Uterine Cancer Flashcards
What are some causes of dysfunctional uterine bleeding?
Endometrial polyps = common, often occur around/after menopause
Endometrial hyperplasia = cause unknown, may be due to persistent oestrogen stimulation
How can endometrial hyperplasia present?
Abnormal bleeding = DUB or postmenopausal bleeding
What are the types of endometrial hyperplasia?
Simple, complex or atypical (precursor of carcinoma)
What are the features of simple endometrial hyperplasia?
General distribution, glands are dilated, affects glands and stroma, normal cytology
What are the features of complex endometrial hyperplasia?
Focal distribution, affects glands, normal cytology and crowded glands
What are the features of atypical endometrial hyperplasia?
Focal distribution, affects glands, atypical cytology and crowded glands
What is the peak incidence of endometrial carcinoma?
Peak incidence in women aged 50-60 = uncommon in women age <40, consider underlying predisposition in young women (e.g PCOS)
What are the two main types of endometrial carcinoma?
Endometrioid carcinoma = precursor is atypical hyperplasia
Serous carcinoma = precursor is serous intraepithelial carcinoma
How does endometrial carcinoma present?
Usually with abnormal bleeding
What is the appearance of endometrial carcinoma?
Macroscopic = large uterus, polypoid Microscopic = most are well differentiated and adenocarcinomas
How can endometrial carcinomas spread?
Local = directly into myometrium and cervix
Lymphatic and haematogenous spread
What are the most common type of endometrial carcinomas?
Endometrioid carcinomas = 80% of tumours
What are some features of endometrioid (type 1) carcinomas?
Related to unopposed oestrogen
Endometrioid and mucinous phenotypes
Microsatellite instability = germline mutations of mismatch repair genes (Lynch syndrome)
What mutations are implicated in endometrioid type carcinomas?
PTEN, KRAS and PIK3CA mutations
What are some features of serous (type 2) carcinomas?
Not associated with unopposed oestrogen
Affect elderly postmenopausal women
Serous and clear cell phenotypes
What mutation is implicated in serous type carcinomas?
TP53 mutations and overexpression
How do serous type carcinomas spread?
Along fallopian tube mucosa and peritoneal surfaces = able to present as extra-uterine disease
How are serous type carcinomas treated?
More aggressive than endometrioid carcinomas = surgery usually more extensive and adjuvant chemo/radiotherapy used more frequently
What characterises serous type carcinomas?
Complex papillary and/or glandular architecture with diffuse marked nuclear pleomorphism
Where do endometrial carcinomas infiltrate?
Typically myometrium
Serous may spread early to peritoneal cavity
Why do endometrioid type carcinomas tend to have good prognosis?
They tend to stay confined to uterus
What does prognosis of endometrial carcinoma depend on?
Stage, histological grade and depth of myometrial invasion
How is endometrial carcinoma treated?
Hysterectomy +/- chemo/radiotherapy
What is used to grade endometrial carcinomas?
Primarily architecture = serous type isn’t formally graded
What are the different grades of endometrial carcinomas?
Grade 1 = 5% or less solid growth
Grade 2 = 6-50% solid growth
Grade 3 = >50% solid growth
What are stages 1 and 2 of endometrial carcinomas?
1A = no or <50% myometrial invasion 1B = invasion >=50% of myometrium 2 = tumour invades cervical stroma
What is stage 3 of endometrial carcinomas?
3A = invades serosa of uterus +/- adnexae 3B = vaginal +/- parametrial involvement 3C = metastases to pelvic +/- para-aortic nodes
What is stage 4 endometrial carcinoma?
Tumour invades bladder +/- bowel mucosa (4A) +/- distant metastases (4B)
Why is obesity a risk factor for endometrial carcinoma?
Due to endocrine and inflammatory effects of adipose tissue
How do adipocytes cause endometrial carcinoma?
Express aromatase that converts ovarian androgens into oestrogens = induces endometrial proliferation
What do effects do lower levels of sex hormone-binding globulin in obese women have?
They have higher levels of unbound, biologically active hormone
What is Lynch syndrome?
Hereditary non-polyposis colorectal cancer = cancer predisposition syndrome
What cancers do people with Lynch syndrome have a high risk of developing?
Colorectal, endometrial and ovarian cancer = tumours show microsatellite instability
What causes Lynch syndrome?
Inheritance of defective DNA mismatch repair gene = autosomal dominant
How can Lynch syndrome be diagnosed?
Staining for mismatch repair proteins in tumours
What grade are endometrial stromal sarcomas?
Either low or high grade (increased atypia, proliferative activity)
What are some features of endometrial stromal sarcomas?
Rare = arise from endometrial stroma
Cells resemble endometrial stroma
Infiltrate myometrium and often lymphovascular spaces
What is the most important prognostic factor for endometrial stromal sarcoma?
Stage = high grade more likely to be fatal
How doe endometrial stromal sarcomas present?
Typically present with abnormal uterine bleeding
Initial presentation may be as metastases = usually ovary or lung
What are carcinosarcomas?
Mixed tumours with malignant epithelial and stromal elements = account for <5% uterine malignancies
What are some features of carcinosarcomas?
High grade carcinomatous and sarcomatous elements
Poor prognosis
What are some heterologous elements seen in carcinosarcomas?
Occur in 50% = rhabdomyosarcoma (worst prognosis), chondrosarcoma, osteosarcoma
What are some smooth muscle tumours of the myometrium?
Leiomyoma = fibroid, very common, menorrhagia and infertility Leiomyosarcoma = rare
What is the most common uterine sarcomas?
Leiomyosarcoma = accounts for 1-2% of all uterine malignancies, poor prognosis
What are some features of leiomyosarcomas?
Commonly displays spindle cell morphology
Most common in women aged >50
Shares same staging system as endometrial stromal sarcoma
What are some common symptoms of leiomyosarcomas?
Abnormal vaginal bleeding, palpable pelvic mass, pelvic pain
What is the prognosis of leiomyosarcoma?
Overall 5 year survival rate of 15-25% = stage most powerful prognostic factor
