ENDOMETRIAL CANCER

Novak 2002

Introduction Epidemiology and risk

factors Endometrial hyperplasia Screening for endometrial Ca

INTRODUCTION

=Most common malignancy in the ♀ genital tract

½ =♀genital tract malignancy in USA =4th most common cause of

malignancy after breast, lung, and bowel

=7th leading cause of death from M =2 – 3 % in the female

Recently ↑ awareness of EC due to: ↓ Ca cervix ↑ life expectancy HRT Earlier diagnosis due to:

- Easier diagnostic tools - Understanding of premalignant

lesions

EC occur primary in postmenopausal

women and virulence ↑ by age Although EC is usually presented in an earlier stage, deaths from EC > that from cervical cancer Unopposed estrogen ↑ risk of EC

In the past decades management ofEC evolved from:

Preoperative intrauterine radium packs External pelvic irradiation followed 6 months later by hysterectomy Single brachytherapy session followed by hysterectomy Hysterectomy and PO ttt depending on

surgical or pathological findings

EPIDEMIOLOGY AND RISK FACTORS

EC is 2 types:(1( )2)

Young OldHormone-dependent Hormone-independentDue to hyperplasia Due to atrophyWell differentiated UndifferentiatedGood prognosis Poor prognosisThe 2nd type ↑ in:

Elderly – thin – obese – postmenopausal

Risk factors: Unopposed estrogen as in: - Nullipara X 2 – 3

times - Infertile - Anovular - Irregular bleeding Overweight 21 – 50 pounds X 3 “ > 50 pounds X 10 “

Menopause > 52 years X 2.4 times PCO Functioning ovarian tumors HRT X 4 – 8 times ↑ risk by ↑ dose and duration Tamoxifen X 2 - 3 DM X 1.3 – 2.8 times HTN and hypothyroidism

ENDOMETRIAL HYPERPLASIA

A spectrum of: biological/ morphological alteration

in endometrial gland/stroma Ranging from:

exaggerated physiological changes to cancer insitu

Due to: estrogen over stimulation of the

endometrium without progesterone

EH may be associated with: Bleeding Functioning ovarian tumors HRT EC

Recent classification depends on: Architectural features Cytological features

Architectural depends on : Crowdening of the glands Complexty of the glands

Non atypic EH: Simple:

Cystic dilatation of the glands Slightly irregular glands

No atypia

Complex: Crowedening, budding, infulding of

the glands with less stromaAtypia:Nucleus = large, variable in size & shapeCytoplasm = ↑ nuclear/cytoplasmic R

= loss of polarityNucleolus = prominent

Chromatin = irregular, clumping = parachromatin clearance

Transformation to malignancy:Nonatypic: Simple 1%

Complex 3%Atypic :

Simple 8% Complex 29%

ER is stable in 18% regress in 74%If D&C show atypia Hystrectomy show EC in 25% of casesPrognosis depends on:

Age Ovarian disease Exogenous hormones Obesity Endocrine function

MPA 10 – 20 mg/day treatment results: Nonatypic Atypic

Regression 84% 50% Recurrence 6% 25% Malignancy 25%

Megestrol acetate treatment in atypia: Regression = 93% Recurrence = 20%

Progestines treatment of EH is less effective in atypic EH than nonatypic EHTreatment in nonatypic EH:

Ovulation induction Cyclic progestines:

MPA 10 – 20 mg/day for 14 days/monthTreatment in atypic EH:

Continues progestines

Megestrol acetate : 20 – 40 mg/day X 2 – 3 months

followed 3 – 4 weeks by EB Follow up by U/S or EB is important due to:

25% undiagnosed malignancy 29% malignancy transformation ↑ recurrence rate

SCREENING OF ENDOMETRIAL CANCER

No screening test is: appropriate

acceptable cost effective

↓mortality Pap smear = inadequate Cytology = ↓ sensitivity &

specificity Progesterone challenge test = only

for estrogen primed endometrium

TVS & EB = too expensiveScreening discover only 50% of ECScreening of high risk women:

HRT without progesterone Familial nonpolypoid colon cancer

Pap smear is +ve only in 30 – 50% of EC

SYMPTOMS

90% of EC represent by abnormal bleeding

Some EC complain of pelvic discomfort or heaviness = uterine enlargement or extrauterine extension

Elderly women with cervical stenosis complain of excessive offensive discharge

with no bleeding = hematometria or pyometria poor prognosis

5% of EC are asymptomatic and discovered accidently by:

- Abnormal pap smear in advanced cases

- CT/ US for other reasons - Hysterectomy for other reasons

Any perimenopausal bleeding must be evaluated even if minimal or recurrent

Causes of vaginal bleeding: Nongenital Genital extrauterine Uterine

Extrauterine causes are evaluated by: History Examination Search of blood in urine/stools

