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.
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.
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.
This is hyperplasia or excessive growth of the endometrial glands.
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.
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 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.
Now, another risk factor is age, since this type of endometrial cancer typically presents in postmenopausal individuals, around 55 to 65 years of age.
In addition, a family history of ovarian cancer, colon cancer, or other gastrointestinal cancers can be a hint for an autosomal dominant disorder known as hereditary nonpolyposis colorectal cancer or Lynch syndrome, where you are also at a higher risk for developing endometrial cancer.
Type 2 makes up the remaining 25% of endometrial carcinoma and it has a number of subtypes.
The most common subtype is serous carcinoma.
Under the microscope, serous carcinomas often form papillary or finger-like structures.
On biopsy, they often contain psammoma bodies, which are circular plaques of calcium deposits around necrotic or dead cells.
What you need to remember is that type 2 carcinomas don’t appear to be linked with estrogen levels.
In contrast, these cancers typically affect females with endometrial atrophy.
Another important distinction is that they also tend to develop later in life than Type 1, usually around the age of 70.
However, they are more aggressive.
For your exams, it’s also important to know that the genetic mutations found most often in serous carcinoma involve the TP53 gene, another tumor suppressor, and aneuploidy, or an abnormal number of chromosomes after cell division.
Alright, let’s talk about symptoms!
Both endometrial hyperplasia and endometrial carcinoma typically present with menorrhagia, which means heavy or prolonged menstrual bleeding, metrorrhagia, bleeding between menstrual cycles, or a combination of both known as menometrorrhagia.
Both of these are usually painless.
Afterwards, then a biopsy is used to confirm the diagnosis.
Treatment for endometrial hyperplasia includes eliminating the underlying cause of excess estrogen, such as weight loss in cases of obesity, stopping unopposed estrogen therapy and correcting the problem of