3. EPIDEMIOLOGY
Endometrial cancer is the most common pelvic genital
cancer in women (US and European databases).
In the US the life time risk of developing endometrial Ca
is 2.4% in white women & 1.3% in black, constituting
the 4th ranked cancer in USA.
In Egypt, ranked 13th female cancer and 6th worldwide.
At NCI-Cairo-Egypt, it is the 3rd most common female
cancer.
Ihab Samy 2013
4. EPIDEMIOLOGY
It is a disease of postmenopausal women with a peak
incidence in the 6th & 7th decade of life
Only 2-5% occur before 40 years
Prognosis is better than other Gynecological Cancers due
to early Diagnosis 75% Stage I
Estrogen excess (Hyperestrinism) has been implicated as
a causative factor in most of cases.
Ihab Samy 2013
5. RISK FACTORS
Age: 65-75 Y , only 2-5% < 40 Y
Excessive endogenous / exogenous estrogens:
- Early menarche < 12 Y
- Late menopause > 52 Y 2 X risk.
- Nulliparity.
- Chronic anovulation as in PCOS
- Obesity aromatization of adrenal androgens in fat
tissue.
- Granulosa-theca cell tumors of the ovary (a rare
estrogen secreting ovarian tumor) endometrial
hyperplasia & Ca in 10% of Pt.
- Cirrhosis of the liver degradation of estrogen.
- Complex atypical endometrial hyperplasia.
Ihab Samy 2013
6. RISK FACTORS
Unopposed estrogen therapy in postmenopausal women
risk 6-8 X
Tamoxifen an anti-estrogen has weak estrogenic
activity on the genital tract 2 X risk when used ≥ 5 Y
risk in women with breast, ovarian (endometrioid) &
colorectal Ca.
Diabetes 3X risk
Hypertension
Previous pelvic radiation therapy.
Family Hx of endometrial Ca.
Ihab Samy 2013
7. ENDOMETRIAL HYPERPLASIA
Excessive proliferation of the endometrial glands & to a
lesser extent endometrial stroma.
Due to excessive estrogen stimulation.
Only 25% of patients with endometrial Ca. have Hx of
hyperplasia.
Ihab Samy 2013
8. CLASSIFICATION OF HYPERPLASIA
1-Hyperplasia without atypia (not premalignant):
A-Simple
Microscopically: crowding of the glands in the stroma.
Glands are cystically dilated & give a “Swiss cheese”
appearance.
Commonly asymptomatic.
1-4% progress to Carcinoma over 15 Y .
80% regress. Ihab Samy 2013
9. B-Complex hyperplasia without atypia
A complex crowded appearance of the glands with very
little stroma
Epithelial stratification & mitotic activity.
3-16% progress to Carcinoma over 13 years.
80% regress.
85% reversal with progestin.
Ihab Samy 2013
10. 2-Hyperplasia with atypia (premalignant)
Histologically endometrial glands are lined by enlarged cells with
nuclear : cytoplasmic ratios. The nuclei are irregular with coarse
chromatin clumping & prominent nucleoli
50-94% regress with progestin therapy
A higher rate of relapse after stopping progestin compared to that
of lesions without atypia.
A-Simple
Progression to carcinoma occur in 7-8%.
B- Complex
Progression to carcinoma occur in 29-47%.
Ihab Samy 2013
11. 3-Carcinoma In Situ
Histologically differentiated from carcinoma by:
Presence of intervening stroma between abnormal
glands
There is no evidence of invasion
It is difficult to differentiate it from Carcinoma.
Ihab Samy 2013
12. PATHOGENESIS
2 different types of Endometrial Ca.:
1- Low grade endometrioid ca. (Estrogen-related)
associated with endometrial hyperplasia in young
perimenopausal women Better prognosis.
2- Idiopathic unrelated to Estrogen stimulation in
older women aggressive types with worst prognosis
(Serous, Clear and Adenosquamous types).
