The Pathology of UTERUS Prof.Dr. Ferda Özkan Prof.Dr. Ferda Özkan

The Pathology The Pathology ofof

UTERUSUTERUS Prof.Dr. Ferda ÖzkanProf.Dr. Ferda Özkan

Anatomy Fundus: cephalad to line connecting the

insertion of fallopian tubes Cornua: lateral regions of fundus

associated with intramural fallopian tubes

Anatomy Isthmus/lower uterine segment:

portion of corpus connecting with cervix

Cervix: lower 1/3 of uterus; at and below level of internal cervical os

Anatomy Uterine cavity: 6 cm long, triangular

shape, lined by endometrial mucosa / endometrium, then myometrium, then serosa, which extends to peritoneal reflection

TerminologyTerminology AmenorrheaAmenorrhea

No menstruationNo menstruation SterilitySterility

Infertility Infertility Menorrhagia / metrorrhagiaMenorrhagia / metrorrhagia

Heavy menstrual periods Heavy menstrual periods Dysmenorrhea Dysmenorrhea

Painful menstruation Painful menstruation Epimenorrhea Epimenorrhea

Irregular bleeding between cycles Irregular bleeding between cycles

DEVELOPMENTAL DISORDERSDEVELOPMENTAL DISORDERS Birth defects of the uterus Birth defects of the uterus

are uncommon.are uncommon. Uterus bifidaUterus bifida Bicornuate uterus –Bicornuate uterus –

presence of uterine septum presence of uterine septum results from nonfusion of results from nonfusion of the müllerian ductsthe müllerian ducts

AgenesisAgenesis Turner's syndrome Turner's syndrome

Development or fusion of Development or fusion of the müllerian ducts. the müllerian ducts. imperfect fusionimperfect fusion

may make it difficult may make it difficult to take a pregnancy to take a pregnancy to term. to term.

THE NORMAL CYCLETHE NORMAL CYCLE During reproductive life, the endometrium During reproductive life, the endometrium

goes through a monthly cycle. goes through a monthly cycle. The first half ("proliferative phase") begins The first half ("proliferative phase") begins

with menstruation and is of rather variable with menstruation and is of rather variable length:length: Early proliferative (some gland mitoses, little Early proliferative (some gland mitoses, little

gland tortuosity) gland tortuosity) Late proliferative (many gland mitoses, some Late proliferative (many gland mitoses, some

gland tortuosity) gland tortuosity) The second half ("secretory phase") begins The second half ("secretory phase") begins

at ovulation, and should be 14 days, with at ovulation, and should be 14 days, with less variability. less variability.

Secretory phase

If a woman bleeds between cycles during her reproductive life, the cause is usually one of the following: complication of pregnancycomplication of pregnancy (ectopic (ectopic

pregnancy, miscarriage, trophoblastic pregnancy, miscarriage, trophoblastic disease) disease)

submucosal leiomyomasubmucosal leiomyoma (interferes with the (interferes with the development of the endometrium) development of the endometrium)

endometrial polypendometrial polyp (abnormal benign patch (abnormal benign patch of endometrium) of endometrium)

endometrial hyperplasiaendometrial hyperplasia cancer cancer dysfunctional uterine bleedingdysfunctional uterine bleeding

some problem with the hormonal symphony; this some problem with the hormonal symphony; this is the most common.is the most common.

Dysfunctional uterine bleeding Anovulatory cycles are common around menarche and Anovulatory cycles are common around menarche and

menopause menopause A granulosa and/or theca tumor in an ovary producing A granulosa and/or theca tumor in an ovary producing

estrogens and/or progesterone estrogens and/or progesterone Endocrine disease elsewhere (especially the pituitary or Endocrine disease elsewhere (especially the pituitary or

thyroid) thyroid) Massive obesity (too much estrogen being converted) Massive obesity (too much estrogen being converted)

All of these will give "unopposed estrogen effect" on All of these will give "unopposed estrogen effect" on biopsy, with a thick endometrium with long glands but biopsy, with a thick endometrium with long glands but without decidual-type change. The endometrium without decidual-type change. The endometrium starts breaking down early in patches, hence the starts breaking down early in patches, hence the bleeding. bleeding.

