 weeks
Pelvic Inflammatory Disease
Ascending infection that begins in the vulva or vagina and
spreads upward to involve most of the structures in the female
genital system, resulting in pelvic pain, adnexal tenderness,
fever and vaginal discharge
Gonococcus and Chlamydia infection; infections after
spontaneous or induced abortions and normal or abnormal
deliveries (called puerperal infections)
Gonococcal ingection:
o Endocervical mucosa is the most common site of initial
involvement
o Smears of the inflammatory exudate disclose the
intracellular gram-negative diplococcus
o Definitive diagnosis requires culture, or detection of
gonoccocal RNA or DNA
Acute complications: peritonitis and bacteremia
Sequelae : infertility and tubal obstruction, increased risk of
ectopic pregnancy, pelvic pain, intestinal obstruction due to
adhesions between the bowel and pelvic organs
Antibiotics and salpingo-oophorectomy
VULVA
Bartholin (Duct) Cyst
Common
Obstruction of Bartholin duct, usually from preceding infection
Accumulation of mucoid, or clear secretion
Epithelial lining: squamous, transitional, or cuboidal
Pain and local discomfort
Management: excision or opened permanently
(marsupialization)
Non-neoplastic Epithelial Disorders
Leukoplakia - opaque, white, plaque-like mucosal thickening
that may produce itching and scaling
Lichen sclerosus
Squamous cell hyperplasia (Lichen simplex chronicus)
Lichen sclerosus : a dermatosis of unknown etiology
characterized by thinning of epidermis and disappearance of
rete pegs, hydropic degeneration of the basal cells, superficial
hyperkeratosis, and dermal fibrosis with a scant perivascular,
mononuclear inflammatory cell infiltrate
Grossly, parchment-like epithelium
Most common in postmenopausal women
Autoimmune reaction (?)
NOT considered a pre-malignant condition
Squamous cell hyperplasia: hyperplastic dystrophy or lichen
simplex chronicus; nonspecific condition resulting from rubbing
or scratching of the skin to relieve pruritus
Marked by epithelial thickening with no atypia, expansion of the
stratum granulosum, and significant surface hyperkeratosis
Increased mitotic activity in both the stratum basalis and
spinosum and leukocytic infiltration of the dermis
Grossly, leukoplakia
NO increased predisposition to cancer
Condyloma acuminatum
Syphilitic condyloma latum
Fibroepithelial polyps (skin tags)
Squamous papillomas
Condyloma acuminatum: HPV types 6 and 11, have verrucous
gross appearance, may be solitary but are more frequently
multifocal; koilocytic atypia
VAGINA
Developmental Anomalies
Septate or double vagina: uncommon anomaly that arises from
failure of total fusion of the mllerian ducts and accompanies a
double uterus (uterus didelphys)
Manifestations of genetic syndrome or exposure in utero to DES
Vaginal adenosis: a remnant of columnar, endocervical-type
epithelium; presents clinically as red, granular areas
contrasting with the normal pale-pink vaginal mucosa
Reported in 35% to 90% of women exposed to DES in utero
Rare cases of clear cell carcinoma arising in DES-related
adenosis
Gartner duct cysts: relatively common lesions found along the
lateral walls of the vagina and derived from wolffian
(mesonephric) duct rests; 1- to 2-cm fluid-filled cysts that occur
in the submucosal location, lined by cuboidal epithelium
Other cysts i.e. including mucus cysts occur in the proximal
vagina and endometriosis, are derived from mllerian
epithelium
CERVIX
Acute and Chronic Cervicitis
Maturation of the cervical and vaginal squamous mucosa and
formation of intracellular glycogen vacuoles in the squamous
cells at onset of menarche
Glycogen - substrate for endogenous vaginal aerobes and
anaerobes
Lactobacilli - maintain pH below 4.5; at low pH, lactobacilli
produce bacteriotoxic H2O2
Infections by gonococci, chlamydiae, mycoplasmas and herpes
simplex virus may produce significant inflammation and are
important to identify due to their association with upper genital
tract disease, complications during pregnancy and sexual
transmission
Abnormal Pap test result
Endocervical polyps
2% to 5% of adult women
Irregular vaginal spotting or bleeding
Vary from small and sessile to large soft, almost mucoid,
lesions composed of a loose fibromyxomatous stroma
harboring dilated, mucus-secreting endocervical glands, often
accompanied by inflammation
Simple curettage or surgical excision
BODY OF UTERUS AND ENDOMETRIUM
Functional Endometrial Disorders (DUB)
AUB can have organic and functional causes
DUB: clinical term for uterine bleeding not caused by any
underlying organic (structural) abnormality
o Anovulatory cycle
o Inadequate luteal phase
o Endometrial changes caused by OCPs
o Menopausal and postmenopausal changes
Anovulatory Cycle - results in excessive and prolonged
estrogenic stimulation without the counteractive effect of the
progestational phase that regularly follows ovulation; most
have no obvious cause, likely due to subtle hormonal
imbalances; endocrine and metabolic disorder and ovarian
tumor
Anovulatory cycle - most common at menarche and in the
perimenopausal period; microscopically seen as cystic
dilatation of glands and stromal breakdown
