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UTERINE BODY TUMORS
DR. IHAB SAMY
Lecturer of Surgical Oncology
National Cancer Institute
Cairo University - Egypt
Ihab Sa...
ENDOMETRIAL CARCINOMA
Ihab Samy 2013
EPIDEMIOLOGY
 Endometrial cancer is the most common pelvic genital
cancer in women (US and European databases).
 In the ...
EPIDEMIOLOGY
 It is a disease of postmenopausal women with a peak
incidence in the 6th & 7th decade of life
 Only 2-5% o...
RISK FACTORS
 Age: 65-75 Y , only 2-5% < 40 Y
 Excessive endogenous / exogenous estrogens:
- Early menarche < 12 Y
- Lat...
RISK FACTORS
 Unopposed estrogen therapy in postmenopausal women
 risk 6-8 X
 Tamoxifen  an anti-estrogen  has weak ...
ENDOMETRIAL HYPERPLASIA
 Excessive proliferation of the endometrial glands & to a
lesser extent endometrial stroma.
 Due...
CLASSIFICATION OF HYPERPLASIA
1-Hyperplasia without atypia (not premalignant):
A-Simple
 Microscopically: crowding of the...
B-Complex hyperplasia without atypia
 A complex crowded appearance of the glands with very
little stroma
 Epithelial str...
2-Hyperplasia with atypia (premalignant)
 Histologically  endometrial glands are lined by enlarged cells with
 nuclear ...
3-Carcinoma In Situ
Histologically differentiated from carcinoma by:
 Presence of intervening stroma between abnormal
gla...
PATHOGENESIS
 2 different types of Endometrial Ca.:
1- Low grade endometrioid ca. (Estrogen-related) 
associated with en...
Pathogenesis
Type IIType IFeature
20%80%Frequency
postmenopausalpremenopausalAge (years)
unrelatedrelatedEstrogen
Serous,c...
Type I and II endometrial cancers: have they different risk factors?
 Parity, oral contraceptive use, cigarette smoking, ...
PRESENTATION
 Abnormal vaginal bleeding  most common 90% in
Premenopausal Patients  heavy flow at the time of
menses
 ...
PRESENTATION
 Asymptomatic women with glandular abnormalities on
routine PAP smear/ abnormalities found in 50% of cases.
...
HISTOPATHOLOGY
1-Adenocarcinomas  80-85%
 Grade 1  well differentiated & difficult to distinguish
from atypical complex...
HISTOPATHOLOGY
2-Adenocarcinoma with squamous differentiation  5%
 Malignant glands with benign squamous metaplasia.
 A...
HISTOPATHOLOGY
4-Papillary Serous Carcinoma  10%
 Older women.
 Less likely to have hyperestrogenic state
 Spread earl...
HISTOPATHOLOGY
5-Clear cell Carcinoma  4%
 Microscopic appearance  clear cells / solid, papillary,
tubular, & cystic pa...
HISTOPATHOLOGY
6-Mucinous Ca  9%
 PAS- positive intracytoplasmic mucin.
7-Secretory Ca  1-2%
 Exhibit sub-nuclear or s...
SPREAD
1-Direct spread
 Through the endometrial cavity  to Cervix.
 Through the fallopian tubes  to ovaries & peritone...
SPREAD
2- Lymphatic spread 
 Never occurs without myometrial invasion
 The incidence of involvement is related to the d...
SPREAD
3-Hematogenous spread  the lungs
 Uncommon with the 1ry tumor limited to the uterus
 Occurs with recurrent or lo...
FIGO 2009 Staging of endometrial carcinoma
In stage IA, cancer is in the endometrium only or less than halfway through the...
FIGO 2009 Staging of endometrial carcinoma
 Stage II endometrial cancer: Cancer has spread into connective tissue of
the ...
FIGO 2009 Staging of endometrial carcinoma
Stage IIIA endometrial cancer:Cancer has spread to the outer layer of the
uteru...
Stage IIIB endometrial cancer: Cancer has spread to the vagina and/or to the
parametrium
Ihab Samy 2013
FIGO 2009 Staging ...
