AssessmentsUterine disorders: Pathology review
USMLE® Step 1 style questions USMLE
A 23-year-old nulliparous woman comes to the office because of chronic episodic pelvic pain. The pain begins 2-3 days before menses and continues throughout the menses, after which it subsides. Menarche was at age 14. She has a regular menstrual cycle of 25 days with 5-6 days of moderate bleeding. Medical history is significant for recurrent migraine headaches with aura. She is not sexually active. Physical examination shows a fixed anteverted uterus and nodularity in the posterior cul-de-sac. The patient is provided with a medication that acts to inhibit the growth of endometrial tissue. Which of the following medications was most likely provided?
Content Reviewers:Yifan Xiao, MD
She has been trying unsuccessfully to get pregnant for the first time for the past 2 years.
Pelvic examination shows a normal sized uterus.
This has been occurring for the past 6 months and is accompanied with a feeling of “fullness” in the lower abdomen as well as fatigue.
On further history, she has never been pregnant.
Physical examination shows an enlarged uterus with multiple round masses.
Laboratory studies reveal iron deficiency anemia.
Based on the initial presentation, Carmen and Susanna both have some form of uterine disorder.
Let’s first review physiology real quick.
The endometrium has two layers, an inner functional layer made up mainly of glands and supporting connective tissue, called stroma, and an outer thin basal layer which regenerates the overlying functional layer after each menstrual cycle.
Okay, now, the first uterine disorder is endometritis or inflammation of the endometrium.
A high yield risk factor to remember is the retention of products of conception, like parts of the placental or fetal tissues, following delivery or abortion.
Another risk factor is the presence of a foreign body, like an intrauterine contraceptive device.
Both can provide a good environment for bacteria to grow and cause an infection in the uterus.
Less commonly, endometritis can be caused by outside bacteria such as Chlamydia trachomatis or Neisseria gonorrhoeae, which are transmitted sexually, or Mycobacterium tuberculosis, which spreads from the lungs into the blood and travels to other organs such as the uterus.
Now, endometritis can be acute or chronic.
On your test, an individual with acute endometritis, typically presents with symptoms like fever, abnormal uterine bleeding, lower abdominal pain, dysuria, which is painful urination, or dyspareunia, which means pain during sexual intercourse.
In contrast, in chronic endometritis, people often have no symptoms and normal physical examination, however, some may experience similar symptoms to those of acute endometritis, although milder.
Diagnosis of is usually based on clinical findings.
An endometrial biopsy can help make the diagnosis, although it’s not routinely done.
What you absolutely have to remember is that microscopic examination of acute endometritis shows neutrophils in the endometrium, which are the hallmark of acute inflammation, while in chronic endometritis, the presence of lymphocytes, especially plasma cells, in the endometrium is diagnostic.
Treatment of endometritis is based on antibiotics.
Next, there is Asherman syndrome.
This occurs when the basal layer of the endometrium undergoes fibrosis so it’s unable to regenerate the functional layer.
Sections of the normal tissue in the uterus is replaced by multiple bands of collagen which leads to intrauterine adhesions where the bands make the uterine walls stick to each other.
Now, for your exams, it’s important to remember that this typically occurs in a female who has undergone uterine instrumentation in the past, like dilation and curettage.
Another uterine disorder that’s high yield is endometrial hyperplasia.
This is hyperplasia or excessive growth of the endometrial glands.
It could also be caused by estrogen secreting tumors, such as granulosa cell tumors of the ovaries.
People with polycystic ovarian syndrome are also at risk of endometrial hyperplasia.
In this condition, the ovary is full of cystic follicles that secrete estrogen.
Now, a person could have normal estrogen production throughout their life, but the number of years the endometrium is exposed to estrogen is also a risk factor for developing endometrial hyperplasia.
This is because these people have experienced a greater number of menstrual cycles, where more follicles have grown, and more estrogen were secreted by these follicles.
The same goes for females who have never given birth, also called nulliparous, who are at a higher risk than those who have been pregnant.
That’s because, during pregnancy, there’s more estrogen and progesterone production, but the balance shifts towards more progesterone, which is protective against endometrial hyperplasia.
Also, we have medications that can cause endometrial hyperplasia, such as estrogen-only hormone replacement therapy, usually taken by postmenopausal females to relieve menopause symptoms, such as hot flashes and vaginal dryness.
In some cases, endometrial hyperplasia can also be caused by tamoxifen, a breast cancer medication which blocks estrogen receptors on the breast, but at the same time, stimulates those on the endometrium.
The number one concerning problem with endometrial hyperplasia is that it increases the risk for endometrial cancer, which is the most common cancer arising from the female reproductive system.
The risk of developing endometrial cancer depends on the histological features of the cells undergoing hyperplasia.
So, zooming into a section of the endometrium, hyperplasia can be simple, where there’s a lot of dilated glands and stroma, but their ratio is similar to normal tissue.
In complex hyperplasia there are way more glands and less stroma, meaning a high gland-to-stroma-ratio, and this type of hyperplasia is more at risk of progression to endometrial cancer.
If we zoom in even more, we can see the nuclei inside these glandular cells.
Αbnormal nuclear features, like larger and hyperchromatic or darker nuclei, are called nuclear atypia, which, for your test, is the most important factor in terms of progression to endometrial cancer.
Now, there are two main types of endometrial cancer.
The most common one, accounting for about 75% of all cases, is Type 1 endometrial carcinoma, which is also called endometrioid carcinoma.
That’s because the classic histology is “endometrioid”, meaning that the cancer cell looks very much like the normal endometrial cells.
And this is the one that can arise from endometrial hyperplasia and is linked to prolonged unopposed estrogen exposure.
Now, another risk factor is age, since this type of endometrial cancer typically presents in postmenopausal individuals, around 55 to 65 years of age.