This document discusses endometrial hyperplasia and carcinoma. It defines endometrial hyperplasia as an abnormal increase in the endometrium that can progress to carcinoma. Causes include prolonged estrogen stimulation without progesterone. Hyperplasia is classified as simple or complex depending on morphological features and risk of progression. Endometrial carcinoma is more common in postmenopausal women and often presents with abnormal bleeding. Risk factors include obesity, diabetes, and infertility. The document also discusses leiomyoma and leiomyosarcoma of the uterus, defining them, describing their morphology and microscopic features, and distinguishing between them.

1. Dr.CSBR.Prasad, M.D.
Endometrium
Hyperplasias - Carcinomas

2. EM - Hyperplasia
• Increase glands to stromal ratio
• Abnormalities of epithelial growth
• May progress to EM carcinoma

3. • Pathogenesis: abnormal prolonged estrogen
stimulation / anovulation.
1-Anovulation
2-Menopause
3-PCOD
4-Granulosa cell tumor
5-Adrenal cortical hyperplasia
6-prolonged administration of estrogens
7-inactivation of PTEN
EM - Hyperplasia

4. Morphology of EM hyperplasia:
1-Low grade (simple)
2-High grade (atypical)
Low grade includesLow grade includes: anovulatory epithelium
and subtle EIN
High grade includesHigh grade includes: Complex hyperplasia and
PTEN mutation of EIN.
EM - Hyperplasia

5. Simple non-atypical hyperplasias:
1-glands of varying sizes
2-glands resemble proliferative endometrium
They rarely progress to carcinoma
They frequently evolve to atrophy of both
glands and stroma
EM - Hyperplasia

6. The endometrial cavity is opened to reveal lush fronds of hyperplastic endometrium. Endometrial
hyperplasia usually results with conditions of prolonged estrogen excess and can lead to
metrorrhagia (uterine bleeding at irregular intervals), menorrhagia (excessive bleeding with
menstrual periods), or menometrorrhagia

7. This uterus is not enlarged, but there is an irregular mass in the upper fundus that
proved to be endometrial adenocarcinoma on biopsy. Such carcinomas are more likely
to occur in postmenopausal women. Thus, any postmenopausal bleeding should make
you suspect that this lesion may be present

8. This is endometrial hyperplasia in which the amount of endometrium is abnormally increased
and not cycling as it should. The glands are enlarged and irregular with columnar cells that have
some atypia. Simple endometrial hyperplasias can cause bleeding, but are not thought to be
premalignant. However, adenomatous hyperplasia is premalignant.

9. This is endometrial hyperplasia in which there is pronounced cystic change to the
glands, with very little stroma. There is a slight proliferation of glands--a
postmenopausal "cystic" atrophy of the endometrium has similar enlarged glands. This
condition is not premalignant, like an adenomatous hyperplasia.

10. Complex hyperplasia:
1-increase in number and size of the EM
glands (crowding)
2-epithelial stratification
3-nuclear enlargement
4-tufting of epithelium
5-mitotic figures are common
23% may progress to adenocarcinoma
EM - Hyperplasia

11. With progesterone Tx:
--50% persisted
--25% recurred
--25% progressed to carcinoma
Treatment:
Hysterectomy
In young a trial of progesterones & follow up
Because of low rate of regression with progesterone Tx
ultimately patients has to undergo hysterectomy.
EM - Hyperplasia

13. Endometrial carcinoma

14. • Occurs mainly in post menopausal women
(55-65yrs) (uncommon <40yrs)
• Presents as post menopausal bleeding
It’s more commonly associated with:
1-Obesity
2-DM
3-Hypertension
4-Infertility
5-EM ca and Breast Ca develop in the same
person
Endometrial carcinoma

15. • In terms of pathogenesis there are two
subgroups of EMca have been identified:
1-EM ca developing in the background of
prolonged estrogen stimulation and EM-
hyperplasia
2-without hyperplasia / hyperestrinism
Endometrial carcinoma

16. Endometrial carcinoma
Support comes from the following evidences:
1-both hyperplasia and cancer are linked to abdominal
obesity anovulatory cycles
2-females with ovarian estrogen secreting tumors develop
carcinoma of EM
3-EM ca is rare in women with ovarian dysgenesis
4-HRT is associated with increased risk of EM Ca.
5-Prolonged administration of DES to lab animals produced
EM polyps and hyperpalsias and carcinomas
6-PTEN mutation is common in EM hyperplasia and
carcinoma

17. • Second subtype – without hyperplasia:
1-old age
2-carcinomas are more poorly differentiated
(tumors may resemble serous carcinoma
of the ovary)
3-overall these tumors have poor prognosis
than estrogen related tumors
Endometrial carcinoma

18. Morphology:
Two types:
1-polypoidal
2-diffuse (involving whole EM surface)
Spread occurs to:
-myometrium
-periuterine structures
-LN mets
-metastasis to lung, liver, bone
-serous type of carcinomas may involve
peritoneal cavity due to different way of spread
i.e. tubal or lymphatic transmission
Histology: 85% are adenocarcinomas
Endometrial carcinoma

20. This adenocarcinoma of the endometrium is more obvious. Irregular
masses of white tumor are seen over the surface of this uterus that has
been opened anteriorly. The cervix is at the bottom of the picture. This
enlarged uterus was no doubt palpable on physical examination. Such
a neoplasm often present with abnormal bleeding.

