Seminar presentation

2. WHAT IS
ENDOMETRIUM?The inner lining or layer of the uterine wall, the one that
grows and sheds during menstruation

3. ANATOMY OF THE
UTERUS

4. Uterus is a female reproductive organ located between the
bladder and the rectum, in the pelvic area.
ANATOMY OF THE
UTERUS

5. ANATOMY OF THE
UTERUS

6. The uterus consists of the following 3 tissue layers.
ANATOMY OF THE
UTERUS

7. ENDOMETRIA
LHYPERPLA
SIA

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

17. MANAGEMENT
Transcervical Resection of Endometrial (TCRE)

18. MANAGEMENT
Microwave Endometrial Ablation (MEA)

19. ENDOMETRIA
LCARCINOM
A

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.

21. ADENOCARCIN
OMA

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

28. DIAGNOSISDIAGNOSIS

29. DIAGNOSIS
1. Pelvic examination
 Bimanual
 Speculum
2. Transvaginal ultrasound scan
3. MRI scan
4. Dilatation and Curettage (D&C)
5. Endometrial biopsy
6. Hysteroscopy
7. Endometrial sampling
 Pipelle
 Vabra devices

30. DIAGNOSIS
PELVIC EXAMINATION

31. DIAGNOSIS
TRANSVAGINAL ULTRASOUND SCAN

32. DIAGNOSIS
MRI SCAN

33. DIAGNOSIS

34. HYSTEROSCOPIC
VIEW
ENDOMETRIAL CARCINOMA ENDOMETRIAL
HYPERPLASIA

35. PIPELLE & VABRA
DEVICES

37. FIGO CLASSIFICATION
2009

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

39. MANAGEMENTMANAGEMENT

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

42. SURGICAL
INTERVENTION

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)

45. SARCOM
A

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
/

52. THANK
YOU