Download - Endometrium carcinoma tantermi előadás
Endometrial cancer
Szabolcs Máté MD.
I. St. Department of Obstetrics and Gyneacology
Epidemiology
Developing countries
Cervical cancer is the most common gyn. malignant tumor
Developed countries
Cervical cancer screening
Incidence is of cervical cancer is declining
Life style risks for endometrial cancer
Incidence is increasing of ENDOMETRIAL and OVARIAN cancer
Epidemiology
Median age at diagnosis (USA)
62 years
Epidemiology - USA
Stage distribution
Staging- FIGO 2009
Clinical signs
Abnormal vaginal bleeding, odorous discharge
Is present in 75-90%
The amount of bleeding is not in connection with the chance of malignancy
Risk of malignancy in the background of an abnormal bleeding depends on:
Age
Risk factors
Risk factors
Hyper oestrogen conditions
Chronic anovulation
Obesity
Peripheral aromatase enzyme
Androgen (suprarenal gland, ovaries)oestrone
Oestrogen producing tumor (Granulosa cell tu.)
Diabetes, hypertension
Obesity
Independent risk factors
Imbalanced hormonal therapy
Oestrogen replacement therapy gestagen opposition is compulsory in case of uterus
Null parity
Protective factors
Hormonal anti-contraceptives (OAC)
Combined OAC Reduces risk at least by 50%
Progesteron only pills (minipill, Levonorgestrel IUD, Depo products) Also effective
Age at last pregnancy
32% less risk if the last delivery is between 35-39 years versus under 25 years
Physical activity
RR ~0,75
Coffee
RR 0,87-0,64
RR 0.87 (95% CI, 0.78-0.97) heavy coffee drinkers, RR 0.64 (95% CI, 0.48-0.86)
Tea
Green tea (RR 0.8, 95% CI 0.7-0.9)
Black tea (RR 0.8, 95% CI 0.5-1.3)
Classification
• Clinical behaviour
• Microscopic features
Type I Type II
Distribution 80% 10-20%
Prognosis Good Bad
Imbalanced oestrogen effect
Yes No
Growing tendency Slow Quick
Precursor Atypical hyperplasia/
Endometrial Intraepithelial Neoplasia
Endometrial Intraepithelialcarcinoma
Grade Low High
Invasion Usually superficial Often deep
Molecular alterations PTEN, KRAS mutations Microsatellite instability
P53, other mutations
Type I endometrial carcinoma
Histological types
Endometrioid adenocarcinoma grade 1,2
Histological grading
According to the proportion of glandular structure
Normal endomertium Endometrioid adenocc grade 1 Endometrioid adenocc grade 3
Type II endometrial carcinoma
Histological types Endometrioid adenocarcinoma
Grade 3
Non-endometrioid
Serous adenocaricinoma
Clear cell adenocaricinoma
Carcinosarcoma (Malignant Mixed Müllerian Tumor)
Undifferenciated
Mucinosus, Squamous, transitional cell, mesonephric
Endometrioid adenocarcinoma
Most common type 75-80%
Majority is well differenciated (glandular structures)
Grade
Proportion of glandular structure
Nuclearis grade
Genetic profile
Microsatellite instability
PTEN, K-ras, and beta-catenin gen mutation
Typically Oestrogen and Progesteron receptor expression
Serous and clear cell adenocarcinoma
Aggressive types
Bad prognosis
High grade
Often diagnosed at advanced stage
Myometrial and vascular invasion is more common
Serous 1-5%
Clear cell 5-10%
Pathogenesis
1994 WHO classification
Hyperplasia simplex
Hyperplasia complex
Hyperplasia simplex atypica
Hyperplasia complex atypica
EIN
79% atypic hyperplasia
44% complex non-atypic hyperplasia
5% simplex hyperlpasia
Pathogenesis
Endometrial Intraepithelial Neoplasia (EIN)
Focal neoplastic lesion
Genetic modifications
PTEN mutation 44%
PAX2 nuclear transcription factor inactivation 78%
Kras mutation
B cathenin mutation
Endometrial Intapeithelial Carcinoma (EIC)
Serous adenocarcinoma - premalignant form
p53 mutation
Pathogenesis
Clear cell carcinoma
No known premalignant lesion
No known epidemiologic risk factor
Gene expression profile is unique
NO oestrogen and progesteron receptor expression
NO p53 mutation
Hepatocyte nuclear factor-1β (HNF-1β) transcription factor - up regulation
ARID1A tumor suppressor gene mutation
Genetic predisposition
BRCA1, 2 mutations does NOT increase the risk
for endometrial cancer!
Cowden syndrome
Rare
Autosomal dominant
PTEN gene mutation
Endometrial cc.- Lifetime risk: 3-28%
Lynch-syndrome
Autosomal dominant
Risk of general population 1/370 in the USA
MMR (Mismatch Repair) genes germline mutation
90% MSH2, MLH1
7-10% MSH6
5% PMS2
1% EPCAM
Recognise and repair the impair / nucleotides
Dysfunction
Microsatellite instability (MSI)
Tumor suppressor gene inactivation
Carcinogenesis
Lynch syndrome
Early onset malignancies
Different organs
Large bowel, rectum
Endometrium
Ovaries
Small bowels, stomach
Bile duct, pancreas
Ureters, pyelons
Glioblastoma
Sweat glands
Lifetime risk (%)
Mean age at diagnosis
(years)
LS / All cancers
(%)
Endometrial ca.
40-60 48–62 2,3
ColorectalCa
40-60 45 2-5%
Ovarian ca. 10-12 42.5
Lynch-syndrome prophylactic surgery
315 patients with Lynch syndrome
61 Hysterectomy
47 Hysterectomy+ salpingo-oophorectomy
Control group
Women with Lynch-syndrome
NO operation Prophylactic surgery group
Endometrium cc., ovarium cc., primer peritoneal cc.
