Uterine Cancer Flashcards
What causes dysfunctional uterine bleeding?
- endometrial polyps
- common
- often occur around/after the menopause
- endometrial hyperplasia
- simple
- complex
- atypical (precursor of carcinoma)
What causes endometrial hyperplasia?
Often unknown, persistent oestrogen stimulation
How does endometrial hyperplasia present?
Abnormal bleeding (DUB or postmenopausal bleeding)
Describe simple endometrial hyperplasia
General distribution
Glands and stroma
Glands are dilated, not crowded
Cytology appears normal
Describe complex endometrial hyperplasia?
Focal distribution
Glands involved
Glands are crowded
Cytology is normal
Describe atypical endometrial hyperplasia
Focal distribution
Glands involved
Glands ar crowded
Atypical cytology
What is the peak incidence of endometrial carcinoma?
50-60, uncommon under 40
In young women with suspected endometrial carcinoma what should be considered?
Underlying predisposition;
- PCOS
- Lynch syndrome
What are the two main groups and different precursor lesions (of endometrial carcinoma)?
Endometroid carcinoma: precursor atypical hyperplasia
Serous carcinoma: precursor serous intraepithelial carcinoma
How does endometrial carcinoma usually present?
Atypical bleeding
Decribe the macroscopic appearance of endometrial carcinoma?
Large uterus; polypoid
Decribe the microscopic appearance of endometrial carcinoma?
Most are adenocarcinomas
Most are well differentiated
How does endometrial carcinoma spread?
Directly into myometrium and cervix
Lymphatics
Haematogenous
________ ( and ______) are type 1 endometrial carcinomas, accounting for __%
________ ( and ____ __) are type 2 endometrial carcinomas
Endometroid (and mucinous) are type 1 endometrial carcinomas, accounting for 80%
Serous ( and clear cell) are type 2 endometrial carcinomas
What are type 1 endometrial carcinomas associated with
Unopposed oestrogen
Associated with atypical hyperplasia
Who is affected by type 2 endometrial carcinomas?
Elderly post-menopausal women
TP53 often mutated
What mutations are associated with endometrial carcinomas?
PTEN, KRAS, PIK3CA
What type of instability is endometrial carcinoma associated with?
Microsatellite instability
- germiline mutation of mismatch repair genes (lynch syndrome)
What is a microsatellite
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
Why is obesity a risk factor for endometrial cancer?
Endocrine and inflammatory effects of adipose tissue
How do adipocytes stimulate endometrial proliferation?
Express aromatase that converts ovarian androgens into oestrogens, which induce endometrial proliferation
Why is the level of biologically active hormone higher in obese women?
Sex hormone-binding globulin levels are lower in obese women, therefore the level of unbound biologically active hormone is higher
How does altered insulin action in obese women predispose to endometrial cancer?
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
What is lynch syndrome?
Hereditary non-polyposis colorectal cancer
High risk of endometrial (lifetime risk of 28%) and an increased probalility of developing ovarian cancer
What causes lynch syndrome?
Inheritance of defective DNA mismatch repair gene. autosomal dominant inheritance.
How can lynch syndrome tumours be identified?
Immunohistochemistry staining of the tumour for mismatch repair proteins can help identify them
Test cancer tissue for microsatellite instability
What mutations are type II endometrial carcinomas associated with?
TP52 mutation and overexpression
How do type II tumours spread?
Spreads along fallopian tube mucosa and peritoneal surfaces so can present with extrauterine disease
Type II endometrial carcinoma is more aggressive than ________/________ carcinoma
Type II endometrial carcinoma is more aggressive than endometroid/mucinous carcinoma
What is the treatment for type II endometrial carcinoma?
Extensive surgery and adjuvant chemo/radiotherapy
How is serous carcinoma characterised?
By a complex papillary and/or glandular architecture with diffuse, marked nuclear polymorphism
Endometrial carcinoma typically infiltrates what?
Myometrium
Serous carcinoma may spread early to the ?
Peritoneal cavity
Why does endometroid carcinoma have a good prognosis?
Is usually confined to uterus at presentation
How is endometrial carcinoma staged?
Stages I-IV
What does prognosis of endometrial carcinoma depend on?
Stage
Histological grade
Depth of myometrial invasion
What is the treatment for endometrial carcinoma?
Hysterectomy; chemo/radiotherapy
How are endometroid carcionomas primarily graded?
By their architecture;
Grade 1: 5% or less solid growth
Grade 2: 6-50% solid growth
Grade 3: > 50% solid growth
Stage I endometrial cancers are confined to the
Uterus
What endometrial cancer arises from stroma?
Endometrial stromal sarcoma
Which endometrial cancer is a mixed tumour with malignant epithelial and stromal elements?
Carcinosarcoma
Describe endometrial stromal sarcoma?
Rare, cells resemble endometrial stroma
Infiltrate myometrium and often lymphovascular spaces
How does endometrial stromal sarcoma present?
AUB but initial presentation may be metastases- most commonly lung or ovary
Carcinomasarcomas are responsible for <_% of uterine malignancies
<5%
What is seen in 50% of carcinosarcoma cases?
Heterologous elements- rhabdomyosarcoma, chondrosarcoma, osteosarcoma
What conveys the worst prognosis in carcinosarcoma?
Presence of rhabdomyosarcomatous component
Which tumour commonly protrudes through the cervical canal?
Carcinosarcoma
What are the smooth muscle tumours of the myometrium?
Leiomyoma (fibroid);
Very common
Associated with menorrhagia, infertility
Leiomyosarcoma (rare)
Describe a leiomyosarcoma?
Malignant smooth muscle tumour commonly displaying a spindle cell morphology
What is the commonest uterine sarcoma?
Leiomyosarcoma
Leiomyosarcoma accounts for _-_% of all uterine malignancies
Most occur in women > __ years
Overall 5 year survival rates __-__%
Leiomyosarcoma accounts for 1-2% of all uterine malignancies
Most occur in women > 50 years
Overall 5 year survival rates 15-25%
What are the commonest symptoms of leiomyosarcoma?
Abnormal vaginal bleeding, palpable pelvic mass and pelvic pain
What do leiomyosarcoma and endometrial stromal sarcoma share?
A scoring system
