VULVAR DYSTROPHY (leukoplakia)
• Age: any but most menopausal
• Gross: smooth-surfaced, dry, stiff, white,
atrophic vulva
• Micro:
− lichen sclerosus: epidermal atrophy,
dermal fibrosis
− squamous hyperplasia: epithelium
thick, hyperkeratotic (now called lichen
simplex chronicus)
• Effects: fissures, uclers, infections, pruritis; few
 ca
• Dx: biopsy
• Differential Dx: lichen sclerosus, lichen simplex
chronicus, chronic dermatitis, Paget Disease,
VIN, vulvar cancer
• Take home message – you have to biopsy these
legion to check for malignancy
VULVAR NEOPLASMS: BENIGN
• Papillary hidradenoma
− localized, benign, sweat gland tumor
− structure: papillae of ductal lining cells
− papillary structure
− well circumscribed, localized mass
• Condylomas (STD-related warts)
− accuminatum: caused by human
papilloma virus infection (HPV) 
koilocytosis (distinct cell type that is
different histologically)
− lata: syphilitic wart
VULVA CARCINOMA
• Precursor: vulvar intraepithelial neoplasia
(VIN)
− some pts present with vulvar dystrophy
(leukoplakia)
− Progressive grades of dysplasia I, II, III
(III also called Bowen’s disease or
carcinoma in situ; high grade or severe
dysplasia)
− HPV associated (especially types 16 &
18)
− Concurrent vaginal and/or cervical CA
in ~20%
• Extramammary Paget disease
− Presents as pruritic, red, crusted, welldelineated lesion usually on labia
majora
− Unlike Paget disease of breast - rarely
associated with underlying invasive
cancer
− Confined to epidermis, hair follicles and
sweat glands, believed to rise from
these adenexal structures
Becky Stepan
−
−
Long survival, but may recur following
surgical excision
Paget cells contain mucin
VULVA: CARCINOMA
• Invasive carcinoma: may be preceeded by
vulvar intraepithelial neoplasia (VIN)
− squamous cell ca = 88%
− spread  pelvic and inguinal nodes
− Rx: radical resection vulva, pelvic +
groin nodes
− Prognosis:
 no nodes + = 85% 5 yr survival
 Groin nodes + = 66%
 pelvic nodes + = 25%
− Dx often delayed
• Verrucous squamous cell carcinoma:
− rarely metastasizes
− histologically bland & grossly mimics
condyloma
− tend to be cured by surgery, usually a
localized problem
• Adenocarcinoma: few
− from sweat glands?
− Bartholin’s?
• Melanoma:
− 5% of vulvar cancer
− delay in Dx  30% 5 yr survival
VULVA: BARTHOLIN’S GLAND
• Normal:
− columnar-lined
− mucus-secreting cyst
− narrow neck
• Chronic inflammation  scarring  obstructs
neck  cyst
• Acute inflammation (often gonococcus,
chlamydia)  abscess
VULVO-VAGINAL INFLAMMATION
• Gonorrhea in children – presents as a purulent
discharge
• Trichomonas (strawberry mucosa — red) –
very inflamed mucosa; strawberry cervix, but
can involve the vagina and vulva
• Moniliasis (candidiasis): white patches –
loaded with fungus
• Herpes (vesicles) – presents as papules then
ulcers
• Senile vaginitis (drynessulcers, fissures) – as
the estrogen tapers off, the epithelium changes
and it dries out. It can itch and be very easily
irritated. May get ulcers, fissures. Very common
problem. Treated by estrogen creams.
Froberg – Vulva & Vaginal Path, Cervical Path, & Uterine Path
Page 1
VAGINA: CONGENITAL LESIONS
• Imperforate hymen:
− Hematocolpos (blood filling uterus)
− reflux
• Septate (“double”) vagina
• Blood is very irritating to the CNS and the
peritoneum. Blood in these areas can be a
problem.
