Uterine Diseases: Endometritis and Adenomyosis

Body of uterus

LEC.2

د.ايمان سعود خليفة

•

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

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.

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.

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.

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

Chronic endometritis

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.

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.

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.

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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

Adenomyosis occurs when endometrial glands and stroma are found

in the myometrium.

Adenomyosis uterus

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

).

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.

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.

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.

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.

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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.

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.

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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.

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.

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.

•

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.

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.

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.



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.

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

Glands are lined

Complex endometrial hyperplasia without atypia

Nuclear and cytoplasmic differences are present between atypical glands  (upper Rt.)

and residual normal endometrial glands (center).

Atypical endometrial hyperplasia

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.

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.

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.

Cystically dilated glands and a fibrous stroma with thick-walled

vessels.

Endometrial polyp LP mic

•

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.

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

).

Markedly distorted uterine

corpus with multiple irregular

masses protruding from its

surface. These are subserosal

leiomyomata.

Leiomyomas uteri



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.

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.

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

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

.

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.

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.

•

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

.

The tumor shown is

Endometrial adenocarcinoma

The tumor shown is extensive,

nodular & highly infiltrating.

)

type, infiltrating myometrium

and displaying cribriform

architecture. B, Higher

magnification reveals loss of

polarity an

Endometrioid adenocarcinoma

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

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

).

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.

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 .

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

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

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.

*

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.

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

(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

Invasive mole

Gross appearance of invasive

mole. A hemorrhagic mass has

permeated half of the thickness of

the myometrial wall.

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.

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.

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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.

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.

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.

•

 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.

Uterine choriocarcinoma showing typical highly hemorrhagic appearance.

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There are both neoplastic cytotrophoblast and syncytiotrophoblast

Choriocarcinoma

THANK YOU