The Pathology of UTERUS Prof.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

Terminology Amenorrhea Sterility Menorrhagia / metrorrhagia No menstruation Sterility Infertility Menorrhagia / metrorrhagia Heavy menstrual periods Dysmenorrhea Painful menstruation Epimenorrhea Irregular bleeding between cycles

DEVELOPMENTAL DISORDERS Birth defects of the uterus are uncommon. Uterus bifida Bicornuate uterus –presence of uterine septum results from nonfusion of the müllerian ducts Agenesis Turner's syndrome Development or fusion of the müllerian ducts. imperfect fusion may make it difficult to take a pregnancy to term.

THE NORMAL CYCLE During reproductive life, the endometrium goes through a monthly cycle. The first half ("proliferative phase") begins with menstruation and is of rather variable length: Early proliferative (some gland mitoses, little gland tortuosity) Late proliferative (many gland mitoses, some gland tortuosity) The second half ("secretory phase") begins at ovulation, and should be 14 days, with less variability.

Secretory phase

If a woman bleeds between cycles during her reproductive life, the cause is usually one of the following: complication of pregnancy (ectopic pregnancy, miscarriage, trophoblastic disease) submucosal leiomyoma (interferes with the development of the endometrium) endometrial polyp (abnormal benign patch of endometrium) endometrial hyperplasia cancer dysfunctional uterine bleeding some problem with the hormonal symphony; this is the most common.

Dysfunctional uterine bleeding Anovulatory cycles are common around menarche and menopause A granulosa and/or theca tumor in an ovary producing estrogens and/or progesterone Endocrine disease elsewhere (especially the pituitary or thyroid) Massive obesity (too much estrogen being converted) All of these will give "unopposed estrogen effect" on biopsy, with a thick endometrium with long glands but without decidual-type change. The endometrium starts breaking down early in patches, hence the bleeding. Too little body fat (too little estrogen being converted) Severe chronic disease (the interleukins) Inadequate luteal phase Persistent luteal phase.

ENDOMETRITIS The endometrium is very resistant to bacterial infection. Infection by common bacteria (strep A, staph) is usually the result of retained products of conception. Surgical removal of the remnants is the mainstay of therapy. Pyometra is a purulent infection of the uterus, as when products of conception are retained or the os is closed.

Clostridial gas gangrene is a lethal complication of attempted self-abortion or criminal abortus. Other infections after childbirth or natural or induced abortion include strep, staph, and E. Coli. Mycoplasma infection: acute endometritis. Tuberculosis ( secondary sterility). Magnesium-rich super-absorbent tampons good culture medium for the staphylococci that produce toxic shock syndrome. Chronic endometritis result of gonococci or chlamydia retained products of conception or an intrauterine contraceptive device. plasma cells in the endometrium

ADENOMYOSIS (endometriosis interna) Sometimes the endometrium penetrates deep into the myometrium in a few places. This can be visible grossly in a resected uterus. It isn't cancer, since the glands are benign and stroma exists Obviously this can cause discomfort just before and during menstruation. It's supposed to be one of the major causes of menstrual cramps.

ENDOMETRIOSIS (endometriosis externa) This is endometrial tissue outside the uterus. The most common site is the ovary. Other localizations: vulva, vagina, the ligaments of the pelvis, the abdomen intestine, umbilicus.

The gross appearance of endometriosis depends on how extensive the disease is: Minor lesions look like powder under the serosal surface. Longstanding ovarian lesions present "chocolate cysts", full of blood. Large lesions where the blood has organized present with extensive fibrosis. This can obliterate the pouch of Douglas, obstruct the bowel, obstruct the oviduct, These lesions can produce dyspareunia (pain on intercourse), constipation, infertility, and dysmenorrhea (pain on menstruation )

The diagnosis of endometriosis: The pathologist must find two of three items: endometrial glands endometrial stroma hemosiderin laden macrophages.