Ihab Samy 2013
14. Type I and II endometrial cancers: have they different risk factors?
Parity, oral contraceptive use, cigarette smoking, age at menarche, and
diabetes were associated with type I and type II tumors to similar extents.
Body mass index, however, had a greater effect on type I tumors than on
type II tumors.
Risk factor patterns for high-grade endometrioid tumors and type II tumors
were similar.
The results of this pooled analysis suggest that the two endometrial cancer
types share many common etiologic factors. The etiology of type II tumors
may, therefore, not be completely estrogen independent, as previously
believed.
J Clin Oncol. 2013 Jul 10;31(20).
Ihab Samy 2013
15. PRESENTATION
Abnormal vaginal bleeding most common 90% in
Premenopausal Patients heavy flow at the time of
menses
persistent intermenstrual bleeding
pre or post menstrual spotting
polymenorrhea that fails to respond to hormonal ttt.
Postmenopausal bleeding is the most common type of
abnormal bleeding 12-15% due to Endometrial Ca.
5-8% due to other cancers like uterine sarcoma,
ovarian Ca, Cx, tubal or vaginal Ca
Postmenopausal intermittent spotting
Postmenopausal vaginal discharge 10%
Ihab Samy 2013
16. PRESENTATION
Asymptomatic women with glandular abnormalities on
routine PAP smear/ abnormalities found in 50% of cases.
Advanced disease symptoms due to local or distant
metastases.
Severe cramps due to hematometra or pyometra
occur in postmenopausal 10%.
Ihab Samy 2013
17. HISTOPATHOLOGY
1-Adenocarcinomas 80-85%
Grade 1 well differentiated & difficult to distinguish
from atypical complex hyperplasia
Grade 2
Grade 3 anaplastic Ca (poorly differentiated)
Ihab Samy 2013
18. HISTOPATHOLOGY
2-Adenocarcinoma with squamous differentiation 5%
Malignant glands with benign squamous metaplasia.
Also subdivided into 3 grades.
3-Adenosquamous Carcinoma 10-20%
Malignant glands & malignant squamous epithelium.
Often grade 3.
Ihab Samy 2013
19. HISTOPATHOLOGY
4-Papillary Serous Carcinoma 10%
Older women.
Less likely to have hyperestrogenic state
Spread early through peritoneal surfaces of the pelvis &
abdomen
Invasion of the myometrium & lymphatic
Prognosis unfavorable
Ihab Samy 2013
20. HISTOPATHOLOGY
5-Clear cell Carcinoma 4%
Microscopic appearance clear cells / solid, papillary,
tubular, & cystic pattern are possible
Commonly high grade & aggressive
Seen in advanced stages
Older women
Not associated with hyperestrogenic states
Behaves like ovarian Carcinoma.
Ihab Samy 2013
21. HISTOPATHOLOGY
6-Mucinous Ca 9%
PAS- positive intracytoplasmic mucin.
7-Secretory Ca 1-2%
Exhibit sub-nuclear or supra-nuclear vacuoles
resembling early secretory endometrium.
Behaves like typical Endometrial Carcinoma.
8-Squamous cell Ca extremely rare , bad prognosis.
Associated with Cx stenosis, pyometra & inflammation
Ihab Samy 2013
22. SPREAD
1-Direct spread
Through the endometrial cavity to Cervix.
Through the fallopian tubes to ovaries & peritoneal
cavity.
Through invading the myometrium to serosal surface,
parametrium & pelvic wall.
Rarely direct invasion of the pubic bone.
Ihab Samy 2013
23. SPREAD
2- Lymphatic spread
Never occurs without myometrial invasion
The incidence of involvement is related to the degree of
differentiation & depth of myometrial involvement.
Pelvic lymph nodes common 35%
Para-aortic lymph nodes 10-20%
Rarely involved without pelvic nodes involvement
Inguinal lymph nodes rare.
