pathology of cervix &uterus

Pathology of the

Cervix & Uterus

Dr. Aye Aye Tun

Senior Lecturer, Pathology Unit

RCMP,UniKL

Learning Objective

Etiopathogenesis

Morphological features

Clinical features

Complications

Investigations and

Learning Objective

The aetiopathogenesis, morphological features, clinical

features, investigations and complications of

CARCINOMA CERVIX

Congenital anomalies of the uterus

Endometrial hyperplasia

Endometriosis & adenomyosis

Uterine tumors: benign & malignant

PATHOLOGY OF CERVIX

INFLAMMATION

METAPLASIA

POLYPS

DYSPLASIA

CIN

INFILTRATING CARCINOMA

Endocervical Polyps

Benign exophytic growths

Occur in 2% to 5% of adult women

Irregular vaginal “spotting” or bleeding

Treatment - Simple curettage or surgical

excision effects a cure

Site:

within the

endocervical canal

Size:

small and sessile to

large

(5-cm masses that

protrude through the

cervical os)

Consistency:

soft& mucoid

Microscopic -

fibromyxomatous stroma

mucus secreting endocervical glands

often accompanied by inflammation

Endocervical Polyps

Premalignant and Malignant Neoplasms

CERVICAL INTRAEPITHELIAL NEOPLASIA

Nearly all invasive cervical squamous cell

carcinomas arise from

precursor epithelial changes referred to as

CIN

CERVICAL INTRAEPITHELIAL NEOPLASIA

Not all cases of CIN progress to invasive

cancer

persist without change or even regress

Classification Systems for

Premalignant Squamous Cervical Lesions

Dysplasia CIN Squamous Intraepithelial Lesion

(SIL)

Mild dysplasia CIN I Low-grade SIL (LSIL)

Moderate dysplasia CIN II High-grade SIL (HSIL)

Severe dysplasia CIN III High-grade SIL (HSIL)

Carcinoma in situ CIN III High-grade SIL (HSIL)

Papanicolaou (Pap) smear

Cytologic examination (Papanicolaou (Pap) smear)

can detect CIN long before any abnormality can be

seen grossly

The Pap smear - the most successful cancer

screening test

In populations that are screened regularly, cervical

cancer mortality is reduced by as much as 99%

The cytology of CIN as seen on the Papanicolaou smear

Normal

exfoliated superficial squamous epithelial

cells CIN I

CIN II CIN III

DYSPLASIA / CIN (CERVICAL INTRAEPITHELIAL NEOPLASIA )

Spectrum of cervical intraepithelial neoplasia:

A. normal squamous epithelium for comparison

B. CIN I with koilocytotic atypia

C. CIN II with progressive atypia in all layers of the epithelium

D. CIN III (carcinoma in situ) with diffuse atypia and loss of

maturation

Carcinoma Cervix

second most common cancer in women

Squamous cell carcinomas (75%)

Adenocarcinomas & adenosquamous

carcinomas (20%)

Small-cell neuroendocrine carcinomas

(<5%)

Nobel Prize in 2008

HARALD ZUR HAUSEN was awarded

For discovery of HPV as a cause of cervical

cancer

Pathogenesis of Carcinoma Cervix

High oncogenic risk HPVs are currently

considered to be the single most important

factor in cervical oncogenesis

HPV 16 and HPV 18

Pathogenesis of Carcinoma Cervix

The risk factors for cervical cancer are related to

both host and viral characteristics

HPV exposure

viral oncogenicity

inefficiency of immune response

presence of co-carcinogens

Risk Factors

1. Multiple sexual partners

2. A male partner with multiple previous or current sexual

partners

3. Young age at first intercourse

4. High parity

5. Persistent infection with a high oncogenic risk HPV, e.g.,

HPV 16 or HPV18

6. Immunosuppression

7. Certain HLA subtypes

8. Use of oral contraceptives

9. Use of nicotine

Smoking, Hormone, Oral contr. parity,

Altered immune response etc.

Cervical Transformation Zone

Sexual Exposure

HPV Infection

Squamous Ep Columnar Ep

Squamous Ca Adeno Ca

High Risk Types (16,18)

Low Risk-6,11

PATHOGENESIS

Role of HPV in carcinoma cervix

How does HPVtransform cells?

