Describe how the endometrium is affected by the menstrual cycle
Endometrial growth in the functional layer is stimulated during the follicular phase of the menstrual cycle by estrogen (via LH) and then by porgesterone from the corpus luteum in the luteal phase of the menstrual cycle. If not fertilization occurs, the functional layer loses its stimulation from the CL and is sloguhed off during menses. Note that the basal layer of the endometrium remains in tact during menses
Describe the layers of the uterus as seen below
The body of the uterus is composed of three layers, the inner most endometrium (which is sloughed during menses), the muscular myometrium, and the outer perimetrium. Circled in this picture is the basal layer of the endometrium
What does the endometrium look like during the proliferative phase of the menstrual cycle
The glands are round, proliferative, and contain mitotic figures (not curly)
What does the endometrium look like during the secretory phase of menstruation?
In the early phase, secretions inside the glands start to be seen and they become corkscrew shaped and sub-nuclei vacoules that eventually secrete into the lumen of the glands
What does the endometrium look like during the menses phase of menstruation?
Tissue begins to almost ball up to be sloughed and hemorrhage can be seen
What are the common causes of dysfunctional uterine bleeding (bleeding from the uterus in the absence of an organic uterine lesion) in pre-pubertal children?
What are the common causes of dysfunctional uterine bleeding in adolescence?
Anovulatory cycle, coag disorders
What are the common causes of dysfunctional uterine bleeding in reproductive age women?
complications of pregnancy (abortion, ectopic preg)
Anatomic lesiosn (leiomyoma, endometrial hyperplasia, carcinoma)
Ovulatory dysfunctional bleeding (e.g. inadequate luteal phase)
What are the common causes of dysfunctional uterine bleeding in peri-menopausal women?
Why would an anovulatory cycle be associated with bleeding?
Failure to ovulate leads to unopposed estrogenic stimulation of the endometrium with low progesterone which causes it to overproliferate and dilate and eventually the top layer breaks down and sheds. The endometrial glands may develop cystic changes and appear disorderly, while the endometrial stroma may be scarce (b/c it requires progesterone to grow)
Biopsy will read as a "disordered proliferative pattern with shedding'
Anovulatory cycles result from subtle hormonal imbalances and are most common when?
at menarche and in the perimenopausal period.
Less commonly, anovulation is the result of:
• Endocrine disorders , such as thyroid disease, adrenal disease, or pituitary tumors
• Ovarian lesions , such as a functioning ovarian tumor (granulosa cell tumors) or polycystic ovaries
• Generalized metabolic disturbances , such as obesity, malnutrition, or other chronic systemic diseases
What is this?
Endometrial polyps are localized overgrowth of endometrial glands and stroma that present as a pedunculated mass typically as a result of unopposed estrogen. These typically dont turn malignant
Patients taking ______ are more likely to get endometrial polyps
tamoxifen (because tamoxifen has weak pro-estrogenic effects in the endometrium.). Hormone replacement and obesity can also increase the risk
T or F. Most endometrial polyps are unresponsive to progesterone
T. A few are hyperfunctional
POC= product of conception (below- chorionic villi)
Look for plasma cells!!
Infection with an IUD, think actinomyces
What is Endometriosis?
the presence of endometrial glands and stroma outside the endomyometrium. It occurs in as many as 10% of women in their reproductive yrs and nearly 50% of women with infertility
Where is endometriosis most commonly seen?
Most often pelvic structures (ovaries, pouch of Douglas, uterine ligaments) and less frequently distant areas of the periotoneal cavity and rarely even lungs, heart, and bone.
What causes endometriosis?
Is the displaced endometrial tissue in endometriosis normal or abnormal?
Abnormal in the sence that it exhibits increased levels of inflammatory mediators, particularly prostalandin E2, and increased estrogen production due to higher aromatase activity. These factors enhance this tissue's ability to survive outside the uterus and can explain the beneficial effects of COX-2 inhibitors and aromatase inhibitors in tx.
When is adenomyosis?
the growth of the basal layer of the endometrium down into the myometrium between muscle bundles that commonly causes the myometrium to hypertrophy.
How mihgt adenomyosis present?
May produce menorrhagia, dysmenorrhea, and pelvic pain before the onset of menses
How does endometriosis presnet?