Ihab Samy 2013
24. SPREAD
3-Hematogenous spread the lungs
Uncommon with the 1ry tumor limited to the uterus
Occurs with recurrent or locally advanced disease.
4-Vaginal metastasis 3-8% of clinical stage I
Occur through direct spread, submucousal lymphatics or
hematogenous spread
More common with high grade & lower uterine segment
or cervical involvement.
Ihab Samy 2013
25. FIGO 2009 Staging of endometrial carcinoma
In stage IA, cancer is in the endometrium only or less than halfway through the
myometrium . In stage IB, cancer has spread halfway or more into the myometrium.
Ihab Samy 2013
26. FIGO 2009 Staging of endometrial carcinoma
Stage II endometrial cancer: Cancer has spread into connective tissue of
the cervix, but has not spread outside the uterus.
Ihab Samy 2013
27. FIGO 2009 Staging of endometrial carcinoma
Stage IIIA endometrial cancer:Cancer has spread to the outer layer of the
uterus and/or to the fallopian tubes, ovaries, or ligaments of the uterus.
Ihab Samy 2013
28. Stage IIIB endometrial cancer: Cancer has spread to the vagina and/or to the
parametrium
Ihab Samy 2013
FIGO 2009 Staging of endometrial carcinoma
29. FIGO 2009 Staging of
endometrial carcinoma
Stage IIIC1
Spread to lymph
nodes in the pelvis.
Stage IIIC2:
Spread to the
paraaortic lymph
nodes.
Ihab Samy 2013
30. FIGO 2009 Staging of
endometrial carcinoma
Stage IVA:
Spread into the bladder
and/or bowel.
Ihab Samy 2013
31. FIGO 2009 Staging of
endometrial carcinoma
Stage IVB:
Spread beyond the
pelvis to other parts of
the body, such as the
abdomen and/or lymph
nodes in the groin.
Ihab Samy 2013
32. PROGNOSTIC FACTORS
Stage overall survival depends on the stage
- Stage I 72 - 90%
- Stage II 40 - 56%
- Stage III 20 - 32%
- Stage IV 5 - 11%
Depth of myometrial invasion correlates with lymph
nodes involvement in early disease.
Tumor grade
Nodal involvement
Histopathologic type clear,serous,adenosquamous
types
Malignant cells in peritoneal washings
Ihab Samy 2013
33. PROGNOSTIC FACTORS
Histological type
- Adenocarcinoma best prognosis
- Clear cell & papillary serous types poorer prognosis
- Absence of estrogen receptors poorer prognosis
Lympho-vascular space involvement important
prognostic factor in terms of survival & recurrence for
stage I disease
Ihab Samy 2013
34. INVESTIGATION
Any patient with signs or symptoms suggestive of
Endometrial Ca. should be investigated
All Patients should have endometrial sampling in the
clinic false -ve 10%
If continues to be symptomatic in spite of –ve biopsy or
suspicious finding on biopsy D&C
In the past the “gold standard” was D&C
The current “gold standard” is hystroscopy with targeted
endometrial biopsy.
Ihab Samy 2013
35. INVESTIGATION
Transvaginal U/S to assess endometrial thickness,
presence of endometrial polyp or ovarian masses.
Endometrium < 5 mm in thickness high -ve predictive
value. (ACOG recommends endometrial sampling only
when the endometrial stripe is thicker than 4 mm)
U/S also helpful in assessing the depth of endometrial
invasion
MRI depth of E invasion, Cx, & LN involvement
Chest X-Ray exclude pulmonary spread.
Ihab Samy 2013
36. STAGING
Surgical staging TAH + BSO + Pelvic washings ?? +
Abdominal exploration + Selective pelvic & PA LN
biopsies.
I confined to the body of the uterus
Ia confined to the endometrium
Ib myometrial invasion < 50% Stage IA
Ic myometrial invasion > 50% Stage IB
II Cervix involved
IIa endocervical gland involvement only
IIb Cx stromal invasion Stage II
Does not extend beyond the body of the uterus
Ihab Samy 2013
37. STAGING
III spread to serosa of uterus, peritoneal cavity or
LNs.
