lecture

1. ENDOMETRIAL
HYPERPLASIA AND
MALIGNANT DS OF THE
CORPUS
1
DR. SWATI SINGH
CONSULTANT
DEPARTMENT OF OBS. AND GYN

2. ENDOMETRIAL HYPERPLASIA
• Represent a spectrum of morphologic and
biologic alterations of the endometrial glands
and stroma, ranging from an exaggerated
physiologic state to carcinoma in situ.
• Usually evolve as a result of estrogen
stimulation
• Usually occurs when a patient is exposed to
unopposed estrogen, i;e in the absence of
progestin influence.
• Precede or occur simultaneously with
endometrial ca.
2

3. RISK FACTORS
• Unopposed estrogen stimulation
• Nulliparity
• Delayed menopause
• PCOS
• Obesity
• Diabetes
• Hypertension
• Previous radiation therapy
• Family Hx and Tamoxifen therapy
3

4. PROTECTIVE FACTOR
• Multiparity
• Normal weight
• Combined oral contraceptives
• Progesterone therapy
• Menopause <49 years of age
4

5. Endometrial Hyperplasia
• Complex hyperplasia with atypia
– One study found incidence of concomitant
endometrial cancer in 40% of cases
– Hysterectomy or high dose progestin tx
• Simple
– Often regress spontaneously
– Progestin treatment used for treating
bleeding may help in treating hyperplasia as
well

6. TTYYPPEE OOFF HHYYPPEERRPPLLAASSIIAA PPRROOGGRREESSSSIIOONN TTOO CCaa
SSIIMMPPLLEE ((ccyyssttiicc wwiitthhoouutt
aattyyppiiaa))
11%%
CCOOMMPPLLEEXX ((aaddeennoommaattoouuss
wwiitthhoouutt aattyyppiiaa))
33%%
AATTYYPPIICCAALL:
SSIIMMPPLLEE ((ccyyssttiicc wwiitthh
aattyyppiiaa))
88%%
CCOOMMPPLLEEXX ((aaddeennoommaattoouuss
wwiitthh aattyyppiiaa))
2299%%
6

7. MMaannaaggeemmeenntt:
• Progestin therapy
effective in -- endometrial hyperplasia without atypia less
effective -- endometrial hyperplasia with atypia.
EEnnddoommeettrriiaall hhyyppeerrppllaassiiaa wwiitthhoouutt aattyyppiiaa:
cyclical progestin therapy (MPA 10—20 mg/d for 14 d/mth) or
continuous progestin therapy (megestrol acetate 20—40 mg/d )
for 6 months.
CCoommpplleexx oorr aattyyppiiccaall hhyyppeerrppllaassiiaa :
continuous progestin– MPA 200 mg/day or megestrol acetate 40-160
mg/d. Therapy given for 9 mth
Hysterectomy --Women with atypical complex hyperplasia who do
not desire fertility.
7

8. • Endometrial Biopsy should be performed 3—4
wk after completion of therapy to assess
response.
• Atypical hyperplasia treated with
progesterone, periodic Endometrial Biopsy or
TVS is advisable because of presence of
undiagnosed cancer in 25% cases, 29%
progression to cancer and high recurrence
rate.
8

9. ENDOMETRIAL CANCER
9

10. Incidence
• Most common gynecological cancer in US.
• Higher in US. Due increased life expectancy
and injudicious use of oestrogen in post
menopausal women
• incidence 1.8 / 10000.
• In Nigeria - 3 cases/year.
• More common between age of 50-60 years.
• Most commonly inherited gynecologic
malignancy.
10

11. RISK FACTORS
IInnccrreeaasseedd rriisskk:
1) Age : 75% are postmenopausal with median age
of 60 years. Incidence increases until about 70
yr
2) Higher socioeconomic status.
3) Higher level of education.
4) Higher among whites than African Americans.
5) Reproductive factors:
 nulliparous women have 2—3 times the risk of
parous women.
 Infertility and a history of menstrual
abnormalities due to anovulatory cycles
increase the risk. 11

12. 6) Early menarche.
7) Late menopause
8) CORPUS CANCER SYNDROME
 Obesity : RR is 2 times if 5-10 kg overweight
and risk rises to 10 times if overweight by 25
kgs.
 Diabetes : increases the risk by 1.8 to 2.3
times.
 Hypertension.
9) Unopposed estrogen stimulation :
 anovulatory disorders: e.g. PCOS
 Estrogen producing tm: granulosa
theca cell tm.
 Estrogen replacement therapy: inc risk
4-8 times.
12

13. 11) Tamoxifen use : 3-6 fold increased risk. Poor
prognosis
12) HNPCC ( hereditary nonpolyposis colon cancer
syndrome) : inactivation of DNA mismatch repair
genes.
40—60 % lifetime risk of endometrial ca.
13) Family history.
13

