Uterine Cancer

Question 1

What are the most common causes of dysfunctional uterine bleeding?

Answer 1

Endometrial polyps

Endometrial hyperplasia

Question 2

What are polyps? When do they normally occur? What do they contain?

Answer 2

• overgrowth of endometrium
• contain glands and stroma
• typically benign but can be malignant
• often occur around or after the menopause

Question 3

If cytology is atypical there is a low risk of progression to cancer. TRUE/FALSE?

Answer 3

FALSE

- high risk of progression to endometrial cancer

Question 4

Describe the difference in histological appearance between simple and complex endometrial hyperplasia?

Answer 4

SIMPLE

• glands irregular shaped rather than round
• glands dilated but not crowded
• Lots of stroma visible

COMPLEX
- glands crowded and push stroma away
=> not much stroma present
- normal nuclei lining up along bottom of cells (as complex hyperplasia is not atypical)

Question 5

Cytology in both simple and complex endometrial hyperplasia is normal. TRUE/FALSE?

Answer 5

TRUE

Question 6

If cytology is abnormal and there is a high risk of developing endometrial cancer what treatment is offered?

Answer 6

Hysterectomy

as long as no contraindications

Question 7

What signs on histology of endometrial hyperplasia would indicate that malignancy is present?

Answer 7

• once glands start to fuse

Question 8

What is thought to cause endometrial hyperplasia?

Answer 8

Causes: often unknown

BUT may be persistent oestrogen stimulation

Question 9

At what age is endometrial carcinoma most common?

Answer 9

Peak incidence 50 ‐ 60 years

uncommon under 40

Question 10

If a younger woman was to present with endometrial carcinoma, what underlying causes may you consider?

Answer 10

• Polycystic ovary syndrome (PCOS)

- Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer)

Question 11

Patients with Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer) are just as likely to have their first presentation be an endometrial cancer instead of a colorectal cancer. TRUE/FALSE?

Answer 11

TRUE

- condition is usually picked up on presentation of either cancer

Question 12

What are the precursor lesions to endometrial cancer?

Answer 12

Endometrioid carcinoma
=> precursor atypical hyperplasia

Serous carcinoma
=> precursor serous intraepithelial carcinoma

Question 13

How does endometrial carcinoma usually appear macroscopically?

Answer 13

Macroscopic

• Large uterus
• polypoid appearance

Question 14

How does endometrial carcinoma usually appear microscopically?

Answer 14

• Microscopic
– Most are adenocarcinomas (glandular tissue)
– Most are well differentiated

Question 15

How do endometrial carcinomas usually spread?

Answer 15

• Spread
– Directly into myometrium and cervix
– Lymphatic
– Haematogenous

Question 16

What are the 2 main types of endometrial carcinoma?

Answer 16

1. Endometrioid (and mucinous) – TYPE 1 tumours (80%)
   - Due to unopposed oestrogen
   - From atypical hyperplasia
2. Serous (and clear cell) – TYPE 2 tumours
   - Not associated with unopposed oestrogen
   - Affect elderly post‐menopausal women
   - TP53 often mutated => aggressive cancers

Question 17

What genetic mutations are associated with Type 1 Endometrioid tumours?

Answer 17

PTEN, KRAS, PIK3CA mutations

Question 18

Why does obesity increase the risk of endometrial cancer?

Answer 18

• Adipocytes express aromatase
  => converts ovarian androgens into oestrogens
  => endometrial proliferation
• Insulin action is often altered in obese women
• insulin-binding globulins = reduced
• free insulin levels = elevated
• Insulin and insulin-like growth factors (IGF) make endometrium proliferate

Question 19

Why does Lynch syndrome put women at an increased risk of cancer?

Answer 19

• inheritance of a defective DNA mismatch repair gene
  => when cells are proliferating and mutate, they are not removed properly
• causes microsatellite instability (short stretches of DNA are not the same across all cells anymore) - this is a symptom of DNA mismatch repair

Question 20

Lynch Syndrome is Autosomal ___________?

Answer 20

• Autosomal dominant

Question 21

How do serous endometrial carcinomas spread ?

Answer 21

Spreads along Fallopian tube mucosa and peritoneal surfaces
=> can easily present with extrauterine disease
=> More aggressive than endometrioid carcinoma

Question 22

Describe the histological appearance of serous endometrial carcinoma?

Answer 22

• complex papillary and/or glandular architecture
• nuclear pleomorphism
• inflammatory cells due to reaction with myometrium
• myometrial invasion

Question 23

Describe the histological appearance of an endometrial clear cell cancer?

Answer 23

• rounded glands

- cogwheel change (lines into centre of round gland)

Question 24

Endometroid carcinoma is usually confined to the uterus at presentation. TRUE/FALSE?

Answer 24

TRUE

=> good prognosis

Question 25

What factors is the prognosis of endometrial carcinoma based upon?

Answer 25

Stage (I-IV) Histological grade Depth of myometrial invasion

Question 26

Describe how endometrioid carcinomas are staged according to their architecture

Answer 26

- if well differentiated - still looks like glandular tissue - if it gets aggressive, glandular cells forget what type of tissue they are meant to form, and instead form solid sheets Grade 1 5% or less solid growth Grade 2 6-50% solid growth Grade 3 >50% solid growth

Question 27

How are endometrial tumours usually staged (I-IV)?

Answer 27

I - myometrial invasion II - cervical stroma invasion III - Local spread IV - Distant metastases or invading bladder/bowel

Question 28

What other endometrial cells can become cancerous?

Answer 28

Endometrial stromal sarcoma - tumour from mesenchyma Carcinosarcoma - Mixed tumour => epithelial and stromal elements - Still a carcinoma but goes crazy and can form bone, cartilage or neuro tissue

Question 29

Once a tumour breaches the serosa of the uterus how does it spread?

Answer 29

"falls off" => into pelvis => onto omentum => into Pouch of Douglas

Question 30

How are carcinosarcomas usually treated and why may this be a problem in the age group this cancer are normally found in?

Answer 30

- Treated like serous carcinomas (aggressive) - Patient group is normally elderly => may not be suitable for surgery/ chemotherapy

Question 31

How do leiomyomas usually appear macroscopically?

Answer 31

- white/grey colour | - covered by layer of endometrium => will bleed at correct time of month

Question 32

What symptoms are common when a patient has uterine fibroids?

Answer 32

menorrhagia | infertility

Question 33

At what age do leiomyosarcomas usually occur and how do they normally present?

Answer 33

>50 years | - present with abnormal bleeding and a palpable pelvic mass (they are usually large when diagnosed)

Question 34

Leiomyomas are easily identified macroscopically but are difficult to identify microscopically. TRUE/FALSE?

Answer 34

TRUE - microscopic appearance looks like almost normal smooth muscle - spindles just run in slightly different directions