Type II endometrial cancer is a more lethal and aggressive form that occurs in 10% of cases, predominantly in older postmenopausal women. It is characterized by poorly differentiated or serous/papillary, clear cell histology without a precursor lesion. Type II cancers have a poor prognosis and are estrogen-independent, with deep myometrial invasion and poor differentiation. Surgical staging includes total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraortic lymphadenectomy, and peritoneal sampling. Adjuvant treatment such as radiation and chemotherapy may be recommended depending on surgical stage, grade, and histology.

1. Clinical Forms
TYPE II
–More lethal variety, 10% of all cases
– In older post menopausal women
– Aggressive high grade nuclei (less/poorly
differentiated) or serous/papillary, clear cell
Histology
– no precursor lesion
– P53 tumor supressor mutation
– Underlying (back ground) endometrium is
Atrophic/ associated with polyps
– No clear epidimologic profile
SAMUEL BEZABIH(MD)- MMeskrem 2005 27

2. TYPE I Vs Type II( Germ. PPT)
•
FEATURES TYPE I TYPE II
ESTROGEN DEPENDENCE E-Dependent E-independent
ASSOCIATION WITH
MENOPAUSE
Pre/Postmenopausal Post Menopausal
DIFFRENTIATION Grade I/II Grade III
MYOMETRIAL INVASION Minimal Deep
HYPERPLASIA Yes No
Sub types Endometroid
adenocarcinoma,
secretory
Adenosquamous,
clear cell, serous
prognosis good Poor
SAMUEL BEZABIH(MD)- MMeskrem 2005 28

3. pathology
SAMUEL BEZABIH(MD)- MMeskrem 2005
WHO Histologic Classification of Endometrial Carcinoma 29

4. Endometrial Ca Diagnosis
Symptoms
• Prolonged, heavy, irregular menstruation
• Postmenopausal V bleeding ( 5-10% likelihood)
• Abnormal vaginal discharge may be another
symptom in older women.
• In more advanced disease, pelvic pressure and
pain may reflect uterine enlargement or extra-
uterine tumor spread.
• Patients with serous or clear cell tumors often
present with signs and symptoms suggestive of
advanced epithelial ovarian cancer
SAMUEL BEZABIH(MD)- MMeskrem 2005 30

5. Endometrial Ca Diagnosis
Endometrial Biopsy
• Office pipelle biopsy,
– if inadequate D and C
• Outpatient hysteroscopy is more sensitive for
focal endometrial lesions and thus has proved
less helpful in diagnosing hyperplasia (Ben Yehuda,
1998).
• Hysteroscopy is shown to have a risk of
Intraperitoneal contamination with malignant
cells.
SAMUEL BEZABIH(MD)- MMeskrem 2005 31

6. Endometrial Ca Diagnosis
Pap smear
• Not sensitive, ~ 50% False Negative
• LBC- better detection of abnormal cells
• inadequate for shift of practice
.
SAMUEL BEZABIH(MD)- MMeskrem 2005 32

7. Lab and Imaging
 Ca 125
 CXR
 CT
SAMUEL BEZABIH(MD)- MMeskrem 2005 33

8. Histologic Grade
• Grading is determined microscopically by the
architectural growth pattern
– Arch is judged by the percentage of differentiated
(glandular) versus nondifferentiated (solid) elements
within the tumor specimen.
• If nuclear atypia is advanced (NG 3) relative to the
architectural grade, then grades 1 or 2 will be
raised by one level
this modification was shown to have prognostic value
in the GOG study(protocol #33) (Zaino, 1995).
– The nuclear grade depends on the appearance of the
nucleus, e.g., size of nucleus, chromatin pattern, and is
more subjective
• Acc. to FIGO Nuclear Grading is used for all serous
and clear cell adeno cas
SAMUEL BEZABIH(MD)- MMeskrem 2005 34

9. Histologic Grading
• The most widely used grading system for Em
Ca is the three-tiered FIGO system.
• Grade 1:
– lesions typically are indolent with little
propensity to spread outside the uterus or
recur.
• Grade 2:
– tumors have an intermediate prognosis.
• Grade 3:
– cancers are associated with an increased potential
for myometrial invasion and nodal metastasis.
SAMUEL BEZABIH(MD)- MMeskrem 2005 35

10. Histopathologic Criteria for Assessing Grade
GRADE DEFFINITIONS(growth pattern)
1 < 5% of a non-squamous or non-morular
solid growth pattern
2 6–50% of a non-squamous or nonmorular
solid growth pattern
3 > 50% of a non-squamous or nonmorular
solid growth
SAMUEL BEZABIH(MD)- MMeskrem 2005
 Areas of squamous differentiation are not considered to be
solid tumor growth.
36