IIIa Ca involving serosa of uterus, adnexae,
+ve ascites or +ve peritoneal washings ??
IIIb vaginal and or parametrial involvement
either direct or metastatic
IIIc pelvic LN 1 or para-aortic 2 involvement
IV local or distant metastasis
IVa Ca involving the mucosa of the bladder or
rectum
IVb distant metastasis & involvement if other
abdominal or inguinal LN.
Ihab Samy 2013
39. COMPLICATIONS
Severe anemia 2ry blood loss or acute hemorrhage
high dose bolus radiation therapy is effective in
controlling the hemorrhage
Hematometra Cx dilatation for adequate drainage.
Pyometra Cx dilatation for adequate drainage +
antibiotics
Perforation of the uterus at the time of D&C or
endometrial sampling laparoscopy or laparotomy to
evaluate & repair the damage + antibiotics
Ihab Samy 2013
40. TREATMENT
1-SURGERY
TAH & BSO stage I & II may require radiotherapy
Surgery alone ≤ stage Ib /grade 1 or 2 adenocarcinoma
Stage III radical surgery (TAH/BSO + max debulking)
followed by radiotherapy
Ihab Samy 2013
41. Lymphadenectomy for endometrial cancer:
There is a lack of consensus on the extent of surgical
staging in endometrial carcinoma.
The ability of surgical staging to accurately identify
lymphatic spread and how this information affects
prognosis and alters the use of adjuvant therapies are a
source of controversy.
Ihab Samy 2013
43. Pelvic and Para-aortic LN dissection recommendation is
based on non-randomized retrospective studies reporting
of prolonged survival after lymphadenectomy.
Systematic para-aortic lymphadenectomy is advocated
on all high-risk patients, or in patients with two or more
positive pelvic lymph nodes.
No evidence of benefit in terms of survival for systematic
lymphadenectomy in women with stage I endometrial
cancer, except for grade 3 cancers. (American Journal of Obstetrics and
Gynecology, Volume 206, Issue 6, June 2012, Pages 500.e1-500.e11)
Ihab Samy 2013
44. The most frequent form of endometrial carcinoma (stage
IA, G1, G2, endometroid type, MI<50%) can be cured in
more than 90% by hysterectomy and bilateral
adnexectomy alone.
It is very unlikely that lymphadenectomy can further
improve survival time.
A radical procedure with pelvic and para-aortic
lymphadenectomy would be overtreatment for this group
of women, leading to an unnecessary impairment of
quality of life for a carcinoma with otherwise good
prognosis.
Ihab Samy 2013
45. Extent of Para-aortic lymphadenectomy
Isolated PA metastasis is rare in endometrial cancer.
If pelvic nodes are involved, PA metastasis is likely, and
PA lymphadenectomy should be performed up to renal
vessels so as not to miss occult metastasis in higher
regions particularly above the IMA. (Dogan et al; 2012)
Int J Gynecol Cancer. 2012 May;22(4)
Ihab Samy 2013
46. Sentinel node biopsy in Endometrial Ca.
In an attempt to avoid complete lymphadenectomy, the
concept of sentinel node identification has been
investigated in endometrial carcinoma.
Data are scant, and studies are still addressing feasibility
and standardization of technique.
Certain issues regarding the primary tumor and the
patterns of lymphatic drainage make sentinel lymph
node biopsy for endometrial carcinoma less practical.
Ihab Samy 2013
47. First, the lymphatic drainage of the uterus is
considerably more complicated than that of the
vulva and cervix.
Second, there is no easily accessible or visible
lesion in endometrial cancer as there is in vulvar
or cervical cancers, making injection difficult.
Third, the variation of reported locations of
sentinel nodes ranges from the parametrium to
the para-aortic region on either side of the body.
