Amy Hempel and Jori S. Carter
History of present illness
A 65-year-old postmenopausal white woman with a past medical history significant for hypertension, diabetes, and hypercholesterolemia presents urgently to your office with profuse vaginal bleeding. The patient states she began to notice intermittent, dark spotting about one month ago. At that time, she used one panty-liner daily. About two weeks later, she began noting bright red blood for one to two days, which she described as“heavy as her prior periods.”Today she presents saying her bleeding has worsened. The patient is nulliparous and reports menopause was at age 55. She is sexually active with her husband and denies any history of sexually transmit- ted diseases. She has no significant surgical history. Her medi- cations include an angiotensin-converting enzyme (ACE) inhibitor, a statin, and metformin. She does not smoke or drink. She is a retired teacher. Review of symptoms is negative for fever, chills, weight loss, vaginal discharge, or dysuria.
Physical examination
General appearance:Pleasant, well-groomed woman who is in no acute distress
Vital signs:
Temperature: 36.4°C Pulse: 78 beats/min Blood pressure: 134/89
Respiratory rate: 16 breaths/min BMI: 40 kg/m2
HEENT:Normal
Cardiovascular:Regular rate, regular rhythm without murmurs
Respiratory:Clear to auscultation bilaterally
Abdominal:Soft, nontender, obese, normal bowel sounds Genitourinary:Normal appearing external genitalia; vaginal vault with one scopette of brown blood. No obvious active bleeding from the cervical os, which was noted to be stenotic. On bimanual examination the uterus was anteverted without obvious masses. Ovaries were not palpated
Laboratory studies:
Comprehensive metabolic panel: Normal Leukocyte count and platelet count: Normal Hb: 11 g/dL (normal 12–16 g/dL)
Imaging:Transvaginal ultrasound is performed (Fig. 92.1)
How would you manage this patient?
This patient is a postmenopausal woman with abnormal vaginal bleeding. The most common differential diagnosis of postmenopausal bleeding in this age group includes vaginal trauma, atrophy, uterine and cervical polyps, and endometrial hyperplasia or neoplasia. In this case, a pelvic ultrasound was performed revealing a thickened endometrial stripe of 20 mm.
An endometrial biopsy was performed in the office after gently dilating the cervix, and pathology revealed an endometrial adenocarcinoma. The patient was referred to a gynecologic oncologist for further surgical management. She ultimately underwent a robotic-assisted laparoscopic total hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and lymph- node dissection. She was diagnosed with stage IB, grade 1, endometrioid adenocarcinoma of the endometrium and did not require any additional treatment (Fig. 92.2).
She follows up with her gynecologic oncologist every three months.
Endometrial cancer
Endometrial cancer is the most common malignancy of the female genital tract in the United States [1] and is the fourth most common cancer in women after breast, lung, and color- ectal cancers [2]. More than 90% of patients with endometrial cancer will present with abnormal vaginal bleeding or dis- charge, allowing for 72% of endometrial cancers to be diag- nosed as stage I [1]. Risk factors for developing endometrial cancer include increased age, white race, nulliparity, history of infertility, late age of menopause and early age of menarche, obesity, diabetes, hypertension, gallbladder disease, and thy- roid disease. Ninety percent of cases occur in women over the age of 50, and 70% of patients with early-stage endometrial cancer are obese [2]. The lifetime endometrial cancer mortality risk is 0.5%, translating into over 7310 deaths each year. The 5-year survival rate is 80.8% for white females and 53.3% for black females with the cause of the discrepancy being unclear, although it is known that black women are diagnosed more commonly at advanced stages and get more aggressive histo- logic types of endometrial cancer [1,3]. Hypotheses that account for the racial discrepancy include lack of access to care, delay in treatments, and more advanced stages of cancer identified at diagnosis. Only 52% of black women over the age of 50 have disease confined to the uterus at diagnosis compared to 73% of white women in the same age group.
Curiously, the death rate per 100 000 population has soared
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
more than 100% during the past 20 years, likely secondary to longer life spans and medical comorbidities [2].
The most common etiology of endometrial cancer is an excess of endogenous or exogenous estrogen with a lack of opposing progesterone. Two classifications of endometrial cancer exist: type I, or estrogen dependent, and type II, which is not related to estrogen status. The former is more common and confers a relatively good prognosis while type II is a more lethal type. Despite type II being the more lethal form, carcinosarcoma is the most aggressive form of endometrial cancer. Carcinosarcomas possess cancerous cells both
originating from epithelial and connective tissue cells and are not estrogen dependent.
To make the diagnosis of endometrial cancer, tissue sam- pling of the endometrium (via endometrial biopsy or sharp curettage) must be obtained. Premenopausal patients being evaluated for abnormal uterine bleeding should have negative pregnancy testing prior to sampling the endometrium. While office endometrial biopsy is the preferredfirst-line approach to obtain endometrial tissue sampling due to the fact that is less expensive and less invasive than dilation and curettage under anesthesia, an endometrial biopsy will not adequately
Fig. 92.2 Excised adenocarcinoma of the endometrium. (Image courtesy of Stephen Cohen, MD.)
Fig. 92.1 Transvaginal ultrasound of uterine endometrial thickness at 20 mm.
Case 92: A 65-year-old woman with profuse vaginal bleeding
characterize lesions in terms of extent of involvement within the uterus. Meta-analyses have showed that the sensitivity of endometrial biopsy to diagnose endometrial hyperplasia or cancer is 68% when compared to surgical pathology obtained at hysterectomy, while the sensitivity of dilation and curettage is 78%. [4].
