Pathology of the female reproductive tract 3

Question 1

% of women with endometrial cancer presenting with menopausal bleeding

Answer 1

80%

Question 2

Endometrium

Answer 2

Composed of glands in a specialised stroma with a specialised blood supply

Growth, maturation and regression of all three components is co-ordinated during each menstrual cycle

Question 3

Endometrial cancer arises

Answer 3

In the glands of the endometrium

Question 4

Name for a malignant neoplasm of glandular epithelium

Answer 4

Adenocarcinoma

Question 5

Adenocarcinomas

Answer 5

From different parts of the body have different RF, pathogenesis, appearances, genetic abnormalities, prognosis and treatment

Question 6

Subtypes of endometrial adenocarcinoma by morphology

Answer 6

Endometrioid

Serous

Clear cell

Mixed (previous 3)

Undifferentiated

Carcinosarcomas

Question 7

Endometrioid

Answer 7

Show differentiation that resembles endometrial glands

Question 8

Serous

Answer 8

Thought to resemble fallopian tube epithelium

Question 9

Clear cell

Answer 9

Have clear cytoplasm

Question 10

Type 1 endometrial adenocarcinoma

Answer 10

Age: 50-60s

Obesity: common

Oestrogenic stimulation: common

Precursor lesion: EIN, atypical hyperplasia

Transition: slow

Type: endometrioid

Spread: lymph nodes

Concurrent ovarian: common

Prognosis: good

Question 11

Type 2 endometrial adenocarcinoma

Answer 11

Age: 60-70

Obesity: uncommon

Oestrogenic stimulation: uncommon

Precursor lesion: EIC

Transition: unknown

Type: serous, mixed

Spread: peritoneum

Concurrent ovarian: uncommon

Prognosis: poor

Question 12

Molecular pathology

Answer 12

The cancer genome atlas (TCGA) classified endometrial cancer in 4 groups

Based on integrated genomic, transcriptomic and proteomic characteristics of c370 endometrial carcinoma

Question 13

TCGA endometrial cancers

Answer 13

Ultramutated cancer 7%

Hypermutated cancer 28%

Endometrial cancer with low frequency of DNA copy number alterations 39%

Endometrial cancers with high frequency of DNA copy number alterations 26%

Question 14

Precursor lesion in the cervix

Answer 14

Cervical intra-epithelial neoplasia (CIN)

Process is dysplasia

Question 15

Precursor lesion in the endometrium

Answer 15

Atypical hyperplasia

Supported by temporal, genetic and morphological continuity with endometrioid endometrial adenocarcinoma

Question 16

Women at risk of endometrial adenocarcinoma

Answer 16

Most common invasive cancer of female genital tract in UK

Fourth most common cancer in women in UK (breast, lung, colorectal)

Lifetime risk 1/46

Usually arises in postmenopausal women

Peak incidence in 55-65 year olds

Most common presenting feature is postmenopausal bleeding

Question 17

Risk factors for endometrial cancer

Answer 17

Endogenous hormones and reproductive factors

Excess body weight

Diabetes mellitus and insulin

Exogenous hormones and modulators

Ethnicity

Familial

Smoking not a risk

Question 18

Endogenous hormones

Answer 18

Excess exposure to oestrogen and unopposed by progestogens

Overweight increases oestrogen levels in post menopausal women

Overweight can disrupt ovulation and progestogen production in pre menopausal women

PCOS

Some rare ovarian neoplasms can produce oestrogens

Question 19

Reproduction

Answer 19

Pregnancy and parity reduce the risk of endometrial cancer

Mechanism includes break from unopposed oestrogen during pregnancy and the removal of abnormal cells at delivery

Early menarche and later menopause increase risk

Question 20

Excess body weight

Answer 20

34% endometrial cancers are linked to excess body weight

2-3 times increased risk in overweight women

Increased risk begins with a moderately elevated BMI

Central adiposity may be more important than BMI

Question 21

Diabetes mellitus and insulin

Answer 21

Women with DM have 2x increased risk of endometrial cancer

Hard to separate effect of insulin from excess body weight but probably a direct effect

Insulin and IGF may increase the effects of oestrogen on the endometrium

Question 22

Exogenous hormones and modulators

Answer 22

HRT- unopposed oestrogen

Tamoxifen

Question 23

Ethnicity

Answer 23

Endometrial carcinoma less common in african american women
- group has higher mortality

Variable involved

• later stage at diagnosis
• unfavourable tumour type
• sociodemographic factors
• comborbidities

Question 24

Three tumour specific parameters

Answer 24

Tumour type

Tumour grade

Tumour stage

Question 25

Grading of neoplasms

Answer 25

Reflects how much a tumour resembles its parent tissue

Done under a microscope

Well differentiation- 1
Moderately differentiated- 2
Poorly differentiation- 3

Question 26

Staging systems

Answer 26

T for tumour: local spread

N for nodes: lymph node deposits

M for metastasis: metastatic deposits

Gynaecological tumours use FIGO

Question 27

Spread of endometrial carcinoma

Answer 27

Malignant glands invade endometrial stroma

Then spread into myometrium

Down into cervix

Reaches vessels and spread via lymphatics or veins to nodes or vagina

Question 28

FIGO staging of endometrial carcinoma

Answer 28

Stage1: confined to corpus

Stage 2: involving cervix

Stage 3: serosa/ adnexa/ vagina/ lymoh nodes

Stage 4: bladder, bowel, distant metastasis