Too little body fat (too little estrogen being converted) Too little body fat (too little estrogen being converted) Severe chronic disease (the interleukins) Severe chronic disease (the interleukins) Inadequate luteal phase Inadequate luteal phase Persistent luteal phase.Persistent luteal phase.

ENDOMETRITIS ENDOMETRITIS The endometrium is very resistant The endometrium is very resistant

to bacterial infection. to bacterial infection. Infection by common bacteria Infection by common bacteria

(strep A, staph) is usually the result (strep A, staph) is usually the result of retained products of conception. of retained products of conception.

Surgical removal of the remnants is Surgical removal of the remnants is the mainstay of therapy. the mainstay of therapy.

Pyometra is a purulent infection of Pyometra is a purulent infection of the uterus, as when products of the uterus, as when products of conception are retained or the os is conception are retained or the os is closed. closed.

Clostridial gas gangrene is a lethal complication Clostridial gas gangrene is a lethal complication of attempted self-abortion or criminal abortus.of attempted self-abortion or criminal abortus.

Other infections after childbirth or natural or Other infections after childbirth or natural or induced abortion include strep, staph, and E. induced abortion include strep, staph, and E. Coli.Coli.

Mycoplasma infection: acute endometritis.Mycoplasma infection: acute endometritis. Tuberculosis (Tuberculosis ( secondary sterility). secondary sterility). Magnesium-rich super-absorbent tamponsMagnesium-rich super-absorbent tampons

good culture medium for the staphylococci good culture medium for the staphylococci that produce toxic shock syndrome. that produce toxic shock syndrome.

Chronic endometritis Chronic endometritis result of gonococci or chlamydia result of gonococci or chlamydia retained products of conception orretained products of conception or an intrauterine contraceptive device. an intrauterine contraceptive device. plasma cellsplasma cells in the endometrium in the endometrium

ADENOMYOSIS ADENOMYOSIS (endometriosis interna)(endometriosis interna)

Sometimes the endometrium penetrates Sometimes the endometrium penetrates deep into the myometrium in a few places. deep into the myometrium in a few places.

This can be visible grossly in a resected This can be visible grossly in a resected uterus. uterus.

It isn't cancer, since the glands are benign It isn't cancer, since the glands are benign and stroma existsand stroma exists

Obviously this can cause discomfort just Obviously this can cause discomfort just before and during menstruation. before and during menstruation.

It's supposed to be one of the major It's supposed to be one of the major causes of menstrual cramps. causes of menstrual cramps.

ENDOMETRIOSIS ENDOMETRIOSIS (endometriosis externa)(endometriosis externa)

This is endometrial tissue outside the This is endometrial tissue outside the uterus. uterus.

The most common site is the The most common site is the ovary.ovary. Other localizations:Other localizations:

vulva, vulva, vagina,vagina, the ligaments of the pelvis, the ligaments of the pelvis, the abdomen the abdomen

intestine, intestine, umbilicus. umbilicus.

The gross appearance of endometriosis The gross appearance of endometriosis depends on how extensive the disease is:depends on how extensive the disease is: Minor lesions look like powder under the Minor lesions look like powder under the

serosal surface. serosal surface. Longstanding ovarian lesions present Longstanding ovarian lesions present

"chocolate cysts""chocolate cysts", full of blood. , full of blood. Large lesions where the blood has organized Large lesions where the blood has organized

present with extensive fibrosis. present with extensive fibrosis. This can obliterate the pouch of Douglas, This can obliterate the pouch of Douglas,

obstruct the bowel, obstruct the oviduct, obstruct the bowel, obstruct the oviduct, These lesions can produce dyspareunia These lesions can produce dyspareunia

(pain on intercourse), constipation, (pain on intercourse), constipation, infertility, and dysmenorrhea (pain on infertility, and dysmenorrhea (pain on menstruation )menstruation )

The diagnosis of The diagnosis of endometriosis:endometriosis:

The pathologist The pathologist must find two of must find two of three items:three items: endometrial glands endometrial glands endometrial stroma endometrial stroma hemosiderin laden hemosiderin laden

macrophages.macrophages.

