The Female Genital Tract-Vulva, Vagina, Cervix & Uterus

Embryology
Mullerian ducts-females: fused portionuterus; unfused portion fallopian tubes
Wolffian ducts males
Urogenital sinus vagina
(both originally ducts but the ducts of the opposite sex are prevented from growing eg in
males, the Mullerian tubes are inhibited from growing by the hormone MIH)
Congenital anomalies
Absent/rudimentary/infantile uterus (various degrees)
Uterus didelpuys
- 2 horns
2 cervices
2 vaginas
Uterus bicornis bicollis
2 horns
2 cervices
Uterus bicornis unicollis
2 horns
1 cervix
Uterus unicornis
Uterus unicornis with rudimentary horn
Uterus septum
PIDs
present with pelvic pain, dysmenorrhoea etc
stricture of fallopian tube (salpingitisinfection & inflammation of the fallopian tubes)
tubo-ovarian abscess (oophoritisinfection & inflammation of the ovaries)
infection of the endometrium
postpartum endometritis
intra-uterine device (IUD)
curettage (abortion)
introduction of organisms via sexual intercourse
gonococcus
streptococcus
staphylococcus
actinomyces
mycoplasma
chlamydia
hydrosalphinx
pyosalphinx
Common Female Genital Infections

Organism
Herpes virus
Molluscum
contagiosum
HPV
Chlamydia
trachomatis
Neisseria
gonorrhoea
Candida
Trichomonas

Location & manifestation of infections:

Source
vulva
vagina cervix
corpus adnexa
STD
Herpetic ulcers
STD
Molluscum
lesions
STD
Genital warts, intraepithelial
neoplasia, invasive carcinoma
STD
Follicular cervicitis,
endometritis, salpingooophoritis
STD
Skene-gland vaginitis, acute cervicitis, acute endometritis
& salpingitis, adenitis in children
Endogenous vulvovaginitis
STD
cervicovaginitis

Infectious diseases of the Vulva

HPV - condyloma acuminatum
HS
- herpes genitalia
Others - syphilissyphilistic ulcers, chancre
- molluscum
- GI
- lymphogranuloma venereum etc
*Intracellular diplococci N. Gonorrhea (infect the vulvovaginal gonads)
- N. Meningitis
Vulva Pagets disease (can be in nipple, perianal area etc too)
Origin: primitive epithelial progenitor cells
Usually secondary to malignancy arising in the glands of these areas
Tumour cells = usually large cells containing clear cytoplasm and glycogen
CIS = epidermis small clusters of malignant cells
Rx = local resection because there is a chance of progressing to malignancy
reddening, edematous, itchiness, thickening
*In situ adenocarcinoma
Carcinoma - Vulva
normal lining is stratified squamous epithelium
VIN (vulva intraepithelial neoplasia)1
Usually caused by HPV
Rx = vulvectomy & draining of LN removal
Can present as exophytic growth / ulceration (endophytic growth)
1 Others: VAIN = vagina intraepithelial neoplasia
CIN = cervix intraepithelial neoplasia
Verrucous carcinoma
Appearance like usual warts
Commonly in vulva (others = tongue etc)

Good prognosis
Very bullous
Verrucous carcinoma
Pushing margin
Rare keratin pearls
Minimal atypia

vs

Squamous carcinoma
Infiltrating margin
Keratin pearls
Moderate atypia

Vagina
Congenital anomalies
VAIN (secondary to HPV infection)
Adenocarcinoma in utero exposure to DES (diethylstilboesterol) glandular
metaplasia (adenosis) adenocarcinoma
Embryonal rhabdomyosarcomacommonly a neoplasia of newborn (to 5 yrs max)
female child
Sarcoma Botryoides Vagina
Grape-like clusters
Infants & children (rarely in this age group, malignancies of the female genital tract
usually in older women)
Rhabdomyosarcoma
Aggressive tumour
Cervix
Endocervix columnar epithelium
*External os squamocolumnar junction (transformation zone) most common site
where neoplasia take place (CINcarcinoma)
Ectocervix stratified squamous epithelium
I LSIL II HSIL
CIN I CIN II CIN III
Normal mild dysplasia moderate dysplasia severe dysplasia CIS

normal maturation process of cells = increase size of cell & nucleus decreases, acquire
keratin (stain pink)
Dysplasia
Cervix
CIN I = low grade squamous intraepithelial lesion (L-SIL)
CIN II & CIN III = high grade squamous intraepithelial lesion (H-SIL)
CIN I mild dysplasia
CIN II moderate dysplasia
CIN III severe dysplasia / CIS

