L3 - Pathology of the female reproductive tracts Flashcards
What do over 80% of women with endometrial cancer present with?
Post menopausal bleeding
Endometrium
Composed of glands in a specialised storm with a specialised blood supply
Growth, maturation and regression of all three components is co-ordinated during each menstrual cycle
Endometrial cancer
The predominant endometrial cancer arises in the glands of the endometrium
Malignant neoplasm of glandular epithelium = adenocarcinoma
Adenocarcinomas
Adenocarcinomas arising at different sites in the body have different risk factors, pathogenesis, appearances, genetic abnormalities, behaviour, prognosis and treatment
Among adenocarcinomas arising at a single site there are multiple subtypes, initially divided by different appearances and increasingly supplemented by understanding molecular genetic pathogenesis
Subtypes of endometrial adenocarcinoma by morphology
Endometrioid
Serous
Clear cell
Mixed (components of the previous 3)
Undifferentiated
Carcinosarcomas
Why the adenocarcinoma subtypes are named endometrioid, serous, clear cell
Endometrioid cancers show differentiation that resembles endometrial glands
Serous cancers were thought to resemble Fallopian tube epithelium
Clear cell cancers have clear cytoplasm
Adenocarcinoma subtypes with similar appearance and the same names occur at other sites
E.g. there is a clear cell carcinoma of the ovary
They are NOT the same disease
If a tumour has spread to other sites it can be very difficult to work out which is the site of origin and which is the site of metastasis
Demographic and histologic studies suggest was about endometrial adenocarcinoma?
That there are two types of women that get it
The two groups differ with respect to?
Cause
Age
Morphologic types of tumour
Molecular genetic abnormalities
Precursor lesions
Prognosis and treatment
Molecular pathology
The cancer genome atlas (TCGA) published an integrated genomic classification of endometrial cancer in 4 groups
Based on integrated genomic, transcriptomic and proteomic characterisation of c370 endometrial carcinomas
TCGA Endometrial cancers
- Ultramutated cancers (DNA pol epsilon mutations) 7%
- Hypermutated cancers (defective mismatch repair and micro satellite instability) 28%
- Endometrial cancers with low frequency of DNA copy number alterations 39%
- Endometrial cancers with high frequency of DNA copy number alterations 26%
Precursor lesions in endometrial adenocarcinoma
In the cerivix, we recognise a precursor lesion to invasive squamous cell carcinoma
Cervial Intra-Epithelial neoplasia (CIN)
The disease process is called dysplasia
Much less is known about precursor lesions in the endometrium
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
The women at risk of endometrial adenocarcinoma
Most common invasive cancer of the female genital tract in UK
4th most common cancer in women in the UK (breast, lung, colorectum)
Lifetime risk of 1 in 46
Usually arises in postmenopausal women
Peak incidence in the 55-65 y/o age group
Most common presenting feature is postmenopausal bleeding (80%)
Endometrial cancer by age
Starts properly rising above 40yrs
Peaks at 60-64
Then decreases
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
Endogenous hormones
Excess exposure to oestrogen unopposed by progestogens
Overweight increases oestrogen levels in post menopausal women
Overweight can disrupt ovulation and progestogen production in pre-menopausal women
PCOS
Some rare ovarian neoplasms can produce oestrogens
Reproduction
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)
Excess body weight
34% endometrial cancers are linked to excess body weight
2-3 times increased risk in overweigh women
Increased risk begins with a moderately elevated BMI
Central adiposity (waist circumference and waist:hip ratios) may be more important than BMI
Diabetes mellitus and insulin
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 oestrogen on the endometrium
Exogenous hormones and modulators
HRT
-unopposed oestrogen (RR 6.0)
Tamoxifen (RR 2.0)
Ethnicity
US studies show endometrial carcinoma is less common in African American women
- 13 per 10^5 in African-American women
- 23 per 10^5 in white
BUT this group has higher mortality (x4)
Many variables involved
- later stage at diagnosis
- unfavourable type
- sociodemographic factors and treatment
- co-morbidities
3 tumour-specific parameters
Tumour type
Tumour grade
Tumour stage
Grading of neoplasms
Grading reflects how much a tumour resembles its parent tissue
Has to be done on tissue under a microscope
Many use a three-point system
Well differentiated - Grade 1
Moderately differentiated - Grade 2
Poorly differentiated - Grade 3
Grading of endometrial carcinoma
Normal endometrial epithelium matures to form glands
Adenocarcinoma also forms glands
The fraction of the tumour forming glands is estimated as a percentage (then divided into 3 groups)
Tumour grade affects prognosis
Staging systems
For all neoplasma a T N M system exists
T for tumour: local spread
N for nodes: lymph node deposits
M for metastasis: metastatic deposits
For gynaecological tumours a different system called FIGO is usually used
Spread of the endometrial carcinoma
Because endometrium has its own storm, initially malignant glands invade endometrial storm
Then spreads into the myometrium
Down into the cervix
Where it reaches vessels and spreads via lymphatics or veins to nodes or vagina
FIGO staging of endometrial carcinoma
Stage 1: confined to corpus
Stage 2: Involving cervix
Stage 3: Serosa/adnexa/vagina/lymph
Stage 4: Bladder, bowel, distant metastasis
