Pathology of the Uterus Flashcards
What cells comprise the stroma and glands of the endometrium?
Stroma - composed of small round to spindle shaped cells
Glands - tubular structures made of pseudostratified epiithelium
How do the glands change in the secretory phase of the endometrium?
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
What happens just before menstruation?
Neutrophils and lymphocytes invade, and endometrial glands / stroma disintegrate into stromal balls before being shed
What is the definition of dysfunctional uterine bleeding (DUB)?
Increasing bleeding during (menorrhagia) or in between (metrorrhagia) with no organic cause
-> caused by menstrual cycle abnormalities or systemic diseases
What is the most common cause of dysfunctional uterine bleeding? Who tends to get it?
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)
What is “inadequate luteal phase” and how does it present?
Inadequate corpus luteal progesterone output
-> presents as infertility (many miscarriages due to underdeveloped decidua) with early dysfunctional uterine bleeding
What will endometrial biopsy show in inadequate luteal phase?
Dyssynchrony between clinical history and development of endometrium
-> endometrial glands poorly developed relative to where patient should be in her cycle
What is the most common cause of dysfunctional uterine bleeding post menopause?
Endometrial atrophy -> lining of endometrium becomes very atrophic, with minimal stroma and atrophic glands, so it sheds and bleeds easily
What causes acute endometritis?
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
What discharge will be seen in acute endometritis and how is the situation remedied?
Purulent BLOODY discharge with many PMNs
- > removal of retained product removes nidus for infection
- > this is an organic cause of uterine bleeding
What is the hallmark of chronic endometritis and what are some common causes?
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
What bacteria is associated with IUDs? Can chronic endometritis cause infertility?
Actinomyces israelii
-> forms large colonies called “sulfur granules” which contain large amounts of bacteria
Yes it can cause infertility if chronic
What is adenomyosis?
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
What is the clinical presentation of adenomyosis?
Dysmenorrhea, menorrhagia (increased bleeding)
What is an endometrial polyp?
Masses of endometrial tissue which protrude into the endometrial cavity
-> overgrowth of endometrium with crowded glands and multiple proliferating cells
What is the clinical presentation of endometrial polyps and what are they associated with?
Painless abnormal uterine bleeding
Associated with the use of tamoxifen for breast cancer (endometrial estrogen agonist causes overgrowth)
What proliferates in endometrial hyperplasia and what is the general underlying cause? How does it present?
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
What does endometrial hyperplasia increased your risk for and what gene is associated with it?
Associated with inactivation of PTEN tumor suppressor gene
-> increased risk for endometrial carcinoma (endometroid type)
What are the two ways in which endometrial hyperplasia is histologically characterized based on its growth? Which is more important?
- Simple vs complex
- > simple = glands look nice
- > complex = glands look complicated with many outpouchings and loss of stroma - Presence of absence of cellular atypia
- > nuclear atypia is more important
What are the two most common types of endometrial hyperplasia?
Simple hyperplasia without atypia (lowest risk)
Complex hyperplasia with atypia (highest risk)
What is the most common invasive tumor of the female genital tract? Which subtype is most common and who tends to get it?
Endometrial carcinoma
Endometrioid subtype is most common (80% of endometrial cancers), tends to be estrogen-related, happens in perimenopausal women (around 60 years)
What are the general risk factors which lead to greater estrogen factor throughout life? This includes risk factors for endometrial cancers, breast cancers, etc.
- Early menarche / late menopause - longer lifespan exposed to estrogen
- Nulliparity - having no kids prolongs your estrogen exposure throughout life b/c you don’t have estrogenfree period after birth
- Anovulatory cycles - prolonged estrogen exposure
- Obesity - increased estrogen conversion
Give one additional risk factor for endometrial carcinoma other than prolonged estrogen exposure.
Lynch syndrome -> typically causes endometrioid type endometrial cancer (microsatellite instabilities and PTEN mutations are seen in this type)
What is the clinical pattern of progression of endometrioid endometrial cancer?
Low stage, with little to no spread. Tumor remains well differentiated with minimal to no myometrial invasion
-> indolent tumor
How is endometrioid tumor graded generally?
Graded 1-3
Grade 1: <5% solid component (confluent cells), rest gland
Grade 3: >50% solid component, worse prognosis
What is the other type of endometrial cancer and who tends to get it?
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
What is the progression of sporadic endometrial cancers? What mutations are associated?
Have a much worse prognosis, automatically considered high grade, with deep invasion of myometrium
Associated with early p53 mutations and very aggressive behavior
What is the most common form of sporadic endometrial carcinoma (Type 2) and what is seen on histology?
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”
Give two other rarer types of Type 2 endometrial carcinoma and their general histology?
- Clear cell carcinoma - Cells with clear cytoplasm with hyalinized stroma with “hobnailing” -> eosinophlia sticking out
- Carcinosarcoma -> high grade adenocarcinoma with a malignant stromal component which can form other random mesenchemyal structures much like teratoma
What is the most common tumor in females?
Leiomyoma - “fibroids”
Beningn neoplasms from smooth muscle of endometrium
What causes fibroids and how will they change with age?
They are estrogen sensitive: tumor increases in size with pregnancy and decreases in size with menopause.
Peak occurrence is in 20-40 years.
How is a leiomyoma told apart from a leiomyosarcoma grossly?
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
What are classic symptoms for leiomyoma?
Usually asymptomatic, but may present with abnormal uterine bleeding (stretch lining of uterus) with iron deficiency anemia, infertility, and a pelvic mass
Who tends to get leiomyosarcoma?
Usually in older (postmenopausal) women, since they are not related to estrogen exposure.
How does the histology of leiomyosarcoma and leiomyoma compare?
Leimyoma - whorled pattern of smooth muscle bundles and well demarcated borders
Leiomyosarcoma - ill-defined borders with significant atypia, mitoses, and necrosis