Ihab Samy 2013
48. Site of injection
There is no agreement regarding the best technique to
do SLNB in women with uterine cancer and this
procedure is still at the stage of determining feasibility.
Since 1996, there have been publications aiming to
determine the most appropriate way to do sentinel node
in uterine cancer.
Blue dye with or without a radiocolloid have been
administered either subserously , cervically, dually, and
hysteroscopically with a wide range of results in terms of
identification rates of sentinel nodes.
Ihab Samy 2013
62. TREATMENT
2-RADIOTHERAPY
Stage I or II most patients require surgery +
radiotherapy if they have any adverse features
Radiotherapy regime :
- high dose intracavitary brachytherapy risk of vault
recurrence
- low dose external beam radiotherapy risk of pelvic
recurrence
Advanced disease as palliation bone pain &
vaginal bleeding
Ihab Samy 2013
63. TREATMENT
3-HORMONE THERAPY
Progestogens (medroxyprogestrone acetate 200-400 mg/D).
Will not prevent recurrence
Used in the management of recurrent disease
response rate 30%
Response is higher in estrogen progestrone receptor +ve
tumors
Other hormonal agents tamoxifen & GnRH limited
responce
Ihab Samy 2013
64. TREATMENT
4-CHEMOTHERAPY
Not commonly used
Should be considered in fit patients with systemic /
advanced disease
Epirubicin, doxorubicin, cisplatin, carboplatin response
rate 25-30% / short lived response.
Ihab Samy 2013
65. PROGNOSIS
The 5 Y survival rate for endometrial Ca :
Stage I 75%
Stage II 58%
Stage III 30%
Stage IV 10%
Overall 5 Y survival 70% most Pt present early
due to abnormal vaginal bleeding
Ihab Samy 2013
67. Account for fewer than 10% of all corpus cancers.
Arise from mesenchymal stem cells (Uni- or Bi-potential).
Abnormal vaginal bleeding most frequent presenting
symptom for all histologic types
No specific staging system (commonly use staging of
endometrial carcinoma).
Ihab Samy 2013
69. Order of incidence: Carcinosarcoma (56-60%),
leiomyosarcoma (27-30%), endometrial stromal sarcoma
(10-17%), and adenosarcoma (<1%)
Higher rates of MMMT and LMS seen in Black women
(2X greater than whites)
Exposure to radiation (5 to 25 years after exposure to
the radiation) may enhance the development of pelvic
sarcomas (seen mainly in mixed sarcomas)
Mean age between 65-75 for carcinosarcoma but earlier
for LMS (45-55) and ESS (40-45).
Ihab Samy 2013
70. ESS is the least common and least aggressive (5-year
survival 55 – 67%).
MMMT is the most common and unfortunately is a very
aggressive tumor (5-year survival 16 – 24%).
Sarcomas of the uterine corpus mainly present as an
advanced or metastatic disease.
Sarcoma botryoids in children mainly affects the cervix
and vagina.
Ihab Samy 2013
71. CARCINOSARCOMA (MMMT)
Contains both carcinomatous and sarcomatous elements.
In homologous MMMT, sarcomatous element is stromal
sarcoma in 60% and LMS in the remainder.
In heterologous MMMT rhabdomyosarcoma most
common element (others: chondrosarcoma,
osteosarcoma and liposarcoma).
Carcinomatous element usually adenocarcinoma
(endometrioid, clear cell, PSA)
Ihab Samy 2013
72. CARCINOSARCOMA (MMMT)
Overall 5 year survival poor (25%) and strongly
associated with degree of myometrial invasion.
~60% have spread outside the uterus at time of
diagnosis
~35% regional lymph node spread in clinical stage 1
patients
Early hematogenous spread to liver and lung is common
In pts without extrauterine disease, 40% chance of
distant recurrence
Ihab Samy 2013
73. TREATMENT
Surgical staging including: TAH, BSO, pelvic lymphadenectomy,
peritoneal bx and omentectomy
Stage I-II: Platin based adjuvant chemotherapy
Node positive (stage III): chemotherapy followed by pelvic
radiotherapy
Stage IV: systemic treatment Ifosfamide (25% response),
cisplatinum(18% response).