11. Patterns of Spread
• Endometrial cancers have several different potential
ways to spread beyond the uterus (Morrow, 1991).
• Type I endometrioid tumors and their variants most
commonly spread, in order of frequency, by:
1. Direct extension,
2. Lymphatic metastasis,
3. Hematogenous dissemination, and
4. Intraperitoneal exfoliation.
• Type II serous and clear cell carcinomas have a
particular propensity for extra-uterine disease, in a
pattern that closely resembles epithelial ovarian
cancer.
• In general, the various patterns of spread are
interrelated and often develop simultaneously.
SAMUEL BEZABIH(MD)- MMeskrem 2005 37

12. Spread Pattern
• Lymphatic channel invasion and metastasis to
the pelvic and paraaortic nodal chains can
follow tumor penetration of the myometrium.
– The lymphatic network draining the uterus is
complex, and patients can have metastases to any
single nodal group as well as combinations of
groups (Burke, 1996).
– This haphazard pattern is in contrast to cervical
cancer, in which lymphatic spread usually follows
a stepwise progression from pelvic to paraaortic
to scalene nodal groups.
SAMUEL BEZABIH(MD)- MMeskrem 2005 38

13. Spread Pattern
• Hematogenesis dissemination
– most commonly results in metastases to the
lung and less commonly, to the liver, brain,
bone, and other sites.
– Deep myometrial invasion is the strongest
predictor of this pattern of spread (Mariani,
2001a).
• Retrograde transtubal transport of exfoliated
endometrial cancer cells is one mechanism
by which malignant cells reach the peritoneal
cavity.
SAMUEL BEZABIH(MD)- MMeskrem 2005 39

14. Spread Pattern
• Serosal perforation of the tumor is another possible
pathway.
• Most types of endometrial cancer cells found in the
peritoneal cavity disappear within a short time and
have low malignant potential (Hirai, 2001).
• Alternatively, in the presence of other high-risk
features, such as adnexal metastases or serous
histology, widespread intraabdominal disease may
result.
• Port-site metastasis is a rare but potential method of
cancer spread.
– Martínez and coworkers (2010)evaluated nearly 300
laparoscopic staging procedures for endometrial cancer.
Port-site metastases complicated 0.33 percent of cases.
SAMUEL BEZABIH(MD)- MMeskrem 2005 40

15. Surgical Staging
• Peritoneal washing/asciteis sampling
• Pelvic and abdominal exploration and resection
of visible lesion
• TAH + BSO
• Pelvic and paraaortic lymphadenectomy
• Patients with low grade T seem at low risk for LN
met ( G1 and 2 Endometroid T, <50%MM, < 2cm T Diam-
Preop biopsy + intraop FS) may not need LN
dissection (ACOG 2015)
• UPSC (uterine papillary serous ca) histology
should have extended surgical staging with an
infracolic omentectomy and bilateral peritoneal
biopsies of the pelvis, percolic gutter, and
diaphragm and resection of any met as in Ov Ca.
SAMUEL BEZABIH(MD)- MMeskrem 2005 41

16. I. Tumor confined to corpus uteri
Ia:-No or < ½ MM invasion
Ib:-> ½ Myometrial (MM)
II.Cx stromal invasion, but no
extension beyond UX (Ecx
glandular involvement alone- S1)
III.Local regional spread of T
IIIa.Serosa of corpus and/or
adnexa.
IIIb.Vagina and /or parametrium
IIIc. Met to pelvic or Paortic LN
IIIc1- Positive Pelvic LN
IIIc2-Paortic LN + Pelvic LN
IV.T invades bladder/bowel
mucosa (distant
metastasis)
– Iva.Bladder and /or bowel
mucosa invasion
– Ivb.Distant Metastasis
•Any stage can be Grade 1, 2 or 3
•Endocervical G involvement alone- no
more S2
•Positve cytology doesn’t change stage,
reported separately
FIGO Staging of Endometrial Ca- ACOG 2015
SAMUEL BEZABIH(MD)- MMeskrem 2005 42

17. SAMUEL BEZABIH(MD)- MMeskrem 2005 43

18. Poor Prognostic Variables in Endometrial Cancer
• Advanced surgical stage
• Older age
• Histologic type:
– UPSC or clear cell adenocarcinoma
• Advanced tumor grade
• Presence of myometrial invasion
• Presence of lymphovascular space invasion
• Peritoneal cytology positive for cancer cells
• Increased tumor size
• High tumor expression levels of ER and PR
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19. Treatment
• Primary RX
– Primary Surgical rx (staging)
• Hysterectomy + Bilateral Salpingoophorectomy
– Primary radiation therapy
– Primary hormonal therapy
• Adjuvant
– Chemotherapy
– Radiation
– Hormonal
SAMUEL BEZABIH(MD)- MMeskrem 2005 45