Vulval/vaginal/cervical lesions : Can be seen and biopsy is taken

Vaginal atrophy =15% of vaginal bleeding

thin and friable vaginaCauses of uterine bleeding:

Endometrial atrophy = 60 – 80% EB insufficient endometrial tissue

( blood and mucus only ) No bleeding after EB

Polyps: = 2 – 12% Difficult to diagnose by D&C or EB Diagnosed by hystroscopy, TVS or

sonohystrography If not diagnosed unnecessary

hystrectomy

HRT: = 15 – 25% X 4 – 8 ↑ risk of EC ↑ risk by ↑ duration and dose ↓ risk by progesterone and follow up by TVS and EB annually and if recurrent bleeding occur Hyperplasia = 5 – 10% Cancer = 10%

Bleeding in EC: Menometrorrhagia Oligomenorrhia Cyclic > menopausal age

Cancer is suspected if: Persistent Recurrent Obese anovular

SIGNS

General examination: Obesity – HTN

Breast - Peripheral LNAbdominal examination in advanced EC:

Ascitis Nodular liver Nodular omentum

Genital examination: -Inspection & palpation:

Vaginal introitus Vagina Suburetheral area Cervix

-Bimanual rectovaginal examination: Uterus size – mobility Adnexa masses Parametrium induration Doglas pouch nodularity

DIAGNOSIS

I – Office endometrial aspiration: Accurate in 90 – 98%

Inexpensive No tenaculum No cramps Well tolerated Adequate tissue sample

2 – Pap smear: unreliable +ve in 30 – 50% of EC

3 - Hystroscopy/D&C for: cervical stenosis patient intolerance inadequate tissue sample recurrent bleeding with –ve EB

4 – TVS/EB: To select patients for hystroscopy or

sonohystrography Patents with endometrial thickness

≥5 mm or with polypoidal mass or fluid require further evaluation

ENDOMETRIAL CANCER

Symptoms Signs Diagnosis Pathology Preoperative evaluation Staging Prognostic variables

SYMPTOMS

90% 0f the patients represent by abnormal bleeding

Some women complain of heaviness and pelvic discomfort = uterine enlargement or extrauterine extension

Some elderly women may have cervical stenosis hematometria – pyometria – offensive discharge = poor prognosis

5% of patients are asymptomatic and discovered accidently at:

- Pap smear advantage stage - Hystrectomy for other reason

- CT/ US for other reasonAny perimenopausal bleeding should be evaluated even if minimal or nonpersistantCauses of bleeding may be:

Nongenital Genital but extrauterine Uterine

Nongenital causes are diagnosed by: C/P + C/E + blood in urine/stool

Vaginal atrophy = 15% of vaginal bleeding Thin and friable vaginaUterine cause should be excluded

Causes of uterine bleeding: Atrophy 60 – 80% HRT 15 – 25% Polyp 2 - 12% Hyperplasia 5 - 10% Cancer 10%

Atrophy: usually occur in women >10 years postmenopausal

EB insufficient tissue ( blood + mucus) no bleeding after EB

Polyp: difficult to diagnose by EB/D&CHystroscopy/sonohystrography betterIf not diagnosed unnecessary hystrectomyHRT: ↑ risk X 4 – 8 times if no progesterone

↓risk by progesterone and follow up by annual TVS/ EB

Cancer :Present by abnormal bleeding:

Menometrorrhgia Oligomenorrhia Cyclic bleeding beyond menopause

Consider malignancy if: Persistent /recurrent bleeding Obese/anovular patient

SIGNS

General examination: Obesity – HTN

Breasts – peripheral LNAbdominal examination:

Ascetis Nodular liver/omentum

Genital examination: -Inspection & palpation:

Vaginal introitus Vagina Suburethral area Cervix

-Bimanual rectovaginal examination: Uterine size/mobility Adenexal masses Parametrial induration Doglas pouch nodularity

DIAGNOSIS

I – Office endometrial aspiration: Accurate in 90 – 98%

Inexpensive No tenaculum Minimal uterine cramps Well tolerated Adequate tissue sample in 90%

-If cervical stenosis paracervical block

cervical dilatation -If cervical pathology suspected

endocervical sample -Premedication by antiprostaglandins

II – Pap smear: Unreliable +ve in 30 – 50% of EC

III – Hystroscopy/ D&C: Indicated in:

Cervical stenosis Patient intolerance Inadequate sample Recurrent bleeding with –ve EB

IV – TVS / sonohystrography:

Helps to select patients with minimal or adequate endometrial thickness

Evaluated any patient with : Endometrial thickness > 4 mm Polypoidal mass Fluid