FIGO 2009 Staging of
endometrial carcinoma
Stage IIIC1
Spread to lymph
nodes in the pelvis.
Stage IIIC2:
Spread to the
par...
FIGO 2009 Staging of
endometrial carcinoma
Stage IVA:
Spread into the bladder
and/or bowel.
Ihab Samy 2013
FIGO 2009 Staging of
endometrial carcinoma
Stage IVB:
Spread beyond the
pelvis to other parts of
the body, such as the
abd...
PROGNOSTIC FACTORS
 Stage  overall survival depends on the stage
- Stage I  72 - 90%
- Stage II  40 - 56%
- Stage III ...
PROGNOSTIC FACTORS
 Histological type
- Adenocarcinoma  best prognosis
- Clear cell & papillary serous types  poorer pr...
INVESTIGATION
 Any patient with signs or symptoms suggestive of
Endometrial Ca. should be investigated
 All Patients sho...
INVESTIGATION
 Transvaginal U/S to assess endometrial thickness,
presence of endometrial polyp or ovarian masses.
 Endom...
STAGING
Surgical staging TAH + BSO + Pelvic washings ?? +
Abdominal exploration + Selective pelvic & PA LN
biopsies.
I  ...
STAGING
 III  spread to serosa of uterus, peritoneal cavity or
LNs.
IIIa  Ca involving serosa of uterus, adnexae,
+ve a...
DIFFERENTIAL DIAGNOSIS
 Various causes of abnormal bleeding
 Premenopausal Pt  exclude pregnancy complications 
aborti...
COMPLICATIONS
 Severe anemia 2ry blood loss or acute hemorrhage 
high dose bolus radiation therapy is effective in
contr...
TREATMENT
1-SURGERY
 TAH & BSO  stage I & II  may require radiotherapy
 Surgery alone ≤ stage Ib /grade 1 or 2 adenoca...
Lymphadenectomy for endometrial cancer:
 There is a lack of consensus on the extent of surgical
staging in endometrial ca...
OvaryEndometriumCervixNodes
RegionalRegionalRegionalPerivisceral
NonNonNonInguinal
RegionalRegionalRegionalInternal iliac
...
 Pelvic and Para-aortic LN dissection recommendation is
based on non-randomized retrospective studies reporting
of prolon...
 The most frequent form of endometrial carcinoma (stage
IA, G1, G2, endometroid type, MI<50%) can be cured in
more than 9...
Extent of Para-aortic lymphadenectomy
 Isolated PA metastasis is rare in endometrial cancer.
 If pelvic nodes are involv...
Sentinel node biopsy in Endometrial Ca.
 In an attempt to avoid complete lymphadenectomy, the
concept of sentinel node id...
 First, the lymphatic drainage of the uterus is
considerably more complicated than that of the
vulva and cervix.
 Second...
Site of injection
 There is no agreement regarding the best technique to
do SLNB in women with uterine cancer and this
pr...
Ihab Samy 2013
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TREATMENT
2-RADIOTHERAPY
 Stage I or II  most patients require surgery +
radiotherapy if they have any adverse features
...
TREATMENT
3-HORMONE THERAPY
 Progestogens (medroxyprogestrone acetate 200-400 mg/D).
 Will not prevent recurrence
 Used...
TREATMENT
4-CHEMOTHERAPY
 Not commonly used
 Should be considered in fit patients with systemic /
advanced disease
 Epi...
PROGNOSIS
The 5 Y survival rate for endometrial Ca :
 Stage I  75%
 Stage II  58%
 Stage III 30%
 Stage IV 10%
 O...
UTERINE SARCOMAS
Ihab Samy 2013
 Account for fewer than 10% of all corpus cancers.
 Arise from mesenchymal stem cells (Uni- or Bi-potential).
 Abnormal...
TYPES
 ENDOMETRIAL STROMAL SARCOMA (ESS)
 ENDOMETRIAL CARCINOSARCOMA (MMMT)
 UTERINE LEIOMYOSARCOMA (LMS)
 ENDOMETRIAL...
