Uterine Cancer

Question 1

What causes dysfunctional uterine bleeding?

Answer 1

• endometrial polyps
  
  • common
  • often occur around/after the menopause
• endometrial hyperplasia
  
  • simple
  • complex
  • atypical (precursor of carcinoma)

Question 2

What causes endometrial hyperplasia?

Answer 2

Often unknown, persistent oestrogen stimulation

Question 3

How does endometrial hyperplasia present?

Answer 3

Abnormal bleeding (DUB or postmenopausal bleeding)

Question 4

Describe simple endometrial hyperplasia

Answer 4

General distribution

Glands and stroma

Glands are dilated, not crowded

Cytology appears normal

Question 5

Describe complex endometrial hyperplasia?

Answer 5

Focal distribution

Glands involved

Glands are crowded

Cytology is normal

Question 6

Describe atypical endometrial hyperplasia

Answer 6

Focal distribution

Glands involved

Glands ar crowded

Atypical cytology

Question 7

What is the peak incidence of endometrial carcinoma?

Answer 7

50-60, uncommon under 40

Question 8

In young women with suspected endometrial carcinoma what should be considered?

Answer 8

Underlying predisposition;

• PCOS
• Lynch syndrome

Question 9

What are the two main groups and different precursor lesions (of endometrial carcinoma)?

Answer 9

Endometroid carcinoma: precursor atypical hyperplasia

Serous carcinoma: precursor serous intraepithelial carcinoma

Question 10

How does endometrial carcinoma usually present?

Answer 10

Atypical bleeding

Question 11

Decribe the macroscopic appearance of endometrial carcinoma?

Answer 11

Large uterus; polypoid

Question 12

Decribe the microscopic appearance of endometrial carcinoma?

Answer 12

Most are adenocarcinomas

Most are well differentiated

Question 13

How does endometrial carcinoma spread?

Answer 13

Directly into myometrium and cervix

Lymphatics

Haematogenous

Question 14

________ ( and ______) are type 1 endometrial carcinomas, accounting for __%

________ ( and ____ __) are type 2 endometrial carcinomas

Answer 14

Endometroid (and mucinous) are type 1 endometrial carcinomas, accounting for 80%

Serous ( and clear cell) are type 2 endometrial carcinomas

Question 15

What are type 1 endometrial carcinomas associated with

Answer 15

Unopposed oestrogen

Associated with atypical hyperplasia

Question 16

Who is affected by type 2 endometrial carcinomas?

Answer 16

Elderly post-menopausal women

TP53 often mutated

Question 17

What mutations are associated with endometrial carcinomas?

Answer 17

PTEN, KRAS, PIK3CA

Question 18

What type of instability is endometrial carcinoma associated with?

Answer 18

Microsatellite instability

• germiline mutation of mismatch repair genes (lynch syndrome)

Question 19

What is a microsatellite

Answer 19

A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from one to six or more base pairs) are repeated, typically 5–50 times

Question 20

Why is obesity a risk factor for endometrial cancer?

Answer 20

Endocrine and inflammatory effects of adipose tissue

Question 21

How do adipocytes stimulate endometrial proliferation?

Answer 21

Express aromatase that converts ovarian androgens into oestrogens, which induce endometrial proliferation

Question 22

Why is the level of biologically active hormone higher in obese women?

Answer 22

Sex hormone-binding globulin levels are lower in obese women, therefore the level of unbound biologically active hormone is higher

Question 23

How does altered insulin action in obese women predispose to endometrial cancer?

Answer 23

The level of insulin binding globulins is reduced and free insulin levels are elevated. Insulin/insulin-like growth factors (IGF) exert proliferative effect on endometrium

Question 24

What is lynch syndrome?

Answer 24

Hereditary non-polyposis colorectal cancer

High risk of endometrial (lifetime risk of 28%) and an increased probalility of developing ovarian cancer

Question 25

What causes lynch syndrome?

Answer 25

Inheritance of defective DNA mismatch repair gene. autosomal dominant inheritance.

