The following module was designed to supplement medical students’ learning in the clinic. Please take the time to read through each module by clicking the headings below. For quick reference, all objectives are answered in point form in the very last page of this module. Summary tables are also placed at the end of every section.
By the end of the tutorial, the following objectives should be addressed:
The female pelvis holds important structures such as the bowels, bladder, uterus and ovaries/fallopian tubes in a structural framework created by bone and muscle. We concentrate our discussion on the relevant reproductive anatomy.
The uterus is comprised of the uterine corpus and the uterine cervix. The corpus, or body, is the shape of an inverted triangle, or pear, while the uterine cervix is a tubular structure that is the conduit between the vagina and endometrial cavity. Take a moment to inspect the figure above and notice the differences in epithelium located in each region.
The most superior portion of the uterine corpus, or body, is called the fundus, the most inferior portion the isthmus. The uterus itself is made up of three layers of distinct tissue: the endometrium, myometrium, and serosa. The endometrium is the lining of the uterine cavity, with a superficial layer of glandular epithelium and stroma. It is this endometrial thickness that changes with the menstrual cycle or other hormonal influences. The myometrium is the thickest layer of the uterus and composed of smooth muscle fibers. The serosa is the thin outer lining of the uterus, which consists of visceral peritoneum – this invests the body of the uterus.
The aorta supplies blood to the pelvic structures and descends as the abdominal aorta. From this abdominal aorta comes the first artery of note: the ovarian or gonadal arteriesh that branch off just below the renal arteries. The ovarian arteries descend in the suspensory ligament of the ovary. The abdominal aorta continues, then bifurcates at vertebrae L5 into the Right and Left Common Iliac Arteries. Then, the common iliacs divide into internal and external iliac arteries. The external iliac gives off several branches including inferior epigastric arteries, recurrent obturator artery and super vesical artery.
The internal iliac artery branches into anterior and posterior divisions. The posterior branches into lateral sacral, iliolumbar and superior gluteal arteries. The anterior division has several branches including obliterated umbilical artery, uterine artery, superior vesical artery, obturator artery, vaginal artery and interior gluteal/pudendal arteries. It is these arteries that become very important in supplying the reproductive organs. The internal iliac is also commonly called the hypogastric artery and is useful to ligate during pelvic hemorrhage.
Endometrial cancer is the most common gynecological cancer in Canada, being the 4th most common cancer in women after breast, lung and colorectal cancers. The incidence is 21 per 100,000 people. The lifetime probability of developing endometrial cancer is 1 in 40. An estimated 5600 new cases of endometrial cancer are expected to be diagnosed in 2013, with 4500 cases having been diagnosed in 2012. (1) However, the 5 year overall survival ratio is 84% – so it’s worth learning how to diagnose and treat!
The median age of diagnosis is 61 yrs of age, and as such is considered a disease of postmenopausal women – however 25% of cases occur in premenopausal women. (2)
There are two types of endometrial cancer that are recognized, with each class having different risk factors. Type 1 and Type 2 Risk factors are presented.
With the exception of women with genetic syndromes – discussed below – routine screening for endometrial cancer is not advised. Data does not support efficacy of screening and there is currently no screening test that is sensitive, specific and acceptable to patients and physicians. Cytology from Pap smear and transvaginal ultrasound to assess endometrial thickness have low sensitivity and specificity. Biopsy is invasive but does meet sensitivity and specificity requirements.
As such the American Cancer Society suggests that women at an average or increased risk (such as those of advanced age, with anovulatory conditions or nulliparity) should be well-informed of symptoms such as abnormal uterine bleed and encouraged to report them should they occur.(1)
Two genetic syndromes are of note in this discussion. The first is a rare autosomal dominant condition called Cowden Syndrome that is a result of mutation in the PTEN tumour suppressor gene. The lifetime risk of endometrial cancer in women with Cowden syndrome is 13-28 percent. There are no established guidelines for screening but management is similar to that of Lynch Syndrome, the second genetic syndrome of note.
