UTERINE CARCINOMA

DR. SALWA NEYAZI

CONSULTANT OBSTETRICIAN GYNECOLOGIST

PEDIATRIC & ADOLESCENT GYNECOLOGIST
 ENDOMETRIAL HYPERPLASIA &-1
CARCINOMA
 Endometrial cancer is the most common pelvic genital
cancer in women
 In the US the life time risk of developing endometrial Ca
is 2.4% in white women & 1.3% in black
 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 Ca due to
early Dx ---75% Dx Stage I
 Estrogen has been implicated as a causative factor
 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 2X > women with 1 child / 3X > women with ≥5
-Chronic anovulation as in PCO
-Obesity  aromatization of adrenal androgens in fat tissue
risk is 3X for Pt 21-50 pounds overweight
10 X for Pt > 50 P overweight
-Granulosa-thicka 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
-Endometrial hyperplasia
 RISK FACTORS
 Unopposed estrogen therapy in postmenopausal women
 risk of E Ca 6-8 X
 Tamoxifen  an anti-estrogen used in the Rx of breast
Ca  has weak estrogenic activity on the genital tract
2 X  risk of E Ca when used ≥ 5 Y
  risk in women with breast, ovarian (endometrial type)
& colorectal Ca
 Diabetes  3X  risk
 Hypertension
 Previous pelvic radiation therapy
 Family Hx of endometrial Ca
 ENDOMETRIAL HYPERPLASIA
 Excessive proliferation of the endometrial glands & to a
lesser extent endometrial stroma
 Due to excessive estrogen stimulation

 Only 25% of Pt with E Ca have Hx of hyperplasia

CLASSIFICATION
1-Hyperplasia without atypia (not premalignant)
1-A-Simple
 Microscopically  crowding of the glands in the stroma

 Glands are cystically dilated & give a “Swiss cheese”

appearance
 Commonly asymptomatic

 1% progress to Ca over 15 Y

 80% regress
 ENDOMETRIAL HYPERPLASIA

1-B-Complex hyperplasia without atypia

 A complex crowded appearance of the glands with very

little stroma
 Epithelial stratification & mitotic activity

 3% progress to Ca over 13 Y

 80% regress

 85% reversal with progestin Rx

 ENDOMETRIAL HYPERPLASIA

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 Rx compared to

that of lesions without atypia

2-A-Simple
 Progression to carcinoma occur in 8%

2-B- Complex
 Progression to carcinoma occur in 29%
 ENDOMETRIAL HYPERPLASIA

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 from Ca

 PRESENTATION OF ENDOMETRIAL CA
 Abnormal vaginal bleeding  most common 90%
 Premenopausal Pt  usually c/o heavy flow at the time
of menses
may present with
 persistent intermenstrual bleeding
 pre or post menstrual spotting
 polymenorrhea that fails to respond to hormonal Rx
 Postmenopausal bleeding is the most common type of
abnormal bleeding  12-15% due to E Ca
 5-8% due to other cancers like uterine sarcoma,
ovarian Ca, Cx, tubal or vaginal Ca
 Postmenopausal Pt  commonly c/o intermittent
spotting
 Postmenopausal vaginal discharge 10%
 PRESENTATION OF ENDOMETRIAL CA
 Asymptomatic women with glandular abnormalities on
routine PAP smear/ abnormalities found in 50% of Pt
with E Ca
 Advanced disease  symptoms due to local or distant
metastases
 Sever cramps due to hematometra or pyometra  occur
in postmenopausal Pt with Cx stenosis ----10%
 HISTOPATHOLOGY
 Microscpically  hyperplasia & anaplasia of glands
Invasion of stroma, myometrium, or vascular spaces

1-Adenocarcinomas  80-85%

 Grade 1  well differentiated & difficult to distinguish

from atypical complex hyperplasia
 Grade 2
 Grade 3  anaplastic Ca (poorly differentiated)
 HISTOPATHOLOGY

