ENDOMETRIAL

CANCERS
PROFESSOR . AJENIFUJA
RELEVANT ANATOMY
LEARNING OBJECTIVES

• At the end of this lecture, students are to know

• 1. Epidemiology of endometrial cancer
• 2. Relationship between endometrial cancer and endometrial hyperplasia
• 3. Types of endometrial cancers
• 4. Risk factors for common endometrial cancer
• 5. Protective factors for endometrial cancer
• 6. Clinical features and diagnosis of endometrial cancer
• 7. Management of endometrial cancer
EPIDEMIOLOGY

• Is the most common gynae cancer in developed countries

• It is a disease of post-menopausal women
• Globally more than half a million were diagnosed with endometrial cancer in 2012
• Despite the high incidence, it accounts for a smaller proportional no of deaths unlike
cancer of the cervix
• Due to early diagnosis
EPIDEMIOLOGY

• There are two distinct types of endometrial cancer

Type 1: Related to hormonal (Oestrogen) stimulation of the endometrium and develops in a
background of endometrial hyperplasia
a. The oestrogen may be endogenous or exogenous
b. Endogenous oestrogen may be from oestrogen secreting tumours in the body e.g. granulosa
tumours
c. Exogenous oestrogen e.g. hormonal replacement therapy
d. Usage of Tamoxiphene
EPIDEMIOLOGY

• The unopposed oestrogen leads to endometrial hyperplasia.

• Simple hyperplasia (1%)

• complex hyperplasia without atypia (3%)

• complex hyperplasia with atypia (28%)

• endometrial cancer (well differentiated adenocarcinoma).

 EPI
• Type 1 Tumours: are
well differentiated, i.e low grade
endometrioid,
Diagnosed early in stage
Good prognosis.
Usually obese patients

Type II Endometrial cancers are unrelated to hormones

• tend to be a higher grade and stage at diagnosis
• poorly differentiated, often non-endometrioid
• (serous, clear cell), and are more virulent.
• Patients are often multiparous
• Poor prognosis
RISK FACTORS

• Age. It is uncommon before 45 years. About 70% of patients are menopausal. 95% occur in women 40 years and above.
• Nulliparity due long years of infertility. Married nulliparous women have higher incidence than single nulliparous women
• Early age of menarche
• Late menopause
• Tamoxifen therapy.
• Obesity. In obese women, adrenal androgens (Androstenedione are converted to oestrone
• Polycystic Ovarian syndrome . Have no ovulation, no corpus luteum, no progesterone hence unopposed oestrogen
• Lack of physical activity. Sedentary life style
 RISK FACTORS

• Hereditary causes
 The Lynch syndrome. Hereditary nonpolyposis colorectal carcinoma
(HNPCC).
It is inherited in an autosomal dominant fashion. It accounts for 2 to 5% of EC especially when
diagnosed below 50 years.
• Since 40-60% of patients with this develop endometrial ca., do an EMB at age 35 in
-women with HNPCC-associated mutations
-women with a family member with this mutation
-women from families with autosomal dominant predisposition to colon ca.
Doing an ultra sound is not enough
PROTECTIVE FACTORS

• Usage of Combined Oral Contraceptive pills. Contains progestrone

• Pregnancy at older ages.
• Short inter pregnancy intervals.
• Cigarette smoking. Causes premature menopause
CLINICAL FEATURES

• Abnormal vaginal bleeding

Differentials of abnormal uterine bleeding
• Exogenous estrogen use- ie tamoxifen
• Atrophic endometritis/vaginitis
• Endometrial/cervical polyps
• Endometrial hyperplasia
• Endometrial Cancer
• Other gynecologic cancers
• 10% of post menopausal women with abnormal uterine bleeding will have cancer on
biopsy
• Abnormal vagina discharge
• Endometrial hyperplasia found incidentally
• On Pap smear, the presence of AGUS, Adenocarcinoma in situ
• Abdominal pain, pelvic pressure and pain in patients with intra peritoneal disease
• Hysteroscopy w/ D & C (gold standard)
• Detection rates of endometrial ca. by pipelle was between 91 and 99%
• Detection of hyperplasia was 81%
• Recommendation: EMB as initial test; Hysteroscopy/D&C if EMB
inconclusive or high suspicion (hyperplasia with atypia, pyometria,
presence of necrosis, or persistant bleeding)
HIGH RISK PATIENTS

