Acknowledgement

Special thanks to Dr. Mohamed Aziz for letting me use his

material for this course.
 Vulva-Vagina: Objectives
❖ Review of Infections of the Genital Tract
❖ Understand the meaning of leukoplakia, and know which lesions
may have this appearance
❖ Know the significance and association of HPV and vulvar carcinoma
❖ Discuss Paget disease of the vulva (Extramammary Paget’s disease) and
know how it is different from Paget disease of the breast
❖ Recognize the clinical and pathologic findings associated with lichen
sclerosis.
❖ Discuss the clinical and pathologic features of sarcoma botryoides.
 Cervix: Objectives
• Understand the molecular biology by which HPV causes
carcinogenesis.
• Identify low-grade and high grade squamous intraepithelial lesions.
• Know clinical and pathologic sequelae of HPV infection and which
HPV subtypes are high risk.
• Make histologic diagnosis of invasive SCC
• Understand how Pap smears, early treatment, and HPV vaccines have
decreased the incidence of cervical carcinoma.
• Discuss risk factors for cervical carcinoma.
Infections of the Genital Tract
(Vulva-Vagina-Cervix)
 Candida albicans infection.

Diagnosis is made by the finding of filamentous fungal

pseudohyphae and spores

 Trichomoniasis
Candida albicans infection
The vaginal mucosa is inflamed and often speckled with
petechial lesions. Sexually transmitted, high carrier. In
adolescents, petechial hemorrhages may also be found on
the cervix, resulting in the so-called strawberry cervix

Trichomoniasis
 Chlamydia trachomatis

May cause ascending infection of uterus and fallopian

tubes, resulting in pelvic inflammatory disease (PID). Most
common cause of cervicitis in sexually active women.
Sexually transmitted and infect the eye
Chlamydia trachomatis
Pelvic Inflammatory Disease (PID)

 Ascending infection

Neisseria gonorrhea is the most common

agent

 Chlamydia trachomatis also important causative agent

 Presence of phagocytosed gram-negative diplococci
within neutrophils in infected material
 Complication: infertility,
tubal obstruction, ectopic
pregnancy, pelvic pain, intestinal obstruction
Epithelial disorders
• Leukoplakia (Vulva)

• Lichen sclerosis (et atrophicus)

• Squamous cell hyperplasia (lichen simplex chronicus)

• Benign exophytic lesions (HPV Condyloma acuminatum)

 Lichen sclerosis (et atrophicus)
Post menopausal most common, benign but 1-5%
can develop squamous cell carcinoma
 Smooth white plaques (leukoplakia)
 Epidermal thinning, loss of rete pegs, dermal
fibrosis

Squamous cell hyperplasia (lichen simplex chronicus)

• No increased risk of developing cancer, Changes
thought to be secondary to chronic irritation, often
pruritus due to other conditions.
• Histology: Marked epithelial thickening, no aty
• Thickened scaly plaques, leukodermic (hypopigmented) Center.
ATROPHIC VAGINITIS

• In postmenopausal, symptoms are mainly due to decreased

ESTROGEN
 symptoms may include: difficult or painful sexual intercourse
“dyspareunia”, red vaginal mucosa, petechiae, ecchymosis,
no mucosal folds, leukocytes, RBCs, etc.
 Benign exophytic lesions
Condyloma acuminatum
 Sexually transmitted, single or multiple lesions occurring anywhere in
anogenital region
 Histology:

 Papillary or tree-like
Koilocytosis which is a perinuclear
cytoplasmic vacuolization and nuclear wrinkling
 Acanthosis and parakeratosis
 Pathogenesis

HPV virus, usually low risk subtypes 6 and

11 which are not usually associated with
progression to cancer (16/18 are the H. risk)
Not considered premalignant lesions
Vulvar and vaginal neoplasms
Extramammary Paget Disease
 Intraepidermal proliferation of malignant epithelial cells,
usually in vulva. Arise from epidermal progenitor cells, not
underlying malignancy (different from mammary Paget
disease of the breast). It has potential to spread and
progress into an invasive tumour
(Recent studies suggest possible presence of underlying malignancy)

 Red scaly crusty lesions mimicking other inflammatory

dermatoses
 Large malignant epitheliod cells in epidermis, pale granular
and/or vacuolated cytoplasm. PAS+ for mucin,
differentiating from melanoma (S100)
 May be present for years without evidence of invasion
 Vaginal adenosis Presence of glands in the vagina

 Normally,there NO glands in vagina

 Red granular area
 Only seen in small percentage of women
 Reported in 35-90% of women exposed to
DES (diethylstilbestrol)
 Women with prior radiation
 Possibly metaplastic changes