Question 26

How can lynch syndrome tumours be identified?

Answer 26

Immunohistochemistry staining of the tumour for mismatch repair proteins can help identify them Test cancer tissue for microsatellite instability

Question 27

What mutations are type II endometrial carcinomas associated with?

Answer 27

TP52 mutation and overexpression

Question 28

How do type II tumours spread?

Answer 28

Spreads along fallopian tube mucosa and peritoneal surfaces so can present with extrauterine disease

Question 29

Type II endometrial carcinoma is more aggressive than \_\_\_\_\_\_\_\_/\_\_\_\_\_\_\_\_ carcinoma

Answer 29

Type II endometrial carcinoma is more aggressive than endometroid/mucinous carcinoma

Question 30

What is the treatment for type II endometrial carcinoma?

Answer 30

Extensive surgery and adjuvant chemo/radiotherapy

Question 31

How is serous carcinoma characterised?

Answer 31

By a complex papillary and/or glandular architecture with diffuse, marked nuclear polymorphism

Question 32

Endometrial carcinoma typically infiltrates what?

Answer 32

Myometrium

Question 33

Serous carcinoma may spread early to the ?

Answer 33

Peritoneal cavity

Question 34

Why does endometroid carcinoma have a good prognosis?

Answer 34

Is usually confined to uterus at presentation

Question 35

How is endometrial carcinoma staged?

Answer 35

Stages I-IV

Question 36

What does prognosis of endometrial carcinoma depend on?

Answer 36

Stage Histological grade Depth of myometrial invasion

Question 37

What is the treatment for endometrial carcinoma?

Answer 37

Hysterectomy; chemo/radiotherapy

Question 38

How are endometroid carcionomas primarily graded?

Answer 38

By their architecture; Grade 1: 5% or less solid growth Grade 2: 6-50% solid growth Grade 3: \> 50% solid growth

Question 39

Stage I endometrial cancers are confined to the

Answer 39

Uterus

Question 40

What endometrial cancer arises from stroma?

Answer 40

Endometrial stromal sarcoma

Question 41

Which endometrial cancer is a mixed tumour with malignant epithelial and stromal elements?

Answer 41

Carcinosarcoma

Question 42

Describe endometrial stromal sarcoma?

Answer 42

Rare, cells resemble endometrial stroma Infiltrate myometrium and often lymphovascular spaces

Question 43

How does endometrial stromal sarcoma present?

Answer 43

AUB but initial presentation may be metastases- most commonly lung or ovary

Question 44

Carcinomasarcomas are responsible for \<\_% of uterine malignancies

Answer 44

\<5%

Question 45

What is seen in 50% of carcinosarcoma cases?

Answer 45

Heterologous elements- rhabdomyosarcoma, chondrosarcoma, osteosarcoma

Question 46

What conveys the worst prognosis in carcinosarcoma?

Answer 46

Presence of rhabdomyosarcomatous component

Question 47

Which tumour commonly protrudes through the cervical canal?

Answer 47

Carcinosarcoma

Question 48

What are the smooth muscle tumours of the myometrium?

Answer 48

**Leiomyoma (fibroid);** Very common Associated with menorrhagia, infertility **Leiomyosarcoma (rare)**

Question 49

Describe a leiomyosarcoma?

Answer 49

Malignant smooth muscle tumour commonly displaying a spindle cell morphology

Question 50

What is the commonest uterine sarcoma?

Answer 50

Leiomyosarcoma

Question 51

Leiomyosarcoma accounts for \_-\_% of all uterine malignancies Most occur in women \> __ years Overall 5 year survival rates \_\_-\_\_%

Answer 51

Leiomyosarcoma accounts for 1-2% of all uterine malignancies Most occur in women \> 50 years Overall 5 year survival rates 15-25%

Question 52

What are the commonest symptoms of leiomyosarcoma?

Answer 52

Abnormal vaginal bleeding, palpable pelvic mass and pelvic pain

Question 53

What do leiomyosarcoma and endometrial stromal sarcoma share?

Answer 53

A scoring system