• Post menopausal bleeding

• Endometrial cells on Pap
• Perimenopausal with irregular heavy menses, increasingly heavy
menses
• Premenopausal with abnormal uterine bleeding with history of
anovulation
SCREENING

• No effective screening method is available

• People at risk should be considered for screening
• Endometrial biopsy
• Easy to do with office EMB
• About 50% of women with endometrial cancer have malignant cells
on Pap smear
• 6% of post menopausal women with normal endometrial cells on Pap
smear have endometrial cancer
• Tamoxifen increases the risk of endometrial cancer by 2-3 folds
• Endometrial cancer should be excluded in
1. Women with post menopausal bleeding
2. Post menopausal women with pyometria
3. Asymptomatic women with endometrial cells on Pap smear
4. Peri menopausal women with inter menstrual bleeding or increasingly heavy periods
5. Pre menopausal women with abnormal uterine bleeding particularly if there is a history
of anovulation
In postmenopausal women, an endometrial thickness more than 4-5 mm is
suggestive.
If there is a thick endometrium then do the following
Dilatation & Curettage
 Endometrial biopsy, has a false negative rate of 10%
Negative endometrial biopsy should have fractional curettage
Hysteroscopy
ENDOMETRIAL BIOPSY
INVESTIGATIONS

• Endometrial biopsy
• Ultrasound
• For suspected advanced stage may need:
• Cystoscopy
• Sigmoidoscopy
• Pelvic and Abdominal CT
• Laboratory investigations
• CBC
• Electrolytes Urea and Creatinine
• Liver function tests
• ECG, CXR
STAGING

• I: Confined to uterine corpus

• IA: limited to endometrium
• IB: invades less than ½ of myometrium
• IC: invades more than ½ of myometrium
STAGING

• II: invades cervix but not beyond uterus

• IIA: endocervical gland involvement only
• IIB: cervical stroma involvement
 STAGING

• III: local and/or regional spread

• IIIA: invades serosa/adnexa, or positive cytology
• IIIB: vaginal metastasis
• IIIC: metastasis to pelvic or para-aortic
lymph nodes
STAGING

• IVA: invades bladder/bowel mucosa

• IVB: distant metastasis
STAGING

• Direct extension
• most common

• Transtubal
• Lymphatic
• Pelvic usually first, then para-aortic

• Hematogenous
• Lung most common
• Liver, brain, bone
• Stage IB or less: total hyst/BSO/PPALND, cytology
• Stage IC to IIB: total hyst/BSO/PPALND, cytology, adjuvant pelvic XRT
• Stage III: total hyst/BSO/PPALND, cytology, adjuvant chemotherapy
• Stage IV: palliative XRT and chemotherapy
TREATMENT

• The most common method of treatment is TAH+BSO

• For type 11 EC, the lymph nodes and the omentum should be removed
• Radiotherapy is an option in patients with severe comorbidities AND and who are anaesthetic risk
Mordibly obese
Hypertensive
DM
PROGNOSIS

• Age. The older the woman the worse the prognosis

• Histological type. Worse with serous and clear cells
• Vascular space invasion
• Grade, the higher the grade the worse the prognosis
OTHER ENDOMETRIAL CANCERS

• Leiomyosarcoma
• Rapidly growing fibroid should be evaluated

• Stromal sarcoma
• Carcinosarcoma (MMMT)
• Leionmyosarcoma
May develop de novo
May arise from an existing leiomyoma
Is very aggressive and spread haematogenously
Prognosis is very poor
Management is by surgery followed by adjuvant therapy
Radiation of Chemotherapy
VULVAR INTRAEPITHELIAL NEOPLASIA

• Preinvasive diseases of the vulva are currently designated by the term Vulvar
Intraepithelial Neoplasia by the International Society for the Study of Vulvovaginal
Diseases
• The term includes both squamous and non squamous lesions
INCIDENCE

• It is an uncommon disease but the incidence is increasing particularly in young women

• The neoplastic biologic continum from VIN1 through VIN111 to invasive cancer has not
been established unlike CIN.
• This is because the progression of VIN 111 to invasive cancer remains controversial, but
the malignant potential is undisputed.
• There is no evidence that VIN1 has any malignant potential
VIN

