Uterine Cancer

Question 1

what are the two causes of dysfunctional uterine bleeding?

Answer 1

endometrial polyps - common, occur around / after menopause

endometrial hyperplasia - can be simple, complex or atypical (precursor of carcinoma)

Question 2

what is shown on this specimen?

Answer 2

endometrial polyp

Question 3

what causes endometrial hyperplasia?

Answer 3

often unknown, may be persistent oestrogen stimulation

Question 4

for each different type of endometrial hyperplasia (simple, complex and atypical) what is the distribution, component, glands and cytology?

Answer 4

Question 5

what is shown on this specimen?

Answer 5

endometrial hyperplasia

Question 6

identify each type of endometrial hyperplasia on histological slides?

Answer 6

Question 7

what is the peak incidence of endometrial carcinoma?

Answer 7

50-60 years old - uncommon under 40

Question 8

if endometrial carcinoma presents in young women, which underlying pathology must you consider?

Answer 8

polycystic ovary syndrome

lynch syndrome

Question 9

what are the two main groups of endometrial carcinoma with precursor lesions?

Answer 9

endometrioid carcinoma = precursor typical hyperplasia

serous carcinoma = precursor serous intraepithelial carcinoma

Question 10

how does endometrial carcinoma generally present?

Answer 10

abnormal bleeding

Question 11

how does endometrial carcinoma look both macroscopically and microscopically?

Answer 11

macroscopic = large uterus; polypoid

microscopic = most are adenocarcinomas and well differentiated

Question 12

how does endometrial carcinoma often spread?

Answer 12

directly into myometrium and cervix

also lymphatic and haematogenous

Question 13

what is the name of type 1 (80%) endometrial carcinoma and what is it associated with?

Answer 13

endometrioid (and mucinous)

related to unopposed oestrogen and associated with atypical hyperplasia

Question 14

what is the name of type 2 (20%) endometrial carcinoma and what is it associated with?

Answer 14

serous (and clear cell)

not associated with unopposed oestrogen, affect elderly post-menopausal women and TP53 often mutated

Question 15

what gene mutations are associated with type 1 and type 2 endometrial carcinomas?

Answer 15

type 1 = PTEN, KRAS, PIK3CA

type 2 = TP53

Question 16

lynch syndrome is associated with what type of endometrial carcinoma - type 1 or 2?

Answer 16

type 1

(microsatellite instability - germline mutation of mismatch repair)

Question 17

what is the main risk factor for endometrial carcinoma and why?

Answer 17

obesity

adipocytes express aromatase that converts ovarian androgens into oestrogens, which induces endometrial proliferation

also sex hormone binding globulin levels low so level of unbound (biologically active) hormone higher and the level of insulin binding globulins is reduced and free insulin levels elevated (insulin exerts proliferative effect on endometrium)

Question 18

what cancers is Lynch syndrome (autosomal dominant) associated with?

Answer 18

colorectal cancer, endometrial cancer and ovarian cancer

Question 19

how can it be identified that tumours are due to Lynch syndrome?

Answer 19

immunohistochemistry staining of tumour for mismatch repair proteins

they also show microsatellite instability (MSI), a characteristic of defective mismatch repair so testing for MSI can be useful

Question 20

why can type II endometrial carcinoma present with extrauterine disease?

Answer 20

because it spreads along fallopian tube mucosa and peritoneal surfaces

Question 21

what is the difference in aggression and treatment of type I vs type II endometrial cancer?

Answer 21

type II is more aggressive than endometrioid (type I)

in type II, surgery is usually more extensive and adjuvant chemo/radiotherapy used more frequently

Question 22

what is the basis of treatment for endometrial carcinoma?

Answer 22

hysterectomy; chemo/radiotherapy

Question 23

how is endometrioid carcinoma primarily graded (histological grade)?

Answer 23

due to their architecture

grade 1 = 5% or less solid growth

grade 2 = 6-50% solid growth

grade 3 = >50% solid growth

*serous carcinoma and clear cell carcinoma are not formally graded

Question 24

how is endometrial cancer staged?

Answer 24

IA = no or <50% myometrial invasion

IB = invasion equal to or >50% of myometrium

II = invades cervical stroma

III = local or regional spread (A = serosa of uterus and/or adnexae, B = vaginal and/or parametrial involvement, C = metastases to pelvic and/or para-aortic lymph nodes)

IV = tumour invades bladder and/or bowel mucosa (IVA) and/or distant metastases (IVB)

Question 25

other than endometrioid and serous / clear cell endometrial carcinoma, what are other kinds of endometrial tumours?

Answer 25

endometrial stromal sarcoma = tumour arising from endometrial stroma

carcinosarcoma = mixed tumour with malignant epithelial and stromal elements (previously called malignant mixed mullerian tumour - poor prognosis)

Question 26

what is commonly seen in about 50% of cases of carcinosarcoma?

Answer 26

heterologous elements (rhabdomyosarcoma, chrondrosarcoma, osteosarcoma)

*the presence of rhabdomyosarcomatous component has worst prognosis

Question 27

what does endometrial stromal sarcoma look like histrologically?

Answer 27

Question 28

what type of “other” endometrial carcinoma can be described as large, bulky tumour which fills cavity and commonly protrudes through cervical canal?

Answer 28

carcinosarcoma

Question 29

what is a leiomyoma?

Answer 29

fibroid - very common smooth muscle tumour associated with menorrhagia and infertility

Question 30

what is the most common uterine sarcoma (myometrium abnormality)?

Answer 30

leiomyosarcoma = malignant smooth muscle tumour commonly displaying a spindle cell morphology

Question 31

what is the common presentation of leiomyosarcoma?

Answer 31

occur in women >50

commonest symptoms = abnormal vaginal bleeding, palpable pelvic mass and pelvic pain

Question 32

what is the prognosis of leiomyosarcoma?

Answer 32

poor prognosis even if confined to uterus at time of diagnosis

overall 5 year survival rates 15-25%, stage is most powerful prognostic factor

*leiomyosarcoma and endometrial stromal sarcoma share the same stagin system which is different to that for endometrial cancer