ENDOMETRIAL CARCINOMA

AND ENDOMETRIAL HYPERPLASIA

 Endometrial carcinoma is the most
common gynaecologic malignancy (equal
to or slightly more common than cancer
cervix).
 The incidence has shown a steady rise in the
last 2 decades with prolonged
postmenopausal period of life and with the
liberal use of oestrogen replacement therapy
in the menopause.
 The disease affects predominantly
postmenopausal women, with average age
55-65 years
 less than 5% of cases are diagnosed in
women under the age of 40 years.
AETIOLOGY

 The cause of endometrial carcinoma is

unknown, however increased oestrogen
levels, unopposed by progesterone, is the
chief high risk factor. The majority of the
circulating oestrogen in postmenopausal
women is derived from peripheral
aromatization of androgens in adipose tissue
into oestrogen (oestrone E1).
 Risk Factors in Endometrial Carcinoma:
 1. Obesity
 2. Nulliparity
 3. Chronic anovulation as PCOD
 4. Delayed menopause
 5. Unopposed oestrogen therapy
 6. Functioning ovarian tumours (oestrogen
producing)
 7. Impaired carbohydrate tolerance
PRE-MALIGNANT LESIONS
(Endometrial Hyperplasia)

 Microscopically: Under the effect of

prolonged unopposed oestrogen, the
endometrial lining of the uterus will grow and
multiply resulting in an exaggerated
proliferative activity known as "endometrial
hyperplasia".
Three types of endometrial hyperplasia
are defined;
 Simple hyperplasia the glands and stroma are hyperplastic,
glands show cystic dilatation with disparity in size, with no
evidence of secretory activity; Such lesions have a very low
malignant potential <1%.
 Complex hyperplasia; If simple hyperplasia goes on new
glands in the endometrial lining will be formed resulting in
crowding of the glands with minimal intervening stroma.
Malignant potential is low <3%
 Complex hyperplasia with atypia; Finally, some cells may
become atypical showing abnormal behaviour with nuclear or
cytoplasmic atypia. Such lesions carry a high risk for
progression to endometrial carcinoma in 15-20% of cases.
PATHOLOGY OF ENDOMETRIAL
CARCINOMA
PATHOLOGY OF ENDOMETRIAL
CARCINOMA
 Adenocarcinoma is the commonest subtype of endometrial
carcinoma, also called endometrioid carcinoma.
 Adenoacanthoma; is an adenocarcinoma in which benign
squamous metaplasia may occur without change in the
behaviour or prognosis.
 Adenosquamous; is the tem used to describe an
adenocarcinoma in which the squamous element is also
malignant.
 Primary squamous cell carcinoma, papillary serous
carcinoma and clear cell carcinoma are particularly
aggressive but fortunately very rare types of endometrial
carcinoma.
SPREAD OF ENDOMETRIAL
CARCINOMA

1. Direct spread:
 EC usually spreads first on the surface of the
endometrium, called surface rider tumour filling the whole
uterine cavity. It may then invade the muscular layer of the
uterus, the myometrium, by direct spread
2. Lymphatic spread:
 EC also spreads through lymphatic channels draining the
fundus, the cornu and the isthmus to the para-aortic, inguinal
and paracervical lymph nodes respectively.
3. Vascular spread:
 Such metastases may invade the ovaries, the adnexa or
the vagina as near by organs with poor prognosis, or may be
carried to distant organs as the liver, lungs, brain and bones
where the disease reaches a terminal stage
GRADING AND STAGING

 Grade: Is the degree of differentiation of the

cells forming the tumour. Well- differentiated
cells look and behave almost like normal
cells.
 Well differentiated tumours (grade I), consist of
glandular formation with less than 5% solid parts,
they are slowly invasive and carry the best
prognosis.
 Poorly differentiated tumours (grade III), consist
of more than 50% solid parts, they are highly
aggressive with early deep myometrial invasion and
generally poor prognosis.
 Moderately differentiated tumours (grade II) lie in
between the previous two categories, and carry
intermediate prognosis.
 Stage: Determines how far has the tumour
extended within or beyond the endometrial
lining of the uterus, to the myometrium,
cervix, vagina, ovaries, adnexa or further to
near by or distant organs.
 a) Clinical staging: EC is first evaluated via a
clinical staging procedure to detect whether the
disease is confined to the uterus or has extended to
the vagina, adnexa, or distant organs.
 b) Surgical staging is performed during laparotomy
to evaluate the depth of myometrial invasion, the
presence of malignant cells in peritoneal wash and
the presence of positive lymph node affection.
FIGO SURGICAL STAGING OF
ENDOMETRIAL CARCINOMA

