PATHOLOGY OF THE FEMALE GENITAL SYSTEM - PowerPoint Presentation

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PATHOLOGY OF THE FEMALE GENITAL SYSTEM

LEC.1

د.ايمان سعود خليفة

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Learning objectives:Discuss benign&malignant tumors of the vulvaDiscuss tumors of the vagina

Discuss types of cervicitis

Spectrum of CIN

Discuss invasive tumors of the cervix

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VULVA

VULVITIS

The most important infectious agents are

1. Human papillomavirus

(HPV), producing

condylomata

acuminata

and vulvar intraepithelial

neoplasia

.

2. Herpes simplex

genitalis

(HSV 1 or 2), causing a vesicular eruption.

3.

Gonococci

producing

suppurative

infection of the

vulvovaginal

glands.

4.

Syphilis

, causing primary chancre at the site of inoculation.

5. Candida

causing

vulvitis

.

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Contact Dermatitis is one of the most common causes of vulvar pruritus

.

It presents as erythematous weeping and crusting papules and plaques.

Causes include urine, soaps, detergents, deodorants, etc.

NON-NEOPLASTIC EPITHELIAL DISORDERS (NNED) (previously vulvar dystrophies)

There are two forms of NNED:-

Lichen

sclerosus

and

2.

Lichen simplex

chronicus

.

Both appear clinically as a white lesion i.e.

leukoplakia

.

The latter, however, has many other underlying conditions including,

vitiligo

, psoriasis, lichen

planus

& carcinoma.

Only biopsy and microscopic examinations can differentiate among these

leukoplakias

.

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Lichen

Sclerosus

is characterized by thinning of the epidermis,

hydropic

degeneration of the basal cells, and dermal fibrosis.

When the entire vulva is affected, the labia become atrophic with constriction of the vaginal orifice.

It is most common in postmenopausal women.

An autoimmune reaction is probably involved in its pathogenesis.

Lichen Simplex

Chronicus

is the end stage of many inflammatory

dermatoses

and is marked by epidermal hyperplasia and significant surface hyperkeratosis.

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TUMOURS OF THE VULVA1.

Condylomas

and Low-Grade Vulvar Intraepithelial

Neoplasia

(VIN)

There are two

biologic forms

of

anogenital

warts

(

condylomas

)

Condylomata

lata

: are manifestations of secondary syphilis & are

flat, and slightly elevated.

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b. Condylomata

accuminata

: are viral (HPV) warts and appear as elevated warty or flat & wrinkled localized lesions.

They are often multiple, red-pink lesions that measure up to several centimeters in diameter.

Microscopically,

there is

acanthosis

and hyper/

parakeratosis

, and

koilocytosis

.

The latter are squamous cells with

perinuclear

cytoplasmic vacuoles and nuclear angulation.

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Spirochaetes

were seen on dark-ground microscopic examination of smears from the lesions. Serological tests for syphilis were positive.

Condylomata lata.

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Condylomata accuminata of the vulva

These appear as elevated warty localized lesions. They are often multiple, red-pink lesions that measure up to several centimeters in diameter

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There is thickening of the epidermis (

acanthosis

), hyper/

parakeratosis

, and cytoplasmic

vacuolation

(

koilocytosis

,

center

).

Condyloma acuminatum

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The koilocytes

are characteristic of HPV infection

.

Condyloma

acuminata

are not precancerous but may coexist with foci of low-grade intraepithelial

neoplasia

in the vulva (VIN 1) and cervix.

Indeed,

VIN I and

condylomas

are both related to

HPV 6 & 11

infections.

2. High-Grade VIN and Carcinoma of the Vulva

Carcinoma of the vulva is used to be seen mostly in elderly women.

However, there has been an increase in the frequency of high grade VIN principally among younger women.

The vast majority of vulvar carcinomas are of

squamous type.

Two

biologic forms of vulvar carcinoma seem to exist

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HPV-positive carcinoma (especially

type 16

) is seen in younger patients, particularly cigarette smokers.

Many cases show coexisting carcinoma in situ, or

condylomata

acuminata

.

B.

HPV-negative carcinoma

is seen in older women; frequently it is not associated with VIN.

VIN and early vulvar carcinomas appear as areas of leukoplakia

due to epithelial thickening.

These areas eventually transform into

exophytic

or ulcerative cancers

.

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The cancer was treated by radical

vulvectomy

. Squamous cell carcinoma of the vulva usually occurs in older women, or as a complication of HPV infection in younger women.

Exophytic SCC vulva arising from Rt. labium minus.

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Microscopic features: HPV-positive neoplasms tend to be poorly differentiated squamous cell carcinoma

,

whereas the HPV-negative lesions tend to be well-differentiated keratinizing.

Ultimately, direct invasion with involvement of regional nodes and more distant spread occurs.

Women with a tumor

less than 2 cm

in diameter have a much better prognosis than those with larger lesions.

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Variably sized, invasive, squamous nests some with central keratinization.