21. The endometrial adenocarcinoma is present on the
lumenal surface of this cross section of uterus. Note that
the neoplasm is superficially invasive. The cervix is at
the right.

22. The endometrial adenocarcinoma in the polyp at the left is
moderately differentiated, as a glandular structure can still be
discerned. Note the hyperchromatism and pleomorphism of the
cells, compared to the underlying endometrium with cystic
atrophy at the right.

23. This is endometrial adenocarcinoma which can be seen invading
into the smooth muscle bundles of the myometrial wall of the
uterus. This neoplasm has a higher stage than a neoplasm that
is just confined to the endometrium or is superficially invasive.

28. • Staging
• Grading (figo)
Endometrial carcinoma

29. Clinical features:
1-Irregular vaginal bleeding
2-Excessive leucorrhea
3-Uterine enlargement
Prognosis:
Stage of the disease
Histological grade and type
Endometrial carcinoma

30. • Carcinosarcoma
• Adenosarcoma
• Stromal nodule to stromal sarcoma
Tumors of Endometrium with
stromal differentiation
(stromal tumors)

31. Tumors of Myometrium
• Leiomyoma
• Leiomyosarcoma

32. Leiomyoma
• Most common tumor of humans
• Commonly called as ‘FIBROIDS’
• More than one genetic abnormality can
lead to leiomyomatous growth – t(12,
14); 7q del; Trisomy 12.

33. Morphology:
• Well circumscribed
• Discrete, round, firm
• Grayish white
• Variable sizes (a few mm to very large
tumors)
• Types (Subserosal, Intramural, Submucosal)
• c/s whorled pattern
• Red degeneration in large tumors
• Other degenerative changes
Leiomyoma

38. In the upper fundus of the
uterus protruding into the
endometrial cavity is a nodule
that proved to be a
leiomyoma. Thus, this is a
submucosal leiomyoma. Such
benign smooth muscle tumors
of the myometrium are very
common--perhaps at least 1 in
5 women has one. They may
be the cause of irregular
bleeding if present in a
submucosal location, as seen
here. Larger leiomyomas may
also produce bleeding or
pelvic discomfort

39. Smooth muscle tumors of the uterus are often multiple. Seen here are submucosal,
intramural, and subserosal leiomyomata of the uterus.

40. Here is a very large
leiomyoma of the uterus that
has undergone degenerative
change and is red (so-called
"red degeneration"). Such an
appearance might make you
think that it could be
malignant. Remember that
malignant tumors do not
generally arise from benign
tumors, which is a good thing,
because leiomyomas are so
common (at least 20% of
women will have one).
Postmenopausally,
leiomyomas tend to regress in
size and become fibrotic.

41. Here is a bifid (septate) uterus. Sometimes even the cervix and/or vagina may be double as well.
This is of no major consequence except that in pregnancy a bifid uterus may not enlarge
normally and lead to fetal loss, or a normal vaginal delivery may not be possible with a double
cervix or vagina. Note that there is also a small intramural leiomyoma on the septum at the left.

42. Whorled appearance – c/s

43. This large squamous
carcinoma (yellow
square) has
obliterated the cervix
and invaded the lower
uterine segment. The
uterus also has a
round leiomyoma up
higher (Red arrow).

44. Microscopy:
1-Whorled bundles of smooth muscle cells
2-Spindle cells with ‘CIGAR’ shaped nucleus
3-Long slender cytoplasmic extensions
4-Cytolpalsm is eosinophilic
5-Necrosis, hemorrhages, calcification,
ossification, cartilage, hyalinization et.c.
Leiomyoma

46. 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

49. • Most of the leiomyosarcomas arise in the uterus
• Peak incidence at 40-60yrs of age
• Two distinct growth patterns
1-Buky fleshy masses that invade the uterine wall &
2-Polypoidal masses that project into the lumen
• Soft fleshy tumors with a whitish cut surface
• Areas of hemorrhage and necrosis
• Periphery of the tumor is not sharply defined
Leiomyosarcoma

51. This is a leiomyosarcoma protruding from myometrium into the endometrial cavity of this uterus
that has been opened laterally so that the halves of the cervix appear at right and left. Fallopian
tubes and ovaries project from top and bottom. The irregular nature of this mass suggests that is
not just an ordinary leiomyoma.

52. Microscopy:
• Apperances vary from resemblence of
leiomyoma to anaplastic tumors
• All smooth muscle tumors with mitotic figures
fewer than 2 / 10hpf are considered benign
(Hendrikson and Kempson)
• Note: Leiomyomas in young and pregnant females may show mitotic
activity and may be mistaken for leiomyosarcoma
• There may be areas of myxoid change
• Extensive necrosis is also an ominous sign
Leiomyosarcoma

53. Here is the microscopic appearance of a leiomyosarcoma. It is much more cellular and
the cells have much more pleomorphism and hyperchromatism than the benign
leiomyoma. An irregular mitosis is seen in the center.

54. As with sarcomas in general, leiomyosarcomas have spindle cells.
Several mitoses are seen here, just in this one high power field.

55. Sarcomas, including leiomyosarcomas, often have very large bizarre giant cells along
with the spindle cells. A couple of mitotic figures appear at the left and lower left

58. Metastasis thru blood stream to lung,
bone and brain
Dissemination also occur thru
abdominal cavity
5yr survival for patients with uterine
leiomyosarcomas is < 40%
Leiomyosarcoma

59. E N DE N D