ENDOMETRIAL POLYPSENDOMETRIAL POLYPS

Clonal overgrowths of endometrium. Clonal overgrowths of endometrium. The result is a nodule on the The result is a nodule on the

endometrium which is likely to bleed endometrium which is likely to bleed between cycles. between cycles.

The lesions are not premalignant. The lesions are not premalignant. The histology may seem normal, or The histology may seem normal, or

show some cystic hyperplasia.show some cystic hyperplasia.

ENDOMETRIAL HYPERPLASIAENDOMETRIAL HYPERPLASIA This is an overgrowth of endometrium, This is an overgrowth of endometrium,

but without the ability to metastasize. but without the ability to metastasize. The risk of transforming into The risk of transforming into

adenocarcinoma,adenocarcinoma, The diagnosis is made only on biopsy The diagnosis is made only on biopsy

and this itself affects the illness and this itself affects the illness (curettage may be curative).(curettage may be curative).

Types of Endometrial hyperplasia:Types of Endometrial hyperplasia: Simple hyperplasiaSimple hyperplasia Complex hyperplasiaComplex hyperplasia Atypical hyperplasiaAtypical hyperplasia

Simple hyperplasiaSimple hyperplasia

Cystic hyperplasia, mild hyperplasiaCystic hyperplasia, mild hyperplasia Features: Features:

glands of very uneven sizes glands of very uneven sizes cystically dilated glands cystically dilated glands no dysplasiano dysplasia no extra cancer risk. no extra cancer risk.

This is quite common. This is quite common.

Simple hyperplasiaSimple hyperplasiaNormalNormal

Simple (cystic) hyperplasiaSwiss cheese

Complex hyperplasiaComplex hyperplasia

Adenomatous hyperplasia without Adenomatous hyperplasia without atypiaatypia crowded glands crowded glands irregularly-shaped glands irregularly-shaped glands no dysplasiano dysplasia about 5% risk of turning into about 5% risk of turning into

adenocarcinoma.adenocarcinoma.

Complex hyperplasia

Atypical hyperplasiaAtypical hyperplasia

Higher grade hyperplasia Higher grade hyperplasia crowded, irregular glands, but there is crowded, irregular glands, but there is

still stroma between them still stroma between them dysplasiadysplasia about 25% risk of turning into about 25% risk of turning into

adenocarcinoma. adenocarcinoma.

Atypical hyperplasiaAtypical hyperplasia

ENDOMETRIAL ADENOCARCINOMAENDOMETRIAL ADENOCARCINOMA

Common cancer in women over age Common cancer in women over age 40. 40.

The risk factors are:The risk factors are: Extra estrogens from any source Extra estrogens from any source

(estrogen replacement, thecoma, obesity) (estrogen replacement, thecoma, obesity) Diabetes Diabetes Hypertension Hypertension InfertilityInfertility Endometrial hyperplasia. Endometrial hyperplasia.

Patients present with bleeding Patients present with bleeding because of the invasion of the inner because of the invasion of the inner wall. wall.

Good prognosisGood prognosis only about 1 woman in 6 with cancer of only about 1 woman in 6 with cancer of

the endometrium will die from it. the endometrium will die from it. Grossly, the lesions look like cottage Grossly, the lesions look like cottage

cheese. cheese. Microscopically, an adenocarcinoma.Microscopically, an adenocarcinoma. Metastases eventually can occur, Metastases eventually can occur,

usually via the lymphatics.usually via the lymphatics.

Subtypes: Adenoacanthoma

if there is squamous metaplasia Adenosquamous carcinoma

If the squamous areas are anaplastic Serous adenocarcinoma of the

endometrium and clear-cell carcinoma of the endometrium more aggressive, linked to high estrogen or to previous

hyperplasia.

MIXED MÜLLERIAN / MIXED MÜLLERIAN / MESENCHYMAL TUMORSMESENCHYMAL TUMORS

Mixed Müllerian tumorsMixed Müllerian tumors Endometrial stromal tumorsEndometrial stromal tumors

Stromal nodules (benign)Stromal nodules (benign) Endometrial stromal sarcomaEndometrial stromal sarcoma (low and (low and

High grade)High grade)

Mixed Müllerian tumors

CarcinosarcomasCarcinosarcomas AdenosarcomasAdenosarcomas

CarcinosarcomasCarcinosarcomas

Arise from the endometrium and contain Arise from the endometrium and contain both malignant glands and malignant both malignant glands and malignant mesenchymal elements (carcinosarcoma). mesenchymal elements (carcinosarcoma).