Factors in CIS / carcinoma

Age of consummation of marriage
HPV 16/18 positivity
Smoking & chewing of tobacco
Promiscuity in either partner
Significance of CIN
The biological significance of dysplasia cannot be predicted for the individual on the
basis of histological appearance
Some (i) regress
(ii) remain unchanged for years
(iii) progress
The more severe the lesion, the higher the chances of it progressing into CIS & invasive
SCC
CIN I = 1-5% progress
CIN II = 6-74% progress
Linkage of HPV to cervical Ca
90% of cancers show HPV DNA (integrated into the host genome)
High risk HPV serotypes (16 & 18)
Specific viral oncogenes E6 & E7
Integrated vs episomal viral DNA

HPV 16,18
HPV 6,11
Cell cycle regulation = E6 p53 block / inactivate
E7 RB
HPV 16 associated with amplification of 3q (regulation region of malignant cell
chromosome)
Koilocytosis (hole in the cytoplasm) CIN I
HPV infection features:
Multinucleation (common in viral infections)
Perinuclear haloes
Crinkled nuclei (irregular shaped nuclei, raisin-like appearance, wrinkled surface)
HPV immunohistochemistry
Anti HPV Ab react together with HPV Ag colour pigment shown (indicating reaction
of Ab & Ag)
Pap smears
Invasive
Normal cytoplasm abundant
small nucleus
CIN III marked enlargement of cell, nucleihyperchromatic nuclei
pleomorphism

Invasive carcinoma presence of necrosis in the background

presence of inflammatory cells (polymorphs) intimately
associated with neoplastic cells
Sexual activity

HPV exposure

Cervical transformation zone

Squamous epithelium
Endocervical columnar
epithelium

squamous intraepithelial lesion (SIL)

glandular intraepithelial
lesion (adenocarcinoma in situ)

HPV 16,18
low grade, low risk
high grade, high risk

HPV 6,11,42-44
HPV 16,18,31,33,35

rare
smoking, oral contraceptives, high parity, altered immune
status etc

invasive squamous carcinoma

invasive adenocarcinoma
Carcinoma Cervix
Incidence = 4th commonest Ca in females in Spore after breast, colon, rectum & lung
Age = mean age:
dysplasia = 30.8 yrs
CIS = 36.7 yrs
invasive Ca = 54.9 yrs
Macroscopic Pathology
Early
Focal induration
Shallow ulceration
Elevated granular area bleeds readily
Late
Endophytic
ulceroinvasive
noduloinvasive
Exophytic
polypoid

 papillary
(* presents with post-coital / post-procedural bleeding)
Microscopic Pathology
Mostly SCC (75-90%)
Subtypes of SCC
5 yr survival
Large cell non-keratinizing
68.3%
Large cell keratinizing
41.7%
Small cell (neuroendocrine type)
20.0%
Remaining
Adenocarcinoma (10-25% of remaining)
Adenosquamous carcinoma
Undifferentiated carcinoma
Clear cell carcinoma (DES exposed women)
Prognosis of remaining group = overall survival 60%
Modes of spread
Direct local invasion = uterus, vagina, bladder, ureters, pelvic organs, rectumfistula
Lymphatics depending on stage, may remove draining LN
higher morbidity
Haematogenous = lung, liver, bone, heart, skin, brain
Cause of Death
Ureteric obstruction uremia (40-50%)
Peritonitis secondary to bowel obstruction
Respiratory failure associated with pulmonary metastases / massive edema
Others hemarrhage, cardiac failure, massive venous thrombosis, pulmonary embolism,
complications of DXT (radiation)
Uterine corpus
Endometrium = normal, polyps, hyperplasia, carcinoma, stromal neoplasms
Myometrium = leiomyomas, leiomyosarcomas, adenomyosis
Mixed Mullerian tumour ( carcinoma & adenomyosis)
Uterus (normal)
Outer SM coat (myometrium)
Specialized inner mucous membrane (endometrium)
shows cyclical changes during each menstrual cycle
Vagina (normal)
Lined with modified skin (stratified squamous epithelium) shows cyclical changes
Glycogen content is greatest towards end of menstrual cycle
Events in Menstrual Cycle