14. DDEECCRREEAASSEEDD RRIISSKK
1) Oral contraceptive use: 12 mths of use
decreases risk by 40% and effect persists
for at least 15 yr after the cessation of use.
2) Phytoestrogens.
3) Physical activity.
4) Cigarette smoking.
5) Nonmedicated plastic or copper IUD.
6) Effect of progesterone containing IUDs is
unknown.
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15. HISTOLOGIC CLASSIFICATION
1. Endometrioid adenocarcinoma ((8800%%))
Variants
Villoglandular or papillary (2%)
Secretory (1%)
With squamous differentiation (15—25 %)
2. Mucinous carcinoma. ((55%%))
3. Papillary serous carcinoma. ((33——44 %%))
4. Clear cell carcinoma. ((<<55%%))
55.. Squamous carcinoma.
6. Undifferentiated carcinoma.
7. Mixed carcinoma.
15

16. PATHOLOGY
• GGRROOSSSS: uterus small, normal or large in size
due to myohyperplasia, myometrial
involvement, pyometra or associated fibroids
• GGRROOWWTTHH:
1) Localised polyp (friable) with ulceration
and necrosis usually at the fundus
2) Diffuse: spread to myometrium & serosa,
also to the cervix
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17. CLINICAL FEATURES
PPAATTIIEENNTT PPRROOFFIILLEE:: usually nulliparous, postmenopausal
or h/o delayed menopause; Younger women with PCOD,
infertility, obese, hypertensive & diabetic.
SSYYMMPPTTOOMMSS::
• 90% of patients with ca endometrium present with PMB
or abnormal vaginal bleeding.
• 10% of pt with postmenopausal bleeding have Ca
endometrium.
• Watery & offensive or purulent discharge due to
pyometra,
17

18. SSIIGGNNSS::
• GPE:
pt is usually obese, hypertensive.
Pallor +
LAP – supraclavicular, axillary, inguinal.
breasts examination.
• P/A
There may be ascites.
Abdominal lump due to pyometra, fibroid.
Hepatomegaly.
• P/S: Cx usually healthy. May be bloody or
purulent discharge through ext os.
18

19. BBiimmaannuuaall eexxaammiinnaattiioonn::
Size of the uterus: small, normal or large, usually
mobile. In advanced cases it is fixed and irregular.
Adnexae : mass in case of simultaneous tumour or
secondary growth in ovary.
Parametrium : for induration.
Cul-de-sac : for nodularity.
RReeccttaall eexxaammiinnaattiioonn
19

20. DIAGNOSIS
• Nearly 75% of cases of Ca endometrium
are seen in postmenopausal women and
most common symptom is PMB. All
women in peri and postmenopausal
period with AUB must be investigated
although only about 20% of PMB is due
to malignancy.
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21. 21

22. TTrraannssvvaaggiinnaall ppeellvviicc UUllttrraassoouunndd:
In a post menopausal
pt finding of ET>
4mm,
• a polypoid
endometrial mass or
• collection of fluid
within the uterus
requires further
evaluation.
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23. • a Office Endometrial assppiirraattiioonn bbiiooppssyy : first step .
• PIPELLE
• Endorette
• Tao brush
• I-sac cell sampler
• Gravele jet washer
• Vabra aspirator
sensitivity for
atypical hyperplasia - 81%
Ca endometrium - 99.6%
Specificity for hyperplasia or malignancy - 98%
A Pap test is unreliable as only 30 – 50% pt with
ca endometrium have abnormal Pap test results.
23

24. DDiillaattaattiioonn aanndd ccuurreettttaaggee : Gold standard
for endometrial sampling. It is
indicated:
• inadequate sample by aspiration biopsy
• Cervical stenosis or patient intolerance
does not permit adequate evaluation.
• Bleeding recurs after a negative
endometrial biopsy.
false negative : 10%
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25. Hysteroscopy wwiitthh ccuurreettttaaggee::
• Safe, reliable and quick office procedure. Provides
inspection of endometrial features like colour,
vascularity, thickness and necrotic areas or growths.
• Excellent method for targeted biopsy that one may
miss at D n C or endometrial aspiration.
• Combined use of hysteroscopy and histopathology
gives 100% accuracy.
• Identification of other uterine pathology as polyps,
submucous myomas.
• Pts undergoing hysteroscopy more likely to have
positive peritoneal washings.
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26. Normal Endometrium Endometrial Polyp
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27. DIFFERENTIAL DIAGNOSIS
• Premenopausal  exclude pregnancy and its
complications like abortion
• Estrogen replacement therapy.
• Endometrial hyperplasia
• Endometrial & Cx polyps
• Fibroid
• Ovarian, Cx or tubal neoplasm
• Postmenopausal  endometrial atrophy,
exogenous estrogens, atrophic vaginitis
• Urethral caruncle
• Trauma
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28. SPREAD
• Direct
• Lymphatic
• Blood borne
Direct : slow growing. Infiltrates the
myometrium, serosa, parametrium & to the
cervix (15%).
Lymphatic: usually late.
Three separate lymphatic pathways:
a) Paracervical and Parametrial – pelvic LN
b) Ovarian – paraaortic LN
c) round ligament –inguinal LN
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29. STAGING
• CCLLIINNIICCAALL SSTTAAGGIINNGG
• SSUURRGGIICCAALL SSTTAAGGIINNGG
EEnnddoommeettrriiaall ccaanncceerr iiss ssuurrggiiccaallllyy
ssttaaggeedd aanndd ttrreeaatteedd..
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30. SURGICAL STAGING
Increased inaccuracy of clinical staging and the
importance of prognostic factors some of which can be
identified only surgically resulted in introduction of
surgicopathologic staging in 1988.
– Better defines extent of disease (metastases, depth
of invasion, cervix involvement, etc.)
– Minimizes over/under treatment
– Minimally increases perioperative
morbidity/mortality
– Decreases overall Rx risks and costs
– Better allows comparison of therapeutic results
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31. REVISED FIGO STAGING (2010)
STAGE I: Tumour confined to the corpus uteri
Ia: No or less than half myometrial invasion
Ib: Invasion equal to or more than half of myometrium
Stage II: Cervical stromal invasion but not beyond the uterus
Stage III: Local and/or regional spread of the tumour
IIIa: Tumour invades the serosa of the corpus uteri and/or
adnexa
IIIb: Vaginal and/or parametrial involvement
IIIc: Metastases to pelvic and /or paraaortic lymph nodes
Stage IV: Tumour invades bladder and/or bowel mucosa, and/or
distant metastases
IVa: Tumour invasion of bladder and/or bowel mucosa
IVb: Distant metastases, including abdominal metastases
and/or inguinal lymph nodes
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32. MMAANNAAGGEEMMEENNTT
32