Ifosfamide and paclitaxel is associated with lower risk of death
compared with ifosfamide alone.
In addition, radiotherapy to the abdomen is not associated with
improved survival (Galaal et l;2013).
Cochrane Database Syst Rev.2013 Feb
Ihab Samy 2013
74. Prognostic factors
Age, heterologous or homologous histology, and type of
adjuvant treatment were not associated with recurrence
or survival.
Depth of myometrial invasion was found to correlate to
disease-free survival but not overall survival.
The number of lymph nodes collected correlated to risk
of recurrence and survival.
Disease-free and overall survival were greater in patients
with higher lymph node count.
Ihab Samy 2013
75. Prognostic factors
The number of lymph nodes collected was the only risk
factor that was found to be correlated to recurrence and
survival in patients with early-stage carcinosarcoma.
Lymphadenectomy is crucial in patients with
carcinosarcomas of the uterus in order to discover occult
metastatic disease and potentially provide patients with
a therapeutic benefit (Temkin et al; 2007).
Int J Gynecol Cancer. 2007 Jan-Feb;17(1):215-9.
Ihab Samy 2013
76. LEIOMYOSARCOMA
One of every 800 fibroids is a leiomyosarcoma (LMS
rarely arises from benign leiomyomata).
Arises in the myometrium, unlike all the other uterine
sarcomas (less likely to be detected on EMC)
Two thirds of LMS are intramural and 10% submucosal
Need > 5-10 mitoses / 10 hpf for diagnosis.
Ihab Samy 2013
77. TREATMENT
Hysterectomy only
Doxorubicin, gemcitabine +/- docetaxel
Low grade: hormonal with resection
NB. only adriamycin appears to have significant activity
(25% response rate)
Ihab Samy 2013
78. ENDOMETRIAL STROMAL SARCOMA
Accounts for ~10% of uterine sarcomas
Tumor group divided into benign stromal nodule , low-
grade ESS and high grade ESS.
Areas of hemorrhage, necrosis, and deep myometrial
invasion common in high grade ESS and 40% extend
beyond the uterus at the time of diagnosis.
Ihab Samy 2013
79. TREATMENT
Hysterectomy only (no BSO)
Adjuvant progestins? Recurrence 31 vs. 67%
Repeat surgery Secondary and tertiary debulking
including organ resection and thoracotomy.
Ihab Samy 2013
80. ADENOSARCOMA
First described in 1974
Rare
Composed of a benign epithelial and a malignant non-
epithelial component
Mean age between 55 and 60 years
Tend to be a solitary mass in uterine fundus
Ihab Samy 2013
81. Recurrent US with peritoneal
dissemination
CRS/HIPEC shows promise as a treatment modality for
the management of selected patients with recurrent
high-grade US with peritoneal dissemination. Further
studies are warranted.
(American Journal of Obstetrics and Gynecology, Available online 7 November 2013)
Ihab Samy 2013
83. Classification of gestational
Trophoblastic disease
WHO Classification
Malignant
neoplasms of
various types of
trophoblats
Malformations of the
chorionic villi that
are predisposed to
develop
trophoblastic
malignacies
Benign entities that
can be confused
with with these
other lesions
Choriocarcinoma
Complete
Hydatidiform moles
Placental site nodule
Exaggerated placental site
Epithelioid trophoblastic
tumors
Placental site
trophoblastic tumor Partial
Invasive
(chorioadenoma destruens)Ihab Samy 2013
84. Hydatidiform Mole
Definition:
In latin
"hydatid" means "drop of water”
"mole" means "spot”
Pathologically,
Hydatidiform moles represents placentas with
abnormally developed chorionic villi (enlarged,
edematous and vesicular villi with variable
amounts of proliferative trophoblast).
