Pathology of the Uterus

Question 1

What cells comprise the stroma and glands of the endometrium?

Answer 1

Stroma - composed of small round to spindle shaped cells

Glands - tubular structures made of pseudostratified epiithelium

Question 2

How do the glands change in the secretory phase of the endometrium?

Answer 2

Basal vacuolization appears, which push pastt he nuclei to become suprabasal and secrete into glandular lumen which appears “saw-toothed”

Vacuoles contain glycogen and other nutrients

Question 3

What happens just before menstruation?

Answer 3

Neutrophils and lymphocytes invade, and endometrial glands / stroma disintegrate into stromal balls before being shed

Question 4

What is the definition of dysfunctional uterine bleeding (DUB)?

Answer 4

Increasing bleeding during (menorrhagia) or in between (metrorrhagia) with no organic cause

-> caused by menstrual cycle abnormalities or systemic diseases

Question 5

What is the most common cause of dysfunctional uterine bleeding? Who tends to get it?

Answer 5

Anovulatory cycle
-> lack of ovulation occurs, so there is excessive estrogen stimulation of proliferative phase, leading to unscheduled breakdown of stroma

Common at menarche and in perimenopausal women (ovulation never occurred, so no secretory phase)

Question 6

What is “inadequate luteal phase” and how does it present?

Answer 6

Inadequate corpus luteal progesterone output

-> presents as infertility (many miscarriages due to underdeveloped decidua) with early dysfunctional uterine bleeding

Question 7

What will endometrial biopsy show in inadequate luteal phase?

Answer 7

Dyssynchrony between clinical history and development of endometrium
-> endometrial glands poorly developed relative to where patient should be in her cycle

Question 8

What is the most common cause of dysfunctional uterine bleeding post menopause?

Answer 8

Endometrial atrophy -> lining of endometrium becomes very atrophic, with minimal stroma and atrophic glands, so it sheds and bleeds easily

Question 9

What causes acute endometritis?

Answer 9

Bacterial infection due to retained products of conception after delivery, miscarriage, abortion, or with a foreign body.
-> i.e. a piece of placenta or instrumentation

Question 10

What discharge will be seen in acute endometritis and how is the situation remedied?

Answer 10

Purulent BLOODY discharge with many PMNs

• > removal of retained product removes nidus for infection
• > this is an organic cause of uterine bleeding

Question 11

What is the hallmark of chronic endometritis and what are some common causes?

Answer 11

Plasma cells in the stroma as part of chronic inflammation, as lympocytes and macrophages are often present in endmetrial stroma

Causes:
Pelvic inflammatory disease
Retained gestational products
IUDs
TB -> will show granulomatous inflammation

Question 12

What bacteria is associated with IUDs? Can chronic endometritis cause infertility?

Answer 12

Actinomyces israelii
-> forms large colonies called “sulfur granules” which contain large amounts of bacteria

Yes it can cause infertility if chronic

Question 13

What is adenomyosis?

Answer 13

Extension of the endometrial tissue into the uterine myometrium (overgrowth of basal layer into myometrium)
-> can be thought of as a local form of endometriosis

Question 14

What is the clinical presentation of adenomyosis?

Answer 14

Dysmenorrhea, menorrhagia (increased bleeding)

Question 15

What is an endometrial polyp?

Answer 15

Masses of endometrial tissue which protrude into the endometrial cavity
-> overgrowth of endometrium with crowded glands and multiple proliferating cells

Question 16

What is the clinical presentation of endometrial polyps and what are they associated with?

Answer 16

Painless abnormal uterine bleeding

Associated with the use of tamoxifen for breast cancer (endometrial estrogen agonist causes overgrowth)

Question 17

What proliferates in endometrial hyperplasia and what is the general underlying cause? How does it present?

Answer 17

Caused by a hyperplasia of endometrial GLANDS relative to stroma

Excess estrogen stimulation, i.e. obesity, estrogen replacement, anovulatory cycles, or polycystic ovarian syndrome (increased circulating estrone)

Presents as postmenopausal uterine bleeding

Question 18

What does endometrial hyperplasia increased your risk for and what gene is associated with it?

Answer 18

Associated with inactivation of PTEN tumor suppressor gene

-> increased risk for endometrial carcinoma (endometroid type)

Question 19

What are the two ways in which endometrial hyperplasia is histologically characterized based on its growth? Which is more important?

