Novak 2002

 Introduction  Epidemiology and risk factors  Endometrial hyperplasia  Screening for endometrial Ca

= Most common malignancy in the ♀ genital tract = ½ ♀ genital tract malignancy in USA = 4 th most common cause of malignancy after breast, lung, and bowel = 7 th 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 of EC 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

EC is 2 types: (1) (2) Young Old Hormone-dependent Hormone-independent Due to hyperplasia Due to atrophy Well differentiated Undifferentiated Good prognosis Poor prognosis The 2 nd 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  DM X 1.3 – 2.8 times  HTN and hypothyroidism

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 stroma Atypia: Nucleus = large, variable in size & shape Cytoplasm = ↑ nuclear/cytoplasmic R = loss of polarity Nucleolus = 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 cases Prognosis 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 EH Treatment in nonatypic EH:  Ovulation induction  Cyclic progestines: MPA 10 – 20 mg/day for 14 days/month Treatment 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

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 expensive Screening discover only 50% of EC Screening of high risk women:  HRT without progesterone  Familial nonpolypoid colon cancer Pap smear is +ve only in 30 – 50% of EC

 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 vagina Causes 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

General examination: Obesity – HTN Breast - Peripheral LN Abdominal 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

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

 Symptoms  Signs  Diagnosis  Pathology  Preoperative evaluation  Staging  Prognostic variables

 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 reason Any perimenopausal bleeding should be evaluated even if minimal or nonpersistant Causes 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 vagina Uterine cause should be excluded

Causes of uterine bleeding:  Atrophy 60 – 80%  HRT 15 – 25%  Polyp %  Hyperplasia %  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&C Hystroscopy/sonohystrography  better If not diagnosed  unnecessary hystrectomy HRT: ↑ 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

General examination: Obesity – HTN Breasts – peripheral LN Abdominal 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

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