 Inadequate luteal phase- stem from inadequate corpus luteum
function resulting in low progesterone output, with subsequent
early menses
Often manifests clinically as infertility, with either increased
bleeding or amenorrhea; endometrial biopsy performed at an
estimated postovulatory date shows secretory endometrium,
which, however, lags in its secretory characteristics expected
at that date
Pill endometrium -discordant appearance between glands and
stroma, usually with inactive glands amid a stroma showing
large cells with abundant cytoplasm reminiscent of the decidua
of pregnancy; these changes have been minimized with newer
low-dose contraceptives
Menopausal and postmenopasusal changes: cystic atrophy
Endometriosis
Presence of endometrial tissue outside of the uterus; most
commonly consists of both endometrial glands and stroma, but
rarely consists only of endometrial stroma
Involve the ovaries, uterine ligaments, rectovaginal septum, cul
de sac, pelvic peritoneum, large and small bowel and appendix;
mucosa of the cervix, vagina and fallopian tubes; and
laparotomy scars
Most often in the third and fourth decades, affecting
approximately 10% of women
Often causes infertility, dysmenorrhea, pelvic pain
Two major theories for the development of endometriosis:
metastatic theory (implantation in abnormal locations,
retrograde menses) and metaplastic theory (metaplasia of
coelomic epithelium)
Specific abnormalities that distinguish normal endometrium
from endometriotic tissue:
o Activation of the inflammatory cascade characterized by
high levels of prostaglandin E2, IL-1, TNF and IL-6
o Upregulatd estrogen production
Clinical signs and symptoms : severe dysmenorrhea,
dyspareunia and pelvic pain due to the intrapelvic bleeding and FALLOPIAN TUBES
periuterine adhesions; pain on defecation and dysuria
Adenomyosis
Defined as the presence of endometrial tissue within the
uterine wall (myometrium)
Clinical symptoms: menometrorrhagia (irregular and heavy
menses), colicky dysmenorrhea, dyspareunia and pelvic pain,
particularly during the premenstrual period
Inflammation Acute Endometritis
Uncommon
Limited to bacterial infections that arise after delivery or
miscarriage; retained products of conception are the usual
predisposing influence
Causative agents include group A hemolytic streptococci,
staphylococci OVARIES
Inflammatory response is chiefly limited to the interstitium and
is entirely nonspecific.
Completion curettage, accompanied by antibiotic therapy
Inflammation Chronic Endometritis
Occurs in the following settings: (1) chronic PID; (2) in
postpartum or post-abortion patients with retained gestational
tissue; (3) in women with IUDs and (4) in women with
tuberculosis
Associated with abnormal bleeding, pain, discharge, and
infertility
In about 15% of cases no cause is obvious
Plasma cells, macrophages and lymphocytes are seen
Chlamydia - associated with both acute and chronic
inflammatory cell infiltrates
Antibiotic therapy
Endometrial Hyperplasia
An important cause of abnormal bleeding
Increased proliferation of the endometrial glands relative to the
stroma, resulting in an increased gland-to-stroma ratio when
compared with normal proliferative endometrium
Has a relationship with endometrial carcinoma - common
genetic alteration is inactivation of the PTEN tumor suppressor
gene
Risk of progression of endometrial hyperplasia
Type Progression rate
SH 4.3% 0-10%
CH 16.1% 3-22%
SAH 7.4% 7-8%
CAH 47.0% 29-100%
SIMPLE
o Increased volume of glands and stroma
o Cystic glands rounded, or with focal outpouchings
o Epithelial lining proliferative type
COMPLEX
o Marked glandular crowding (back to back)
o Highly variable and irregular gland outlines
ATYPICAL
SIMPLE OR COMPLEX HYPERPLASIA + CYTOLOGIC ATYPIA
o Large, rounded nuclei, varied in size
o Prominent nucleoli
o Hyperchromasia
o Increased N:C ratio
Endometrial Polyps
Exophytic masses of variable size that project into the
endometrial cavity
Single or multiple and are usually sessile,, but are occasionally
large and pedunculated
Asymptomatic or may cause abnormal bleeding
(intramenstrual, menometrorrhagia, or postmenopausal)
Hyperplastic or atrophic or functional
Observed in association with the administration of tamoxifen
Stromal cells in endometrial polyps contain chromosome (6p21)
rearrangements involving the HMGIY gene
Common disorders:
o Infections
o Ectopic pregnancy
- onset of severe abdominal pain, most commonly about
6 weeks after a previous normal menstrual period,
rupture of a tubal pregnancy constitutes a medical
emergency
o Endometriosis
Inflammation
Suppurative salpingitis - caused by any of the pyogenic
organisms; 60% is due to gonococcus followed by chlamydiae;
part of pelvic inflammatory disease
Tuberculous salpingitis
Follicle and Luteal Cysts
Cystic follicles -unruptured graafian follicles or in follicles that
have ruptured and immediately sealed -- cysts are usually
multiple. They range in size up to 2 cm in diameter, are filled
with a clear serous fluid, and are lined by a gray, glistening
membrane
Corpus luteum cysts - cysts are lined by a rim of bright yellow
tissue containing luteinized granulosa cells; occasionally
