8. Increased proliferation of the endometrial glands relative
to the stroma, resulting in an increased gland-to-stroma
ratio when compared with normal proliferative
endometrium.
DEFINITION
9. Inactivation of the PTEN tumor suppressor
gene. When PTEN is inactive, AKT
phosphorylation and it stimulates protein
synthesis and cell proliferation and inhibits
apoptosis. Loss of PTEN function may also
activate pathways normally activated by
estrogen.
PATHOPHYSIOLOGY
10. Endometrial hyperplasia is classified as simple and
complex. It also is classified by whether certain cell
changes are present or absent. If abnormal changes are
present, it is called atypical. The terms are combined to
describe the exact kind of hyperplasia.
TYPES
1. Simple hyperplasia
2. Complex hyperplasia
3. Simple atypical hyperplasia
4. Complex atypical hyperplasia
11. Incidence without atypia and with atypia peaks in the early
postmenopausal years and in the early 60s, respectively.
Simple : 142 in100,000 woman in early 50s
Complex : 213 in 100,000 women in early 50s 1995 - 2014
Atypical : 56 in 100,000 women in early 60s.
INCIDENCE
12. Most common sign of hyperplasia is abnormal uterine
bleeding.
SIGNS AND
SYMPTOMS
1. Heavy bleeding during menstrual period
2. Period lasts longer than usual
3. Menstrual cycle shorter than 21 days
4. Any bleeding after menopause
13. RISK FACTORS
ENDOGENOUS
OESTROGEN
EXOENOUS OESTROGEN
OTHERS
① Nulliparity
② Infertility / PCOS
③ Early menarche or late
menopause
④ Obesity
⑤ Functioning ovarian tumor
① Hormone replacement
therapy
② Use of Tamoxifen
Diabetes | Hypertension | Hypothyroidism
Hereditary Non-polyposis Colorectal Syndrome
14. AETIOLOGY
Failure of ovulation
Prolonged administration of estrogenic
steroids
Polycystic ovaries
Cortical stromal hyperplasia
Granulosa-theca cell tumors of the ovary.
15. TYPES OF ENDOMETRIAL
HYPERPLASIASIMPLE HYPERPLASIA WITHOUT ATYPIA
COMPLEX HYPERPLASIA WITHOUT ATYPIA
COMPLEX HYPERPLASIA WITH ATYPIA
Cystic Hyperplasia or Mild hyperplasia
Cystic dilated glands, non-neoplastic, due to
anovulatory cycles.
Adenomatous Hyperplasia
Overcrowded, closely opposed glands where some
are neoplastic with PTEN mutation
Complex / Adenomatous Hyperplasia with Atypia
Overcrowded glands with cytological atypid. Most
are neoplastic andcontain PTEN mutation.
16. MANAGEMENT
MEDICAL
SURGICAL
Simple endometrial hyperplasia without atypia responds to high-dose
progestogens, with repeat histology after three months.
This can be effectively delivered by the levonorgestrel intrauterine system
(IUS)
It is also given orally, higher regression rates and reduced need for
hysterectomy, even for atypical hyperplasia.
Relapse occurs relatively frequently (approximately 14% with the IUS and
30% with oral treatment) after regression, especially in complex hyperplasia,
so long-term follow-up is advised.
Transcervical resection of the endometrium (TCRE)
Hysterectomy - usually advised for atypical endometrial hyperplasia
20. ENDOMETRIAL
CARCINOMA
The most common type of CA affecting the
uterus is Adenocarcinoma which arises from the
lining of uterus (endometrium)
Endometrial cancer is now the most common
gynaecological malignancy worldwide and the
fourth most common female cancer after breast,
colon and lung.
