Endometrial Carcinoma - Gynaecology MBBS

Describes etiopathogenesis, risk factors, clinical features, diagnosis and management of endometrial carcinoma

1. General Description
» A malignant
epithelial disease
that occurs in
endometrial gland
of uterus
» Also called
endometrial cancer

2. INCIDENCE
» The incidence is higher amongst the white
population of the United States and lowest in
India and Japan.
» In North America, amongst the whites,
carcinoma body is the leading site of genital
malignancy followed by ovary and cervix.
» In the USA, a woman has about 1 percent
chance of developing endometrial carcinoma
during her lifetime.
» In India, it ranks third amongst genital
malignancy next to cervix and ovary.
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3. ETIOLOGY
» Estrogen—Persistent stimulation of
endometrium with unopposed estrogen is the
single most important factor for the
development of endometrial cancer.
» Age—About 75 percent are postmenopausal
with a median age of 60.About 10 percent of
women with postmenopausal bleeding have
endometrial cancer.
» Parity—It is quite common in unmarried and
in married, nulliparity is associated in about
30 percent.
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4. » Late menopause—The chance of carcinoma
increases, if menopause fails to occur beyond
52 years.
» Corpus cancer syndrome — encompasses -
obesity, hypertension and diabetes.
» Obesity leads to high level of free estradiol as
the sex hormone binding globulin level is low

5. » Unopposed estrogen stimulation in
conditions such as functioning ovarian
tumors (granulosa cell) or polycystic ovarian
syndrome (PCOS) is associated with increased
risk of endometrial cancer.
» Unopposed estrogen replacement therapy in
postmenopausal women is associated with
increased risk of endometrial cancer. Use of
cyclic progestin reduces the risk. Prior use of
combined oral contraceptives reduces the risk
significantly (50%).

6. » Tamoxifen is antiestrogenic as well as weakly
estrogenic. It is used for the treatment of
breast cancer. Increased risk of endometrial
cancer is noted when it is used for a long
time due to its weak estrogenic effect.
» Family history or personal history of colon,
ovarian or breast cancer increases the risk of
endometrial cancer. Genetic inheritance
(Lynch 11 syndrome family) is currently
thought Of.

7. » Fibroid is associated in
about 30 percent
cases.
» Endometrial
hyperplasia precedes
carcinoma in about 25
percent cases.
—_

8. » Fibroid is associated in
about 30 percent
cases.
» Endometrial
hyperplasia precedes
carcinoma in about 25
percent cases.

9. High risk factors for endometrial
carcinoma
» late menopause [
» nulliparity O
» Unopposed estrogen therapy O
» History of persistent anovulation (PcoS) O
» History of irregular and excessive
premenopausal bleeding O
» Obesity
» Diabetes

10. » hypertension O
Personal or family history of breast, ovary,
colon or endometrial cancer O
Atypical endometrial hyperplasia O
Tamoxifen therapy O
v
L4
-
g Radiation menopause
—

11. Pathology:
» Naked eye—The uterus may be smaller, normal
or even enlarged (due to myohyperplasia,
myometrial involvement, pyometra or associated
fibroid).
» Two varieties are found
0 Localized (& Diffuse
Localized: The usual site is on the fundus. It is
either sessile or pedunculated. Myometrial
involvement is late.
Diffuse: The spread is through the endometrium.
The myometrium is commonly invaded; may
invade to reach the serosal coat

12. » Microscopic appearances
The following varieties are noted: O
» Adenocarcinoma (endometrioid 80%)
Adenocarcinoma with squamous elements. [
Papillary serous carcinoma (5-10%) (virulent).
Mucinous adenocarcinoma (5%).
Clear cell adenocarcinoma (5%).
Secretory carcinoma (1%).
Squamous cell carcinoma.
Mixed carcinoma.
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v
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13. SPREAD
» Direct: As it is slow growing, it is confined to
the stroma for a long time but eventually, it
spreads in all directions.
Thus, it may infiltrate the myometrium and
spread to the parametrium or into the
peritoneal cavity. It may spread downwards to
involve the cervix in about 15 percent.
—

14. » The tubes and ovaries are involved (3-5%)
either by direct spread or by lymphatics. The
vagina is involved in about 10-15 percent
cases. The metastasis to the lower-third of
the anterior vaginal wall is probably through
lymphatic or by retrograde venous flow. The
vault metastasis following hysterectomy may
be due to direct implantation or may be
explained by previous lymphatic or venous
embolism.

15. » Hematogenous: Blood borne spread occurs
late. The common sites of metastases are
lungs, liver, bones and brain.