Well-differentiated SCC of vulva

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3. Paget Disease of the vulva is a form of intraepithelial carcinoma.

The majority of cases have no underlying carcinoma (unlike ,mammary Paget disease); it is considered as carcinoma of progenitor cells of the epidermis.

The condition presents as a red, scaly, crusted plaque.

Microscopically,

large epithelial cells infiltrate the epithelium, singly and in groups, with abundant granular cytoplasm and occasional cytoplasmic

mucin

vacuoles.

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Paget's disease of vulva in 87-year-old woman. Disease involves labia

majora

and labia

minora

. Note clinical similarity to leukoplakia.

Paget disease of the vulva

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There are scattered large, clear tumor cells within the squamous epithelium

Paget disease of the vulva

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Malignant Tumors of vagina:

1. Squamous cell carcinoma

is very rare & usually occurs in elderly women, with risk factors similar to those for cervical carcinoma. Vaginal intraepithelial

neoplasia

is a precursor lesion associated with HPV infection.

2. Clear cell adenocarcinoma

usually affects adolescent and young females whose mothers took

diethylstilbestrol

during pregnancy.

The tumor may arise from the cervix rather than the vagina in a third of the cases.

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Vaginal adenosis

presents as red foci consisting of small glands lined by columnar cells; this is a benign condition from which the clear cell adenocarcinoma is thought to arise.

3. Sarcoma

botryoides

(

embryonal

rhabdomyosarcoma

), produces soft

polypoid

masses and is usually seen in infants and children younger 5 years of age.

 

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The grape-like configuration of this lesion is characteristic.

Sarcoma botrryoides (embryonal rhabdomyosarcoma) of vagina

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THE CERVIX UTERI

Cervicitis

is a very common condition that is associated with a

mucopurulent

discharge.

Cytologic

examination of the discharge reveals inflammatory cells admixed with cervical epithelial cells, and possible microorganisms.

It

is

often due to vaginal flora, streptococci, staphylococci, and

E. coli.

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Much more important are Chlamydia trachomatis,

Ureaplasma

,

Trich

.

vaginalis

, Candida spp., Neisseria

gonorrhoeae

, herpes simplex II (

genitalis

), and HPV.

Many of these microorganisms are transmitted sexually, and so the cervicitis may represent a sexually transmitted disease.

Among these pathogens,

C. trachomatis is by far the most common

sexually transmitted cervicitis

.

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Herpetic infections

of the cervix are important because the infection may be transmitted to the infant during its passage through the birth canal, sometimes resulting in a serious, sometimes fatal, systemic infection.

Pathologic features

Nonspecific cervicitis may be either

acute or chronic

.

Excluding

gonococcal

infection, the uncommon

acute nonspecific cervicitis

is limited to postpartum women and is usually caused by staphylococci or streptococci.

Slide25

Cervical Tumors:

Despite dramatic improvements in early diagnosis and treatment, cervical carcinoma continues to be one of the major causes of cancer-related deaths in women in the developing world.

Cervical Intraepithelial

Neoplasia

(CIN)

The Pap smear, introduced 50 years ago by

Papanicolaou

, remains the most successful cancer screening test ever developed.

In populations that are screened regularly, cervical cancer mortality is reduced by up to 99%

.

Nearly all invasive cervical squamous cell carcinomas arise from precursor epithelial changes referred to as

cervical intraepithelial

neoplasia

(CIN).

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Detection of CIN by the Pap smear at an early stage permits curative treatment. Cytological examination can detect CIN long before any abnormality can be seen grossly

.

CIN begins as low-grade lesion that may progress to higher grade CIN, or it is a high-grade lesions from the outset; this depends on the location of the HPV infection in the

transformation zone

, the type of HPV infection (high versus low risk), and other host factors.

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On the basis of histology, precancerous changes are graded as:-

CIN I: Mild dysplasia.

CIN II: Moderate dysplasia.

CIN III: Severe dysplasia/carcinoma in situ.

The current

Bethesda system

divides the precancerous lesions into only two groups:

1. Low-grade SIL

(SIL for squamous intraepithelial lesions), equivalent to CIN I

2. High-grade SIL

. Equivalent to CIN II & III

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Progression from low- to high-grade SIL may or may not occur. The higher the grade of CIN the greater the likelihood of progression to invasive carcinoma, this reaches to 70% with CIN III.

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Epidemiology and Pathogenesis

The peak age of CIN incidence is about 30 years, whereas that of invasive carcinoma is about 45 years i.e. precancerous changes usually take many years to evolve into overt carcinomas.

Important risk factors for the development of CIN and invasive carcinoma are:

1.

Early age at first intercourse.

2. Multiple sexual partners.

3. Persistent infection by "high-risk" papilloma viruses.

4. Low socio-economic status.

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All of the above favor a sexually transmitted causative agent (HPV). Indeed, HPV can be detected by molecular techniques in nearly all precancerous and cancerous lesions

. Specifically,

high-risk HPV types including 16 & 18,

account for the majority of cervical carcinomas.