 Stage I: Carcinoma confined to the corpus

 I a:Tumour restricted to the endometrium
 I bI:nvasion to less than the inner ½ of the myometrium
 I c:Invasion to more than the inner ½ of the myometrium
 Stage II:Carcinoma extending to the cervix, but not outside the
uterus
 II a:Tumour invaded cervical glands (mucosa)
 II b:Tumour affected cervical stroma (tissue)
 Stage III:Carcinoma extending outside the uterus, but not outside
true pelvis
 III a:Extension to uterine serosa, and or adnexa (tubes and ovaries)
 III b:Extension to the upper vagina
 III c:Affection of lymph nodes especially paraaortic or pelvic
 Stage IV:Carcinoma extending to other pelvic organs or
metastasizing
 IV a:Invasion of bladder or rectum
 IV b:Distant extrapelvic metastases (Liver, lung, brain and bones)
Staging of Endometrial Carcinoma
PROGNOSIS

correlates with:
 Both the stage and grade of the tumour.
 Depth of myometrial invasion.
 Lymph node involvement.
 Endometrial carcinomas generally has a
good prognosis with > 85% 5 year survival
when diagnosed in stage I.
 Grade III tumours have a poorer prognosis
stage by stage compared to grade I and II.
 The presence of tumour cells in the
peritoneal cavity detected by cytology from
peritoneal wash will upstage the tumour from
stage I to stage III.
CLINICAL PRESENTATION
 Post-menopausal bleeding is the chief clinical
presentation in early cases of endometrial carcinoma
to the extent that any bleeding in elderly women
should be promptly investigated to exclude
malignancy.
 Irregular uterine bleeding will be the main
complaint in patients who still have their cycles.
Bleeding is usually profuse, persistent and recurrent
even after attempts using medical treatment.
 Other symptoms include vaginal discharge, lower
abdominal pain & menstrual like cramps
DIAGNOSIS
 Fractional Curettage (endocervical and endometrial
curettage), under aneasthesia, is the gold standard
in the diagnosis of endometrial carcinoma.
 Diagnosis on outpatient setting is established via
TVS for determination of endomtrial thickness, and
outpatient endometrial sampling using
instruments as the pipette sampler, or Novak curette,
in cases with abnormal endometrial thickness in the
menopause (>6.0 mm)
 Outpatient hysteroscopy
 abdominal examination, PV & PR, bimanual
pelvic vaginal examination
 Cytology is not very reliable, in contrast to
cancer cervix, with < 50% accuracy in the
diagnosis.
 Cystoscopy, CT scan and MRI may have a role in
determining the spread of the disease within the
myometrium and outside the uterine corpus
Curettage

Hysteroscopy
TREATMENT OF ENDOMETRIAL
CARCINOMA

 Treatment depends on many factors,

including the patient's general health, age,
and stage of the disease.
 In general, early stages of endometrial
carcinoma are usually treated with surgery
alone, or surgery and adjuvant
radiotherapy.
 Later stages are commonly managed with
irradiation or hormonal therapy.
 Stage I: endometrial carcinoma: The treatment of
choice is total abdominal hysterectomy and bilateral
salpingo-oophorectomy (TAH-BSO)
 Postoperative radiotherapy is necessary if cells are
immature (Grade III), or if invasion of the
myometrium has occurred to more than the inner
half of the myometrium (stage Ic) or if lymph node
sampling revealed positive node involvement.
 Stage II: endometrial carcinoma: is treated
similar to that of stage I cancer cervix. If the
patient is surgically fit, a Wertheim’s radical
hysterectomy is performed (TAH-BSO +
pelvic lymphadenectomy and removal of
upper cuff of the vagina). Additional para-
aortic lymph node sampling should be also
done. If the patient is surgically unfit then
radiotherapy will be a better choice.
 Stage III: cases; are generally treated with
combined radical hysterectomy and
adjuvant pre-operative or post-operative
radiotherapy However the treatment in
many cases is only palliative rather than
curative, and this may limit the extent of
surgical intervention.
 Stage IV: cases; are treated individually according to
the condition of each case. Surgery is obviously not
the first line of treatment. Radiotherapy is usually
performed and in some cases residual disease is
managed surgically.
 The aim of treatment is generally palliative not
curative. Chemotherapy and especially hormonal
therapy are superior to surgery in the treatment of
stage IV disease and recurrent cases.
RADIOTHERAPY FOR ENDOMETRIAL
CANCER
 A. External beam irradiation: After an initial hysterectomy has
been performed therapy may be beneficial for cases that are at
higher risk for lymph node spread or pelvic recurrences.
 B. Intracavitary irradiation: Loading the uterine cavity and the
vagina with radioactive cylinders. Its use in endometrial
carcinoma is limited to cases that are unfit for surgery and /or
having advanced disease.
 C. Postoperative Vaginal Vault Irradiation (brachytherapy):
Postoperative vaginal vault irradiation is often used to minimize
recurrences in the upper 1/3 of the vagina commonly due to
possible retrograde lymphatic spread..
PROGESTAGENS

 Synthetic progestational compounds

(progestagens) have long been used for
prevention of endometrial carcinoma in high-
risk cases by correcting the unopposed effect
of oestrogen on endometrial cells.