 Order of incidence: Carcinosarcoma (56-60%),
leiomyosarcoma (27-30%), endometrial stromal sarcoma
(10-17%), and adenosar...
 ESS is the least common and least aggressive (5-year
survival 55 – 67%).
 MMMT is the most common and unfortunately is ...
CARCINOSARCOMA (MMMT)
 Contains both carcinomatous and sarcomatous elements.
 In homologous MMMT, sarcomatous element is...
CARCINOSARCOMA (MMMT)
 Overall 5 year survival poor (25%) and strongly
associated with degree of myometrial invasion.
 ~...
TREATMENT
 Surgical staging including: TAH, BSO, pelvic lymphadenectomy,
peritoneal bx and omentectomy
 Stage I-II: Plat...
Prognostic factors
 Age, heterologous or homologous histology, and type of
adjuvant treatment were not associated with re...
Prognostic factors
 The number of lymph nodes collected was the only risk
factor that was found to be correlated to recur...
LEIOMYOSARCOMA
 One of every 800 fibroids is a leiomyosarcoma (LMS
rarely arises from benign leiomyomata).
 Arises in th...
TREATMENT
 Hysterectomy only
 Doxorubicin, gemcitabine +/- docetaxel
 Low grade: hormonal with resection
NB. only adria...
ENDOMETRIAL STROMAL SARCOMA
 Accounts for ~10% of uterine sarcomas
 Tumor group divided into benign stromal nodule , low...
TREATMENT
 Hysterectomy only (no BSO)
 Adjuvant progestins?  Recurrence 31 vs. 67%
 Repeat surgery  Secondary and ter...
ADENOSARCOMA
 First described in 1974
 Rare
 Composed of a benign epithelial and a malignant non-
epithelial component
...
Recurrent US with peritoneal
dissemination
 CRS/HIPEC shows promise as a treatment modality for
the management of selecte...
GESTATIONAL TROPHOBLASTIC
TUMORS
Ihab Samy 2013
Classification of gestational
Trophoblastic disease
WHO Classification
Malignant
neoplasms of
various types of
trophoblats...
Hydatidiform Mole
 Definition:
 In latin
"hydatid" means "drop of water”
"mole" means "spot”
 Pathologically,
Hydatidif...
In the United States,
•1in 600 therapeutic
abortions
•1 in 1,500
pregnancies
In Asian countries,
•The rate is 10 times
hig...
Pathogenesis and Cytogenetics of HM
Genetic
ConstitutionDiploid Triploid/ teraploid
Patho-genesis
4%
Fertilization
of an e...
Complete Mole, Pathogenesis
Duplication 46XX
Empty ovum
23X
Diandric diploidy
Androgenesis
Paternal
chromosomes only
Ihab ...
Risk factors for hydatidiform mole
1-prevous molar pregnancies
2-maternal age: advanced maternal age , younger women
or ad...
Complete Mole, Pathogenesis
46XX
Empty ovum
23X
Dispermic diploidy
Paternal
chromosomes only
23X 23X
23X
Ihab Samy 2013
Partial Mole, Pathogenesis
69XXY
Normal ovum
23X
Dispermic triploidy
Paternal extra set
23Y 23X
23Y 23X
23X
Ihab Samy 2013
Complete Hydatidiform Mole
Macroscopically :
 Edema and swelling of virtual Villi without identifiable
fetal parts or amn...
Clinical findings :
1-One third to one half of uterine enlargement
2-Vaginal bleeding
3-Theca lutein cysts 20%
5-Pregnancy...
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 ...
Diagnosis
 The diagnosis of molar pregnancy is nearly always made
by ultrasonography.
 Serum hCG levels:
Serum hCG level...
 Complete moles : 10% to 30% incidence of malignant.
 Partial moles : fewer than 5% of the patients.
 Invasive mole : i...
Choriocarcinoma
 Chorio-carcinoma rapidly invades the myometrium and
uterine vessels , and systemic metastasis.
 No chor...
 50% of cases are preceded by hydatidform mole
 Gestational choriocarcinoma has been observed several
years after last k...