20. Surgical Rx
• Hysterectomy, BSO with surgical staging
• Few CIs to surgery:
• Fertility desire,
• Massive obesity,
• High operative risk,
• unresectable tumor
– Often Extrafacial (simple) Hysterectomy is
sufficient
– Class III Hysterectomy may be preferable if there
is clinically obvious extension of Em Ca to Cx.
– VH + BSO- an option for those who can’t tolerate
systematic S staging due to comorbidities
SAMUEL BEZABIH(MD)- MMeskrem 2005 46

21. SAMUEL BEZABIH(MD)- MMeskrem 2005
Distribution of Endometrial Cancer by FIGO Stage
(n =5281 patients)
47

22. Endometrial Cancer 5-Year Survival Rates for Each Surgical
Stage (n = 5562 Patients)
SAMUEL BEZABIH(MD)- MMeskrem 2005 48

23. Post Op Surveillance
• Follow up visit Q 3-6 mths for 2yrs, then Q6mths for 01
year , annually there after.
• At each visit;
– Hx on symptoms of recurrence V bleeding, pelvic pain,
wt loss, lethargy
– Thorough speculum, pelvic and RV exam
• Not recommended are:-
– Vaginal cytology and annual CXr -recurrences are detected
by clinical exam, Cxr low utility in detecting recurrence.
– Routine radiologic exm (CT,PET) unless in suspicion of
recurrence (ACOG 2015)
• Advanced disease that requires chemo/Radiorx warrant
more aggressive monitoring.
– Ca125 for UPSC
– Intermittent CT? MRI
SAMUEL BEZABIH(MD)- MMeskrem 2005 49

24. Adjuvant Chemorx
• For advanced or recurrent disease
• Only three cytotoxic drugs with definite
activity have been identified to date:
– doxorubicin, cisplatin, and paclitaxel (Barrena Medel, 2009).
• Other agents, 5-fluorouracil, vincristine,
ifosfamide, and ixabepilone, have possible
activity based on collected data (Miller, 2009a).
• TAP Paclitaxel (Taxol),doxorubicin
(Adriamycin), and cisplatin chemotherapy is
the adjuvant treatment of choice for
advanced endometrial cancer following
surgery. SAMUEL BEZABIH(MD)- MMeskrem 2005 50

25. Treatment of UPSC
• Comprehensive surgical staging
–Peritoneal washing
–TAH + BSO
–Infracolic omentectomy
–pelvic/and Para aortic LN dissection
–Peritoneal biopsy
–Aggressive debulking
SAMUEL BEZABIH(MD)- MMeskrem 2005 51

26. Treatment of UPSC ……
Postop. Follow up
• Stage IA
– simple observation
• Stages Ib and Ic
– chemoradio ( taxol + Carboplatin 3-6 cycles and
vaginal brachytherapy)
• stageII
– benefit from chemo +/- radio
• Stage III
– prone to have recurrence ,Chemoradiatio Taxol
cisplatin+ tumor directed radio
• Stage IV
– debulking- prognostic, atleast 6cycles of Taxol and
Cplatin SAMUEL BEZABIH(MD)- MMeskrem 2005 52

27. Prevention of Endometrial Ca
Screening
• No role for those with average or increased
risk
• Only for high risk group>35, potential
HNPCC mutation carriers ( family Hx---)
• Genetic counselling to identify those who may
benefit from specific germ line testing
• EmCa- common ‘sentinel Ca’ for Lynch S (Em,
Colonic,Small B, ureter, Renal Pelvis, Ovarian Ca) Gynecologists
play a pivotal role in identification of those
with the syndrome
SAMUEL BEZABIH(MD)- MMeskrem 2005 53

28. Prevention of Endometrial Ca
Prophylactic Surgery
• Since women with HNPCC have such a high
lifetime risk of developing endometrial cancer
(40 to 60 %) prophylactic hysterectomy is
another option.
• In a cohort of 315 HNPCC-mutation carriers,
Schmeler (2006) confirmed the benefit of this
approach by reporting a 100-percent risk
reduction.
• In general, BSO should also be performed due
to the 10--12% lifetime risk of ovarian cancer.
SAMUEL BEZABIH(MD)- MMeskrem 2005 54

29. Prevention of Endometrial Cancer
Can phyto-estrogens prevent EC ?
(Xu WH et al. BMJ 328, 2004:1285-1288)
• Case control study 832 patients
• RR for EC 0.67 in group with highest soya intake
Explanation:
• Soya contains “isoflavones“ (Genistein, Daidzein)
• Isoflavones block the estrogen receptor and are
• therefore not phytoestrogens, but phyto-SERM‘s
(selective estrogen receptor blockers)
• Therefore women with high BMI profit the most in
the study!
SAMUEL BEZABIH(MD)- MMeskrem 2005 55