Medical Treatment ofEndometrial Hyperplasia
AndEndometrial Cancer
May /14/2015
Hatim Al-Dabbagh MBBS.FRCSC Gynecologic Oncologist
Dhahran Health CenterJohns Hopkins Aramco Healthcare
Endometrial Hyperplasia / Cancer –A disorder of the Glands
Endometrial Hyperplasia
It represents a spectrum of morphologic and biologic alterations of the endometrial glands and stroma, ranging from an exaggerated physiologic state to carcinoma in situ
It results from protracted estrogen stimulation in the absence of progestin influence
Endometrial Hyperplasia
The risk of endometrial hyperplasia progressing to carcinoma is related to the presence and severity of cytologic atypia
Progestin therapy is very effective in reversing endometrial hyperplasia without atypia but is less effective for endometrial hyperplasia with atypia
Diagnosis
Office endometrial aspiration is the first step in evaluating a patient with abnormal uterine bleeding
The diagnostic accuracy of office-based endometrial biopsy is 98%
A critical review of 33 reports of 13,598 D&Cs and 5851 office biopsies showed that D&C had a higher complication rate than office biopsy but that the adequacy of the specimens was comparable
Diagnosis
If the initial biopsy result is negative, further evaluation is recommended in patients with persistent symptoms, due to the high risk (11%) of an existing lesion having been overlooked
Feldman S, gynecol Oncol, 1994;55:56-9
Diagnosis
Endometrial thickness of less than 4mm as measured by ultrasonography is highly suggestive of endometrial atrophy (sensitivity 96-98%, specificity 36-68%, false negative rate 0.2%)
Endometrial Biopsy
Safe, relatively simple procedure useful in perimenopausal or high risk women
Not sensitive for detecting structural abnormalities (eg, polyps or fibroids)
Office-based techniques (gold standard replacing D&CDisposable devices (eg, Pipelle, Tis-u-Trap, Accurette, Z-
sampler)Reusable instruments (eg, Novak Curette, Randall
Curette, Vabra Aspirator)
Possible Endometrial Biopsy Findings
Proliferative, secretory, benign, or atrophic endometrium
Inactive endometriumTissue insufficient for analysisNo endometrial tissue seenSimple or complex (adenomatous) hyperplasia
without atypiaSimple or complex (adenomatous) hyperplasia with
atypiaEndometrial adenocarcinoma
Endometrial Hyperplasia
SUMMARY AND RECOMMENDATIONS
Hysterectomy is the treatment of choice for women with endometrial hyperplasia with atypia who are not planning future pregnancy.For postmenopausal women with atypical hyperplasia, Hysterectomy with concomitant bilateral salpingo-oophorectomy (BSO) rather than hysterectomy alone is the right choice.For premenopausal women undergoing treatment with hysterectomy, BSO remains controversial.
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Progestin therapy is an option for women with atypical endometrial hyperplasia who wish to preserve fertility or who cannot tolerate surgery. Oral Megestrol acetate 80 mg twice per day every day. This may be increased to 160 mg twice per day if there is no regression of the hyperplasia on follow-up endometrial sampling.
Approximately 35 percent of women will fail conservative management.
Progestins rather than surgery for treatment of endometrial hyperplasia without atypia is the rigt choice.
Medroxyprogesterone acetate 10 mg daily for three to six months. Other progestin preparations may also be used. Observation with follow-up sampling, especially for simple hyperplasia without atypia, is also reasonable, especially in patients who cannot tolerate progestin therapy
Endometrial Cancer – “The Usual Suspects”
Endometrial Carcinomas
• Make up more than 95% of uterine cancers
• Most common invasive gynecologic malignancy
Endometrial Carcinoma
• Stereotyped as a disease of the obese patient and the disease usually proceeds through a precursor of endometrial hyperplasia
• Such tumors have endometrioid histology and are usually of early stage and low grade
Endometrial Carcinoma
• However, such a stereotype does not account for many endometrial cancers
• Nonendometrioid histologies include papillary serous & clear cell carcinomas
Symptoms of Endometrial Cancer
90% of women have vaginal bleeding or discharge as their only presenting complaint
Less than 5% of women diagnosed with endometrial cancer are asymptomatic
Postmenopausal Bleeding
Postmenopausal Bleeding
60-80% of patients with postmenopausal bleeding have endometrial atrophy
Only about 10% of the patients have endometrial cancer
The older the patient is, the greater the risk of cancer
Endometrial Carcinoma -Natural History
• Most common route of spread is direct penetration of the myometrium and direct extension into the cervix and endocervix; tumor may also gain access to lymphatic spaces resulting in nodal metastases
• Endometrial cancers may spread to pelvic lymph nodes, as well as the paraaortic chain
Endometrial Carcinoma -Natural History
• The occasional presence of malignant cells in peritoneal washings demonstrates the potential for transtubal migration of disease
• Hematogenous spread can result in distant disease
• Tumors with clear cell & papillary serous histology are biologically more aggressive than typical endometrioid carcinomas
Endometrial Carcinoma -Staging
• Staging of endometrial cancer is surgical • Grade is assessed by the percentage of
solid growth pattern
Endometrial Carcinoma -Grading
• G1 = <5% of a nonmorular, solid growth pattern
• G2 = 6% to 50% of a nonmorular, solid growth pattern
• G3 = > 50% of a nonmorular, solid growth pattern
Endometrial Carcinoma -Grading
• Papillary serous, clear cell and adenosquamous carcinomas are graded according to the nuclear grade of the glandular component
Staging of Corpus Cancer
• Stage IA Tumor limited to Endometrium or Invasion to < 1/2 of myometrium
• Stage IB Invasion of > 1/2 of myometrium, but not to serosa
Staging of Corpus Cancer
• Stage II Cervical stromal invasion
Staging of Corpus Cancer
• Stage IIIA Tumor invades serosa, and/or adnexa, and/or + peritoneal cytology
• Stage IIIB Vaginal metastases
Staging of Corpus Cancer
• Stage IVA Tumor invasion of bladder and/or rectal mucosa
• Stage IVB Distant metastases -intraabdominal contents or inguinal nodes
Carcinoma of Endometrium -Stage Distribution
• Stage I - 72.8%• Stage II - 10.9%• Stage III - 13.2% • Stage IV - 3.1%
– J Epidemiol Biostat 3:35, 1998
Endometrial Carcinoma -Treatment
• The cornerstone of treatment is total abdominal hysterectomy and bilateral salpingo-oophorectomy
• This operation should be performed whenever possible
• Some patients require sampling of the regional (pelvic & paraaortic) lymph nodes as based on the pathologic information available
Endometrial Carcinoma -Treatment
• Patients with stage III and IV disease require individualization as to therapy -this often involves radiotherapy and surgery in selected cases
Endometrial Carcinoma -Prognostic Factors
• Tumor Stage• Grade/Histologic type• Depth of Invasion• Peritoneal cytologies• Receptor status (ER/PR)• Patient age• Vascular space invasion• DNA Ploidy
Follow-up of Affected Patients
• Patients seen every 3-4 months for first two years
• Seen every 6 months thereafter until 5 years after treatment
• Seen yearly thereafter• Majority of recurrences found by
symptoms, exam, CXR and Pap smear
Recurrent Disease
• Approximately three quarters of patients who experience recurrence will do so in the first three years after primary therapy
• Isolated vaginal metastases are the most amenable to therapy
• Patients with vaginal metastases should be evaluated to rule out further metastatic spread
Thank You
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