Placental site trophoblastic tumor
 Locally invasive neoplasms derived from intermediate
cells of the placenta
 Human Pl...
Clinical classification of malignant
gestational trophoblastic neoplasia
Non-metastatic GTN
 Not defined in terms of good...
 Poor pregnosis (i.e., any single high-risk factor )
1. Pretreatment serum B-hCG level >40,000 Iu/ml.
2. More than 4-mont...
Staging
 Stage I  Strictly confined to uterine corpus
 Stage II  Extends outside the uterus , but limited to genital
s...
Who Orgnaization prognostic scoring system for gestational trophoblastic neoplasia
Prognostic factor 0 1 2 4
Age <39 >39 _...
 Chemotherapy alone is successful in curing 85% of
patients with non metastatic and good-prognosis.
 Hysterectomy rarely...
 Stage I  Single agent chemotherapy
Resistant  Combination chemotherapy or hysterectomy with
adjuvant chemotherapy
 St...
Chemotherapeutic agents
 ACT-D: actinomycin D.
 EMACO: etoposide, methotrexate, actinomycin D,
cytoxan, oncovin.
 MAC: ...
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,
d...
THANK YOU
Ihab Samy 2013
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Uterine body tumors.

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Uterine body tumors

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Uterine body tumors.

  1. 1. UTERINE BODY TUMORS DR. IHAB SAMY Lecturer of Surgical Oncology National Cancer Institute Cairo University - Egypt Ihab Samy 2013
  2. 2. ENDOMETRIAL CARCINOMA Ihab Samy 2013
  3. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
  13. 13. 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) Ihab Samy 2013 Kantarjian et al;2012
  14. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 30. FIGO 2009 Staging of endometrial carcinoma Stage IVA: Spread into the bladder and/or bowel. Ihab Samy 2013
  31. 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. 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. 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. 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. 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. 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. 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
  38. 38. 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 Ihab Samy 2013
  39. 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. 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. 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
  42. 42. OvaryEndometriumCervixNodes RegionalRegionalRegionalPerivisceral NonNonNonInguinal RegionalRegionalRegionalInternal iliac RegionalRegionalRegionalExternal iliac RegionalRegionalRegionalCommon iliac RegionalRegionalNonParaaortic Ihab Samy 2013
  43. 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. 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. 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. 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. 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. 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
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  62. 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. 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. 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. 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
  66. 66. UTERINE SARCOMAS Ihab Samy 2013
  67. 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
  68. 68. TYPES  ENDOMETRIAL STROMAL SARCOMA (ESS)  ENDOMETRIAL CARCINOSARCOMA (MMMT)  UTERINE LEIOMYOSARCOMA (LMS)  ENDOMETRIAL ADENOSARCOMA (AS) Ihab Samy 2013
  69. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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
  82. 82. GESTATIONAL TROPHOBLASTIC TUMORS Ihab Samy 2013
  83. 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. 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. 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. 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
  87. 87. Complete Mole, Pathogenesis Duplication 46XX Empty ovum 23X Diandric diploidy Androgenesis Paternal chromosomes only Ihab Samy 2013
  88. 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
  89. 89. Complete Mole, Pathogenesis 46XX Empty ovum 23X Dispermic diploidy Paternal chromosomes only 23X 23X 23X Ihab Samy 2013
  90. 90. Partial Mole, Pathogenesis 69XXY Normal ovum 23X Dispermic triploidy Paternal extra set 23Y 23X 23Y 23X 23X Ihab Samy 2013
  91. 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. 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. 93. The snow storm appearance of complete hydatidiform mole Ihab Samy 2013
  94. 94. Complete Hydatidiform Mole Vaginal bleeding Severe anemia Passage of hydropic villi Ihab Samy 2013
  95. 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. 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. 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. 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. 99.  50% of cases are preceded by hydatidform mole  Gestational choriocarcinoma has been observed several years after last known pregnancy . Ihab Samy 2013
  100. 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. 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. 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. 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. 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. 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. 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. 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. 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
  109. 109. THANK YOU Ihab Samy 2013

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