22. 30% of all gynaecological malignancies
The lifetime risk of developing the cancer is 1.1%
The lifetime of death probability is 0.4%
Good prognosis with early diagnosis
The mean age of diagnosis is 54, can also be diagnosed at their
reproductive age
Rises sharply in the mid 40s
INCIDENCE
23. RISK FACTORS
1. Post menopause
2. Atypical hyperplasia of endometrium
3. Nulliparity
4. Early puberty
5. Late menopause
6. Treatment with unopposed oestrogen
7. Treatment with tamoxifen
8. Family history of endometrium cancer
9. Obesity
10. Hypertension
11. Diabetes
12. Associated medical conditions (breast, colon, ovarian CA)
24. AETIOLOGY
Idiopathic, however it is associated with high circulating levels of oestrogen
Post-menopause women: conversion of androgens to oestrogens occurs in
adipose tissue
– Selective oestrogen receptor modulator (SERM)
– Increase risk of endometrial CA, most likely d/t weak oestrogenic effect on
endometrium
– Most common genetic link is with hereditary non-polyposis colorectal cancer
syndrome (HNPCC), an autosomal dominant inheritance resulting in mismatch
repair genes MLH1, MSH2 and MSH6.
TAMOXIFEN
GENETIC CAUSES
25. ENDOMETRIOID ADENOCARCINOMA
(TYPE 1)
Account for 90% of endometrial adenocarcinomas
Oestrogen dependant (obesity, polycystic ovarian
syndrome / Stein-Leventhal syndrome, exogenous
estrogen use, tamoxifen use)
Occur in younger women
Good prognosis
Includes endometrioid and mucinous carcinoma
PTEN, KRAS and PAX2 gene alterations are common
Endometrial intraepithelial neoplasia (EIN) / atypical
hyperplasia is regarded as the precursor lesion
26. SEROUS PAPILLARY CARCINOMA
(TYPE 2)
High grade carcinomas
Non-oestrogen dependant
Elderly women
Poorer prognosis than Type 1
Includes serous, clear cell, undifferentiated carcinoma
and carcinosarcoma
Characterized by early alterations in TP53
Serous intraepithelial carcinoma, referred to as
‘endometrial intraepithelial Carcinoma’ (EIC) has been
proposed as the preinvasive precursor lesion.
27. CLINICAL FEATURES
PRE-MENOPAUSAL MENOPAUSAL
Abnormal bleeding
Intermenstrual bleeding
Blood stained vaginal
discharge
Heavy menstrual bleeding
Lower abdominal pain
Dyspareunia.
Abnormal bleeding
Post-menopausal bleeding
(10% most likely to have
malignancy
38. FIGO CLASSIFICATION
2009
In general, a two tier system can be also applied, with Grade 1 and 2 being
considered low grade, and FIGO 3 being considered high grade
Other carcinoma types; serous, clear cell, carcinosarcoma, undifferentiated,
mixed) are by definition HIGH GRADE
Grade 1: predominant glandular growth and < 5% non-squamous solid
component; glandular architecture is identified by the presence of
patent lumina within the gland, relatively preserved polarity of the
epithelium and absent to mild epithelial stratification
Grade 2: 6-50% non-squamous solid component
Grade 3: more than 50% non-squamous solid component
Architectural grading described above is upgraded by one if there is severe
nuclear atypia (pleomorphism, enlargement, prominent nucleoli)
HISTOLOGICAL GRADING
40. CONSERVATIVE
MANAGEMENT
Progestogens are used, particularly administered by
intrauterine system (IUS) or orally, as a conservative
management of disease.
Complications in young women with severe endometrial
atypia or low-grade endometrial cancer who wish to
preserve their fertility.
However, it is risky to use in obese patients with
endometrial cancer, thus, it may not necessarily apply to
obese patients with endometrial cancer.
41. SURGICAL
INTERVENTION Primary treatment, including hysterectomy, bilateral salpingo-
oophorectomy, abdominopelvic washings, lymph node
evaluation
Most common with Stage 1
The extent of surgery depends on grade, MRI stage, patient’s
comorbidities
Standard surgery = total hysterectomy and bilateral
salpingectomy
Patient low grade or MRI staging (< Stage 1B) surgery
If MRI staging suggest cervical involvement radical
hysterectomy + pelvic node dissection.
Tumour high grade (grade 3) / papillary serous pelvic and
para-aortic node dissection.
