ENDOMETRIAL HYPERPLASIA
ENDOMETRIAL HYPERPLASIA
ENDOMETRIAL HYPERPLASIA• Endometrial hyperplasia is
defined as an increased proliferation of endometrial glands, relative to stroma resulting in increased gland to stromal ratio than normal endometrium.• The proliferative glands vary in size & shape and may shows cytological atypia, which may progress or co-exist with endometrial carcinoma.
ENDOMETRIAL HYPERPLASIA
Age : Peri-menopausal women, if
estrogen level more than progesterone.
ENDOMETRIAL HYPERPLASIACauses of endometrial hyperplasia :
Endometrial hyperplasia associated with prolonged estrogen stimulation of the endometrium, which may be due to-
1. Anovulation 2. Increased estrogen production
from endogenous source or exogenous estrogen.
3. Obesity 4. Polycystic ovarian disease 5. Functional granulosa cell tumors
of ovary 6. Estrogen replacement therapy 7. Cortical stromal hyperplasia 8. Idiopathic.
ENDOMETRIAL HYPERPLASIA
Molecular genetics :
Mutation in PTEN genes ( 20% of hyperplasia )
ENDOMETRIAL HYPERPLASIA
Classification : According to architectural
& cytological factors endometrial hyperplasia divided into four groups-
1. Simple hyperplasia2. Complex hyperplasia3. Atypical hyperplasia ( has
more change to developed malignancy )
ENDOMETRIAL HYPERPLASIASimple hyperplasia :
Glands are various size and irregular shapes with cystic dilatation with mild hyperplasia. Epithelial growth pattern and cytology are similar to those of proliferative endometrium.Mitosis are not prominent.1% chance of develop carcinoma.
ENDOMETRIAL HYPERPLASIA
Complex hyperplasia :Increase in the number and size of the glands, marked gland crowding and branching occurs. Gland form finger like projection but not invasion towards stroma, epithelial cell remains cytologically normal.3% chance to develop carcinoma .
ENDOMETRIAL HYPERPLASIAAtypical hyperplasia :
In simple atypical hyperplasia, there is cytological atypia within the glandular cells- such as loss of polarity, vesicular nuclei, prominent nucleoli, cells become rounded and loss the normal perpendicular orientation to the basement membrane.8% may progress to carcinoma.
ENDOMETRIAL HYPERPLASIA
In complex atypical hyperplasia consists of back-to-back crowding of glands lined by atypical cells. Lipid laden “ foam” cells may be noted in the intervening stroma.
23% to 48% women have the chances to develop carcinoma.
ENDOMETRIAL CARCINOMA
ENDOMETRIAL CARCINOMA
Endometrial carcinoma is the most common invasive cancer of the female genital tract.
It is about 7% of all invasive cancer in women.
ENDOMETRIAL CARCINOMA
Age :• Common in women >40
years of age ( peri & post menopausal women )• Relatively unknown in
young age.• Peak incidence 55 to 65
years of age.
ENDOMETRIAL CARCINOMARisk factor of endometrial carcinoma :
1. Obesity2. Diabetes3. Hypertension4. Infertility5. Unopposed estrogen
stimulation6. Family history7. Endometrial atrophy
ENDOMETRIAL CARCINOMA
Classification :A. According to the clinico-pathological & molecular studies :
1. Type - I2. Type - II
ENDOMETRIAL CARCINOMAB. According to the histopathology----
1. Endometroid adenocarcinoma2. Adenocarcinoma with squamous differentiation
3. Adenosquamous carcinoma 4. Serous carcinoma 5. Clear cell carcinoma 6. Malignant mixed mullarian tumor
ENDOMETRIAL CARCINOMAType - I endometrial carcinoma :
It is the most commonest type, about 80% of all cases. Usually occurs in 55-65 years. The majority are well differentiated and estrogen related, present histologically as a endometroid tumor associated with atypical endometrial hyperplasia.
Prognosis is better and have superficial myometrial invasion.
ENDOMETRIAL CARCINOMAMolecular genetics of Type-I :
1. Mutation in PTEN tumor suppressor gene – 80%
2. PIK3CA mutation – 39%3. Mutation in KRAS & beta
catenin oncogen4. Mutation in KRAS gene5. Mutation in p53 gene ( upto
50% in poorly differentiated endometroid carcinoma )
ENDOMETRIAL CARCINOMAType – II tumor :
About 15% of endometrial carcinoma. It is arise in the sitting of endometrial
atrophy. Not related to estrogen stimulation or endometrial hyperplasia. They are poorly differentiated, high grade tumor with poor prognostic cell type like - serous endometrial carcinoma, clear cell tumor.
ENDOMETRIAL CARCINOMA
Usually occurs in older or post menopausal women and not related to obesity, HTN, DM.
Develop finger like papillary projection.
Aggressive in behavior.