Lynch Syndrome, or Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is an autosomal dominant inherited cancer susceptibility syndrome caused by mutation in certain DNA mismatch repair genes. The syndrome predisposes an individual to a variety of cancers, namely colorectal and endometrial cancer. Women with Lynch syndrome have a 27-71% risk of endometrial cancer, and as such management includes surveillance, chemoprevention and risk reducing surgery.(2)
Screen with annual endometrial sampling, starting 5-10 years before earliest age of Lynch-related cancer diagnosed in the family. Transvaginal ultrasound to assess endometrial thickness is useful in postmenopausal women, if endometrial sampling is not acceptable. Risk reducing hysterectomy and bilateral salpingo-oophrectomy is effective prevention.
Endometrial carcinomas may be Type 1 or Type 2, depending on light microscopic appearance, clinical behavior and epidemiology.
*Non-endometroid tissue includes serous, clear cell, mucinous, squamous, transitional cell and undifferentiated
A classic presentation of endometrial cancer is postmenopausal bleeding. Premenopausal women may present with heavy/or irregular periods and this may be associated with vaginal discharge. Signs on pelvic examination include bulky uterus, with bleeding or vaginal discharge from the os apparent. However, it is often that no physical signs can be detected.
Occasionally abnormal endometrial cells will be detected incidentally on a pap smear.
Considering the possible mechanisms of spread is important when considering presenting symptoms:
Local Invasion – to myometrium, cervix, fallopian tubes, ovaries, bladder, rectumLymphatic Spread – to pelvic or lumbar lymph nodesHematogenous – to lungs or boneWith these mechanisms of spread and organs in mind, other symptoms such as change in bowel or bladder habits, bony pain or cough maybe present. For this reason, it is very important complete a full history, with an emphasis on any associated symptoms.
Abnormal Uterine BleedAbnormal Cytology (pap) findings noted incidentally on papIncidental finding from other procedure : eg hysterectomy
Though abnormal bleeding from the female genital area is often attributed to a uterine source, it may arise from any site in the lower genital tract, upper genital tract or from a non-gynecological source such as the urethra, bowels, or local trauma. It may also be helpful to separate possible causes depending on if the patient is pre or post menopausal.(1)
Premenopausal – fibroids, polyps, anoulavtory cycles (PCOS), cervical cancer (post coital)Postmenopausal – atrophy (50%), polyps, cervical cancer, endometrial hyperplasia, endometrial cancer** Note that this differential does not take into account Tamoxifen therapy (which can also cause gynecological bleed), coagulation abnormalities, herbal supplements or trauma.
Abnormal uterine or vaginal bleeding has a wide array of etiologies and needs thorough investigation beginning with a history and physical examination. A differential diagnosis will change based on age, reproductive status, underlying conditions and family history.(2) Note that terminology around changes in bleed frequency, time, and duration have become so elaborate that “abnormal uterine bleeding” is now more often used in place of terms such as menorrhagia, amenorrha, oligomenorrhea etc.(3)The following page will take you through the steps required to investigate a woman with abnormal uterine bleed.
