Vulva and Vagina

Normal Histology – vagina is most inferior; endocervical canal connects to uterus

(1) Vagina and ectocervix (lower part of endocervical canal) – non-keratinized stratified squamous epithelium

4 layers:

(a) basal cell layer – flat single cell layer against basement membrane, small cells with large N:C ratio

(b) parabasal cell layer – 2-3 layers, cells have more cytoplasm than ones in basal layer

(c) intermediate cell layer – comparatively huge amount of cytoplasm, nucleus shrinks in size

(d) superficial squamous cell layer – nucleus either tiny or not present

as epithelium matures, cells become bigger and change from round to oval to polygonal; Ý cytoplasm volume and ß nuclear size lead to ß N:C ratio; long axis of nucleus changes from perpendicular to parallel; mitotic activity only in basal and parabasal cells; cyanophilic basal cells mature to pink/orange staining cells

this maturation is under influence of estrogen – without it, epithelium will become atrophic – this squamous mucosa composed of entirely basal and parabasal cells

epithelium can become keratinized under some situations (uerine prolapse, major surgeries causing damage, severe infection/inflammation, pre-neoplastic/neoplastic lesion)

(2) Endocervix (upper part of endocervical canal) – columnar mucus-producing cells

although endocervix has same histological features of endometrium, endocervix does not undergo menstural cycle
fibrosis and inflammation of wall can lead to formation of Nabothin cyst

Reserve cells – replenish endocervix epithelium (small round cells under epithelium)
columnar cells of endocervix can undergo metaplasia to become stratified squamous cells
this causes a shift in the Transition Zone (T-Zone) (where the ectocervix becomes the endocervix)

95% of precancerous lesions of cervix happen here, usually caused by Human Papilloma Virus (HPV)

(3) Endometrium - tall columnar mucus-secreting epithelium

Disorders of Vagina and Endocervical Canal – usually caused by Human Papilloma Virus, types 16,18,30

Condyloma Acuminatum – genital wart on vulva and vagina, classic lesion of HPV

in the ectocervix HPV causes flat lesions (as opposed to wart)
perinuclear clearing (halo effect); nucleus remains large with raisin wrinkled appearance (cells called koilocytes)
number of koilocytes is inversely proportional to severity of dysplasia

Dysplasia (Cervical Intraepithelial Neoplasia, CIN) – histologic grading:

(1) CIN1 - mild dysplasia - Main bulk of abnormality is in lower third of epithelium, top looks ok. Basal/parabasal cells lose polarity and get abnormal maturation, look crowded, larger, darker, mitoses moves up.

(2) CIN2 - moderate dysplasia - Abnormal cells grow to middle third, maturation to top still normal.

(3) CIN3 - severe dysplasia – abnormal pre-malignant cells from bottom to top, some maturation still present.

(4) Carcinoma in situ, also CIN3 – next step, total loss of maturation.

(5) Micro invasion – <3mm = micro-invasion (pt can still get conservative therapy), >5mm Þ carcinoma has high percent of metastases to lymph nodes.

(6) Squamous cell carcinoma – can see it by eye

Bethesda System – used in clinical practice to describe histology, to decide on treatment:

(1) SIL low grade – Mild dysplasia (CIN1)

(2) SIL high grade – Moderate dysplasia and worse (>CIN2)

Risk Factors for Cervical Cancer – multiple sexual partners, intercourse at an early age (<18 yrs), smoking, compromised immune system, sexual partners who are infected with HPV, have had multiple sexual partners, have or had a sexual partner with cervical cancer.

Who should have a pap smear? All women who are sexually active, and all women >18 years old

Why? Because development of cervical cancer is unpredictable, no test is 100% accurate.

Disorders of Vulva

(1) Non-neoplastic epithelial disorders

Lichen sclerosus – atrophy of skin, whitish, irritated

Histology: atrophy of mucusa, hyalinzation of dermis, zone of chronic inflammation

Squamous cell hyperplasia (hypertrophic dystrophy) – skin thickened, white, irritated; keratin but no dysplasia

Other – lichen simplex chronicus, candidiasis, lichen planus, psoriasis, seborrheic or allergic contact dermatitis

(2) Neoplastic epithelial disorders

Vulvar intraepithelial neoplasia (VIN) – Ý incidence in younger age groups, epidemiological profile suggests infection-HPV, 20-30% have carcinoma in situ or invasive carcinoma of cervix or vagina, 1/3 of cases are unicentric and 2/3 multicentric or confluent, progression of invasive carcinoma not invariable:

VIN I	mild dysplasia (formally mild atypia)
VIN II	moderate dysplasia (formally moderate atypia)
VIN III	severe dysplasia (formally severe dysplasia)
VIN III	carcinoma in situ
VIN III	squamous cell carcinoma of vulva (Bowens' disease)

Invasive squamous cell carcinoma of vulva – 3-4% of gynecologic carcinomas, 6^th-7^th decade, 80-90% are keratinizing, superficially invasive (conservative therapy): single lesion, <2 cm in diameter, £ 1 mm invasion

Vaginal intraepithelial neoplasia (VAIN) – incidence and prevalence unknown; risk factors similar to CIN (mid-40s)

Most common malignancy of vagina is metastasis from cervix, endocervix, ovary