ENDOMETRIAL POLYPS Clonal overgrowths of endometrium. The result is a nodule on the endometrium which is likely to bleed between cycles. The lesions are not premalignant. The histology may seem normal, or show some cystic hyperplasia.

ENDOMETRIAL HYPERPLASIA This is an overgrowth of endometrium, but without the ability to metastasize. The risk of transforming into adenocarcinoma, The diagnosis is made only on biopsy and this itself affects the illness (curettage may be curative). Types of Endometrial hyperplasia: Simple hyperplasia Complex hyperplasia Atypical hyperplasia

Simple hyperplasia Cystic hyperplasia, mild hyperplasia Features: glands of very uneven sizes cystically dilated glands no dysplasia no extra cancer risk. This is quite common.

Simple hyperplasia Normal

Simple (cystic) hyperplasia Swiss cheese

Complex hyperplasia Adenomatous hyperplasia without atypia crowded glands irregularly-shaped glands no dysplasia about 5% risk of turning into adenocarcinoma.

Complex hyperplasia

Atypical hyperplasia Higher grade hyperplasia crowded, irregular glands, but there is still stroma between them dysplasia about 25% risk of turning into adenocarcinoma.

Atypical hyperplasia

ENDOMETRIAL ADENOCARCINOMA Common cancer in women over age 40. The risk factors are: Extra estrogens from any source (estrogen replacement, thecoma, obesity) Diabetes Hypertension Infertility Endometrial hyperplasia.

Grossly, the lesions look like cottage cheese. Patients present with bleeding because of the invasion of the inner wall. Good prognosis only about 1 woman in 6 with cancer of the endometrium will die from it. Grossly, the lesions look like cottage cheese. Microscopically, an adenocarcinoma. Metastases eventually can occur, usually via the lymphatics.

Adenosquamous carcinoma 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 / MESENCHYMAL TUMORS Mixed Müllerian tumors Endometrial stromal tumors Stromal nodules (benign) Endometrial stromal sarcoma (low and High grade)

Mixed Müllerian tumors Carcinosarcomas Adenosarcomas

Carcinosarcomas Arise from the endometrium and contain both malignant glands and malignant mesenchymal elements (carcinosarcoma). In addition to bizarre spindle cells, there may be muscle, bone, fat, and/or cartilage; nevertheless, these will usually stain with epithelial markers. There is often a history of previous radiation. They tend to be aggressive and to metastasize as adenocarcinomas.

Carcinosarcoma, showing both epithelial (upper right) and stromal (arrow) differentiation.

Adenosarcomas 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 tumors Stromal nodules (benign) -are little whorly balls of stroma Endometrial stromal sarcoma (malignant) Low grade ESS High grade ESS

LEIOMYOMA UTERI “Fibroids” At least 25% of women have these during reproductive life. They are more common in blacks. The etiology is mysterious. They grow in response to estrogen, and disappear after menopause. Usually leiomyomas are asymptomatic, or cause problems by mass effect. A submucosal leiomyoma can produce bleeding between periods (epimenorrhea), and interfere with fertility, Rapid increase during pregnancy, Large leiomyomas can cause problems with pregnancy.

The tumors are rubbery white spheres: Mural (within the uterine wall) Submucosal (under the mucosa) Subserous (under the serous membrane). Grossly, the "whorled silk" pattern seen on cross-section is famous. Submucosal leiomyomas can produce bleeding. Subserosal leiomyomas are visible on the surface.

Leiomyoma (mural) Leiomyoma (submucosal)

Leiomyoma(subserous) and teratoma

bundles of smooth muscle may calcify may show central necrosis Microscopy : bundles of smooth muscle may calcify may show central necrosis watershed infarct when this becomes infected it's a "pyomyoma" and/or fatty ingrowth.

Other tumors of Myometrium Intravascular leiomyomatosis a bunch of leiomyomas with a proclivity to grow down the veins. regresses after menopause. Leiomyosarcomas common a smooth muscle tumor of the uterus with ten or more mitotic figures per ten high power fields, or with anaplasia.

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