Body of uterus LEC.2 د.ايمان سعود خليفة - PowerPoint Presentation

Slide1

Body of uterus

LEC.2

د.ايمان سعود خليفة

Slide2

Learning objectives:

Discuss diseases of the uterus like

endometritis,adenomyosis,endometriosis

Endometrial

hyperplasia&there

types

Tumors of the

endometrium&myometrium

Diseases of pregnancy like

H.mole,invasive

mole&choriocarcinoma

Slide3

BODY OF UTERUS

Endometritis

This may be associated with retained products of conception subsequent to miscarriage or delivery, or a foreign body such as an intrauterine device.

Slide4

Retained tissues or foreign bodies act as a

nidus

for infection, frequently by flora ascending from the vaginal or anal region.

Endometritis

is either acute or chronic depending on whether there is a predominant

neutrophilic

or

lymphoplasmacytic

response; however, components of both may be present in otherwise normal endometrium.

Slide5

Generally the diagnosis of chronic

endometritis

requires the presence of plasma cells

.

Acute

endometritis

is frequently due to

N.

gonorrhoeae

or C. trachomatis.

Microscopically

,

neutrophilic

infiltrate in the superficial endometrium and glands coexists with a stromal

lymphoplasmacytic

infiltrate.

Slide6

There is a large number of plasma cells (arrows).

Chronic endometritis

Slide7

All forms of

endometritis

may present with menstrual abnormalities, infertility and ectopic pregnancy due to extension of the damaging inflammation to the fallopian tubes.

Occasionally

tuberculosis

may present as granulomatous

endometritis

, frequently with

tuberculous salpingitis and peritonitis.

Slide8

Adenomyosis

This refers to the “

invagination of the stratum

basalis

of endometrium down into the myometrium.”

Nests of endometrial

stroma

, glands, or both, are found well down in the myometrium between the muscle bundles. The latter become hypertrophied.

Slide9

Accordingly, the uterine wall often becomes thickened and the uterus is enlarged and globular.

Because these glands derive from the stratum

basalis

,

they do not undergo cyclical bleeding

. Nevertheless, marked

adenomyosis

may produce menorrhagia, dysmenorrhea, and pelvic pain before the onset of menstruation.

Slide10

Adenomyosis uterus

Gross appearance of uterus involved by

adenomyosis

. The wall is irregularly thickened and contains small hemorrhagic foci (arrow).

The thickened and spongy appearing

myometrial

wall of this sectioned uterus is typical of

adenomyosis

. There is also a small white leiomyoma at the top

Slide11

Adenomyosis

occurs when endometrial glands and

stroma

are found in the myometrium.

Adenomyosis uterus

Slide12

Endometriosis

This is characterized by “

the presence of

endometrial glands and

stroma

in a location outside the

endomyometrium

.”

It occurs in as many as 10% of women in their reproductive years and in nearly half of women with infertility. It may present as a pelvic mass filled with degenerating blood (chocolate cyst).

Slide13

It is frequently multifocal and may involve any tissue in the pelvis (ovaries, pouch of Douglas, uterine ligaments, tubes, and

rectovaginal

septum), less frequently in more remote sites of the peritoneal cavity and about the umbilicus.

Three possibilities have been

suggested

to explain the origin of these lesions.

Slide14

1.

The regurgitation theory

,

currently the most accepted, proposes menstrual backflow through the fallopian tubes with subsequent implantation.

2.

The

metaplastic

theory

proposes endometrial differentiation of coelomic epithelium. 3.

The vascular or lymphatic dissemination theory has been raised to explain extrapelvic endometriosis.

Slide15

Gross features

Endometriosis almost always contains functioning endometrium, which undergoes cyclic bleeding.

Because blood collects in these ectopic foci, they usually appear grossly as red-blue to yellow-brown nodules.

They vary in size from microscopic up to 2 cm in diameter and lie on or just under the affected

serosal

surface.

Often individual lesions coalesce to form larger masses.

Slide16

When the ovaries are involved, the lesions may form large, blood-filled cysts that are transformed into so-called

chocolate cysts

as the blood ages .

Seepage and organization of the blood leads to widespread fibrosis, adherence of pelvic structures, sealing of the tubal

fimbriated

ends, and distortion of the oviducts and ovaries.

Slide17

Endometriosis ovary

Inner surface of cyst in a case of ovarian endometriosis. The color is typically brown.

This is a section through an

enlarnged

12 cm ovary to demonstrate a cystic cavity filled with old blood typical for endometriosis with formation of an

endometriotic

, or "chocolate", cyst.