Ihab Samy 2013
85. In the United States,
•1in 600 therapeutic
abortions
•1 in 1,500
pregnancies
In Asian countries,
•The rate is 10 times
higher than in Europe
and North America
In Saudi Arabia;,
•1.48 in 1000 live births
Ihab Samy 2013
86. Pathogenesis and Cytogenetics of HM
Genetic
ConstitutionDiploid Triploid/ teraploid
Patho-genesis
4%
Fertilization
of an empty
ovum by two
sperms
“Diandric
dispermy”
90%
Triploid
fertilization of
a normal
ovum by two
sperms
“Dispermic
triploidy”
96%
Fertilization
of an empty
ovum by one
spermsthat
undergoes
duplication
“Diandric
diploidy”
10%
Tetraploid
fertilization of
a normal
ovum by
three sperms
“Trispermic
tetraploidy”
Karyotype
46XX
69XXX
69YXX
69YYX
46XX
46XY
Complete Partial
Ihab Samy 2013
88. Risk factors for hydatidiform mole
1-prevous molar pregnancies
2-maternal age: advanced maternal age , younger women
or adolescents
3-Animal fat
4-Deficiency of folate – carotene and protein
5-Low socioeconomic state
Ihab Samy 2013
91. Complete Hydatidiform Mole
Macroscopically :
Edema and swelling of virtual Villi without identifiable
fetal parts or amniotic membranes
Microscopically:
The chorionic villi are hydropic with marked interstitial
edema .
Fetal vessels are absent.
Proliferation of cytotrophoblast and syncytiotrophoblast.
Ihab Samy 2013
92. Clinical findings :
1-One third to one half of uterine enlargement
2-Vaginal bleeding
3-Theca lutein cysts 20%
5-Pregnancy – induced hypertension
4-Pulmonary decompensation
6-Hyperthyroidism
7-Snowstorm (ultrasonography).
8-Markedly elevated hCG 100,000 mIU/mL
Ihab Samy 2013
93. The snow storm appearance of complete hydatidiform mole
Ihab Samy 2013
95. Partial mole
History:
Vaginal bleeding
Usually diagnosed as missed or incomplete abortion.
Physical:
A uterus small or equal to gestational age.
Identifiable fetal parts or amniotic membranes
Ihab Samy 2013
96. Diagnosis
The diagnosis of molar pregnancy is nearly always made
by ultrasonography.
Serum hCG levels:
Serum hCG levels of greater than 92 000 IU/l associated
with absent fetal heart beat indicate a diagnosis of
complete hydatidiform moles.Serum hCG level decreases
quickly if the patient has an abortion, but it does not in
molar pregnancy.
Histopathological examination:
It should always be done as far as possible and samples
should be kept for DNA analysis for a final diagnosis when
histology can not differentiate molar pregnancy from
abortion
Ihab Samy 2013
97. Complete moles : 10% to 30% incidence of malignant.
Partial moles : fewer than 5% of the patients.
Invasive mole : invasion into the myometrium without
intervening endometrial stroma uterine perforation
and hemorrhage.
Ihab Samy 2013
98. Choriocarcinoma
Chorio-carcinoma rapidly invades the myometrium and
uterine vessels , and systemic metastasis.
No chorionic villi are identified
Hematogenous embolization (affinity of trophoblast cell
for blood vessel).
Most cases have no tissue for pathologic study, hCG
level has raise
Ihab Samy 2013
99. 50% of cases are preceded by hydatidform mole
Gestational choriocarcinoma has been observed several
years after last known pregnancy .