rupture and cause a peritoneal reaction
Polycystic Ovarian Disease
Stein Leventhal syndrome
affects 3% to 6% of reproductive-age women
Pathologic abnormality is numerous cystic follicles or follicle
cysts, often associated with oligomenorrhea
Persistent anovulation, obesity (40%), hirsutism (50%), and
rarely, virilism
Ovaries 2x the normal size and have a smooth, gray-white
outer cortex studded with subcortical cysts 0.5 to 1.5 cm in
diameter.)
 Histologic examination, there is a thickened, fibrotic superficial
cortex beneath which are innumerable follicle cysts associated
with hyperplasia of the theca interna (follicular hyperthecosis
Increased secretion of luteinizing hormone may stimulate the
theca-lutein cells of the follicles, to produce excessive
androgen (androstenedione), which is converted to estrone
Insulin resistance
Stromal Hyperthecosis
Cortical stromal hyperplasia
Disorder of ovarian stroma most commonly seen in
postmenopausal women
Uniform enlargement of both ovaries (up to 7 cm), which has a
white to tan appearance on sectioning
Microscopically shows hypercellular stroma and luteinization of
the stromal cells, which are visible as discrete nests of cells
with vacuolated cytoplasm
Lutein hyperplasia of pregnancy - physiologic condition
mimicking PCOD and SH syndromes -- proliferation of theca
cells and expansion of the perifollicular zone
GESTATIONAL AND PLACENTAL DISORDERS
Disorders of Early Pregnancy Spontaneous Abortion
Miscarriage, is defined as pregnancy loss before 20 weeks of
gestation
Causes are both fetal and maternal
Chromosomal anomalies such as aneuploidy, polyploidy, and
translocations are present in approximately 50% of early
abortuses
Maternal factors include luteal-phase defect, poorly controlled
diabetes, and other uncorrected endocrine disorders
Physical defects of the uterus may prevent implantation
adequate to support fetal development
Systemic disorders affecting maternal vasculature,
coagulopathies and hypertension
Infections with bacteria such as Toxoplasma, Mycoplasma, and
Listeria, as well as viral infections -- ascending infection is
particularly common in second-trimester losses
10% of women develop HELLP syndrome (hemolysis, elevated
liver enzymes and low platelets)
Placenta plays a central role in the pathogenesis of the
syndrome
Critical abnormalities in preeclampsia are diffuse endothelial
dysfunction, vasoconstriction (leading to hypertension) and
increased vascular permeability (resulting in proteinuria and
edema)
Principal pathophysiologic aberrations appear to be the
following:
o Abnormal placental vasculature
o Endothelial dysfunction and imbalance of angiogenic and
anti-angiogenic factors -high levels of sFlt1 and soluble
endoglin bring about a decrease in angiogenesis much
earlier than in normal pregnancy
o Coagulation abnormalities decreased endothelial
production of PGI2
Pre-eclampsia Morphology
Placenta reveals various microscopic changes: placental
infarcts, ischemic changes in the chorionic villi (increased
syncytial knots and the appearance of accelerated villous
maturity); retroplacental hematomas ; thrombosis, fibrinoid
necrosis or acute atherosis of decidual vessels
Liver, renal and cerebral findings
Pre-eclampsia Clinical Features
Most commonly starts after 34 weeks of gestation
For term pregnancies, delivery is the treatment of choice
For preterm pregnancies, where delivery may not be in the best
interest of the fetus, patients with mild disease can be
managed expectantly with close monitoring of the mother and
fetus
Proteinuria and hypertension usually disappear within 1 to 2
weeks after delivery
20% of women develop hypertension and microalbuminuria
within 7 years of a pregnancy complicated by preeclampsia.
Two-fold increase in the long-term risk of vascular diseases of
the heart and the brain

Disorders of Late Pregnancy

Twin placentas
o Monozygotic
o Dizygotic
3 types of twin placentation
Monochorionic placentas imply monozygotic (identical) twins
One complication of monochorionic twin pregnancy is twin-twin
transfusion syndrome

Abnormalities of Placental Implantation

Placenta previa is a condition in which the placenta implants in
the lower uterine segment or cervix, often with serious third-
trimester bleeding
Placenta accreta is caused by partial or complete absence of
the decidua with adherence of the placental villous tissue
directly to the myometrium and failure of placental separation;
an important cause of postpartum bleeding; common
predisposing factors are placenta previa and history of previous
cesarean section

Placental Infections
Two pathways: (1) ascending infection through the birth canal
most common and almost always bacterial (2) hematogenous
(transplacental) infection e.g. TORCH (toxoplasmosis and others
[syphilis, tuberculosis, listeriosis], rubella, cytomegalovirus,
herpes simplex)

Pre-eclampsia and Eclampsia

Preeclampsia refers to a systemic syndrome characterized by
widespread maternal endothelial dysfunction presenting
clinically with hypertension, edema, and proteinuria during
pregnancy
3% to 5% of pregnant women, usually in the last trimester
more common in primiparas
Severe form - eclampsia