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Medical Treatment of
Endometrial Hyperplasia
And
Endometrial Cancer
May /14/2015
Hatim Al-Dabbagh MBBS.FRCSC
Gynecologic Oncologist
Dhahran Health Center
Johns 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&C
Disposable 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 endometrium
Tissue insufficient for analysis
No endometrial tissue seen
Simple or complex (adenomatous) hyperplasia
without atypia
Simple or complex (adenomatous) hyperplasia with
atypia
Endometrial 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.
.
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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2-medical treatment of endometrial hyperplasia and endometrial cancer

  • 1. Medical Treatment of Endometrial Hyperplasia And Endometrial Cancer May /14/2015 Hatim Al-Dabbagh MBBS.FRCSC Gynecologic Oncologist Dhahran Health Center Johns Hopkins Aramco Healthcare
  • 2. Endometrial Hyperplasia / Cancer – A disorder of the Glands
  • 3. 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
  • 4. 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
  • 5. 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
  • 6. 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
  • 7. 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%)
  • 8. 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&C Disposable devices (eg, Pipelle, Tis-u-Trap, Accurette, Z- sampler) Reusable instruments (eg, Novak Curette, Randall Curette, Vabra Aspirator)
  • 9. Possible Endometrial Biopsy Findings Proliferative, secretory, benign, or atrophic endometrium Inactive endometrium Tissue insufficient for analysis No endometrial tissue seen Simple or complex (adenomatous) hyperplasia without atypia Simple or complex (adenomatous) hyperplasia with atypia Endometrial adenocarcinoma
  • 11. 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. .
  • 12. 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
  • 13. Endometrial Cancer – “The Usual Suspects”
  • 14. Endometrial Carcinomas • Make up more than 95% of uterine cancers • Most common invasive gynecologic malignancy
  • 15. 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
  • 16. Endometrial Carcinoma • However, such a stereotype does not account for many endometrial cancers • Nonendometrioid histologies include papillary serous & clear cell carcinomas
  • 17. 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
  • 19. 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
  • 20. 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
  • 21. 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
  • 22. Endometrial Carcinoma - Staging • Staging of endometrial cancer is surgical • Grade is assessed by the percentage of solid growth pattern
  • 23. 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
  • 24. Endometrial Carcinoma - Grading • Papillary serous, clear cell and adenosquamous carcinomas are graded according to the nuclear grade of the glandular component
  • 25. 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
  • 26. Staging of Corpus Cancer • Stage II Cervical stromal invasion
  • 27. Staging of Corpus Cancer • Stage IIIA Tumor invades serosa, and/or adnexa, and/or + peritoneal cytology • Stage IIIB Vaginal metastases
  • 28. Staging of Corpus Cancer • Stage IVA Tumor invasion of bladder and/or rectal mucosa • Stage IVB Distant metastases - intraabdominal contents or inguinal nodes
  • 29. 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
  • 30. 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
  • 31. Endometrial Carcinoma - Treatment • Patients with stage III and IV disease require individualization as to therapy - this often involves radiotherapy and surgery in selected cases
  • 32. 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
  • 33. 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
  • 34. 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