ENDOMETRIAL CARCINOMA
Molecular genetics of Type-II : 1. Mutation in p53 gene 2. Aneuploidy 3. PIK3CA
ENDOMETRIAL CARCINOMAEndometroid carcinoma : 85% of endometrial carcinoma.
Endometrial carcinoma either localized polypoid tumor or diffuse tumor involving the endometrial surface.
ENDOMETRIAL CARCINOMA Endometrial adenocarcinoma formed
well differentiated to poorly differentiated glandular structure mixed with solid sheet of malignant cells. Poorly differentiated type have barely recognizable glands and greater degree of nuclear atypia and mitotic activity.
Upto 20% of endometroid carcinoma contain foci of squamous differentiation.
ENDOMETRIAL CARCINOMASerous carcinoma:
Generally arise in the sitting of small atrophic uterus, often form large bulky tumor or deep invasion in to the myometrium.
The precursor of serous carcinoma is endometrial intraepithelial carcinoma.
ENDOMETRIAL CARCINOMA• Lesion may have papillary growth
pattern composed of cells with marked cytological atypia, including high nuclear to cytoplasmic ratio, atypical mitotic figure,heterocromastia and prominent nucleoli.
• They can also have predominantly glandular pattern, different from adenocarcinoma by marked cytological atypia.
ENDOMETRIAL CARCINOMA
Malignant mixed mullarian tumor :MMTs consist of endometrial adenocarcinomas with malignant changes in the stroma.The stroma tends to differentiate into a verity of malignant mesodermal components, including muscle, cartilage and even osteoid.
MMTs occur in the post-menopausal women and present with post menopausal bleeding. This is a highly malignant tumor.
ENDOMETRIAL CARCINOMAIn gross appearance: MMTs are fleshier than adenocarcinomas, may be bulky and polypoid and sometimes protrude through the cervical os.On histology: the tumor consist of adenocarcinoma mixed with malignant mesenchymal elements(striated musce,adipose tissue, bone)
ENDOMETRIAL CARCINOMAGrading :
The step-grading system applied to endometroid tumor –G1 : Well differentiated adenocarcinoma, less than 5% solid growth.( with easily recognizable glandular pattern )G2 : Moderately differentiated adenocarcinoma with partly solid growth <50% ( showing well formed
glands mixed with solids sheets of malignant cells .
ENDOMETRIAL CARCINOMA
G3 : Poorly differentiated adenocarcinoma with predominantly solid growth >50% ( solid sheets of cell with barely recognizable gland with greater degree of nuclear atypia and mitotic activity ) All non-endometroid carcinoma classified as grade-3 irrespective of histological pattern.
ENDOMETRIAL CARCINOMAStaging :Stage I :Carcinoma is confined to
the corpus uteri itself.Stage II :Carcinoma involves the
corpus and the cervix.Stage III :Carcinoma extends outside
the true but not outside the true pelvis.
Stage IV :Carcinoma extends outside the true pelvis or involves the mucosa of the bladder or rectum.
ENDOMETRIAL CARCINOMA
Route of spread :1. Direct spread 2. Lymphatic spread and
Transtubal spread
3. Heamatogenous spread
ENDOMETRIAL CARCINOMA
Clinical presentation :1. Asymptomatic2. Abnormal uterine bleeding3. Abnormal menstrual cycle
& Menorrhagia4. Lower abdominal pain &
pelvic pain5. Vaginal discharge in post menopausal
women.
ENDOMETRIAL CARCINOMA
How to diagnosed :1. Pelvic examination2. TVS3. Pap’s smear4. Endometrial
sampling5. D & C
ENDOMETRIAL CARCINOMA
Complications :1. Anemia may result, caused by
chronic loss of blood.( This may occur if the women has ignored symptoms of prolonged or frequent abnormal menstrual bleeding.)
2. Perforation of the uterus may occur during D & C or an endometrial biopsy.
ENDOMETRIAL CARCINOMA
Management :Surgery and Radiation therapy are the only methods of successful treatment.
ENDOMETRIAL CARCINOMA
Women with the early stage-I disease treatment with surgical hysterectomy either abdominal or vaginal.
Women with late stage-I disease and stage-II disease are often offered surgery in combination with Radiation therapy.
ENDOMETRIAL CARCINOMA
Prognosis :Stage-I & well differentiated
endometrial carcinoma – 75% to 80% prognosis
Stage-II & III : < 50% prognosis
ENDOMETRIAL CARCINOMA
Prevention :1. All women should have regular pelvic examination and pap’s smear ( beginning at the onset of sexual activity or at the age of 20 if not sexually active ) to help detect signs of any abnormal development.
ENDOMETRIAL CARCINOMA
2. Women with estrogen replacement therapy should report immediately to the doctor if any of the following symptoms arise
I. Bleeding or spotting after intercourse or douching
II. Bleeding that lasts longer than 7 days
III. Reappearance of blood or staining after 6 months or more of no bleeding at all.
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