Viral oncoproteins E6 and E7

E6 binds - the product of tumor

suppressor gene TP53 and inactivates it

E7 binds - the retinoblastoma gene (RB)

protein

MORPHOLOGY

pink-tan, friable

Fungating (exophytic) lesion

on the anterior cervical lip

Squamous cell carcinoma of the cervix

Microinvasive squamous cell carcinoma

with invasive nest breaking through the basement membrane of HSIL

MORPHOLOGY

Invasive nest of tumor cells

squamous cell carcinomas are composed of

nests and tongues of malignant squamous epithelium

either keratinizing or non keratinizing

invading the underlying cervical stroma

MORPHOLOGY

MORPHOLOGY

Adencarcinoma in situ

Adenocarcinomas are characterized by proliferation of glandular epithelium

composed of malignant endocervical cells with large, hyperchromatic nuclei

and relatively mucin-depleted cytoplasm, resulting in dark appearance of the glands

as compared with the normal endocervical epithelium

Invasive adencarcinoma

CLINICAL FEATURES

Asymptomatic

unexpected vaginal bleeding

Leukorrhea

painful coitus (dyspareunia)

Dysuria

BODY OF UTERUS AND

ENDOMETRIUM

The uterus has two major components:

Myometrium - composed of tightly

interwoven bundles of smooth muscle that

form the wall of the uterus

Endometrium - composed of glands

embedded in a cellular stroma

BODY OF UTERUS AND

ENDOMETRIUM

Diseases of uterus result from

endocrine imbalances

complications of pregnancy

neoplastic proliferation

BODY OF UTERUS AND

ENDOMETRIUM

D.U.B. (Dysfunctional Uterine Bleeding)

Inflammation

Adenomyosis/Endometriosis

Polyps/Hyperplasia

Malignant Tumors of the Endometrium

Tumors of the Endometrium with Stromal

Differentiation

Tumors of the Myometrium

Adenomyosis/EndometriosisEndometriosis

presence of endometrial tissue both endometrial glands and

stroma outside of the uterus

It occurs in the following sites

(1) Ovaries

(2) uterine ligaments

(3) rectovaginal septum

(4) cul de sac

(5) pelvic peritoneum

(6) large and small bowel and appendix

(7) mucosa of the cervix, vagina, and fallopian tubes

(8) laparotomy scars

Adenomyosischaracterizedby functional endometrial nests

within the myometrium

producing foci of hemorrhagic cysts within the uterine wall

Endometrosis in ovarycystic and contains dark blood and debris resembling chocolate

