L3 - Pathology of female repro tract 3

Question 1

ENDOMETRIAL CANCER

i) how has age standardised incidence changed over the last 20 years?
ii) how do 80% of women with endometrial cancer present?
iii) what area of the endometrium does the cancer most commonly arise from?
iv) what is the name of this type of malignancy (in relation to the tissue it arises from)
v) which group of women have rates of endometrial cancer not been falling for?

Answer 1

i) incidence has increased over last 20 years
ii) post menopausal bleeding
iii) glands of the endometrium
iv) neoplasm of glandular epitheium = adenocarcinoma
v) those over the age of 85

Question 2

THE ENDOMETRIUM

i) what three things is it composed of?
ii) what three things happen to each component during the menstrual cycle?
iii) name two things that are seen on microscopy in endometrial cancer compared to a healthy slide

Answer 2

i) glands, specialised stroma and blood supply
ii) growth, maturation and regression
iii) decreased architecture and increased mitotic figures

Question 3

ADENOCARCINOMAS

i) which type of tissue do they arise from?
ii) how do adenocarcinomas arising from different sites in the body differ?
iii) what can adenocarcinomas arising at a single site be divided by? (2)
iv) which six subtypes of endometrial carcinoma can be seen under the MS?
v) what is the most common type?

Answer 3

i) glandular epithelium
ii) arising from different sites can have different risk factors, pathogenesis, appearance, genetic abnorms, behav, prognosis, treatment
iii) arising at a single site can be divided by appearance and molecular/genetic pathogenesis
iv) endometrioid, serous, clear cell, mixed, undifferen/dedifferen, carcinosarcoma
v) endometroid is the most common

Question 4

ADENOCARCINOMA SUBTYPES

i) how do glands look in endometroid AC? how do nuclei look?
ii) what does the differentiation of endometrioid resemble? what does serous resemble?
iii) what is the hallmark feature of clear cell cancers?

Answer 4

i) endometroid has lots of glands but reduced architecture

ii) endometroid resembles endometrial glands
- serous resembles fallopian tube epithelium

iii) clear cell cancers have clear cytoplasm

Question 5

TWO GROUPS OF WOMEN WITH ENDOMETRIAL AC

i) what may different morphological subtypes reflect?
ii) what two age groups are there different types of AC seen?
iii) which age group is endometroid mostly seen in? which age group is serous/mixed seen in?
iv) which group more commonly have a P53 mutation?
v) are molecular genetics the same or different between groups?

Answer 5

i) the behaviour of the tumour
ii) 50-60s and 60-70s

iii) endometroid - 50 to 60s
serous/mixed - 60 to 70s

iv) 60-70s more commonly have p53 mut
v) molecular genetics differ between groups

Question 6

MOLECULAR PATHOLOGY

i) what have the cancer genome atlast published in relation to endometrial cancer? what three characterisations is this based on? (3)
ii) what are the four subtypes of endometrial cancer in relation to molecular pathol?
iii) which category do lots of tumours fall into?

Answer 6

i) cancer genome atlas have published integrated genomic classification of endometrial cancer into 4 groups
- charac based on integrated genomic, transcriptomic and proteomic data

ii) 1) ultramutated cancer (DNA polymerase epsilon mutation)
2) hypermutated (defective mismatch repair/microsat instab)
3) low freq of DNA copy number alterations
4) high frequency of DNA copy number alterations

iii) most fall into low frequency of DNA copy number alterations

Question 7

PRECURSOR LESIONS

i) what are precursor lesions in the cervix called? what is this disease process called?
ii) what is the precursor lesion for endometrioid endometrial cancer?
iii) what happens if these lesions are left? what is the character of the genetic abnorms in these precusors? what is similar in the precusor lesion and in adenocarcinoma?