Answer 19

1. Simple vs complex
   - > simple = glands look nice
   - > complex = glands look complicated with many outpouchings and loss of stroma
2. Presence of absence of cellular atypia
   - > nuclear atypia is more important

Question 20

What are the two most common types of endometrial hyperplasia?

Answer 20

Simple hyperplasia without atypia (lowest risk)

Complex hyperplasia with atypia (highest risk)

Question 21

What is the most common invasive tumor of the female genital tract? Which subtype is most common and who tends to get it?

Answer 21

Endometrial carcinoma

Endometrioid subtype is most common (80% of endometrial cancers), tends to be estrogen-related, happens in perimenopausal women (around 60 years)

Question 22

What are the general risk factors which lead to greater estrogen factor throughout life? This includes risk factors for endometrial cancers, breast cancers, etc.

Answer 22

1. Early menarche / late menopause - longer lifespan exposed to estrogen
2. Nulliparity - having no kids prolongs your estrogen exposure throughout life b/c you don’t have estrogenfree period after birth
3. Anovulatory cycles - prolonged estrogen exposure
4. Obesity - increased estrogen conversion

Question 23

Give one additional risk factor for endometrial carcinoma other than prolonged estrogen exposure.

Answer 23

Lynch syndrome -> typically causes endometrioid type endometrial cancer (microsatellite instabilities and PTEN mutations are seen in this type)

Question 24

What is the clinical pattern of progression of endometrioid endometrial cancer?

Answer 24

Low stage, with little to no spread. Tumor remains well differentiated with minimal to no myometrial invasion
-> indolent tumor

Question 25

How is endometrioid tumor graded generally?

Answer 25

Graded 1-3

Grade 1: <5% solid component (confluent cells), rest gland

Grade 3: >50% solid component, worse prognosis

Question 26

What is the other type of endometrial cancer and who tends to get it?

Answer 26

Sporadic endometrial cancer -> Type 2, occurs in older (POST-menopausal women, i.e. 70s/80s), no associatd with estrogen
-> Occurs in the setting of atrophic endometrium with no precursor lesion

Question 27

What is the progression of sporadic endometrial cancers? What mutations are associated?

Answer 27

Have a much worse prognosis, automatically considered high grade, with deep invasion of myometrium

Associated with early p53 mutations and very aggressive behavior

Question 28

What is the most common form of sporadic endometrial carcinoma (Type 2) and what is seen on histology?

Answer 28

Serous carcinoma. Forms papillary structures which can necrose around fibrovascular cores, leading to psammoma body formation.

To remember it forms psammoma bodies, alot of people remember it as “papillary-serous carcinoma”

Question 29

Give two other rarer types of Type 2 endometrial carcinoma and their general histology?

Answer 29

1. Clear cell carcinoma - Cells with clear cytoplasm with hyalinized stroma with “hobnailing” -> eosinophlia sticking out
2. Carcinosarcoma -> high grade adenocarcinoma with a malignant stromal component which can form other random mesenchemyal structures much like teratoma

Question 30

What is the most common tumor in females?

Answer 30

Leiomyoma - “fibroids”

Beningn neoplasms from smooth muscle of endometrium

Question 31

What causes fibroids and how will they change with age?

Answer 31

They are estrogen sensitive: tumor increases in size with pregnancy and decreases in size with menopause.

Peak occurrence is in 20-40 years.

Question 32

How is a leiomyoma told apart from a leiomyosarcoma grossly?

Answer 32

Leiomyoma -> appears as a well-defined white, whorled mass with no hemorrhage or necrosis, and there are usually MULTIPLE

Leiomyosarcoma -> appears as a SINGLE lesion with areas of necrosis and hemorrhage

Question 33

What are classic symptoms for leiomyoma?

Answer 33

Usually asymptomatic, but may present with abnormal uterine bleeding (stretch lining of uterus) with iron deficiency anemia, infertility, and a pelvic mass

Question 34

Who tends to get leiomyosarcoma?

Answer 34

Usually in older (postmenopausal) women, since they are not related to estrogen exposure.

Question 35

How does the histology of leiomyosarcoma and leiomyoma compare?

Answer 35

Leimyoma - whorled pattern of smooth muscle bundles and well demarcated borders

Leiomyosarcoma - ill-defined borders with significant atypia, mitoses, and necrosis