PATHOLOGY

FEMALE GENITAL TRACT

1. INFECTIONS

DM, antibiotics, pregnancy,

Affecting the Lower Genital Tract

immunocompromised

Involving the Lower and Upper Genital Tract

Vulvovaginal pruritus, erythema,

swelling, curdlike discharge

INFECTIONS AFFECTING THE LOWER GENITAL

Diagnosis: pseudopores/ filamentous

TRACT

fungal hyphae in wet KOH mounts of

1. Herpes Simplex Virus 2 (HSV 2)

discharge or pap smear

Lesions (3-7 days)

Red papulesvesiclespainful coalescent

4. Trichomonas vaginalis

ulcers (vulvar skin and mucosa)

Protozoa

Purulent discharge

Wet mounts of discharge

Lesions heal spontaneously

STD=> 4 days to 4 weeks

Transmission to neonate during birth

Yellow, frothy vaginal discharge and

Diagnosis: Tissue culture, PCR, ELISA

discomfort, dysuria, dyspareunia

Detection (serum): + recurrent/latent infection

Vaginal and cervical mucosa: fiery-red

appearance due to prominence of

2. Molluscum contagiosum (MCV 2) STD

capillaries (strawberry cervix)

Incubation period: 6 weeks

Central core: cells with intracytoplasmic viral

5. Gardenella vaginalis

inclusions

Gram (-)

Dome-shaped with dimpled center

Cause of bacterial vaginosis (vaginitis)

Due to premature labor

3. Yeast (Candida)

Thin, green-gray, fishy vaginal

Disturbance in vaginal microbial

ecosystem

discharge
Squamous cells covered by multiple
coccobacilli in pap smear (clue cells)

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Gonococcal lipopolysaccharide and

6. Ureaplasma urealyticum and

mediators (TNF) cause epithelial injury

Mycoplasma hominis

and sloughing of plicae (mucosal folds)

Causes of vaginitis and cervicitis

Tubo-ovarian abscess, pyosalpinx

San hahanapin? WBC (cytoplasm of

7. Chlamydia trachomatis

neutrophils)

Cause of cervicitis, endometritis and

Fallopian tube: simple columnar ciliated

salpingitis

epithelium

Also cause Pelvic Inflammatory

Disease (PID)

PID: COMPLICATIONS

1. Peritonitis
INVOLVING THE LOWER AND UPPER

2. Intestinal obstruction due to adhesions

GENITAL TRACT

between bowel and pelvic organ

3. Bacteremia endocarditis, meningitis,

1. Pelvic Inflammatory Disease (PID)

Pelvic pain, adnexal tenderness, fever,

suppurative arthritis
4. Tubal obstruction and infertility (

vaginal discharge

hydrosalpinx due to fusion of fimbriae

Infection by gonococci and chlamydia

and accumulation of secretions and tubal

Most serious complication of

distension, lack of flexible fimbriae

gonorrhea in women

prevents uptake of oocyte after

Infection after abortion and deliveries

ovulation)= increase risk of ectopic

are important causes of PID

pregnancy

(polymicrobial)

VULVA

2. Gonococcus

Bartholin Cyst

Intracellular gram (-)

Non-Neoplastic Epithelial Disorders

Inflammatory changes (2-7 days)

Benign Exophytic Lesions

Spread to tubesacute suppurative

Neoplasms

salpingitis salpingo-oophoritis

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PATHOLOGY

BARTHOLIN CYST

Scant perivascular mononuclear cell

Obstruction of the bartholin duct

infiltrate

Cyst lined by squamous metaplasia

Pain and local discomfort

2. Squamous cell hyperplasia

Excision and marsupialization (opened

Hyperplastic dystrophy/ lichen simplex

permanently)

chronicus

Non-specific condition resulting from

NON-NEOPLASTIC EPITHELIAL

rubbing or scratching the skin to relieve

DISORDERS

pruritus

LEUKOPLAKIA (white plaques): benign,

Appears clinically as an area of

pre-malignant, malignant

leukoplakia

1. Inflammatory dermatoses (psoriasis,

chronic dermatitis)

Epithelial thickening with no atypia

Expansion of stratum granulosum

2. Vulvar intraepithelial neoplasia, Pagets

disease or invasive cancer

Hyperkeratosis
Leukocytic infiltration of the dermis

3. Epithelial disorders of unknown etiology

NNED of Unknown etiology

BENIGN EXOPHYTIC LESIONS

1. Lichen sclerosus

Unknown etiology

Smooth, white plaques/papules

Condyloma acuminatum (genital wart)

Labial atrophy

and latum (broad- based, elevated

Narrowed introitus

plaques)= STD

Most common in post menopausal

Fibroepithelial polyps= skin tags

women

(mushroom appearance); stratified sq.