• 30% risk of nodal disease
43. ADJUVANT
THERAPYPOST-OPERATIVE
RADIOTHERAPY
CHEMOTHERAPY
Reduce local recurrence rate
No effects on survival
1. Local radiotherapy to vaginal vault
High dose radiotherapy (HDR)
Short period of time
2. External beam radiotherapy + HDR
For locally advanced disease
(stage 3)
Combat risk of distant spread of
cancer
44. PROGNOSIS
Five year survival rate : 80 %
Stage 1- 88%
1A: 99%
1B: 66%
Stage 2 - 75%
Stage 3 - 55%
Stage 4 - 16%
Adverse prognostic feature for
survival:
>70 years
High BMI
Grade 3 tumour
Papillary serous / clear cell
histology
Lymphovascular space
involvement
Metastases (nodal / distant)
46. SARCOMAS
Rare tumors (5%) arising from stroma or myometrium.
Classification depends on histological specimen
1. Pure sarcomas (ESS & Leiomyosarcomas)
2. Mixed epithelial sarcomas (Carcinosarcomas)
3. Heterologous sarcomas (Rhabdomyosarcoma)
Most common: Leiomyosarcomas and
Carcinosarcomas
47. PURE SARCOMAS
ENDOMETRIAL STROMAL SARCOMAS (ESS)
LEIOMYOSARCOMA
Perimenopausal women (45 – 50 years old)
Clinical features: Irregular bleeding with soft and enlarged uterus
Majority low grade
Main treatment: Surgery
Rare tumor of uterine smooth muscle (myometrium)
0.75% associated with benign fibroids
Clinial features: Rapidly growing pelvic mass with pain, enlarged and soft uterus
Pre-op diagnosis: MRI (delineate areas of necrosis within the fibroid)
Main treatment: surgery
Adjuvant treatment if mitotic count is high (>10 mitoses per high powered field)
Metastatic spread usually vascular to distant sites such as lungs and brain
48. MIXED EPITHELIAL
SARCOMAS Formerly known as mixed mesenchymal tumors
Containing both carcinoma and sarcoma
Carcinomatous element: glandular
Sarcomatous element: endometrial, stromal, (rare) bone / cartilage / muscle
Majority: post-menopause
Occasionally: previous history of pelvic radiation
Clinical Features:
History of PMB
Fleshy mass protruding from cervix along with enlarged soft uterus
Treatment: surgery followed by post-op radiotherapy
Prognosis:
73% 5 years survival if confined to uterus
25% 5 years survival if spread outside uterus
49. HETEROLOGOUS
SARCOMAS
Rare group of tumors
Consists of sarcomatous tissue not usually found in
the uterus (striated muscle, bone, cartilage)
Most common: Rhabdomyosarcoma
– In children
– Grape-like mass protruding from cervix with a watery
discharge
– Histologically primitive rhabdomyoblasts
– Recurrence rate is high with distant metastases
50. Endometrial stromal
sarcoma (ESS) Leiomyosarcomas Carcinosarcoma Rhabdomyosarcoma
Definition
Tumors of uterine smooth
muscle (myometrium)
Mixed tumors consisting
carcinomatous element
& sarcomatous element
Tumor consists of
sarcomatous tissue not
usually found in uterus
Affecting
Peri-menopausal
Post-menopausal or
previous history of
pelvic radiation
Children
Presentation Irregular
bleeding
Soft and
enlarged uterus
Associated with benign
fibroids
Rapidly growing pelvic
mass
Pain
History of PMB
Fleshy mass
protruding from
cervix
Soft and enlarged
uterus
Grape-like mass
protruding from cervix
with watery discharge
Histologically:
primitive
rhabdomyoblast
Diagnosis History
Abdominal palpation
MRI
Abdominal palpation
Treatment Surgery Surgery
Adjuvant treatment if high
mitotic count
Surgery with post-
operative radiotherapy
Prognosis Low grade Metastatic spread is
vascular to distant sites
5 years survival rate
(75% confined to
uterus, 25% spread out
of uterus)
Recurrence occur with
distant metastases
51. REFERENCES
1. GYNAECOLOGY by Ten Teachers, 19th edition, edited by
Ash Monga and Stephen Dobbs
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1002466
/
HNPCC - Autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers including endometrial cancer, ovary, stomach, small intestines, hepatobiliary tract, upper urinary tract, brain and skin.
The preoperative use of pelvic MRI scan showing (A) deep myoinvasion with (B) extension to the uterine serosa and cervix, and (C) a complex ovarian cyst. Metastatic disease was identified in the pelvic lymph nodes following staging surgery (stage IIIC).