16. Staging
» The staging is based on
endometrial histology and surgical evaluation,
adopted by FIGO .
Approximately 75 percent patients present
with stage | disease.
——

17. Clinical Stage
(FIGO 1971)
» Stage |
la The carcinoma is confined to the corpus and
the length of the uterine cavity is < 8 cm
Ib The carcinoma is confined to the corpus and
the length of the uterine cavity is > 8 cm
» Stage Il The carcinoma has involved the corpus and the
cervix, but has not extended outside the uterus

18. Clinical Stage
(FIGO 1971)
» Stage Ill The carcinoma has extended outside the
uterus, but not outside the true pelvis
» Stage IV
IVa The carcinoma has extended outside the
uterus and involves the mucosa of the bladder or
rectum (a bullous oedema as
such does not permit the case to be allotted to Stage IV)
IVb The carcinoma has extended outside the true
pelvis and spread to distant organs

19. SURGICAL AND HISTOPATHOOGICAL STAGING OF
CARCNINOMA ENDOMETRIUM (FIGO 2023)
STAGE I: CONFINED TO THE UTERUS CORPUS AND
OVARY
\
|
% IA: Disease limited to the endometrium OR non-
; aggressive histological type i.e. low-grade
- endometroid, with invasion of less than half of
- myometrium with no or focal lymphovascular space
involvment (LVSI) or good prognosis disease
IA1: Non-aggressive histological type limited to the
endometrial polyp or confined to the endometrium
IA2: Non- aggressive histological types involving less
than half of the myometrium with non or focal LVSI
i

20. IA3 Low grade endometroid carcinomas limited to the
uterus and ovary
IB: Non aggressive histological types with invasion of half
or more of the myometrium, and with no or focal LVSI
IC: Aggressive histological types limited to a polyp or
confined to the endometrium
STAGE II: INVASION OF CERVICAL STROMA WITH
EXTRAUTERINE EXTENSION OR WITH SUBSTANTIAL LVSI OR
AGGRESSIVE HISTOLOGICAL TYPES WITH MYOMETRIAL
INVASION
IIA: Invasion of cervical stroma of non- aggressive
histological types

21. [IB: Substantial LVSI of non-aggressive histological
types
lIC: Aggressive histological types with any
myometrial involvement
STAGE IlI: LOCAL AND/ OR HISTOLOGICAL TYPES
WITH ANY MYOMETRIAL INVOLVEMENT
IA: Invasion of uterine serosa, adnexa, or both by
direct extension or metastasis
A1l: Spread to ovary or fallopian tube (Except
when meeting IA3 criteria)
A2: Involvement of uterine subserosa or spread
~.through the uterine serosa

22. B: Metastasis or direct spread to the vagina and/or
parametria or pelvic peritoneum
B1: Metastasis or direct spread to the vagina and/
or the parametria
B2: Metastasis to the pelvic peritoneum
IIC: Metastasis to the pelvic or para-aortic lymph
nodes or both
[IC1: Metastasis to the pelvic lymph nodes
IHC1i: Micrometastasis
INICT1ii: Macrometastasis
P ——

23. I1IC2: Metastasis to the para- aortic lymph nodes up to the
rerzjal vessels, with or without metastasis to the pelvic lymph
nodes
IC2ii: Macrometastasis
STAGE IV: SPREAD TO THE BLADDER MUCOSA AND/ OR
INC2i: Micrometastasis
INTESTINAL MUCOSA AND/ OR DISTANCE METASTASIS
IVA: Invasion of the bladder mucosa and/ or intestinal
mucosa and/ or distance metastasis
IVB: Abdominal peritoneal metastasis beyond the pelvis
IVC: Distant metastasis, including metastasis to any extra- or
intra-abdominal lymph nodes above the renal vessels, lungs,
liver, brain or bone

24. MOLECULAR STAGING
» complete molecular classification (POLEmut,
MMRd, NSMP, p53abn) is encouraged in all
endometrial cancers.
» If the molecular subtype is known, this is
recorded in the FIGO stage by the addition of
“m” for molecular classification and subscript
indicating the specific molecular subtype.
» When molecular classification reveals p53abn
or POLEmut stages in stages, | and I, this
results in upstaging or downstaging of the
disease.

25. CLINICAL FEATURES
» Patient profile: The patient is usually a
nullipara, likely to be postmenopausal. There
may be history of delayed menopause. She
may be obese; likely to have hypertension or
diabetes
» symptoms :Postmenopausal bleeding (75%)
which may be slight, irregular or continuous.
The bleeding at times may be excessive.
» In premenopausal women, there may be
irregular and excessive bleeding.

26. » At times, there is watery and offensive
discharge due to pyometra.
» Pain is not uncommon. It may be colicky due
to uterine contractions in an attempt to expel
the polypoidal growth. Few patients (< 5%)
remain asymptomatic.
» Signs: The patient presents with the features
as mentioned in patient profile. There may be
varying degrees of pallor.
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27. » Rectal examination corroborates the
bimanual findings. Regional lymph nodes and
breasts are examined carefully.

28. DXS OF ENDOMETRIAL
CARCINOMA
» The following guidelines are
prescribed: A case of
postmenopausal bleeding is
considered to be due to
endometrial carcinoma unless
proved otherwise.
» Finding a benign condition to
account for post- menopausal
bleeding does not negate a
thorough investigation to rule out
carcinoma.