Slide18

Ovarianendometriosis

In this area endometrial tissue faithfully reproduces the appearance of normal endometrium, in terms of both glands and stroma. Lt., collection of lipofuscin-laden histiocytes below the endometriotic epithelium.

Endometriosis ovary

Slide19

Microscopic features

The histologic diagnosis depends on finding two of the following three features within the lesions:

1. Endometrial glands.

2. Endometrial

stroma

, or

3. Hemosiderin pigment.

Extensive scarring of the oviducts and ovaries often causes sterility.

Slide20

Pain on defecation

reflects rectal wall involvement, and dyspareunia (painful intercourse) and dysuria reflect involvement of the uterine and bladder serosa, respectively.

In almost all cases, there is severe dysmenorrhea and pelvic pain as a result of

intrapelvic

bleeding and

periuterine

adhesions.

Slide21

Endometrial Hyperplasia

This is an exaggerated endometrial proliferation induced by sufficiently prolonged excess of estrogen relative to progestin.

The severity of hyperplasia is classified according to two parameters:-

a.

architectural crowding of the glands &

b.

cytologic

atypia

.

Accordingly there are three categories:-1. Simple hyperplasia. 2. Complex hyperplasia.

3. Atypical hyperplasia.

Slide22

These three categories represent a spectrum based on the level and duration of the estrogen excess.

The risk of developing carcinoma depends on the

severity

of the hyperplastic changes and associated

cellular

atypia

.

Simple hyperplasia carries a negligible risk, while a woman with atypical hyperplasia has a

20%

risk of developing endometrial carcinoma.

Thus When atypical hyperplasia is discovered, it must be carefully evaluated for the presence of cancer and must be monitored by repeated endometrial biopsy.Any estrogen excess may lead to hyperplasia.

Slide23

Potential contributors include:-

1. Failure of ovulation,

e.g. around the menopause.

2. Prolonged administration of estrogenic steroids.

3. Estrogen-producing ovarian lesions such as

a. polycystic ovaries (Stein-

Leventhal

syndrome).

b. cortical stromal hyperplasia.

c.

granulosa-theca cell tumors of the ovary.

4. Obesity, because adipose tissue processes steroid precursors into estrogens.

Slide24

Gross features

In simple hyperplasia the endometrium is diffusely thickened.

In complex & atypical hyperplasia there is usually focal thickening of the endometrium.

Microscopic features

Simple hyperplasia

involves both the glands &

stroma

; the normal gland to

stroma

ratio is maintained.

The glands are proliferative and some are cystically dilated.

Complex hyperplasia: there is glandular crowding with little stroma separating the proliferative glands. Typically, this is a focal process.

Slide25

Simple and complex

hyperplasias

are further divided into atypical and non-atypical

Atypical hyperplasia

: characterized by atypical nuclei of the proliferative glands as evidenced by nuclear stratification, nuclear rounding and the presence of nucleoli.

Slide26

The prominent folds of endometrium in this uterus (opened to reveal the endometrial cavity) are an example of hyperplasia. The hyperplasia involves both endometrial glands and

stroma

.

Diffuse endometrial hyperplasia

Slide27

Glands

are lined

Complex endometrial hyperplasia without atypia

Slide28

Nuclear and cytoplasmic differences are present between atypical glands (upper Rt.) and residual normal endometrial glands (center).

Atypical endometrial hyperplasia

Slide29

Tumors of the Endometrium and Myometrium

The most common neoplasms of the body of the uterus are:-

1. Endometrial polyps,

2. Smooth muscle tumors, and

3. Endometrial carcinomas.

All tend to produce bleeding from the uterus as the earliest manifestation.

Slide30

Endometrial Polyps

are usually sessile, hemispheric lesions up to 3 cm in diameter. Larger polyps tend to be

pedunculated

& may project from the endometrial mucosa into the uterine cavity & sometimes through the cervix into the vagina.

Microscopically

,

they are composed of

basalis

-type, often

cystically dilated glands with a rather fibroblastic stroma. Small

muscular arteries are often prominent.

Slide31

Endometrial polyp

Huge endometrial polyp filling the endometrial cavity. There is also a smaller polyp and

The uterus has been opened anteriorly through cervix and into the endometrial cavity. High in the fundus and projecting into the endometrial cavity is a small endometrial polyp. Such benign polyps may cause uterine bleeding.

Slide32

Cystically

dilated glands and a fibrous

stroma

with thick-walled vessels.

Endometrial polyp LP mic

Slide33

Leiomyomas

are benign tumors that arise from the smooth muscle cells in the myometrium.

Because of their firmness they are also called

fibroids

.

They are the most common benign tumor in females

and are found in 30% to 50% of women during reproductive life. Estrogens and possibly oral contraceptives stimulate their growth; conversely, they shrink postmenopausally.