VAGINA: VAGINAL ADENOSIS
• Islands of cervical glands beneath squamous
ectocervix
− cervical eruption
• Cause:
− rarely congenital
− most = maternal exposure to
diethylstilbesterol (DES) (synthetic
estrogen)
• Asymptomatic but 0.1%  adenocarcinoma
• Actually common finding
VAGINAL: CANCER
• Types: squamous cell carcinoma;
adenocarcinoma; sarcoma botryoides; yolk sac
tumor
• Squamous cell carcinoma:
− precursors: ca cervix or vulva;
intraepithelial neoplasia (VIN)
− spread: upper  pelvic nodes, lower
vagina  inguinal
− staging: like cervix
− prognosis is stage dependent: stage 1 =
80% 5 yr; 3-4 = <20%
• Adenocarcinoma: clear cell type = DES-related;
young
• Embryonic rhabdomyosarcoma (sarcoma
botryoides)
− age: <5yr
− gross: rounded, grape-like (Greek:
Botrys = grape) bulky mass
− histology: small blue cell tumor may
show myoblastic or strap cells;
striations in some
− behavior: locally destructive; large
ones metastasize
− Prognosis good if found and treated
early
Becky Stepan
•
Endodermal sinus (yolk sac) tumor
− like same tumor in ovary
− histo: sheets & Schiller-Duval body
(central blood vessel surrounded by 2
layers of germ cells)
− synthesizes alpha fetoprotein (hyaline
droplets that stain + by IHC; also  in
blood) and alpha-1-trypsin
− prognosis: awful
CERVIX: NORMAL ANATOMY
• External os
• Internal os
• Endocervical canal
• Transitional (transformation) zone
CERVIX: BENIGN
• Acute cervicitis: gonococcus or chlamydia; also
herpes et al.
• Chronic cervicitis:  squamous metaplasia of
endocervical mucosa. This obliterates mouth of
mucus glands  Nabothian cysts  erosions
and uclers, simulate cancer
• Endocervical polyps: soft, edematous stroma,
epithelial-covered may erode  bleed. They
are another cause of vaginal bleeding.
• “Pill” cervix: microglandular hyperplasia
(progesterone effect?)
CERVIX: CANCER
• Epidemiology:
− 50,000 precancerous cases/yr, but 13,000
invasive/yr (75% prevented-Rx or
spontaneous regression)
− 13,000 invasive cases/yr, but <5,000 die
(60% cure rate)
 Papanicolaou smear = effective
 one of few examples of value of
early cancer detection
• Risk factors
− early age of first sexual intercourse
− multiple sexual partners
− male partner who has multiple other
partners
− penile condylomas
• HPV virus (Human papillomavirus)
− causes condyloma accuminatum & warts
(virus remains episomal)
− Types 16, 18, 31, 33 stainable in
precancerous cervical mucosa (virus
integrates into host genome), therefore
capable of transforming it to a malignant
phenotype
Froberg – Vulva & Vaginal Path, Cervical Path, & Uterine Path
Page 2
−
−
−
Transforms squamous epithelial cells in
vitro
E6 oncoprotein product of HPV binds with
and degrades p53
E7 oncoprotein binds hypophosphorylated
pRb, frees E2F transcription factor to drive
cell cycle
CERVIX: CANCER
• HPV virus (Human papillomavirus) found in
~90% of tumors
• HPV infected cells called koilocytes
−  nuclear size of the cell, 
Nuclear/Cytoplasmic ratio with the
nucleus dominating the cell, irregular
nuclear contours, hyperchromasia and
perinuclear clearing
• Dysplastic cells also show loss of polarity which
means they have a disorganized growth,  &
atypical mitoses
• HPV types 16 & 18 are found in high-grade
cervical lesions; over 90% of invasive cancers
will have 16 & 18
• HPV 6 & 11 – these are commonly found in
condylomas
• HPV 31, 33, & 35 are also found in cancers but
not as much as 16 & 18
Cervical Cancer Classification of precancerous lesion
• Cervical intraepithelial neoplasia: CIN
• Progresses through succession (CIN I  II 
