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

2. Anatomy
Fundus: cephalad to line connecting the insertion of fallopian tubes
Cornua: lateral regions of fundus associated with intramural fallopian tubes

3. 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

4. Anatomy
Uterine cavity: 6 cm long, triangular shape, lined by endometrial mucosa / endometrium, then myometrium, then serosa, which extends to peritoneal reflection

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

7. 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.

8. 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.

9. Secretory phase

10. 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.

11. 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.

12. 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.

13. 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

15. 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.

17. 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.

18. 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 )

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

21. 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.

23. 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

25. 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.

26. Simple hyperplasia
Normal

27. Simple (cystic) hyperplasia
Swiss cheese

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

29. Complex hyperplasia

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

31. Atypical hyperplasia

32. 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.

33. 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.

35. 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.

38. MIXED MÜLLERIAN / MESENCHYMAL TUMORS
Mixed Müllerian tumors
Endometrial stromal tumors
Stromal nodules (benign)
Endometrial stromal sarcoma (low and High grade)

39. Mixed Müllerian tumors
Carcinosarcomas
Adenosarcomas

40. 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.

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

42. 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.

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

44. 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.

45. 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.

46. Leiomyoma (mural)
Leiomyoma (submucosal)

47. Leiomyoma(subserous) and teratoma

48. 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.

50. 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.

54. THANK YOU