Uncertain pathogenesis= autoimmune?

epithelium (vulva) with central core

Histology: atrophy (thinning) of

(fibrous/blood vessels)

epidermis

Squamous papillomas= benign

Hydropic degeneration of basal cells

exophytic proliferations covered by non-

Hyperkeratosis

keratinized squamous epithelium

Dermal fibrosis

Condyloma acuminatum (venereal

wart)= STD

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Caused by low oncogenic risks HPV (6 &
11)

1/8 as frequent as cervical cancer

Virus life cycle is completed in mature

superficial cells resulting in cytologic

TWO GROUPS:
1. BASALOID AND WARTY CARCINOMAS:

changes (koilocytotic atypia)

with high oncogenic risks HPVs (30%)

Not considered pre-cancerous lesions

2. KERATINIZING SCCAs: not related to

Verrucuous/ wart-like (solitary or

multifocal)

HPV infection (70%)

Branching, tree-like cores of stroma

covered by squamous epithelium with
viral cytoplasmic changes (koilocytotic
atypia virally induced changes with

BASALOID AND WARTY CARCINOMAS

Pre-cancerous in situ lesion called Vulvar
VIN
Classic VIN: nuclear atypia of squamous

superficial epithelium); koilocytes:

cells, nuclear crowding, increase mitoses,

enlarged nucleus, darkly stained with

lack of cellular maturation

irregular borders with clear cytoplasm.

VIN analogous to cervical squamous

intraepithelial lesions (SIL)

TUMORS

Risk factors: same as those associated

1. Squamous Neoplastic Lesions- Vulvar

Intraepithelial Neoplasia (VIN) and
Vulvar carcinoma

with cervical SIL related to HPV infection

(STD)
Occurs in reproductive age women

2. Glandular= Papillary Hidradenoma,

Extramammary Pagets disease

Multicentric
10-30% VIN have vaginal/cervical HPV

3. Malignant Melanoma

related lesions

majority: + HPV 16

VULVAR CARCINOMA

Risk of progression to invasive

Uncommon

carcinoma: >45 y/o or

>60 y/o (2/3)

immunosuppression

Squamous cell carcinoma: most

common histologic subtype

3% of all genital carcinoma type in

female

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PATHOLOGY

Unknown etiology: chronic epithelial

irritation

BASALOID

WARTY

Nests & cords of

Exophytic, papillary

small, tightly

architecture

VULVAR INTRAEPITHELIAL NEOPLASIA
Risk of cancer development is principally

packed malignant
squamous cells

a function of age, extent of tumor and

lacking

immune status.
Metastatic spread is limited to the size

maturation

of tumor, depth of invasion and

Resembles

involvement of lymphatic vessels

Prominent koilocyte

immature cells

atypia

from basal layer

PAPILLARY HIDRADENOMA

of normal

Sharply circumscribed nodule on labia

majora or interlabial folds

epithelium

May be confused with carcinoma

Foci of central

tendency to ulcerate

Identical in appearance to intraductal

necrosis

papilloma of the breast

KERATINIZING SQUAMOUS CELL

Papillary projections covered with 2

layers of cells: columnar, secretory cells

CARCINOMAS

and underlying layer of flattened

Arise in patients with long standing

lichen sclerosus or squamous cell
hyperplasia
Immediate pre malignant lesion is
differentiated VIN or VIN simplex
Differentiated VIN: marked atypia of
basal layer with normal epithelium

myoepithelial cells

EXTRAMAMMARY PAGETS DISEASE
Pruritic, red, crusted sharply demarcated
maplike area in the labia majora
Large tumor cells lying singly or in small

maturation and differentiated in the

superficial layers

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clusters within the epidermis and its

appendages

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Cells are distinguished by clear

5. Endometriosis: mullerian derived

separation (halo) from the surrounding

epithelial cells.

lesions

With clusters and single pale tumor cells

spreading along the basal portion

ADENOCARCINOMA
Increase frequency of clear cell

Nuclear lesions are confined to the

adenocarcinoma in young women whose

epidermis of the skin and adjacent

mother has been exposed with DES

hair follicles and sweat glands

during pregnancy

Anterior wall, upper 3rd of vagina

MALIGNANT MELANOMA

15-20 years

Rare, <5% of all

vaginal adenosis (remnant of columnar,

6th-7th decades of life

endo, cervical, type epithelium)=

prognosis is linked principally to the

embryonal development extends from

depth of invasion, with >60% mortality

for lesions invading deeper than 1mm.
intraepidermal growth of Pagetoid cells.