33. TREATMENT
• SSUURRGGEERRYY
• RRAADDIIAATTIIOONN TTHHEERRAAPPYY
• SSYYSSTTEEMMIICC TTHHEERRAAPPYY
Treatment is essentialy surgical with postoperative
adjuvant therapy added when unfavourable prognostic
features are found at surgery ．
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34. MMOODDEESS OOFF SSUURRGGEERRYY
Abdominal
Vaginal
Laproscopic
Laprotomy has been the principal surgical approach to
hysterectomy and surgical staging for Ca endometrium.
 ABDOMINAL HYSTERECTOMY (LAPAROTOMY):
a) extrafascial
b) Radical
Includes:
thorough exploration of peritoneal contents, pelvic washings,
hysterectomy, BSO, B/L pelvic and paraaortic LN
dissection.
• The uterine specimen should be opened in the perating room
and Tumor size, Depth of myometrial involvement, and
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cervical extension assessed.

35. POST – 0P ADJUVANT MANAGEMENT
RADIATION
SYSTEMIC THERAPY
HORMONE THERAPY
CHEMOTHERAPY
35

36. Treatment according to clinical staging
STAGE I:
Surgery is the mainstay of treatment.
• Extrafascial hysterectomy with B/l salpingo-oopherectomy
+/- LN node sampling.
• Vaginal hysterectomy in selected cases
• LAVH
Post op vaginal cuff irradiation is given in Ia G3 and Ib
G123.
Primary RT in pts with co-morbidities not fit for surgery.
36

37. Stage II
Two approaches
a) Radical hysterectomy , Bilateral salpingo-oopherectomy,
and pelvic and para-aortic
lympnadenectomy followed by pelvic and vaginal
cuff irradiation.
Radical hysterectomy does not improve pts survival
and often increases morbidity.
b) Combined radiation and surgery: external pelvic
irradiation and intracavitary radium or cesium
followed in 6 wk by TAH and BSO.
Primary surgery f/b post op irradiation is preffered
to pre op irradiation as more accurate surical
taging of the disease is possible. 37

38. Stage III and IV : treatment should be
individualised.
RT, chemotherapy, hormonal therapy or surgery
alone or combination of all these are the Rx
modalities available for the advanced tumours.
A recent GOG trial has demonstrated,
chemotherapy with doxorubicin and cisplatin is
superior to whole abdominal RT.
Combination chemotherapy
• doxorubicain and cisplatin
• Cyclophosphamide, doxorubicain and cisplatin
• Paclitaxel and cisplatin with or without doxorubicin.
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39. Hormonal therapy is also an option for advanced
stage disease. Especially if hormone receptor
positive tumours.
MPA 400mg IM weekly or oral 150 mg/ day
or megestrol acetate 160 mg/ day.
If there is an objective response the progestin
therapy can be continued indefinitely.
Complete remission of lung metastasis has also
been seen with progestin alone.
Tamoxifen and progesterone – no added benefit.
39

40. • Surgery should be performed to determine
the extent of disease and to remove the bulk
of disease if possible.
• Goal of surgery is eradication of macroscopic
disease.
• Postoperative therapy can be tailored
according to the extent of disease.
• Positive impact of cytoreductive surgery on
survival. ( 3 times greater)
40

41. 55--yyrr ssuurrvviivvaall rraattee
STAGE Survival
I 87%
II 76%
III 59%
IV 18%
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42. FFOOLLLLOOWW UUPP
• Education of pts regarding symptoms of recurrence.
• Every 3-4 mths during the first 2 yrs and every 6 mths
thereafter.
• History.
• Physical examination.
• Routine surveillance with pap testing and CXR can not
currently be recommended.
• Serial CA 125 in patients with papillary serous
carcinoma.
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