Uterine malignancy Flashcards
What are two causes for dysfunctional uterine bleeding?
Endometrial polyps
-common
-often occur around/after the menopause
Usually benign, can be malignant
Endometrial hyperplasia -Simple
- Complex
- Atypical (precursor of carcinoma)
Endometrial carcinoma:
- peak incidence
- in young women, what is considered?
- what are the two main groups of precursor lesions?
- Peak incidence 50 ‐ 60 years; uncommon under 40
- In young women, consider underlying predisposition e.g. polycystic ovary syndrome or Lynch syndrome
• Two main groups with different precursor lesions
– Endometrioid carcinoma: precursor atypical hyperplasia
– Serous carcinoma: precursor serous intraepithelial carcinoma
• Generally presents with abnormal bleeding
Endometrial carcinoma:
- Macroscopically
- Microscopically
- Spread
• Macroscopic
– Large uterus; polypoid
• Microscopic
– Most are adenocarcinomas
– Most are well differentiated
• Spread
– Directly into myometrium and cervix
– Lymphatic
– Haematogenous
What are the two different types of endometrial carcinoma?
- Endometrioid (and mucinous) – type 1 tumours (80%)
Related to unopposed oestrogen
Associated with atypical hyperplasia - Serous (and clear cell) – type 2 tumours
Not associated with unopposed oestrogen
Affect elderly post‐menopausal women
TP53 often mutated
Type 1 tumours:
- what mutations are seen?
- what is this assoc. with?
Endometrioid and mucinous phenotypes
PTEN, KRAS, PIK3CA mutations
Associated with atypical hyperplasia as precursor lesion
Microsatellite instability– Germline mutation of mismatch repair genes (Lynch syndrome)
What is a major risk factor for endometrial cancer and why?
What other risk factors exist?
Obesity is a known risk factor for endometrial cancer.
This excess risk is associated with the endocrine and inflammatory effects of adipose tissue.
Adipocytes express aromatase that converts ovarian androgens into oestrogens, which induce endometrial proliferation.
Sex hormone-binding globulin levels are lower in obese women, and therefore the level of unbound, biologically active hormone is higher.
Insulin action is often altered in obese women: 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.
Weight loss (loss of adipose tissue) are associated with a reduction in risk.
Other risk factors:
Oestrogen exposure – HRT, Tamoxifen
o Although tamoxifen in the breast is a estrogen blocker, in the endometrium it can cause proliferation
Genetics – HNPCC
What is lynch syndrome?
- is this autosomal dominant or recessive?
- how can tumours due to lync syndrome be identified?
- what quality do tumours have?
Lynch syndrome (Hereditary non-polyposis colorectal cancer) is a cancer predisposition syndrome - high risk of colorectalcancer. High risk of endometrial cancer (lifetime risk 28%) and an increased probability of developingovarian cancer.
Due to the inheritance of a defective DNA mismatch repair gene. Autosomal dominant inheritance.
Immunohistochemistry staining of the tumour for mismatch repair proteins can help identifytumours due to Lynch syndrome.
Lynch syndrome tumours also show microsatellite instability (MSI), a characteristic of defective mismatchrepair. Testing cancer tissue for MSI can be a useful.
Type II endometrial tumours:
- what mutation is seen?
- what is the precursor lesion?
- how can it present?
- how does it behave?
- what treatment is used?
Serous and clear cell phenotypes
TP53 mutation and overexpression
Precursor lesion serous endometrial intraepithelial carcinoma
Spreads along Fallopian tube mucosa and peritoneal surfaces so can present with
extrauterine disease
More aggressive than endometrioid/mucinous carcinoma
Surgery usually more extensive and adjuvant chemo/radiotherapy used more frequently
Endometrial carcinoma:
- where does it typically infiltrate?
- prognosis?
• Typically infiltrates myometrium
• Serous carcinoma may spread early to
the peritoneal cavity
- Prognosis related to stage
- Endometrioid carcinoma has good prognosis as usually confined to uterus at presentation
What does prognosis endometrial carcinoma depend on? what treatment options are available?
Prognosis depends on
• Stage (I-IV)
- Histological grade
- Depth of myometrial invasion
Treatment:
Mainstay is surgical
o total abdominal hysterectomy with bilateral salpingo oophorectomy
o controversy over role of lymphadenectomy
• radiotherapy
o adjuvant radiotherapy: vault brachytherapy/external beam
♣ vault brachytherapy is delivering brachytherapy to top 4cms of vaginal stump as this is most common area of relaps
♣ external beam is used if feel like pt is likely to relapse
• Chemotherapy
o Adjuvant chemotherapy if fit and high grade tumour
Describe endometrial carcinoma grading?
Endometrioid carcinoma are primarily graded by 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
Describe endometrial cancer staging
Stage I Tumour confined to the uterus
IA no or < 50% myometrial invasion
IB Invasion equal to or > 50% of myometrium
II Tumour invades cervical stroma
III Local and or regional tumour spread
IIIA Tumour invades serosa of uterus and/or adnexae
IIIB Vaginal and/or parametrial involvement
IIIC Metastases to pelvic and/or para-aortic lymph nodes
IV Tumour invades bladder and or bowel mucosa (IVA) and/or distant metastases (IVB)
What other 3 endometrial tumours exist?
Endometrial stromal sarcoma:
-Tumour arising from endometrial stroma
Carcinosarcoma:
- Mixed tumour with malignant epithelial and stromal elements
- Older term – malignant mixed Müllerian tumour.
- Poor prognosis
Leiomyosarcoma
Endometrial stromal sarcoma:
- what different grades can this be?
- is this common?
- What do cells resemble?
- where does it infiltrate?
- presentation?
- prognosis?
Low grade endometrial stromal sarcoma
High grade endometrial stromal sarcoma (increased atypica, proliferative activity)
Rare, cells resemble endometrial stroma. Infiltrate myometrium and often lymphovascular spaces
High grade more likely to die of disease.
Typically presents with abnormal uterine bleeding but initial presentation may be as metastasis (most commonly ovary or lung)
Stage is the most important prognostic factor
Carcinosarcoma:
- is this common?
- what elements does this tumour have?
- prognosis?
<5% of uterine malignancies
High grade carcinomatous and sarcomatous elements
Heterologous elements commonly seen in about 50% cases (rhabdomyosarcoma, chrondrosarcoma, osteosarcoma)
The presence of a rhabdomyosarcomatous component has the worst prognosis
Usually associated with a poor outcome