the endocervix

PRE-MALIGNANT AND MALIGNANT

NEOPLASM
Most common malignant tumor of the

VAGINA

vagina: carcinoma metastic from the

Developmental Anomalies

cervix

Premalignant and Malignant Neoplasms

1. Vaginal Intraepithelial Neoplasm and

Squamous cell carcinoma

1. Atresia and total absence

2. Septate or double vagina : failure of
total fusion of mullerian ducts and assoc.
double uterus (uterus didelphys)
3. Gartner duct cyst: found in the lateral
walls of vagina derived from wolfian
duct nests
4. Mucuos cyst: in proximal vagina;
derived from mullerian epithelial

2. Embryonal Rhabdomyosarcoma

Vaginal IN
Primary Carcinoma of Vagina:
Uncommon; 1%
Almost all=> squamous cell carcinoma
(high oncogenic risk HPV associated)
Greater risk factor: previous cancer of
cervix or vulva

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PATHOLOGY

Arise from Vaginal IN (premalignant,
analogous to cervical SILs)

CERVICAL CARCINOMA
8TH leading cause of cancer mortality

Pap smear screening: detection of low

EMBRYONAL RHABDOMYOSARCOMA
Sarcoma botryoides

stage cancer and pre-invasive lesions

High oncogenic risk HPV: single most

Infants and children <5 y/o

important factor in cervical emergencies;

Polypoid, rounded, bulky masses with

also detected in vaginal SCCA, vulvar,

appearance and consistency of grape-

penile, anal, tonsilar, oropharyngeal

like clusters

carcinomas.

Malignant

HPV 16: accounts for almost 60% of

Conservative surgery with

cervical cases; HPV 18: 10% of cases

chemotherapy

Cambium-layer (tumor cellscrowded

there)

1. Multiple sexual partners

2. A male partner with multiple

previous/current sexual partners

CERVIX

3. Young age at first intercourse

Inflammation: Acute/ Chronic

4. High parity

Endocervical Polyps
Pre-malignant-Malignant Neoplasms
(CIN and Cervical Carcinoma)

8. Use of OCP

Irregular vaginal spotting/bleeding

Simple curettage or excision
epithelium

9. Use of nicotine

Simple columnar mucin-secreting

oncogenic risk HPV

7. Certain HLA subtypes

ENDOCERVICAL POLYPS

5. Persistent infection with a high risk

6. Immunosuppresions

Risk Factors:

CERVICAL IN
Cervical pre-cancerous lesions
Classification
1. Dysplasia/ carcinoma in situ
2. CIN I (mild dysplasia) to II (ca in situ)

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3. Low grade (CIN I) and high grade (CN II

CERVICAL INTRAEPITHELIAL NEOPLASM

& III) squamous intraepithelial lesions

LOW GRADE SQUAMOUS

(CIN)
>80% of LSILs and 100% HSILs are

INTRAEPITHELIAL LESIONS (LSIL)

associated with high oncogenic risk

Associated with productive HPV

HPVs

infection

HPV 16: single most common HPV

No significant disruption or alteration

of host cell cycle

type detected in both categories

Majority of HSILs develop from LSILs;

Most regress spontaneously, a small %

20% of cases of HSILs develop de novo,

age progress to HSIL

without pre-existing LSIL

Does not progress directly to invasive

Risk of developing pre-cancer and cancer

carcinoma

is confined only in part by HPV type and

depends also in immune status and

HIGH GRADE SQUAMOUS

environmental factors

INTRAEPITHELIAL LESIONS (HSIL)

Progressive degeneration of cell host
cycle by HPV

CERVICAL CARCINOMAS
SCCA: most important histologic

Increase cellular proliferation, decrease

or arrested epithelial maturation and

subtype (80%)
HSIL: immediate precursor of cervical

lower rate of viral replication, as

SCCA

compared with LSIL

Nests and tongues of malignant

(Review figure 22-17 sa robbins )

squamous epithelium, either

I: with koilocytic atypia

keratinizing/non-keratinizing invading

II: progressive atypia and expansion of

cervical stroma

the immature basal cells above the lower

3rd of epithelial thickness

ADENOCARCINOMA

III: with diffuse atypia, loss of

maturation and expansion of the

adenoCA in situ: precursor lesion

immature basal cells to epithelial

Proliferation of glandular epithelium

surface.