Proliferative phase of endometrium

Secretory phase of endometrium
influence of progesterone
outpouching develop secretions
Types of endometrial hyperplasia
(*usually due to hyperestrogenemia either due to local tumour or production of estrogen
ectopically)
Simple (dilation of glands, a little outpouching, glands widely separated, no atypia); Rx
hormone therapy
Complex (adenomatous without atypia) glands closely packed, hardly any stroma
between them; Rx = hormonal therapy to regulate hormonal levels back to normal so that
uterus could return to normal too
Atypical (adenomatous with atypia)
high chance of developing endometrial Ca; hence Rx usually hysterectomy
D & C to look for malignancies
Failure of ovulation eg in menopause
Corpus Uteri = neoplasms
Classification
Epithelial

Non-epithelial

Mixed Mullerian
(rare)

Benign
Adenomatous
polyp

Leiomyoma
Stromal nodule
Adenomatoid
tumour
Adenofibroma

Malignant
Adenocarcinoma (85%)
Clear cell carcinoma
Adenocanthoma (adenocarcinoma with
squamous metaplasia)
SCC
Leiomyosarcoma
Endometrial stromal sarcoma
Adenosarcoma

Endometrial carcinoma
Gross = hemorrhagic, fills up uterine cavity
Microscopic = if poorly differentiated gland formation not seen clearly
pinkish areas squamous differentiation (quite
characteristic)
(can be well differentiated too)
Metastases
Via lymphatics
para-aortic nodes
internal iliac nodes

by local lymphatic channels to the vagina

Via blood vessels
Secondary deposits in the vagina & ovaries maybe due to this mode of spread
Via fallopian tubes
ovaries
peritoneal spread
Distant metastases
At a late date, secondary deposits may appear in the liver, lungs & bones. These may be
the result of lymphatic / blood spread.
Smooth Muscle Tumour = Leiomyoma
Occur in 20-30% of women older than 30 years of age
Most common uterine neoplasms
Usually in middle-aged women; may regress after menopause
Increase in size with estrogen receptor (in nucleus)
Progestins, progesterone, clomiprene & pregnancy
Multiple tumours in 2/3 of the neoplasms
Types
Pedunculated
Subserous
Intramural
Pedunculated fundal
Submucous
Intraligamentous
Histology = well circumscribed
Leiomyosarcoma
Malignant counterpart of the SM tumour
Mitoses 5 mitotic figures per 10
Endometrial stromal neoplasms
Endometrial stromal nodules
Endometrial stromal sarcoma different grading
Endometriosis (ectopic location of endometrial tissue)
Sites = umbilicus
abdominal wall etc
Adenomyosis
Condition of endometrial deposits in the myometrium
Accompanying overgrowth of muscle & CT
2 types: adenomyoma (localized)
adenomyosis (diffused)

Causes of abnormal uterine bleeding by age group

Prepuberty
Adolescence
Reproductive
age

Perimenopausal
Postmenopausal

Precocious puberty (hypothalamic, pituitary / ovarian origin)

Anovulatory cycle
Complications of pregnancy (abortion, trophoblastic disease, ectopic
pregnancy)
Organic lesion (leiomyoma, adenomyosis, polyps, endometrial
hyperplasia, carcinoma)
Anovulatory cycle
Ovulatory dysfunctional bleeding (eg in inadequate luteal phase)
Anovulatory cycle
Irregular shedding
Organic lesion (carcinoma, hyperplasia, polyps)
Organic lesion (carcinoma, hyperplasia, polyps)
Endometrial atrophy