ENDOMETRIAL MALIGNANCIES

PRESENTER:
JUDITH EDWARD

FACILITATOR
DR WANGWE
 OUTLINE
• Introduction
• Epidemiology
• Etiology
• Clinical presentation
• Diagnosis
• Staging
• Treatment
• Prognosis
• Summary
• References
 INTRODUCTION
• Endometrial cancer is the most common
gynaecologic malignancy in high income
countries and the second most common
gynaecologic cancer world wide
• It represents the sixth most common
malignant disorder worldwide.
• An estimated 320 000 new cases are
diagnosed with this malignancy annually.
 EPIDEMIOLOGY
• EC develops in 1 to 2 percent of women in the
United States and is the fourth most common
cancer in United States women after cancer of the
breast, lung/bronchus, and colon/rectum
• The incidence peaks between ages 60 and 70
years, but 2 to 5 percent of cases occur before age
40 years.
• Women under age 50 who develop EC are often at
risk because of chronic anovulation and/or obesity
There are two types of endometrial cancer,
based on epidemiology & clinical
presentation. Those related to and those
unrelated to estrogen stimulation, type 1 & 2
respectively ).
• Type I endometrial carcinoma is estrogen
related,comprise approximately 80% of EC
tends to be associated with atypical
endometrial hyperplasia.
• Type II endometrial cancer is unrelated to
estrogen or endometrial hyperplasia;
Account for 10 to 20% of EC.
Tends to present with higher grade tumors or
poor prognostic cell types, eg, papillary
serous, or clear cell tumors.
Pts are often multiparous, older; no increased
prevalence of obesity, DM, or Hypertension.
 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 (c.f. Carcinoma cervix is
more common in perimenopausal period). 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.
• 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.
• 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.
• 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.
• Fibroid is associated in about 30 percent
cases.
• Endometrial hyperplasia precedes carcinoma
in about 25 percent cases.
 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.
• Lymphatic: The lymphatic spread is usually late.
Lymphatic spread involves pelvic, paraaortic
(through infundibulopelvic ligament) and rarely
inguinal and femoral (through lymphatics of
round ligament) nodes.
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.
• Hematogenous: Blood borne spread occurs
late. The common sites of metastases are
lungs, liver, bones and brain.
 CLINICAL PRESENTATION
• Abnormal uterine bleeding (AUB) in the peri/
postmenopausal women.
• Watery and offensive discharge due to pyometra.
• Pain,may be colicky due to uterine contractions in
an attempt to expel the polypoidal growth.
• Few patients (< 5%) remain asymptomatic
Pelvic examination
• Speculum examination reveals the cervix
looking healthy and blood or purulent
offensive discharge escapes out of the
external os.
• Bimanual examination reveals—The uterus is
either atrophic, normal or may be enlarged
due to spread of the tumor, associated fibroid
or pyometra.
• Rectal examination corroborates the bimanual
findings.
• Regional lymph nodes and breasts are examined
 DIAGNOSIS
• 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.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.
• Ultrasound and color Doppler (TVS): Findings
suggestive of endometrial carcinoma are —
(i) Endometrial thickness > 4 mm.
(ii) Hyperechoic endometrium with irregular
outline.
(iii) Increased vascularity with low vascular
resistance.
(iv) Intrauterine fluid. However, it cannot replace
definitive biopsy.
• 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.
• SONOHYSTEROGRAPHY
-Placement of fluid within the endometrial
cavity to enhance examination of endometrial
lining; improves delineation of polyps VS
other pathologies.
• FBP & LFTS, RFTS
• Glucose tolerence test
• Serum electrolytes
• CXR
• ECG
• + /- CYSTOSCOPY, COLONOSCOPY
• MRI /CT SCAN.
HISTOPATHOLOGIC CLASSIFICATION
• ENDOMETRIOID ADENOCARCINOMA
Is the most common type of EC, accounting for
75 to 80 percent of cases. These tumors are
stimulated by estrogen, are typically are
preceded by endometrial hyperplasia
Most are well differentiated; ciliarly, secretory,
papillary/ villoglandular; adenocarcinoma with
squamous differentiated.
• Mucinous carcinoma
Mucinous EC, by World Health Organization
(WHO) definition, is composed of >50 percent
mucinous cells, and the remainder of the
tumor shows endometrioid morphology.
These are type 1 tumors, which are graded
using the FIGO system. These tumors are
typically low grade with a good prognosis.
• Serous carcinoma
Serous carcinoma is the second most common type
of EC but only accounts for approximately 10
percent of cases.Most serous endometrial
carcinomas have a worse prognosis.
• Clear cell carcinoma
Clear cell EC is an uncommon histologic type (<5
percent) of EC.Like serous carcinoma, this tumor
is typically high grade and often presents at an
advanced stage.
• Mixed cell tumors
Mixed carcinoma with both endometrioid and high-
grade nonendometrioid patterns (usually serous)
may occur.
• Carcinosarcoma (malignant mixed müllerian
tumor) — Carcinosarcomas are rare endometrial
carcinomas (<5 percent) that contain both a
malignant epithelial component (carcinoma) and a
malignant stromal component (sarcoma)
Rare subtypes — Rare EC subtypes include:
• Neuroendocrine carcinomas (low-grade and
high-grade) and undifferentiated ECs can
occur in the endometrium, but are rare.
• Dedifferentiated carcinomas that are
composed of FIGO grade 1 or 2 endometrioid
adenocarcinoma
 STAGING
I Tumor confined to the corpus uteri
• IA No or less than half myometrial invasion
• IB Invasion equal to or more than half of
the myometrium
II Tumor invades cervical stroma, but does not
extend beyond the uterus
IIILocal and/or regional spread of the tumor
• IIIA Tumor invades the serosa of the corpus
uteri and/or adnexae
• IIIB Vaginal involvement and/or parametrial
involvement
• IIIC Metastases to pelvic and/or para‐aortic
lymph nodes
• IIIC1 Positive pelvic nodes
• IIIC2 Positive para‐aortic nodes with or without
positive pelvic lymph nodes
IVTumor invades bladder and/or bowel mucosa,
and/or distant metastases
• IVA Tumor invasion of bladder and/or bowel
mucosa
• IVB Distant metastasis, including intra‐
abdominal metastases and/or inguinal nodes)
 MANAGEMENT OF ENDOMETRIAL CARCINOMA

