ENDOMETRIAL HYPERPLASIA AND

MALIGNANT DS OF THE CORPUS

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DR. SWATI SINGH CONSULTANT

DEPARTMENT OF OBS. AND GYN

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.

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

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PROTECTIVE FACTOR

• Multiparity• Normal weight• Combined oral contraceptives• Progesterone therapy• Menopause <49 years of age

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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

TYPE OF HYPERPLASIATYPE OF HYPERPLASIA PROGRESSION TO CaPROGRESSION TO Ca

SIMPLE (cystic without SIMPLE (cystic without atypia)atypia)

1%1%

COMPLEX (adenomatous COMPLEX (adenomatous without atypia)without atypia)

3%3%

ATYPICAL:ATYPICAL:

SIMPLE (cystic with SIMPLE (cystic with atypia) atypia)

8%8%

COMPLEX COMPLEX (adenomatous with (adenomatous with atypia)atypia)

29%29%

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Management:Management: • Progestin therapy effective in -- endometrial hyperplasia without atypia less

effective -- endometrial hyperplasia with atypia. Endometrial hyperplasia without atypiaEndometrial hyperplasia without atypia: 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.

Complex or atypical hyperplasia : Complex or atypical hyperplasia : 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.

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• 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.

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ENDOMETRIAL CANCER

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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.

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RISK FACTORS Increased risk:Increased risk: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.

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6) Early menarche.7) Late menopause8) 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

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.

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DECREASED RISKDECREASED RISK1) 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.14

HISTOLOGIC CLASSIFICATION

1. Endometrioid adenocarcinoma (80%)(80%) Variants Villoglandular or papillary (2%) Secretory (1%) With squamous differentiation (15—25 %)2. Mucinous carcinoma. (5%)(5%)3. Papillary serous carcinoma. (3—4 %)(3—4 %)4. Clear cell carcinoma. (<5%)(<5%)5.5. Squamous carcinoma.6. Undifferentiated carcinoma.7. Mixed carcinoma.

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PATHOLOGY

• GROSSGROSS: uterus small, normal or large in size due to myohyperplasia, myometrial involvement, pyometra or associated fibroids

• GROWTHGROWTH: 1) Localised polyp (friable) with ulceration

and necrosis usually at the fundus 2) Diffuse: spread to myometrium &

serosa, also to the cervix16

CLINICAL FEATURES

PATIENT PROFILE:PATIENT PROFILE: usually nulliparous, postmenopausal or h/o delayed menopause; Younger women with PCOD, infertility, obese, hypertensive & diabetic.

SYMPTOMS: SYMPTOMS: • 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

SIGNS:SIGNS:• 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.

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Bimanual examinationBimanual examination::

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.

Rectal examinationRectal examination19

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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Transvaginal pelvic UltrasoundTransvaginal pelvic Ultrasound:

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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• Office Endometrial aspiration biopsyOffice Endometrial aspiration biopsy : 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.

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Dilatation and curettageDilatation and curettage : 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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Hysteroscopy with curettage: Hysteroscopy with curettage: • 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. 25

Normal Endometrium Endometrial Polyp

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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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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 28

STAGING

• CLINICAL STAGINGCLINICAL STAGING• SURGICAL STAGINGSURGICAL STAGING

Endometrial cancer is surgically Endometrial cancer is surgically staged and treatedstaged and treated..

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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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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 myometriumStage 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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MANAGEMENTMANAGEMENT

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TREATMENT

• SURGERYSURGERY• RADIATION THERAPYRADIATION THERAPY• SYSTEMIC THERAPY SYSTEMIC THERAPY

Treatment is essentialy surgical with postoperative adjuvant therapy added when unfavourable prognostic features are found at surgery ．

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MODES OF MODES OF SURGERYSURGERYAbdominal Vaginal Laproscopic

Laprotomy has been the principal surgical approach to hysterectomy and surgical staging for Ca endometrium.

ABDOMINAL HYSTERECTOMY (LAPAROTOMY): a) extrafascial b) RadicalIncludes: 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 cervical extension assessed.

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POST – 0P ADJUVANT MANAGEMENT

RADIATIONSYSTEMIC THERAPY HORMONE THERAPY CHEMOTHERAPY

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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.

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Stage IITwo 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

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. 38

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.

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• 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)

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5-yr survival rate5-yr survival rate

STAGE Survival

I 87%

II 76%

III 59%

IV 18%

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FOLLOW UPFOLLOW UP• 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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