Uterine body tumors.

UTERINE BODY TUMORS
DR. IHAB SAMY
Lecturer of Surgical Oncology
National Cancer Institute
Cairo University - Egypt
Ihab Samy 2013

ENDOMETRIAL CARCINOMA
Ihab Samy 2013

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

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.
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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.
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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.
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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.
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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

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.
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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%.
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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.
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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).
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Pathogenesis
Type IIType IFeature
20%80%Frequency
postmenopausalpremenopausalAge (years)
unrelatedrelatedEstrogen
Serous,clear,squamousEndometioid,mucinousHistology
highlowBiologic grade
-ve+veHormone receptor
atrophyhyperplasiaAssociated endometrium
P53,p16Vimentin +veImmunophenotyping
deepminimalMyometrial invasion
independentdependentHormone therapy
10%90%Prognosis (5y-survival)
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Kantarjian et al;2012

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).
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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%
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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%.
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HISTOPATHOLOGY
1-Adenocarcinomas  80-85%
 Grade 1  well differentiated & difficult to distinguish
from atypical complex hyperplasia
 Grade 2
 Grade 3  anaplastic Ca (poorly differentiated)
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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.
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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
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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.
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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
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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.
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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.
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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.
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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.
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 Stage II endometrial cancer: Cancer has spread into connective tissue of
the cervix, but has not spread outside the uterus.
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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.
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Stage IIIB endometrial cancer: Cancer has spread to the vagina and/or to the
parametrium
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FIGO 2009 Staging of
endometrial carcinoma
Stage IIIC1
Spread to lymph
nodes in the pelvis.
Stage IIIC2:
Spread to the
paraaortic lymph
nodes.
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Stage IVA:
Spread into the bladder
and/or bowel.
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Stage IVB:
Spread beyond the
pelvis to other parts of
the body, such as the
abdomen and/or lymph
nodes in the groin.
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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
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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
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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.
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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.
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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
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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.
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DIFFERENTIAL DIAGNOSIS
 Various causes of abnormal bleeding
 Premenopausal Pt  exclude pregnancy complications 
abortion
 Endometrial hyperplasia
 Endometrial & Cx polyps
 Fibroid
 Ovarian, Cx or tubal neoplasms
 Postmenomausal Pt  atrophic vaginitis, endometrial
atrophy, exogenous estrogens
 Trauma
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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
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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
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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.
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OvaryEndometriumCervixNodes
RegionalRegionalRegionalPerivisceral
NonNonNonInguinal
RegionalRegionalRegionalInternal iliac
RegionalRegionalRegionalExternal iliac
RegionalRegionalRegionalCommon iliac
RegionalRegionalNonParaaortic
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 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)
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 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.
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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)
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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.
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 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.
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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.
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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
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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
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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.
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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
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UTERINE SARCOMAS
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 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).
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TYPES
 ENDOMETRIAL STROMAL SARCOMA (ESS)
 ENDOMETRIAL CARCINOSARCOMA (MMMT)
 UTERINE LEIOMYOSARCOMA (LMS)
 ENDOMETRIAL ADENOSARCOMA (AS)
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 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).
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 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.
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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)
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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
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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
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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.
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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.
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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.
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TREATMENT
 Hysterectomy only
 Doxorubicin, gemcitabine +/- docetaxel
 Low grade: hormonal with resection
NB. only adriamycin appears to have significant activity
(25% response rate)
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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.
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TREATMENT
 Hysterectomy only (no BSO)
 Adjuvant progestins?  Recurrence 31 vs. 67%
 Repeat surgery  Secondary and tertiary debulking
including organ resection and thoracotomy.

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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
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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)
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GESTATIONAL TROPHOBLASTIC
TUMORS
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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

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).
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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
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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
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Complete Mole, Pathogenesis
Duplication 46XX
Empty ovum
23X
Diandric diploidy
Androgenesis
Paternal
chromosomes only
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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
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Complete Mole, Pathogenesis
46XX
Empty ovum
23X
Dispermic diploidy
Paternal
chromosomes only
23X 23X
23X
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Partial Mole, Pathogenesis
69XXY
Normal ovum
23X
Dispermic triploidy
Paternal extra set
23Y 23X
23Y 23X
23X
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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

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

The snow storm appearance of complete hydatidiform mole
Ihab Samy 2013

Complete Hydatidiform Mole
Vaginal
bleeding
Severe
anemia
Passage of
hydropic
villi
Ihab Samy 2013

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

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

 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

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

 50% of cases are preceded by hydatidform mole
 Gestational choriocarcinoma has been observed several
years after last known pregnancy .
Ihab Samy 2013

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

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

 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

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

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.

 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

 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

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

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

Uterine body tumors.

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