29. » The two lesions may co-exist.
» History and clinical examination are to be
recorded, as mentioned earlier.
» Endometrial biopsy - using a Sharman
curette or a soft, flexible, plastic suction
cannula (pipelle) has been done with
reliability (90%). This is done as an outpatient
procedure.

30. » Histology is the definitive diagnosis.
Papanicolaou smear is not a reliable
diagnostic test for endometrial carcinoma.
» It is positive only in 30 percent cases of
endometrial cancer.
» Adenocarcinoma of the endometrium, the
commonest histologic type. There is
significant cellular mitotic activity. The glands
are arranged back-to-back. i

31. » Ultrasound and color Doppler (TVS):
» Findings suggestive of endometrial
carcinoma are —
v (i) Endometrial thickness > 4 mm.
» (i) Hyper- echoic endometrium with irregular
outline.
» (iii) Increased vascularity with low vascular
resistance.
» (iv) Intrauterine fluid. However, it cannot
replace definitive biopsy

32. » Hysteroscopy—It helps in direct visualization
of endometrium and to take target biopsy.
» Fractional curettage—It is not only the
definite method of diagnosis but can detect
the extent of growth.
» This is done under anesthesia with utmost
gentleness to prevent perforation of the
uterus. If pyometra is detected, the procedure
is withheld for about 1 week to avoid
perforation and systemic infection.

33. The orderly steps for fractional
curettage
» :Endocervical curettage (ECC). (To pass an
uterine sound to note the length of the
uterocervical canal. (Dilatation of the internal
0s. O
» Uterine curettage at the fundus and lower
part of the body. The endometrial tissue is
usually profuse and often dark color. O

34. » Finally, a polyp forceps is introduced in case
any endometrial polyp has escaped the
curette.
» The specimens, so obtained, should be
placed in separate containers, labelled
properly and submitted for histological
examination. [
———

35. + Computed Tomography (CT) scan of pelvis
and abdomen may be used to detect lymph
node metastases . .
v Magnetic Resonance Imaging (MRI) can detect
myometrial invasion .
+ Positron Emission Tomography .

36. » Surgical staging: Increased inaccuracy of
clinical staging and the importance of
prognostic factors, some of which can only be
identified surgically, resulted in introduction
of surgicopathological staging by FIGO in
20009.

37. Differential DXs
» Senile endometritis / vaginitis
» Dysfunctional uterine bleeding
» Submucous myoma / Endometrial polyps
» Cervix cancer / Sarcoma of uterus/ Primary
carcinoma of fallopian tube

38. Management of Endometrial
carcinoma
» Preventive
» Curative Preventive: Primary prevention
includes:
» Strict weight control beginning early in life.
» To restrict the use of estrogen after
menopause in nonhysterectomized women.
v If at all it is needed, cyclic administration of
progestogen preparations are added and
continued under supervision.
—

39. Methods
» The cytologic specimens are obtained by
either endometrial aspiration or endometrial
lavage. If suspicious cells are detected,
histological specimen is obtained by uterine
curettage.
» The presence of abnormal endometrial cells
in vaginal pool cytology requires a diagnostic
curettage.
» Judicial hysterectomy in premalignant lesions
of the corpus

40. Treatment
» Surgery Radiation
» Chemotherapy Hormone
therapy
~Early stage
-—- surge+ postoperative adjuvant
therapy
~Advanced stage
--- radiation+ surge+ medicine

41. Principle of choice
» General condition (Age, complication)
» Clinical stage
» Tumour pathologic type
——

42. Surgery a0 AN
Object
Operative pathologic stage, finding prognosis risk
factors
+ Remove uterus and metastasis tumour
» Stage | :
+ Abdorminal hysterectomy + bilateral
salpingoophorectomy + selective lymphadenectomy
o clear cell or papillary carcinoma-
omentectomy-+appenditectomy

43. » Stage I
- Radical hysterectomy + pelvic
lymphadenectomy + paraortic
lymphadenectomy
» Stage I, 1V
> Cytoreductive surgery
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44. Indications of pelvic lymphadenectomy
» Special pathogenetic pattern
» Endometrial cancer, grade 3 or no
differentiation
» Myo-invasion more than %
» Size of lesion more than 50% of uterine
cavity
» Involvement in isthmus of uterus

45. Radiation therapy
» Radiation alone
» Radiation with surgery

46. Hormone Therapy
» mechanism
Most endometrial cancers have both ER &
PR.(Estrogen dependent subtype)
. Indications:
Advanced or recurrent stage
Early stage and desire for fertility
» Used drugs
MPA

47. Prognostic Factors
» Tumour bilologic bihavior
Cell type
Histological grade
Depth of myometrium infiltration
lymph-node metastasis
- Presence of lymph vascular space
involvement
- Positive peritoneal cytology
» General condition
- Old age
- Acute or chronic medical illness
» Choice of treatment