III) of increasing degrees of dysplasia without
invasion  mild, moderate, severe (same as
CIN III)
• CIN III also called “carcinoma in situ”
BIOLOGICAL features of Cervical Cancer:
• % of cases progressing to next-highest grade 
with the grade (i.e., % CIN II  III > I  II)
• Most mild dysplasia regresses; stage 2 goes to
stage 3 more than stage 1 progresses to stage 2
• lesions begins @ squamo-columnar junction
(“transformation zone”)
• initial lesions may be any grade
• time in any grade varies from months to many
years
• detection: grossly visualizing the lesion or an
iodine (Schiller’s) test—stains glycogen in
normal cells
DIAGNOSIS of Cervical Cancer:
• screening: “pap” smear
• definitive diagnosis:
− pap smear repeat
− colposcopy
 Schiller test
 biopsy visible lesion
 conization
• follow: with repeat smears & colposcopy
CERVIX: CANCER
• Invasive carcinoma
− type: 80% = squamous cell carcinoma
 remainder: undifferentiated,
adenosquamous &
adenocarcinoma
 In DES-Rxed patients = clear cell
carcinoma
• Staging of invasive cervical cancer:
− Stage 0:
CIN III
− Stage I:
limited to cervix
− Stage II: beyond cervix, upper 1/3
vagina, does not reach pelvic
wall
− Stage III: lower 1/2 vagina & reaches
pelvic wall
− Stage IV: beyond pelvis or invaded
bladder or colon; distant
metastases
*If we can stop the virus, we can stop the progression
to cancer.
Becky Stepan
Froberg – Vulva & Vaginal Path, Cervical Path, & Uterine Path
Page 3
•
•
•
Treatment of Cervical Cancer:
− CIN I, II, III: pap, cryoRx, laser,
conization, wire loop
− invasive: hysterectomy and radioRx
Prognosis: stage-dependent
− Stage I = 90% 5 yr
− Stage III = 10%
Complications: local invasion  bladder,
ureters, colon
UTERUS: INFLAMMATION
• Acute bacterial
− only in puerperium (strep, staph,
clostridium, mixed)
− NOT gonococcal, chlamydia or STD’s
• Chronic bacterial
− chronic PID (pelvic inflammatory
disease)
− tuberculosis
− IUD
− retained placental products
− actinomycetes are found in these
infections
Uterus: ADENOMYOSIS (Endometriosis interna)
• Non-malignant, non-neoplastic
• Islands of endometrial glands and stroma deep
in myometrium probably in continuity with
endometrium
• Benign but may cause 
− Menorrhagia
− Dysmenorrhea
− Dyspareunia
− Pelvic pain
• Seen in up to 20% of uteri
Becky Stepan
UTERUS: ENDOMETRIOSIS (EXTERNAL)
• Endometrium at ectopic sites (tubes, ovary
[most common site], sigmoid wall, uterine
serosa, bladder, vulva, peritoneum, umbilicus,
eye).
• Found under the serosa, found in the muscle
• Causes: mostly unknown, many theories
− one theory is menstrual reflux,
− metaplasia
− lymphatic dissemination?
− induction? Pre-existing epithelium
− Iatrogenic (laproscopic hysterectomy)
• Problem: they respond to hormones of
menstrual cycle  bleed (pain)
− Infertility
− intestinal obstruction
− “chocolate” cysts  infertility
(chocolate cysts are old, dark blood
clots)
− dysmenorrhea, pelvic pain
• Dx: biopsy  endometrial glands, stroma,
and/or hemosiderin pigment (need 2 of 3
for Dx)
• Rx: hormonal; surgical. Often unsatisfactory
because it can be difficult to find these because
there are multiple lesions that cause obscure
pain. Patients have chronic pain related to the
menstrual cycle
Dysfunctional Uterine Bleeding
• Excessive bleeding during or between
menstrual periods
• Differential Dx includes polyps, endometrial
hyperplasia, trophoblastic disease,
adenomyosis, & carcinoma
• Bx endometrium to rule out malignancy
• Most often due to anovulatory cycle which
leads to prolonged estrogenic stimulation.