Ihab Samy 2013
100. Placental site trophoblastic tumor
Locally invasive neoplasms derived from intermediate
cells of the placenta
Human Placental Lactogen from cytotrophoblast cell
Small amounts of HCG
Rare systemic metastasis
Significantly more resistant to standard chemotherapy
than other forms of GTN
Hysterectomy is the initial therapy of choice
Ihab Samy 2013
101. Clinical classification of malignant
gestational trophoblastic neoplasia
Non-metastatic GTN
Not defined in terms of good versus poor prognosis
Metastatic GTN
Good prognosis (i.e., absence of high-risk factors )
1. Pretreatment serum B-hCG level < 40,000 mIU/ml
2. Less than 4-month duration of symptoms attributable to
disease
3. No evidence of brain or liver metastasis
4. No significant prior chemotherapy
5. No antecedent term pregnancy
Ihab Samy 2013
102. Poor pregnosis (i.e., any single high-risk factor )
1. Pretreatment serum B-hCG level >40,000 Iu/ml.
2. More than 4-month duration of symptoms attributable
to disease.
3. Brain or liver metastasis or both.
4. Failed prior chemotherapy .
5. Antecedent term pregnancy.
Ihab Samy 2013
103. Staging
Stage I Strictly confined to uterine corpus
Stage II Extends outside the uterus , but limited to genital
structures
Stage III Extends to the lungs with or without genital tract
involvement
Stage IV All other metastatic sites
Sub stages assigned for each stage as follows :
A: No risk factors present
B: One risk factor
C: Both risk factors
Risk factors used to assign substages :
1- pretherapy serum hCG> 100,000 mIU/ml
2- Duration of disease > 6 monthsIhab Samy 2013
104. Who Orgnaization prognostic scoring system for gestational trophoblastic neoplasia
Prognostic factor 0 1 2 4
Age <39 >39 _ -
Antecedent
pregnancy
Hydatidiform Abortion ,
ectopic
Term pregnancy -
Interval (months) <4 4-6 7-12 >12
hCG level (IU/liter) <1000 <10000 <100000 >100000
ABO blood groups
(female/male)
O/A B A/O AB
Largest tumor (cm) <3 3-5 >5 _
Site of metastasis lung Spleen,
kidney
Gastrointestinal
tract, liver
Brain
Number of
metastases
_ 1-3 4-8 >8
Prior chemotherapy _ _ Single drug Multiple
druge
Ihab Samy 2013
The total score is obtained by adding the individual scores for each prognostic factor . Total score:
<4 , low risk ; 5-7 , intermediate risk ;>8 , high risk .
Interval :between antecedent pregnancy and start of chemotherapy.
105. Chemotherapy alone is successful in curing 85% of
patients with non metastatic and good-prognosis.
Hysterectomy rarely is indicated as Initial therapy for
women with malignant GTN
Persistence of a lung nodule after hCG normalization
(less than 5 IU/L)should not necessarily need surgery
Whole-brain and whole-liver irradiation in conjunction
with chemotherapy.
Ihab Samy 2013
106. Stage I Single agent chemotherapy
Resistant Combination chemotherapy or hysterectomy with
adjuvant chemotherapy
Stage II,III low risk Single agent chemotherapy
high risk Combination chemotherapy
Resistant Second line chemotherapy
Stage IV combination chemotherapy + radiotherapy
Resistant Second line chemotherapy
Ihab Samy 2013
107. Chemotherapeutic agents
ACT-D: actinomycin D.
EMACO: etoposide, methotrexate, actinomycin D,
cytoxan, oncovin.
MAC: methotrexate, actinomycin D, cytoxan.
MTX: methotrexate.
Used in stage II and III high risk:
EMAEP: etoposide, methotrexate, actinomycin D,
carboplatin
VBP: vinblastine, bleomyCin, carboplatin.
Ihab Samy 2013
108. Follow Up
Follow-up period of 12 months for women with stage I,
II, and III GTN and of 24 months for stage IV disease,
during which the patient is advised not to conceive.
This is not only crucial to the appropriate interpretation
of the hCG levels but also to the well-being of the
subsequent gestation.
Pregnancies within 6 months of treatment completion
are at increased risk for spontaneous miscarriages,
stillbirths, and repeat moles.
Ihab Samy 2013