Confirmative diagnosis of endometrial carcinoma is made based on pathology of tissue obtained via biopsy, curettage or hysterectomy.(4) If biopsy confirms endometrial cancer, additional measures will need to be taken, namely:
All patients with suspected endometrial cancer should have a complete:
Endometrial hyperplasia is characterized by a proliferation of endometrial glands that results in a greater gland to stroma ratio than would be seen in normal endometrial tissue. It is characterized by proliferation of endometrial glands that almost always results from chronic estrogen stimulation unopposed by progesterone. The hyperplasia may be non-neoplastic or neoplastic, however neoplastic hyperplasia is a precursor to the most common form of endometrial carcinoma – so the presence of either type of hyperplasia is notable.(1)
The World Health Organization’s classification system for endometrial hyperplasia is based on the architecture of the glands and stroma, and level of nuclear atypia. Nuclear atypia is defined as the presence of nuclear enlargement where the chromatin may be arranged in a clump pattern or be evenly dispersed. These two dimensions yield four categories, seen below with more information. For comparison, normal endometrium exhibits no crowding of glands in the stroma – thus is said to have less than 50% gland:stroma ratio. (1)
For simple and complex hyperplasia, the risk of developing endometrial cancer is approximately 1-3%. Complex atypical hyperplasia however is considered synonymous with carcinoma-in-situ and 30% of these cases will develop into endometrial carcinomas.(2)
The World Health Organization and International Society of Gynecological Pathologists have developed the following classification system for endometrial carcinomas.(3)
Staging of endometrial cancer is based on the joint 2010 International Federation of Gynecology and Obstetrics (FIGO)/TNM classification system, an abbreviated version of which is below:
The standard treatment of endometrial carcinoma is Total Abdominal Hysterectomy and Bilateral Salpingo-Oophorectomy (TAH-BSO). Surgery alone is reserved for patients with low recurrence risk, such as those with Grade 1 or 2 lesions as adjuvant therapy has not been shown to improve overall survival. Adjuvant therapy is recommended for those with risk factors. Surgery may be undesirable for some due to its implications for fertility.(1)
Adjuvant therapies that may be offered include:
pelvic radiation, or vaginal brachytherapy chemotherapyhormone/high-dose progestin treatments. (4)
The decision to pursue adjuvant therapy is based on the risk of persistent or recurrent disease and is guided by stratifying patients into low, intermediate or high risk groups as outlined below.
Low Risk – women with grade 1 or 2 endometrioid cancers that are limited to the endometrium.
Intermediate risk – if the cancer invades the myometrium, or cervical stroma or is of grade 2 or 3.
High Risk – stage 3 disease, uterine sarcoma or clear cell carcinoma of any stage.
A large percentage of endometrial carcinoma recurrences occur within three years post-treatment, with the most common sites of recurrence being the vaginal vault, pelvis, abdomen, and lungs. Around 70% of recurrences are associated with symptoms; symptoms suggestive of recurrence include vaginal bleeding, abdominal or pelvic pain, persistent cough, or unexplained weight loss.(1)
The BC Cancer Society has carrying recommendations for follow up, dependent on the treatments given to patients. A history and physical is always recommended, followed by any investigations that are indicated by symptoms or signs on exam. A summary table can be found below. (2)
Endometrial cancer is the most common gynecological cancer in Canada, being the 4th most common cancer in women after breast, lung and colorectal cancers. The incidence is 21 per 100,000 people. The lifetime probability of developing endometrial cancer is 1 in 40.
It is notable that protective factors for endometrial carcinoma include estrogen-progestin oral contraceptives, physical activity tea and coffee.
Screening is not recommended unless a genetic syndrome is identified.
Premenopausal – fibroids, polyps, anoulavtory cycles (PCOS), cervical cancer (post coital)Postmenopausal – atrophy (50%), polyps, cervical cancer, endometrial hyperplasia, endometrial cancer
** note that this differential does not take into account Tamoxifen therapy (which can also cause gynecological bleed), coagulation abnormalities, herbal supplements or trauma.
Endometrial hyperplasia is characterized by a proliferation of endometrial glands that results in a greater gland to stroma ratio than would be seen in normal endometrial tissue. It is characterized by proliferation of endometrial glands that almost always results from chronic estrogen stimulation unopposed by progesterone. The hyperplasia may be non-neoplastic or neoplastic.
Pathologically, endometrial carcinoma can be classified based on cell type with a correlated prognosis.
This case study was designed to supplement your knowledge on the workup of endometrial cancer and test what you have learned after going through module. Use your mouse to click through the slides and answer each question in the text box provided.
Note: This case can be completed on an iPad. To do this download the (free) Articulate Mobile Player for the iPad by clicking here.