Slide34

Gross features:

They are sharply circumscribed

,

firm gray-white masses with a characteristic whorled cut surface

.

They may occur singly, but are often multiple tumors scattered within the uterus, ranging in size from small seedlings to massive neoplasms that dwarf the size of the uterus.

Some are embedded within the myometrium (

intramural

), whereas others may lie directly beneath the endometrium (submucosal) or directly beneath the serosa (

subserosal).

Slide35

Markedly distorted uterine corpus with multiple irregular masses protruding from its surface. These are

subserosal

leiomyomata

.

Leiomyomas uteri

Slide36

Larger neoplasms may show foci of ischemic necrosis with areas of hemorrhage and cystic softening (red degeneration).

After menopause they may become densely collagenous and even calcified.

Slide37

Microscopic features

There are

whorling

bundles of smooth muscle cells

.

Foci of fibrosis, calcification, ischemic necrosis, cystic degeneration, and hemorrhage may be present.

Leiomyomas

of the uterus may be entirely asymptomatic and be discovered only on routine pelvic examination or imaging studies.

The most frequent manifestation, when present, is

menorrhagia

. Large masses in the pelvic region may become palpable or may produce a dragging sensation. Benign leiomyomas

rarely transform into sarcomas.

Slide38

Here is the microscopic appearance of a benign leiomyoma. Normal myometrium is at the left, and the neoplasm is well-differentiated so that the leiomyoma at the right hardly appears different. Bundles of smooth muscle are interlacing in the tumor mass.

Leiomyoma uteri

Slide39

Endometrial Carcinoma (EMC)

After the dramatic drop in the incidence of cervical carcinoma,

EMC is currently the most frequent cancer occurring in the female genital tract.

Epidemiology and Pathogenesis

EMC appears most frequently around the age of 60 years.

There are two

clinico

-pathological settings in which endometrial carcinomas arise:

1. In

perimenopausal

women with estrogen excess; these are of endometrioid type.

2. In older women with endometrial atrophy; these are of serous type.

Slide40

Well-defined risk factors for

endometrioid

carcinoma include

a. Obesity:

associated with increased synthesis of estrogens in fat depots.

b. Diabetes.

c. Hypertension.

d. Infertility

:

women tend to be nulliparous, often with

anovulatory cycles.At least some of these risk factors point to increased estrogen stimulation, and

indeed it is well recognized that prolonged estrogen replacement therapy and estrogen-secreting ovarian tumors increase the risk of this form of cancer.

Slide41

Gross features

EMC may be

exophytic

(

fungating

,

polypoid

) or infiltrative.

Microscopic features

The endometrioid

carcinoma consists of malignant endometrial-like tubular glands of varying grades. Squamous metaplasia is frequent. Sometimes, the tumor is adeno-squamous carcinoma.

Tumors originate in the mucosa and may infiltrate the myometrium and enter vascular spaces, with metastases to regional lymph nodes.

Slide42

Serous carcinoma

forms small tufts and papillary arrangements rather than the glands seen in

endometrioid

carcinoma, and has much greater

cytologic

atypia

.

They are particularly aggressive

.

Slide43

The tumor shown is

Endometrial adenocarcinoma

The tumor shown is extensive, nodular & highly infiltrating.

)

Slide44

type, infiltrating myometrium and displaying cribriform architecture. B, Higher magnification reveals loss of polarity an

Endometrioid adenocarcinoma

Slide45

C, displaying formation of papillae and marked cytologic atypia. D, Immunohistochemical stain for p53 reveals accumulation of mutant p53 in serous carcinoma.

Serous carcinoma of the endometrium

Slide46

Diseases of pregnancy

 

Gestational trophoblastic disease:

3 morphological categories:

(

1)

Hydatidiform

mole (H mole):

Voluminous mass of swollen sometimes cystically dilated chorionic villi, appear grossly as grape like structure,

It is of 2 subtypes:A: Complete mole: characterized by:

*not permit embryogenesis & never contain fetal parts.

* all chorionic villi are abnormal (

hydropic

changes--- cystic dilated

).

Slide47

the chorionic

epith

. cells are diploid (46XX or 46XY), it result from fertilization of empty egg by 2 sperms or diploid sperm.

* Incidence of complete mole is much higher in

Asian than Western countrie

s, much more common

before 20 & after 40yr. age

,

Clinically:

painless vaginal bleeding 12-14week after conception, when discovered early by ultrasound, uterus may or may not be too large for date but no fetal parts or heart sounds present.

Slide48

Lab test:

increase

HCG

present in maternal blood & urin

e, when discovered in 4

th

month of gestation---uterine cavity filled with delicate friable masses of thin wall translucent cystic structures without fetal parts.