By contrast,

condylomas

, which are benign lesions, are caused by

low-risk HPV

types (i.e., 6 & 11).

In these benign lesions the viral DNA does not integrate into the host genome.

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By contrast, HPV types 16 & 18 usually integrate into the host genome with subsequent inactivation of the tumor suppressor genes p53 and RB.

The result is a transformed cell, capable of autonomous growth and susceptible to the acquisition of further mutations (cancer progression).

The recently introduced HPV vaccine is very effective in preventing HPV infections and hence cervical cancers.

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Although many women harbor these viruses, only a few develop cancer, suggesting other pathogenetic

influences play a role e.g. cigarette smoking and immunodeficiency states such as AIDS.

Microscopic features

CIN & Carcinoma in situ

CIN begins with

CIN I

This lesion is characterized by

koilocytotic

changes mostly in the superficial layers of the epithelium.

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Koilocytosis

is composed of nuclear

hyperchromasia

and angulation with

perinuclear

vacuolization produced by

cytopathic

effect of HPV.

The dysplastic epithelium is limited to the lower third of the mucosa.

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In CIN II the dysplasia is more severe, involving the lower two-thirds of the mucosa.

The superficial layer in some cases shows the

koilocytotic

changes.

CIN III

shows dysplastic changes that affect virtually all layers of the epithelium.

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Surface cells and their koilocytotic

changes are usually absent.

In time, dysplastic changes become more atypical and may extend into the

endocervical

glands, but the alterations are confined to the epithelial layer and its glands

.

These changes constitute

carcinoma in situ

.

Slide36

Normal squamous epithelium for comparison; CIN I with

koilocytotic

atypia

; CIN II with progressive

atypia

in lower 2/3 of the epithelial mucosa; CIN III (carcinoma in situ) with diffuse

atypia

and loss of maturation.

Spectrum of CIN

Slide37

The next stage is invasive carcinoma.

The above progression sequences do not occur in all the cases.

Cervical cytology and cervical colposcopy remain the basis of cervical cancer prevention.

Slide38

The most common cervical carcinomas are (in descending order):-

1. Squamous cell carcinomas (75%).

2. Adenocarcinomas and

adenosquamous

carcinomas (20%).

3. Small-cell neuroendocrine carcinomas (<5%).

The squamous cell carcinomas are increasingly appearing in younger women, (peak incidence at about 45 years); 10 to 15 years after detection of their precursors (CIN).

Slide39

Invasive carcinomas of the cervix develop in the region of the transformation zone

(the

squamo

-columnar junction) and range from invisible microscopic foci of early stromal invasion to grossly visible

exophytic

ulcerating masses or deeply infiltrative cancer that encircle the

os

.

Slide40

A

fungating

ulcerative

tumor

that involves the cervix circumferentially

Advanced Carcinoma of the cervix

Slide41

a large,

polypoid

lesion present within the

ectocervix

. The mass appears hemorrhagic.

Squamous cell ca cervix G

Slide42

This is a large cervical squamous cell carcinoma which spread to the vagina. A total abdominal hysterectomy with bilateral

salpingo-oopherectomy

was performed.

Squamous cell carcinoma, cervix

This is a pelvic

exenteration

done for stage IV cervical carcinoma. Below is the dark vulvar skin leads to vagina and to cervix in the center, where an irregular tan tumor mass is seen infiltrating anteriorly to the bladder. A slit-like endometrial cavity is surrounded by myometrium. rectum and sigmoid colon are at the right.

Slide43

Spread to pelvic lymph nodes is determined by tumor depth of invasion, ranging from less than 1% for tumors under 3 mm in depth to over 10% once invasion exceeds 5 mm.

Three microscopic variants of cervical SCC

squamous cell carcinoma

exist, although admixtures and intermediate forms occur:

1. Large cell

nonkeratinizing

.

2. Keratinizing.

3. Small cell;

this should be distinguished from small cell neuroendocrine carcinoma.

Slide44

At high magnification, nests of neoplastic squamous cells are invaded through a chronically inflamed stroma. This cancer is well- differentiated, as evidenced by keratin pearls. However, most cervical squamous carcinomas are non-

Keratinizing.

Squamous cell ca WD keratinizing

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Ideally cervical carcinomas should be diagnosed in the preinvasive

phase; these appear as white areas on

colposcopic

examination after application of dilute acetic acid

(Schiller test).

More advanced cases of cervical cancer are invariably seen in women who either have never had a Pap smear or have waited many years since the prior smear.

Slide46

Such tumors call to attention by unexpected vaginal bleeding, leukorrhea

, painful coitus (dyspareunia), and dysuria.

Mortality

is most strongly related to the tumor stage.

The

5-year survival in stage 1 is 90% but this figure drops to 10% in stage 4.

Slide47

Endocervical Polyp

This

may protrude, sometimes, through the

exocervix

.

The trend is to regard these polyps as inflammatory rather than neoplastic.

They are generally small, soft, and have smooth, glistening surface and subjacent

cystically

dilated spaces filled with mucinous secretion.

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Thank you