Answer 7

i) CIN = dysplsia
ii) endomet precursor = atypical hyperplasia

iii) if left > progress
- genetic abnorms are similar to malignancy
- similar morphology between precursor and malignant cells

Question 8

WOMEN AT RISK OF ADENOCARCINOMA

i) how common is it in relation to invasive cancer of the genital tract and cancer in women in the UK?
ii) what is the lifetime risk?
iii) which group of women does it most commonly arise in? what is the peak age of incidence?
iv) what is the most common presenting feature
v) name five risk factors
vi) is smoking a risk factor?

Answer 8

i) most common cancer of genital tract and the fourth most common cancer in women
ii) 1 in 46

iii) most common in post menopausal women
- peak age of incidence is 55-65yrs

iv) post menopausal bleeding
v) endogenous hormones, excess body weight, DM/insulin, exogenous hormones, ethnicity, familial
vi) no

Question 9

ENDOGENOUS HORMONES

i) why can these affect tumours?
ii) oesotrogen unopposed by what can be a problem?
iii) how does weight affect oestrogen levels in post meno women?
iv) name two effects of increased weight in pre menopausal women?
v) name a disease that can inc risk of endomet cancer due to oestrogens

Answer 9

i) many tumours have oestrogen receptors
ii) oestrogen unapposed by progestogen
iii) in post meno women inc weight can increase oestrogen levels
iv) in pre meno women inc weight can disrupt ovulation and progestogen production
v) PCOS

Question 10

REPRODUCTION & ENDOMETRIAL CANCER

i) what effects do pregancy and birth have on risk of endometrial cancer?
ii) what two things may underlie the mechansim for the effect of pregnancy and birth?
iii) name two things that increase the risk of EC in relation to menstruation

Answer 10

i) reduce the risk
ii) break from unopposed oestrogen during pregnancy and removal of abnormal cells at delivery
iii) early menarche and late menopause can increase risk

Question 11

EXCESS BODY WEIGHT AND ENDOMETRIAL CANCER

i) what % of ECs are linked to excess body weight? what x increased risk are overweight women at?
ii) when does the increased risk begin in relation to BMI
iii) what factor may be more important than BMI?

Answer 11

i) 34% of ECs linked to inc body weight
- 2-3x extra risk

ii) moderately inc BMI
iii) central adiposity (weight circumference and wait:hip ratio)

Question 12

DIABETES MELLITUS/INSULIN/EXOGENOUS HORMONES AND ENDOMETRIAL CANCER

i) what x increase do women with DM have of developing EC?
ii) what effects may insulin and insulin like growth factors have on oestrogen?
iii) what other type of hormone therapy can give a big inc risk of EC?
iv) name a hormonal modulator that may increase risk

Answer 12

i) 2x increase
ii) insulin and IGF can increase effects of oestrogen in the endometrium
iii) hormone replacement therapy = unopposed oestrogen
iv) tamoxifen

Question 13

ETHNICITY AND ENDOMETRIAL CANCER

i) what group of women is it less common in?
ii) which group has a higher mortality?

Answer 13

i) less common in african american women
ii) african americans have a higher mortality

Question 14

GRADING OF NEOPLASMS

i) what does grading reflect? what must be used to grade a tumour?
ii) what is seen in grade I, II and III?

iii) what does normal endometrial epithelium mature to form?
what do adenocarcinomas form?

iv) which two things can tumour grade affect?

Answer 14

i) how much a tumour resembles its parent tissue
ie how differentiated is it?

ii) grade I = well differentiated
grade II = moderately differentiated
grade III = poorly differenitated

iii) normal endometrial ep matures to form glands
- AC also forms glands but this may be reduced

iv) tumour grade can affect prognosis and treatment

Question 15

TUMOUR STAGING

i) what does staging indicate?
ii) what does TNM stand for?
iii) which staging system is used for gynae cancers?
iv) what is stage I and II of endometrial carcinoma confined to?

Answer 15

i) how far the tumour has spread

ii) tumour - local spread
nodes - LN spread
metastasis - spread to distant sites

iii) gynae = FIGO system

iv) stage I - confined to corpus
stage II - involves cervix