In addition to bizarre spindle cells, there In addition to bizarre spindle cells, there may be muscle, bone, fat, and/or cartilage; may be muscle, bone, fat, and/or cartilage; nevertheless, these will usually stain with nevertheless, these will usually stain with epithelial markers. epithelial markers.

There is often a history of previous There is often a history of previous radiation. radiation.

They tend to be aggressive and to They tend to be aggressive and to metastasize as adenocarcinomas. metastasize as adenocarcinomas.

Carcinosarcoma, showing both epithelial Carcinosarcoma, showing both epithelial ((upper rightupper right) and stromal () and stromal (arrowarrow) )

differentiation.differentiation.

AdenosarcomasAdenosarcomas Adenosarcomas present most commonly as

large broad-based endometrial polypoid growths, and may prolapse through the cervical os.

The diagnosis is based on malignant appearing stroma, which coexists with benign but abnormally shaped endometrial glands.

These tumors predominate in women between the fourth and fifth decades and are generally considered to be of low grade malignancy; recurrences develop in one-fourth and are nearly always confined to the pelvis.

Endometrial stromal tumorsEndometrial stromal tumors

Stromal nodules (benign)Stromal nodules (benign)

-are little whorly balls of stroma-are little whorly balls of stroma

Endometrial stromal sarcoma Endometrial stromal sarcoma (malignant)(malignant)

- Low grade ESSLow grade ESS- High grade ESSHigh grade ESS

LEIOMYOMA UTERI LEIOMYOMA UTERI “Fibroids”“Fibroids”

At least 25% of women have these during At least 25% of women have these during reproductive life. reproductive life.

They are more common in blacks. They are more common in blacks. The etiology is mysterious. The etiology is mysterious.

They grow in response to estrogen, and disappear They grow in response to estrogen, and disappear after menopause. after menopause.

Usually leiomyomas are asymptomatic, or Usually leiomyomas are asymptomatic, or cause problems by mass effect. cause problems by mass effect. A submucosal leiomyoma can produce bleeding A submucosal leiomyoma can produce bleeding

between periods (epimenorrhea), and interfere with between periods (epimenorrhea), and interfere with fertility,fertility,

Rapid increase during pregnancyRapid increase during pregnancy, , Large leiomyomas can cause problems with Large leiomyomas can cause problems with

pregnancy. pregnancy.

The tumors are rubbery white The tumors are rubbery white spheres:spheres: Mural (within the uterine wall)Mural (within the uterine wall) Submucosal (under the mucosa)Submucosal (under the mucosa) Subserous (under the serous membrane). Subserous (under the serous membrane).

Grossly, the "whorled silk" pattern Grossly, the "whorled silk" pattern seen on cross-section is famous. seen on cross-section is famous.

Submucosal leiomyomas can produce Submucosal leiomyomas can produce bleeding. bleeding.

Subserosal leiomyomas are visible on Subserosal leiomyomas are visible on the surface. the surface.

Leiomyoma (mural) Leiomyoma (submucosal)

Leiomyoma(subserous) and teratoma

Microscopy :Microscopy : bundles of smooth musclebundles of smooth muscle may calcifymay calcify may show central necrosismay show central necrosis

watershed infarctwatershed infarct when this becomes infected it's a when this becomes infected it's a

"pyomyoma""pyomyoma" and/or fatty ingrowth. and/or fatty ingrowth.

Other tumors of Other tumors of MyometriumMyometrium

Intravascular leiomyomatosisIntravascular leiomyomatosis a bunch of leiomyomas with a proclivity to a bunch of leiomyomas with a proclivity to

grow down the veins. grow down the veins. regresses after menopause. regresses after menopause.

LeiomyosarcomasLeiomyosarcomas common common a smooth muscle tumor of the uterus a smooth muscle tumor of the uterus

with ten or more mitotic figures per ten with ten or more mitotic figures per ten high power fields, or with anaplasia.high power fields, or with anaplasia.

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