2nd most common type (15%)

composed of malignant endocervical

cells

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PATHOLOGY

Stage III: Carcinoma has extended to the

ADENOSQUAMOUS CARCINOMA

pelvic wall. On rectal examination there

Intermixed malignant glandular and

is no cancer free space between the

malignant squamous epithelium

tumor and the pelvic wall. Tumors

involve the lower third of the vagina.

NEUROENDOCRINE CARCINOMA

Stage IV: Carcinoma has extended beyond

Appearance similar to small cell cancer

true pelvis or has involved the mucosa of

of the lungs

the bladder and rectum. This stage also

Very poor prognosis

includes cancers with metastatic

dissemination.

STAGING: CERVICAL CANCER

Stage 0: carcinoma in situ (CIN III, HSIL)

MANAGEMENT OF CERVICAL CANCER

Stage I: Carcinoma confined to the cervix

Cytologic screening and management of

Ia: preclinical carcinoma, diagnosed only

papanicolaou smear abnormalities (HPV

by microscopy

testing)

Ia1: Stromal invasion no deeper than

Histologic diagnosis and removal of

3mm and no wider than 7mm

precancerous

(microinvasive carcinoma)

Surgical removal of invasive cancer with

Ia2: maximum depth of invasion of

adjunctive radiation and chemotherapy

stroma deeper than 3mm and no deeper

Use of vaccines for prevention

than 5mm taken from base of

Review figure 22-21

epithelium; horizontal invasion not more

than 7mm

Ib: histologically invasive carcinoma

confined to the cervix and greater than
stage Ia2

UTERUS AND ENDOMETRIUM

Menstrual cycle:
1. Proliferative

Stage II: carcinoma extends beyond the

cervix but not to the pelvic wall.
Carcinoma involves the vagina but not

2. Secretory
3. Menstrual

the lower third.

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Gland mitoses: proliferative

Plasma cells are seen with macrophages

Tortuosity of glands: secretory

and lymphocytes

Basal vacuolation: earliest morphologic

evidence of ovulation

ENDOMETRIOSIS

Secretion: secretory

Presence of endometrial glands and

Stromal edema: LATE secretory

stroma in abnormal locations outside

Predecidual reaction: evident around

uterus

arterioles and progress just before

(1) Ovaries, (2) uterine ligaments, (3)

menstruation (day 11 post ovulation)

rectovaginal septum, (4) cul de sac, (5)

Leukocytic infiltration:??? Hindi ko alam

pelvic peritoneum, (6) large and small

anong phase.

bowel and appendix, (7) mucosa of the

cervix, vagina and fallopian tubes, (8)

INFLAMMATION

laparotomy scars.

ACUTE ENDOMETRITIS

3rd and 4th decades of life

CHRONIC ENDOMETRITIS

chocolate-like fluid (chocolate cyst):

zona functionalis shed off

ACUTE ENDOMETRITIS

Origins:

Uncommon

1. METASTATIC THEORY: endometrial

Limited to bacterial infections that arise

after delivery or miscarriage

tissue is implanted at abnormal location

Retrograde menstruation through

Retained products of conception are the

tubes occurs regularly-> mediate spread

usual predisposing influence

of endometrial tissue to the peritoneal

Inflammatory response: limited to the

interstitium and nonspecific.

cavity
Spread of endometriosis to distant

sites via hematogenous and lymphatic

CHRONIC ENDOMETRITIS

metastases.

Chronic PID

2. METAPLASTIC THEORY: endometrium

Post partal/ post abortion patients with

could arise directly from coelomic

retained gestational tissue

IUD

epithelium.

Tuberculosis

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PATHOLOGY

Foci of endometriosis respond to both

Glands: hyperplastic or atrophic,

extrinsic cyclic (ovarian) and intrinsic

demonstrate secretory changes

hormonal stimulation with periodic

(functional polyps)

bleeding

HMGIY gene rearrangements

Infiltrate tissues and cause fibrosis and

adhesions

ENDOMETRIAL HYPERPLASIA

Clinical Features: severe

Most important cause of abnormal

dysmenorrhea, dyspareunia, pelvic pain

due to intrapelvic bleeding and

bleeding
Increase proliferation of endometrial

periuterine adhesions.

glands relative to stroma

Infertility: 30-40% of women

Increase gland-stroma ratio when

Malignancies can develop suggesting

compared to normal proliferative

that endometriosis contains at-risk

epithelium.

endometrium
Associated with prolonged estrogen

stimulation of the endometrium,

ADENOMYOSIS

anovulation, increase estrogen

Presence of endometrial tissue in the

production from endogenous sources or

myometrium.

exogenous.