Preventive
Primary prevention includes:
• Strict weight control beginning early in life.
• To restrict the use of estrogen after
menopause in nonhysterectomized women. If
at all it is needed, cyclic administration of
progestogen preparations are added and
continued under supervision
• Education as regard the significance of
irregular bleeding per vaginum in
perimenopausal and postmenopausal period.
Secondary prevention includes:
• Screening of ‘high risk’ women at least in
menopausal period to detect the
premalignant or early carcinoma is a positive
step.
Curative
• Surgery „
• Radiotherapy
• „ Chemotherapy „
• Combined therapy
In stage 1,surgery is the mainstay of treatment
• Patients with endometrial cancer should
undergo hysterectomy, Bilateral
Salpingoophorectomy, and surgical staging
(including pelvic washings and
lymphadenectomy
In stage II,management options are:
• A. Radical hysterectomy bilateral
salpingooophorectomy with pelvic and para-
aortic lymphadenectomy
• B. Combined radiation and surgery: Radiation
(external and intracavitary) followed in 6
weeks by total abdominal hysterectomy and
bilateral salpingo-oophorectomy.
• C. Initial surgery (modified radical
hysterectomy) followed by external and
intravaginal radiation.
Stage III and IV
• In locally advanced disease: Adjuvant
chemotherapy followed by pelvic radiation is
done.
Combination chemotherapy is commonly used.
Drugs comprise: adriamycin, cisplatin and
cyclophosphamide.
External pelvic and intracavitary radiation
followed by extended hysterectomy 6 weeks
later in cases of :
− Highly anaplastic tumor
− Papillary serous carcinoma
− Clear cell carcinoma.
These tumors have got high rate of recurrence
both locoregional and systemic.
 PROGNOSIS
Poor Prognostic Variables in Endometrial Cancer
• Advanced surgical stage
• Older age
• Histologic type: UPSC or clear cell adenocarcinoma
• Advanced tumor grade
• Presence of myometrial invasion
• Presence of lymphovascular space invasion
• Peritoneal cytology positive for cancer cells
• Increased tumor size
• High tumor expression levels of ER and PR
 SUMMARY
Endometrial cancer is the most common
gynaecologic malignancy in high income
countries and the second most common
gynaecologic cancer world wide
Hysterectomy is the most aggressive approach;
more conservative approaches include
achieving and maintaining a normal body
mass index and using progestin-dominant
contraceptives
 REFERENCES
• FIGO cancer report 2018
• DC Dutta’s textbook of Gynaecology 6th edition
• www.uptodate.com
• Williams Gynaecology 3rd Edition
• WHO Classification of tumors of the uterine co
rpus