L3 Pathology of the female reproductive tract Flashcards
What percentage of women with endometrial cancer present with post menopausal bleeding
- 80%
What is the endometrium composed of
- Composed of glands in a specialised stroma with a specialised blood supply
- Growth, maturation and regression of all three components is co-ordinated during each menstrual cycle
Where does endometrial cancer predominantly arise
- The predominant endometrial cancer arises in the glands of the endometrium
- Malignant neoplasm of glandular epithelium = adenocarcinoma
Subtypes of endometrial adenocarcinoma
- Endometrioid
- Serous
- Clear cell
- Mixed (components of the previous 3)
- Carcinosarcomas
What do endometroid cancers show similar differentiation to
- Endometrioid cancers show differentiation that resembles endometrial glands
What do serous cancers resemble
- Serous cancers were thought to resemble fallopian tube epithelium
- Clear cell cancers have clear cytoplasm
TCGA endometrial cancers - genetic features
- Ultramutated cancers (DNA pol epsilon mutations) 7%
- Hypermutated cancers (defective mismatch repair and microsatellite instability) 28%
- Endometrial cancers with low frequency of DNA copy number alterations 39%
- Endometrial cancers with high frequency of DNA copy number alterations 26%
What are precursor lesions in endometrial adenocarcinoma classified as
- In the cervix, we recognise a precursor lesion to invasive squamous cell carcinoma
- Cervical intra-epithelial neoplasia (CIN)
- The disease process is called dysplasia
Origin of endometrial carcinomas
- It is assumed that the common (endometrioid) form of endometrial carcinoma has its origin in a lesion called atypical hyperplasia
- This is supported by temporal, genetic and morphologic continuity with endometrioid endometrial adenocarcinoma
Women at risk of endometrial adenocarcinoma
- Most common invasive cancer of the female genital tract in UK
- Fourth most common cancer in women in the UK
- Usually arises in postmenopausal women
- Peak incidence in the 55-65 y/o age group
Most common presenting feature of endometrial adenocarcinoma
- Most common presenting feature is postmenopausal bleeding
Risk factors for endometrial cancer
- Endogenous hormones and reproductive factors
- Excess body weight
- Diabetes mellitus and insulin
- Exogenous hormones and modulators
- Ethnicity
- Familial (cowden’s syndrome; HNPCC)
- Smoking not a risk
Effect of being overweight on estrogen levels in post menopausal women
- Being overweight increases estrogen levels in post menopausal women
- Being overweight can disrupt ovulation and progestagen production pre menopausal women
Other risk factors for endometrial cancer - linked to endogenous hormones
- Excess exposure to estrogen unopposed by progestagens
- Polycystic ovarian disease
- Some rare ovarian neoplasms can produce estrogens
How can pregnancy decrease the risk of endometrial cancer
- Pregnancy and parity reduce the risk of endometrial cancer
- Mechanism includes the break from unopposed oestrogen during pregnancy and the removal of abnormal cells at delivery
- Early menarche and late menopause increase risk (reduced by 7% for each year fewer)
What percentage of endometrial cancers are linked to excess body weight
- 34%
What might be a better measure of risk of endometrial cancer than BMI
- Central adiposity(waist circumference and waist:hip ratios) may be more important than BMI
Link between diabetes mellitus and endometrial cancer
- Women with diabetes mellitus have a two-fold increased risk of endometrial cancer
- Hard to separate effect of insulin from excess body weight but a probably direct effect
- Insulin and insulin-like growth factors may increase the effects of estrogen on the endometrium
Other risk factors for endometrial cancer - exogenous hormones and modulators
- Hormone replacement therapy (unopposed estrogen)
- Tamoxifen
Endometrial cancer - ethnicity
- US studies show endometrial carcinoma is less common in African American women
- But this group has higher mortality (x4)
- Many variables involved(later stage at diagnosis, unfavourable tumour type, sociodemographic factors and treatment and comorbidities)
Tumour-specific parameters
- Tumour type
- Tumour grade
- Tumour stage
What is grading (neoplasms)
- Grading reflects how much a tumour resembles its parent tissue
- Has to be done on tissue under a microscope
Grading scale for neoplasms
Many use a three-point system
Well differentiated - grade 1
Moderately differentiated - grade 2
Poorly differentiated - grade 3
TNM system for neoplasms
T for tumour - local spread
N for nodes - lymph node deposits
M for metastasis - metastatic deposits
FIGO system for gynaecological tumours
Stage 1 - confined to corpus
Stage 2 - Involving cervix
Stage 3 - Serosa/adnexa/vagina/lymph nodes
Stage 4 - Bladder, bowerl, distant metastasis
Most common type of adenocarcinoma
- The most common is called endometrioid because it resembles endometrial glands
Precursor lesion for endometrioid cancer
- Atypical hyperplasia
Tumour grading vs staging
- Tumour grading estimates the degree to which the neoplasm matures and informs prognosis and treatment
- Tumour staging demonstrates the extent to which a neoplasm has spread and informs prognosis and treatment