Mic

: hydropic swelling of villi & chorionic epithelia show some degree of proliferation of cyto & syncytial trophoblast .

Slide49

The grape-like villi of a hydatidiform mole are seen here suspended in saline. With molar pregnancy, the uterus is large for dates, but no fetus is present. HCG levels are markedly elevated. Patients with a hydatidiform mole are often large for dates and have hyperemesis gravidarum more frequently. Patients may present with bleeding, and may pass some of the grape-like villi.

Complete hydatidiform mole

Slide50

Histologically, the hydatidiform mole has large avascular villi and areas of trophoblastic proliferation. Of course, ultrasound confirms the diagnosis before currettage is done to evacuate this tissue seen here.

Complete hydatidiform mole

Slide51

B: Partial mole:

* The villous edema

involve only some villi

& trophoblastic proliferation is focal &slight.

* In Partial: compatible with early embryo formation, some villi are abnormal & almost always triploid (

e.g

69XXY), normal egg fertilized by 2 sperms or diploid sperm.

In partial mole there are parts of fetus.

*

Slide52

Partial mole with attached fetus. The diagnosis was confirmed by biopsy and flow cytometry. The fetus showed no abnormality and was connected to the mole by a normal umbilical cord.

Partial Hydatidiform mole

Gross appearance of partial mole. The hydropic degeneration of the villi is not as pronounced as in the classical complete mole.

Slide53

In partial moles, some villi (as seen here at the lower left) appear normal, whereas others are swollen. There is minimal trophoblastic proliferation.

Partial hydatidiform mole

Slide54

(2)Invasive mole:

* It is intermediate between benign mole &

choriocarcinoma

.

* Invasive mole are complete moles that are more invasive locally (make it difficult to remove completely) but do not have aggressive metastatic capacity.

Gross:

There are

hydropic villi which penetrate uterine wall deeply----rupture & life threatening hemorrhage,, local spread to broad ligament &vagina also occur

Slide55

Invasive mole

Gross appearance of invasive mole. A hemorrhagic mass has permeated half of the thickness of the myometrial wall.

Intermediate between the HM and chorioca is the invasive mole. Despite its invasive properties in that it may invades into the myometrium and even through the uterine wall and extension into the vagina, there are still villi and thus the mole is not malignant. It may also embolizes to the lungs. Curretement alone may not achieve removal, so chemotherapy may be needed to produce resolution.

Slide56

Whole-mount view of invasive mole. Abnormal villi are seen permeating the thickened myometrium (arrows).

Hydropic villi covered by proliferating trophoblast are seen permeating the myometrium in this invasive mole.

Invasive mole

Slide57

Choriocarcinoma

(CC):

*

Very aggressive malignant tumor

.

Origin:

arise

either from gestational trophoblastic epithelium (gestational

choriocarcinoma

). Or less frequently from totipotential

cells within gonads (non gestational choriocarcinoma).Incidence: much more common in Asia &Africa than West

.Age incidence: the risk greater before 20 & after 40 yr.

50% follow complete mole & rarely follow partial mole, 25% after abortion &most of the remainder occur in previously normal pregnancy.

Slide58

Clinical presentation:

*

Bloody brownish discharge.

*

Increase titer of HCG B subunit in blood & urine

(much higher than with mole).

*

Absence of marked uterine enlargement

.

GROSS: very hemorrhagic, necrotic masses within uterus,

sometimes complete necrosis may be occur, which make anatomic diagnosis difficult because of little viable parts of neoplasm, the primary tumor may self destruct & only metastases will present.

Slide59

Mic

:

In contrast to H. mole & invasive mole, villi are not formed in

choriocarcinoma

. The tumor is purely epithelial, composed of anaplastic cuboidal

cytotrophoblst

&

syncytio

trophoblast.Notes: * By the time of diagnosis of

choriocarcinoma, there is widespread dissemination of malignancy through blood to lung, vagina, brain, liver & kidney.

Slide60

Lymphatic invasion uncommon.

Despite aggressiveness, chemotherapy achieve 100% cure even with tumor that spread beyond pelvis, vagina & into the lung.

There is relatively poor response to chemotherapy in CC that arise in gonads (ovary & testis) due to presence of paternal Ag on placental

choriocarcinoma

but not on gonadal lesion, so maternal immune response against foreign(paternal Ag) help by acting as an adjuvant to chemotherapy.

Slide61

Uterine choriocarcinoma showing typical highly hemorrhagic appearance.

Choriocarcinoma uterus

Slide62

There are both neoplastic cytotrophoblast and syncytiotrophoblast

Choriocarcinoma

Slide63

THANK YOU