0 (0%)
Control group
Endometrial cancer
69 (33%)
Ovarian cancer
12 (5%)
Abnormal uterine bleeding
Workup
Physical examination
Origin of bleeding
Size and mobility of uterus
Adnexal tumor(metastasis, synchronic tumor)
Surgery planning (laparoscopy, laparotomy, trans-vaginal)
Laboratory tests
Exclude pregnancy
Blood count
Coagulogram (Oral anticoagulant therapy?)
Transvaginal sonography
Size of uterus
Leiomyoma
Endometrium thickness and structure
Myometrium infiltration
Cervical stroma invasion
Ovaries (cyst, tumor?)
Ascites?
Transvaginal sonography
< 45 years
• Long lasting irregular bleedings +
• Hyper-oestrogen / imbalanced oestrogen condition
• Obesity
• Chronic anovulation (PCO syndrome)
• Failure of medical treatment
• Genetic predisposition (Lynch syndrome)
Abnormal uterine bleeding
Tissue sampling is needed
45 years - menopause
• Cycles shorter than 21 days
• Heavy bleeding
• Menstruation longer than 7 days
• (Higher risk in case of amenorrhoeal periods)
Endometrial cancer
19% 45-54 years
6% 35-44 yearsPostmenopausal
• Any type of bleeding
• Endometrial ca. in the background of bleeding 3-20%
• Endometrial hyperplasia 5-15%
Diagnosis- tissue samplingEndometrial sampling
• Endometrial biopsy
• Pipelle
• No anaesthesia
• The least invasive
(D&C) Dilatation and Curettage
• Gold standard
• Anaesthesia, One day surgery
• Indicated
• 2x negative endometrial biopsy
• Heavy bleeding (to stop bleeding)
Hysteroscopy, visual guided biopsy
Not the first choice
Gold standard
Screening
General population
Not indicated
Early signs, good prognosis
TVS not specific enough
Tamoxifen therapy
TVS
Endometrial thickness measuring <6-8mm
Genetic predisposition
Lynch syndrome
Cowden syndrome
Screening regular endometrial sampling
Prophylactic hysterectomy
Preoperative evaluation
Physical examination
Uterus size, mobility
Adnexal tumor
Vaginal vault infiltration
Staging
Digital imaging (Abdomino-pelvic CT, MRI)
CT
Lymph node metastasis
Distant / Parenchymal metastasis, Ascites
MRI
Detailed examination of small pelvis
Myometrial-, cervical infiltration
TVS
Myometrial-, cervical infiltration
Adnexal region
Ascites
Tumor marker
CA-125 elevates in case of dissemination
Peritoneal, Lymph node
General work-up
Risk assessment
anaesthesia
perioperative complications
Therapy
Irradiation
Adjuvant
Definitive
EBRT
Brachy therapy
HDR-AL
Surgery
Hysterectomy
Adnexectomy
Lymphadenectomy
Pelvic
Para-aortic Chemotherapy
Adriamycin Cisplatin
Paclitaxel Carboplatin
Adjuvant
Palliative
Hormonal therapy
Receptor positive
Gestagen
Palliative
Hysterectomy + adnexectomy
Total (cervix+corpus)
Route
Laparotomy
Laparoscopy
Vaginal
Grade 1, Stage I/a,
Descensus
Bad general condition
(Robotic)
Advantage Disadvantage
Less surgical stress Longer
Less bleeding More difficult?
Less wound healing complication Trendelenburg position
Faster recovery More expensive equipment
Hot topics in surgery- Lymphadenectomy
Small pelvic
Para-aortic
Indication
Suspicious / positive node on imaging
Intraoperative finding of enlarged node
Risk based
Grade1, St Ia 3-5%
Grade3, St Ib 20%
High risk for lymph node met.
Serous, Clear cell, High-grade
Myometrial infiltration >50%
St II (cervix stroma infiltration)
Large tumor >2cm
Questions:
Total lymphadenectomy
Selective lymphadenectomy
(Removal of enlarged nodes)
Sampling (random removal)
Para-arotic region (up to the left renal vein)
Higher operative load
Higher postop risk
Commonly - Limited surgical stress tolerability
Obesity, Age, Co-morbidity
Kismedencei lymphadenectomia
Para-aortikus lymphadenectomia
Hot topics in surgery
Cervical stromal infiltration (Stage II)
Formerly
Radical hysterectomy
Up to date
Simple hysterectomy
Assessment of myometrial infiltration – intraop.
Macroscopic
sensitivity 75%, specificity 92%
Frozen section
Indication for lymphadenectomy
Omentectomy
Serous adenocarcinoma
Peritoneal fluid
Formerly it was a part of staging
Now it isn't
Cytoreduction
In case of peritoneal dissemination operate as ovarian cancermaximal debulking
Survival benefit
Adjuvant treatment
Low risk
NO benefit of adjuvant treatment
Endometrioid
Grade 1 or 2
Stage Ia
Medium risk
Higher chance for local, but low for distant
recurrence
Can be beneficial
Adjuvant irradiation
EBRT / HDR-AL
Deep myometrial
invasion
Cervical stromal
invasion
Grade 3, LVSI +
High risk
High risk for recurrence and for cancer related death
Adjuvant chemotherapy / Chemo-radion therapy is needed
A cervical stromal
infiltration
Stage III, IV
Serous, Clear cell
histological subtype
Depends on
Residual tumor
Risk of recurrance
Risk groups
Histology
Stage
LVSI
(Lymphovascular
space invasion)
Prognosis
Stage Histological Type and grade
Thank you for your attention!