• A.
• SQUAMOUS INTRAEPITHELIAL NEOPLASIA
• VIN1-Mild dysplasia
• VIN11-Moderate dysplasia
• VIN111-Severe dysplasia/ carcinoma in situ
• B
• Non squamous intraepithelial Neoplasia
NON SQUAMOUS INTRAEPITHELIAL NEOPLASIA

• A Paget disease
• B. Tumours of the melanocytes, non invasive melanoma in situ
RISK FACTORS

• Specific HPV esp serotype 16, cigarette smoking, nutritional deficiency, poor personal
hygiene, granulomatous vulvar diseases, endogenous and exogenous systemic immune
suppression.
• VIN is best divided into low grade and high grade.
• Low grade—VIN1
• High grade VIN11 to VIN 111
VIN

• High grade lesions tend to belocalised and unifocal in older patients while in young
women they are frequently multi focal and extensive
• SYMPTOMS
• Unlike CIN most VIN esp the high grade are symptomatic.
• Pruritus
TREATMENT

• The therapeutic alternatives for VIN 3 are simple excision, laser ablation, and
• superficial vulvectomy with or without split-thickness skin grafting.
VULVAR CANCER

• It is a rare disease
• Accounts for 4% of Gynae cancer
• It is a disease of post menopausal women
• Majority over 85% are squamous carcinoma
• Others are:
 Malignant melanoma
 Bartholin’s gland carcinoma
 Pagets disease
AETIOLOGY

• Is a matter of great debate and controversies

• VIN
• HPV infection
• Squamous hyperplasia
• Lichen Sclerosus
• Smoking
• Immuno suppression
SYMPTOMS

• Most patients are symptomatic

• Vulval mass or swelling
• Ulcerating lesions
• Vulval itching
 Despite this, delay is common
Due to embarrassment
DIAGNOSIS

• Wedge biopsy of the vulva to include both normal and abnormal tissues.
Investigations
• CBC.
• Blood sugar.
• Biochemistry.
• RFT & LFT.
• CXR.
STAGING

• Stage I Tumor confined to the vulva

• IA Lesions ≤2 cm in size, confined to the vulva or perineum and with stromal
• invasion ≤1.0 mm⁎, no nodal metastasis
• IB Lesions N2 cm in size or with stromal invasion N1.0 mm⁎, confined to the
• vulva or perineum, with negative nodes
STAGING

• Stage II Tumor of any size with extension to adjacent perineal structures (1/3 lower
• urethra, 1/3 lower vagina, anus) with negative nodes
• Stage III Tumor of any size with or without extension to adjacent perineal structures
• (1/3 lower urethra, 1/3 lower vagina, anus) with positive inguino-femoral
• lymph nodes
STAGING

• IIIA (i) With 1 lymph node metastasis (≥5 mm), or

• (ii) 1–2 lymph node metastasis(es) (b5 mm)
• IIIB (i) With 2 or more lymph node metastases (≥5 mm), or
• (ii) 3 or more lymph node metastases (b5 mm)
• IIIC With positive nodes with extracapsular spread
STAGING

• Stage IV Tumor invades other regional (2/3 upper urethra, 2/3 upper vagina), or
• distant structures
• IVA Tumor invades any of the following:
• (i) upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or
• fixed to pelvic bone, or
• (ii) fixed or ulcerated inguino-femoral lymph nodes
STAGING

• IVB Any distant metastasis including pelvic lymph nodes

• The depth of invasion is defined as the measurement of the tumor from the epithelial
stromal
• junction of the adjacent most superficial dermal papilla to the deepest point of
FIGO STAGE FIVE-YEAR SURVIVAL (%)

• Stage I. 90+%
• Stage II. 81%
• Stage III. 48%
• Stage IV. 15%
• Overall survival 75%
DEFINTIVE TREATMENT

• FOR LOCAL DISEASE

 Wide local excision
• LOCAL REGIONAL DISEASE
 Radical vulvectomy
OTHER VULVAR CANCERS

• Malignant melanoma
• Adenocarcinoma of the Bartholin’s gland
• Metastatic cancers
VAGINA CANCER

• Very rare cancers

• Types are :
• Squamous cell carcinoma
• Malignant melanoma
• Sarcoma (from the smooth muscle of the vagina)
RISK FACTORS

• Age, more in older women

• Use of DES. Diethyl stilboestrol
• Vagina adenosis
• Smoking HPV