2-Adenocarcinoma with squamous differentiation  5%

 Malignant glands with benign squamous metaplasia

 Also subdivided into 3 grades

3-Adenosquamous Ca  10-20%
 Malignant glands & malignant squamous epithelium

 Often grade 3
 HISTOPATHOLOGY

4-Papillary Serous Ca  10%

 Older women

 Less likely to have hyperestrogenic state

 Simillar to Papillary Serous Ca of the ovaries

 Spread early through peritoneal surfaces of the pelvis &

abdomen
 Invasion of the myometrium & lymphatic

 Prognosis unfavorable
 HISTOPATHOLOGY

5-Clear cell Ca  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 Ca

 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 E Ca

8-Squamous cell Ca  extremely rare

 Associated with  Cx stenosis, pyometra & inflammation
 SPREAD

1-Direct spread
 Through the endometrial cavity  to Cx

 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
 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 lymphnodes  common 35%

 Para-aortic lymphnodes  10-20%

Rarely involved without pelvic nodes involvement

 Inguinal lymphnodes  rare
 SPREAD

3-Hematogenous spread to the lungs

 Uncommon with the 1ry tumor limited to the uterus

 Occurs with recurrent or disseminated 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 Cx involvement
 PROGNOSTIC FACTORS
 Stage  overall survival depends on the stage at Dx
-Stage I  72%
-Stage II  56%
-Stage III  32%
-Stage IV  11%
 Depth of myometrial invasion correlates with lymph

nodes involvement in early disease

-also correlates with tumor grade
 Malignant cells in peritoneal washings
 PROGNOSTIC FACTORS
 Tumor grade as it    depth of invasion & LN
involvement
-grade I  90% limited to endometrium or inner ½ of the
myometrium
-grade III  50% invading the outer half of the
myometrium
 Histological type

-adenocarcinoma  best prognosis

-clear cell & papillary serous types  poorer prognosis
-absence of estrogen receptors  poorer prognosis
 Lymphovascular space involvement  important
prognostic factor in terms of survival & recurrence for
stage I disease
 INVESTIGATION
 Any Pt with signs or symptoms suggestive of E Ca
should be investigated
 All Pt 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
 INVESTIGATION
 As an alternative  endometrial sampling with a pipelle
+ transvaginal U/S to assess endometrial thickness,
presence of endometrial polyp or ovarian masses
 Endometrium < 5 mm in thickness  high –ve
predictive value
 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
 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%
Ic-------------------myometrial invasion > 50%

II --------------------- Cx involved
IIa-----------------endocervical gland involvement only
IIb-----------------Cx stromal invasion
does not extend beyond the body of the uterus
 STAGING
III ----------------spread to serosa of uterus, peritoneal
cavity or LN
IIIa --------------Ca involving serosa of uterus, adnexae,
+ve ascites or +ve peritoneal washings
IIIb --------------vaginal involvement either direct or
metastatic
IIIc --------------para-aortic or pelvic LN 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
 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
 Urethral caruncles
 Trauma
 COMPLICATIONS
 Severe anemia 2ry tochronic 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
toevaluate &repair the damage + antibiotics
 TREATMENT

1-SURGERY

 TAH & BSO  stage I & II  may require radiotherapy

 Surgery alone ≤ stage Ib /grade 1or 2/adenocarcinoma

 Stage III  radical surgery (TAH/BSO + max debulking)

followed by radio therapy
 TREATMENT

2-RADIOTHERAPY
 Stage I or II  most Pt 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 palliative Rx  bone pain &

vaginal bleeding
 TREATMENT

3-HORMONE THERAPY
 Progestogens (medroxyprogestrone acetate 200-

400mg/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
 TREATMENT

4-CHEMOTHERAPY

 Not commonly used

 Should be considered in fit Pt with systemic / advanced
disease
 Epirubicin, doxorubicin, cisplatin, carboplatin 
response rate 25-30% / short lived response
 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