Gross: yellow brown areas,

Inactivation of PTEN tumor suppressor

hypertrophied smooth muscles

gene

(nodular)

Conditions associated with

hyperplasia:

ENDOMETRIAL POLYPS

1. Obesity

Sessile masses of variable size that

2. Menopause

project into endometrial cavity

3. PCOS (Stein-Leventhal Syndrome)

Asymptomatic

4. Functioning granulosa cell tumors of the

Abnormal bleedins: ulcerate and

undergo necrosis

ovary
5. Excessive cortical function (cortical
stromal hyperplasia)

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6. Prolonged administration of estrogenic

COMPLEX HYPERPLASIA WITHOUT

substance (estrogen replacement

ATYPIA

therapy)

Increase in number and size of glands

4 CATEGORIES:

with marked glandular crowding,

1. Simple hyperplasia without atypia

branching.

2. Simple hyperplasia with atypia

Crowded, back to back glands with little

3. Complex hyperplasia without atypia

intervening stroma; abundant mitotic

4. Complex hyperplasia with atypia

figures; distinct and nonconfluent glands

Cytologically normal epithelial cells

SIMPLE HYPERPLASIA WITHOUT

3%--> carcinoma

ATYPIA

Cystic/mild hyperplasia

COMPLEX HYPERPLASIA WITH ATYPIA

Glands of various sizes and irregular

Morphologic overlap with well

shape with cystic dilation

differentiated endometrioid

Mild increase in gland to stroma ratio

adenocarcinoma

Epithelial growth pattern and cytology

23 to 48% of women with this diagnosis

similar to proliferative endometrium

have carcinoma when hysterectomy is

Uncommonly progress: 1%

performed

Reflect a response to persistent

cytologic features have changed

estrogen stimulation

ENDOMETRIAL CARCINOMA

SIMPLE HYPERPLASIA WITH ATYPIA

Most common invasive cancer of the

Appearance of simple hyperplasia with

cytologic atypia within glandular

female genital tract

Accounts for 7% of all invasive cancer in

epithelium

women

Loss of polarity, vesicular nuclei,

Arise mainly in post menopausal women

prominent nucleoli

(peak 55-65)

Cells: rounded, lose normal

Two categories: Type 1 and 2

perpendicular orientation to basement

TYPE I:

membrane

- Most common type, 80%

8% progress to carcinoma

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PATHOLOGY

- Well-differentiated and mimic

Type II:

proliferative endometrial glands

-Occur a decade later than type I

(endometrioid cancer)

-Arise in the setting of endometrial

- Arise in the setting of endometrial

hyperplasia

atrophy
-By definition poorly differentiated (G3)

Associated with:

tumors

1. Obesity

-Account for 15% of case of endomentrail

2. Diabetes (abnormal glucose tolerance is

>60%)

cancer
-Most common subtype is SEROUS

3. Hypertension

CARCINOMA.

4. Infertility (single or nulliparous, hx of

-Less subtype: (1) clear cell carcinoma

functional menstrual irregularities

(uterus), (2) malignant mixed mullerian

consistent with anovulatory cycle)

tumor

5. Unopposed estrogen stimulation

-Endometrial intraepithelial carcinoma

(EIC): precursor of serous carcinoma

Mutations in the PTEN tumor

-Poorer prognosis due to the consequence

suppressor gene

of propensity to exfoliate, undergo

Endometrium and breast cancer: can

transtubal spread and implant on

occur in the same patient

peritoneal surfaces.

Most endometrial carcinomas (85%) are

endometrioid adenocarcinomas

All non-endometrial carcinomas are

Grading

G3

G1: WD adenocarcinoma. <5% solid growth

G2: moderately differentiated adenoCA

MALIGNANT MIXED MULLERIAN

with partly <50% solid growth

TUMORS (MMMT)

G3: poorly differentiated adenoCA with

predominantly solid growth >50%

Carcinosarcomas
Consist of endometrial adenoCA in which

malignant stromal differentiation

(mesodermal components: muscle,

cartilage, osteoid) takes place

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Post menopausal women, and present

to adenoCA)

with post menopausal bleeding (similar

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