While tissue sampling is the gold standard to rule out endometrial cancer, other options to characterize the uterine anatomy in an effort to diagnose the etiology of postme- nopausal bleeding include hysteroscopy and transvaginal ultrasound. Hysteroscopy allows one to directly visualize the uterine cavity, which aids in identifying a focal lesion, as well as allows one to biopsy such a lesion under direct visualiza- tion, and assess for other sources of uterine bleeding includ- ing polyps and leiomyomas. When hysteroscopy is negative, the likelihood of actual endometrial cancer existing is 0.4–0.5% [4]. Transvaginal ultrasound can also be used to identify the thickness of the endometrial lining, which is related to the amount of estrogen exposure at the endomet- rium. When the endometrial thickness measures less than 5 mm, a 99% negative predictive value exists for the diagnosis of endometrial cancer [2]. Similarly, 96% of women with endometrial cancer have an endometrial stripe of greater than 5 mm [2]. The patient in this case was found to have an endometrial stripe of 20 mm on ultrasound prompting an endometrial biopsy and, thus, the diagnosis.
Once endometrial cancer is diagnosed, the patient should be referred to a gynecologic oncologist. A physical examin- ation and chest radiograph are the only components of preoperative staging, and a physical examination specifically provides information regarding the most beneficial surgical approach and planning for removal of the uterus. MRI and CT are not routinely required preoperatively.
Endometrial cancer is surgically staged by performing a total hysterectomy with bilateral salpingo-oophorectomy with pelvic washings for cytology and bilateral pelvic and para- aortic lymph node dissection. Staging of endometrial cancer includes assessments of histologic grade by the International Federation of Gynecology and Obstetrics (FIGO) system, nuclear grade, myometrial depth of invasion, stromal involve- ment of the cervix, and assessments of metastasis to the vagina or ovaries, as well as spread to the lymph nodes, other com- ponents of the abdomen, or distant structures (Table 92.1[5]).
The staging of the disease guides prognosis as well as treat- ment. Site of metastasis is the primary indicator of prognosis, and therapy including radiation and chemotherapy will depend on the surgical stage at time of diagnosis. When stage I endometrial carcinoma is diagnosed, about 75% of women are cured with total hysterectomy, bilateral salpingo- oophorectomy, and lymph node dissection alone [2]. Multiple randomized trials have shown no survival benefit to adjuvant radiation for stage I disease despite better local control of recurrence. Adjuvant radiation may be offered for patients if they have high risk factors including serous or clear cell cancer; or if they have intermediate- to high-risk factors at
specific ages. Intermediate-risk factors include FIGO grade 2 or 3, outer half of myometrial invasion, and lymphovascular space invasion. Patients at any age with all 3 risk factors qualify for radiation, as well as patients between the ages of 50 and 69 with 2 risk factors, or patients 70 years or older with 1 risk-factor. [6] If stage II–IV endometrial cancer is diagnosed, attention is turned to radiation of affected areas.
Extrauterine disease requires pelvic radiation and consider- ations are made for systemic therapy including chemotherapy especially in cases of intraperitoneal disease. After completion of recommended therapy, most patients should be followed clinically every 3–4 months for 2–3 years, then twice yearly thereafter to monitor for any signs of recurrence on speculum or rectovaginal exam, as up to 70% of recurrences are detected within 3 years [1].
Key teaching points
Any patient with postmenopausal bleeding must be evaluated as to the etiology and ruled out for endometrial cancer.
A diagnosis of endometrial cancer requires tissue histology obtained from the endometrium by office endometrial biopsy or by sharp curettage in the operating room.
Table 92.1 International Federation of Gynecology and Obstetrics (FIGO) staging of endometrial cancer as defined by surgical and pathologic findings*
FIGO stage
Surgical/pathologicfindings
I Tumor confined to corpus uteri IA No or less than half myometrial invasion IB Invasion equal to or more than half of the
myometrium
II Tumor invades cervical stroma, but does not extend beyond the uterus.
III Local and/or regional spread of the tumor.
IIIA Tumor invades the serosa of the corpus uteri and/or adnexa
IIIB Vaginal and/or parametrial involvement
IIIC Metastases to pelvic and/or para-aortic lymph nodes IIIC1 Positive pelvic nodes
IIIC2 Positive para-aortic lymph nodes with or without positive pelvic lymph nodes
IV Tumor invades bladder and/or bowel mucosa, and/
or distant metastases
IVA Tumor invasion of bladder and/or bowel mucosa IVB Distant metastases, including intra-abdominal
metastases and/or inguinal lymph nodes
* From Pecorelli [5].
When pelvic ultrasound is used in the diagnostic workup of postmenopausal bleeding, an endometrial stripe measuring greater than 5 mm requires follow-up tissue sampling.
Endometrial cancer is surgically staged and requires a total hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and bilateral pelvic/para-aortic lymph-node dissection by a surgical specialist.
References
1. American College of Obstetricians and Gynecologists. Management of endometrial cancer. Practice Bulletin No. 65.Obstet Gynecol2005;106:
413–25.
2. Sorosky, J. Endometrial cancer.Obstet Gynecol2012;120:383–97.
3. Long, B; Liu, FW; Bristow, RE.
Disparities in uterine cancer
epidemiology, treatment, and survival among African Americans in the United States.Gynecol Oncol 2013;130:652–9.
4. American College of Obstetricians and Gynecologists. Management of abnormal uterine bleeding associated with ovulatory dysfunction.
Practice Bulletin No. 136.
Obstet Gynecol2013;122:
176–85.
5. Pecorelli, S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium.Int J Gynaecol Obstet 2009;105:103–4.
6. Keys, H; Roberts, J; Bruno, V; et al.
A phase III trial of surgery with or without adjuvant external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma:
A Gynecologic Oncology Group study.
Gynecol Oncol2004;92:744–51.
Case 92: A 65-year-old woman with profuse vaginal bleeding