Extensive scarring of the oviducts and ovaries can often produce discomfort in the lower abdominal quadrants and eventually sterility. Rectal wall involvement can produce pain on defecation, or possible dysparenuria if the bladder is involved. Almost all cases involve dysmenorrhea
T or F. In contrast with adenomyosis, endometriosis almost always contains functioning endometrium
T. So it undergoes cyclic bleeding. And becuase blood can collect in these abnormal areas, they usually appear grossly red. When the ovaries are involved, the lesions may form large, blood filled cysts that turn brown (Chocolate cysts) as the blood ages and possible even fibrosis if the blood organizes (possible sealing the ovarian tubes)
What is menorrhagia?
profuse or prolonged bleeding at the time of a period
What is metorrhagia?
irregular bleeding between periods
What are the most common proliferative lesions of the uterine wall?
smooth muscle tumors
What induces endometrial hyperplasia?
Typically a prolonged excess of estrogen relative to progestin can cause this to occur which is important because hyperplasia is a precursor of endometrial carcinoma!
What are some potential causes of estrogen excess?
-Failure of ovulation (common in perimenopause)
-prolonged admin of estrogen
-estrogen producing ovarian lesions (such as polycystic ovary disease and grnaulosa-theca cell tumors of the ovary)
How is endometrial hyperplasia categorized?
Primarily by cellular crowding (simple vs. complex) and the presence or absence of cytologic atypia (which is more closely related to the risk of transformation to carcinoma)
Endometrial hyperplasia (and the eventual transformation to carcinoma) is associated with what mutations?
PTEN tumor suppressor gene
When you start to not see any stroma in between the glands (i.e. the glands are back-to-back, that is more suggestive of transformation to a carcinoma)
Things to look for: cellular atypia is diagnosed via cytology and is characterized by high N/C ratio, appearance of nucleoli, loss of polarity, and course chromatin
Higher power to show atypia
What is the most common tumor of the female genital tract?
endometrial carcinoma. This most commonly presents in post-menopausal women (around 60 yo) and needs to be considered if you see bleeding in postmenopausal women
Endometrial carcinom includes what cancer types?
endometriod and serous carcinoma of the endometrium
How do endometrioid cancers arise?
They arise in association with estrogen excess and endometrial hyperplasia in perimenopausal women (type I), whereas serous cancers arise in the setting of endometrial atrophy in older postmenopausal women (type II)
Endometrioid cancers are the most common of the two. What are the risk factors?
obesity, diabetes, HTN, infertility, breast carcinoma, and exposure to unopposed estrogen (exogenous or from an ovarian carcinoma) (most lead to more estrogen causing endometrial hyperplasia)
What mutations are common in endometriod cancers of the endometrium?
mutations in PTEN (Cowden syndrome is due to the germline mutation- can be spontaneous) and MSI
•***Defects involving DNA mismatch repair genes are found in about 20% of sporadic tumors and are particularly prevalent in endometrial carcinomas arising in women from families with hereditary nonpolyposis colorectal carcinoma (HNPCC-lynch syndrome)****
What mutations are common in serous cancers of the endometrium?
Which type of endometrial carcinoma is more aggressive?
serous are aggressive and tend to spread via lymph and intraperitoneal while endometriod are indolent (and also spread via lymph)
What is leukorrhea?
a whitish or yellowish discharge of mucus from the vagina.
How do endometrial carcinomas present?
usually with leukorrhea and irregular bleeding, often in postmenopausal women. With progression, the uterus can become affixed to surround tissue as the cancer spreads. These tumors are usually slow to met usually, however.
What is the prognosis of endometrial carcinomas?
With therapy, the 5 yr survival is 90% in early-stage tumors
Look for the medusa head cellular appearance
Both the glandular and stroma components are malignant
Leiomyomas are aka?
fibrinoids because of their hardness
When are leiomyomas common?
Mostly in reproductive age and more common in black women
How do leiomyomas present?
They are often asymptomatic, being discovered incidentally on routine pelvic exam OR presenting with menorrhagia. Leiomyomas almost never transform into sacromas, and the presence of multiple lesions does not increase risk of malignancy
arise de novo from mesenchymal cells of the myometrium, not from preexisting leiomyomas. They are almost always solitary (leiomyomas are more often multiple) and most commmonly occur in post-menopausal women
Seeding of these tumors is very common!