 Diethylstilbestrol Can be a risk for clear

cell carcinoma
 Embryonal rhabdomyosarcoma

 Rare primary vaginal tumor, usually in

infants and young children composed of
malignant embryonal rhabdomyoblasts
 Presents as polypoid grape like lesions
composed of small cells with a
superficial crowded “cambium” layer
 Tends to invade locally
 Skeletal muscle tumor: positive for
Desmin and Myogenin
 Treat with conservative surgery and
chemotherapy

Smooth muscle: Leiomyosarcoma: ONLY Desmin

Skeletal muscle: Rhabdomyosarcoma: BOTH Desmin and Myogenin
Pathology of the Cervix
Uterine Cervix: Normal

 Columnar mucous cells lined endocervix meets

squamous-lined exocervix at the cervical os TZ
 Endocervical glands undergo squamous
metaplasia
 Region where squamous transforms to columnar
epithelium is known as the transformation zone
(location varies with age, going upward with age)
 The area most at risk of neoplasia in all age groups
is the transformation zone (TZ).
 The TZ must be sampled to maximize efficacy of
the Papanicolaou smear.
 Cervix: normal flora

▪ Alterations in pH Alterations in normal

flora (Bacterial vaginosis, fishy smell)
(intercourse, bleeding, antibiotics) cause alterations
in normal flora
▪ Chlamydia Trachomatis most common cause of
cervicitis in STD clinic
▪ Herpes Simplex Virus (HSV) very important because
of maternal fetal transmission Herpes Simplex
Cervical Intraepithelial Neoplasia (lesions)
CIN-I (Condyloma-Low grade dysplasia)

CIN-II (Intermediate grade dysplasia)

High grade
and CIN-III (High grade dysplasia)
 The Papanicolaou (Pap) smear

NORMAL LSIL
(Lower 1/3 and/or Koilocytes)
HSIL
(More than 1/3)
Cervical intraepithelial neoplasia

CIN is a precancerous
epithelial lesion that may
progress to overt cancer
◼ LSIL (low-grade squamous
intraepithelial lesions), which
is CIN I.
◼ HSIL (high-grade squamous
intraepithelial lesions), which
is CIN II and CIN III
(Expansion of immature basal cells
to the epithelial surface)
Human papillomavirus (HPV)
❖ Double stranded DNA virus
❖ 50% of HPV infections cleared in 8 months and 90% in 2 years (mostly low risk subtypes)
❖ HPV infects basal layer of transition zone but replication of HPV DNA occurs in more mature cells.

❖ Due to expression of E6 and E7, two oncoproteins which bind and inactivate 2 tumor suppressors: p53
and Rb, preventing cell cycle arrest and promoting carcinogenesis.
Grouped into:
▪ low risk (6,11), . Associated with development of condyloma,
. No integration with cell genome (rare progression to cancer <1%)
▪ High risk (16,18) (frequent progression to cancer, >20%)

. The virus encodes several proteins including E6 and E7, integrates into cell genome, causing inhibition of
the cell cycle regulatory proteins (p53 & Rb)
. Immunosuppression is the highest risk factor
. Lack of barrier contraception
Looking for HPV in biopsies
p16
 Morphology
• Koilocytes (low risk, 6/11)
• Immunohistochemistry
 In situ hybridization for HPV
 Nucleic acid hybridization to allow for localization in tissue

p16 Immunohistochemistry
 Surrogate marker of HPV
 Accumulates in transformed cells
 Sensitive but not entirely specific for HPV
Prevention: HPV vaccine
 Two HPV vaccines are currently on the market: Gardasil and
Cervarix.
 Both vaccines protect against HPV-16 and 18; GARDISIL
also against HPV-6 and 11.
 Both vaccines have been shown to prevent precancerous
lesions of the cervix.
 HPV vaccine is recommended for young women to prevent
cervical cancer and condyloma
 Boys, like girls, should get the two doses of the HPV
vaccine at age 11 or 12
 Continued Pap test necessary to detect those already
infected and those caused by other sub-types (31 and 33)
Squamous cell carcinoma
Cervical Squamous cell carcinoma
 Risk factors for progression
 Cigarette smoking, HIV, HPV, Herpes, Age, Socioeconomic factors,
exposure to diethylstilbestrol (DES)
 Diagnosis: Lesions must be biopsied to determine if invasive lesion present.
 Range from microscopic tumors to exophytic tumors.
 Present with vaginal bleeding, leucorrhea, dyspareunia or dysuria,
 Treatment varies from cone biopsy to hysterectomy and lymph node
dissection.
 Mortality linked to tumor stage.
 Renal complications and failure a significant cause of morbidity
 Invasive squamous cell carcinoma

Microinvasion: Still is an invasion Invasion Histology