described as “chocolate cysts

Polyps/Hyperplasia

Endometrial Polyps

Exophytic masses of variable size that project

into the endometrial cavity

Asymptomatic or cause

abnormal bleeding

(intramenstrual, menometrorrhagia, or

postmenopausal) if they ulcerate or undergo

necrosis

single or multiple

usually sessile, measuring from 0.5 to 3 cm in diameter

occasionally large and pedunculated

MORPHOLOGY

Endometrial Hyperplasia

defined as an increased proliferation of the

endometrial glands relative to the stroma

resulting in an increased gland-to-stroma

ratio

when compared with normal proliferative

endometrium

an important cause of abnormal bleeding

Endometrial Hyperplasia

associated with

prolonged estrogen stimulation of the

endometrium

Have the malignant potential of endometrial

hyperplasia

endometrial hyperplasia and carcinoma share

specific molecular genetic alterations

inactivation of the PTEN tumor suppressor

gene

MORPHOLOGY

Simple hyperplasia without atypia

with architectural abnormalities including mild glandular crowding

cystic glandular dilatation

MORPHOLOGY

Complex hyperplasia without atypia

increased glandular crowding with areas of back-to-back glands

cytologic features similar to proliferative endometrium

MORPHOLOGY

Complex hyperplasia with atypia

similar to complex hyperplasia without atypia

the cytologic features have changed

MORPHOLOGY

High magnification of complex hyperplasia

with atypia showing rounded, vesicular nuclei with prominent nucleoli

Malignant Tumors of the Endometrium

Carcinoma of the endometrium

peak incidence is in 55 - 65 year

classification of endometrial carcinoma

two broad categories

type I and type II

Characteristics of Type I and Type II Endometrial

Carcinoma

Characteristics Type I Type II

Age 55–65 yr 65–75 yr

Clinical setting Unopposed estrogen Atrophy

Thin physique

Obesity

Hypertension

Diabetes

Morphology Endometrioid Serous

Clear cell

Mixed m?llerian

Characteristics of Type I and Type II

Endometrial Carcinoma


Precursor Hyperplasia Endometrial intraepithelial carcinoma

Molecular genetics PTEN p53

PIK3CA Aneuploidy

KRAS PIK3CA

MSI β-catenin

p53

Characteristics of Type I and Type II

Endometrial Carcinoma


Behavior Indolent

Aggressive

Spreads via lymphatics Intraperitoneal and

lymphatic spread

Schematic diagram depicting

the development of type I endometrial carcinoma

arising in the setting of hyperplasia

molecular genetic alterations are shown at the time

during the progression of the disease

Type I Adenocarcinoma endmetrium

MORPHOLOGY

Sagittal section of the uterus shows

a friable, tan-yellow tumor

that is filling the uterine cavity

and extending into the myometrium

MORPHOLOGY

Endometrial adenocarcinoma

a fungating mass

in the fundus of the uterus

Well-differentiated (grade 1)

endometrioid adenocarcinoma

preserved glandular architecture

lack of intervening stroma

Moderately differentiated (grade 2)


glandular architecture admixed

with solid areas

Poorly differentiated (grade 3)


with predominantly solid growth

Schematic diagram of the development of type II endometrial carcinoma.

Type II Adenocarcinoma endmetrium

MORPHOLOGY

Endometrial intraepithelial carcinoma

Strong, diffuse expression of p53

as detected by immunohistochemistry

in endometrial intraepithelial carcinoma

Serous carcinoma of the endometrium

with papillary growth pattern

Strong, diffuse expression of p53

as detected by immunohistochemistry

in serous carcinoma endometrium

Clinical course of adenocarcinoma of the

endometrium

irregular or postmenopausal vaginal bleeding

excessive leukorrhea

Uterine enlargement may be absent in the early

stages

The diagnosis of endometrial cancer must

ultimately be established by biopsy or

curettage and histologic examination of the

tissue

Staging of types I and II of endometrial

adenocarcinoma

Stage I

Carcinoma is confined to the corpus uteri itself

Stage II

Carcinoma involves the corpus and the cervix

Stage III

Carcinoma extends outside the uterus but not

outside the true pelvis

Stage IV

Carcinoma extends outside the true pelvis or

involves the mucosa of the bladder or the

rectum

Tumors of the Myometrium

Leiomyoma(commonly called fibroids)

most common tumor in women

benign smooth muscle neoplasms

approximately 40% have a simple chromosomal abnormality

Several cytogenetic subgroups have been recognized

t(12;14)(q14–q15;q23–q24)), del(7)(q22–q32)), trisomy

12

rearrangements of 6p, 3q, and 10q

The rearrangements of 12q14 and 6p involving the

HMGIC and HMGIY genes

Morphology

Site – Leiomyoma can occur

within the myometrium - intramural

just beneath endometrium - submucosal

beneath the serosa - subserosal

Size - varying in size from small to massive

tumors that fill the pelvis

Number – single or most often multiple

Morphology

Shape - sharply circumscribed, discrete,

round

Color & Consistency - firm, gray-white

tumors

on cut section - characteristic whorled

pattern of smooth muscle bundles

red degeneration- areas of yellow-brown to

red softening in large tumors

Morphology

On histologic examination

leiomyoma is composed of

whorled bundles of smooth muscle cells that

resemble the uninvolved myometrium

the individual muscle cells

- uniform in size and shape

- have the characteristic oval nucleus

- long, slender bipolar cytoplasmic processes

Leiomyomas of the myometrium

The uterus is opened to reveal multiple tumors

in submucosal (bulging into the endometrial cavity)

intramural, and subserosal locations

a firm white appearance on sectioning

MORPHOLOGY

well-differentiated, regular

spindle-shaped smooth muscle cells

associated with hyalinization

Leiomyosarcoma

A large hemorrhagic tumor mass

distends the lower corpus

is flanked by two leiomyomas

MORPHOLOGY

Leiomyosarcoma

pathology of cervix &uterus

Health & Medicine