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

10. Endometrial Hyperplasia

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

18. Postmenopausal Bleeding

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

35. Thank You