Froberg – Vulva & Vaginal Path, Cervical Path, & Uterine Path
Page 4
Other Endometrial Changes
• Oral contraceptives:
− Inactive glands
− Predecidualized stroma (abundant
cytoplasm as in pregnancy)
• Postmenopausal:
− Senile cystic atrophy
− Atrophic endometrium with cystic
dilatation of glands
UTERUS: ENDOMETRIAL HYPERPLASIA
• Clinical presentation: abnormal uterine
bleeding, usually post-menopausal
• Mechanism: prolonged estrogenic stimulation
(polycystic ovary, estrogen-producing tumors,
estrogen Rx, etc.)
• Histo: simple or complex cystic hyperplasia,
adenomatous or atypical hyperplasia (25% of
endometrial hyperplasia leads to cancer)
• Dx and Rx: D&C; hormonal, surgery  if postmenopausal then they will have a hysterectomy
UTERUS: POLYPS
• Pathology: cystic endometrial glands with
stroma; benign (rarely cancer may arise within
polyp), arise from the fundus, tend to bleed
• Age: any but especially perimenopausal
• Sx: ulceration on the surface  bleeding
• They infaract more than cervical polyps do. It is
not unusual to be partially or entirely
infaracted.
• Rx: D&C
UTERUS: LEIOMYOMA (“FIBROID”)
• Location: submucosal, intramural, subserosal,
broad ligament, cervix
• Most common soft tissue tumor other than a
lipoma; benign; estrogen-responsive.
• CSx: bleeding; large obstruct birth (dystocia);
spontaneous abortion; if large, can cause
malformation of the fetus.
• Histo: whorled fascicles of smooth muscle cells;
clear cell and pleomorphic variations; also
“intravenous leiomyomyosis ” which is not
malignant even though it invades the lymph
nodes
• Leiomyosarcoma: arise de novo; they do NOT
arise from Leiomyoma.
− Sarcomatous histo
− usually fatal
*polyps and leiomyomas are the most common
Becky Stepan
UTERUS: ENDOMETRIAL ADENOCARCINOMA
• Epidemiology: risk factors
− postmenopausal
− obesity (related to estrogenic effects)
− diabetes
− hypertension
− infertility
− hyperestrinism
 nulliparous
 anovulatory cycles
 estrogenic tumors
 estrogen therapy
• Histology:
− most endometrioid (adenocarcinomas
with villoglandular histology)
− some adenoca with foci of squamous
metaplasia (adenoacanthoma)
− some adenoca with malignant
squamous foci (adenosquamous ca)
− variations:
 clear cell ca
 papillary serous ca
 variations are very aggressive
• Staging: similar to cervix
• Grading: FIGO system, I < 5% solid, II = 5-50%
solid, III > 50% solid (serous papillary & clear
cell are grade III tumors)
• Sx: postmenopausal bleeding
• Dx and Rx: D&C; hysterectomy; radiation
• Prognosis: stage 1 = 90%; III = 20% 5 yr
UTERUS: Carcinosarcoma (Malignant Mixed
Mullerian Tumor)
• Histo: endometrial adenocarcinoma with
malignant stromal differentiation
− Muscle, cartilage, osteoid
• Otherwise similar to poorly differentiated
endometrial adenocarcinoma
• Prognosis: overall = 25% 5 yr survival
Endometrial Stromal Tumors
• Two classes:
− Benign stromal nodules  wellcircumscribed aggregate of stromal cells
within myometrium
− Stromal sarcoma  neoplastic endometrial
stroma invading myometrium:
 Diffuse between muscle bundles, or
 Intralymphatic
 High recurrence rate (80% for stage
III/IV)
 5 yr survival~ 50%
Froberg – Vulva & Vaginal Path, Cervical Path, & Uterine Path
Page 5