Pathology of the female reproductive tract 3 Flashcards
% of women with endometrial cancer presenting with menopausal bleeding
80%
Endometrium
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
Endometrial cancer arises
In the glands of the endometrium
Name for a malignant neoplasm of glandular epithelium
Adenocarcinoma
Adenocarcinomas
From different parts of the body have different RF, pathogenesis, appearances, genetic abnormalities, prognosis and treatment
Subtypes of endometrial adenocarcinoma by morphology
Endometrioid
Serous
Clear cell
Mixed (previous 3)
Undifferentiated
Carcinosarcomas
Endometrioid
Show differentiation that resembles endometrial glands
Serous
Thought to resemble fallopian tube epithelium
Clear cell
Have clear cytoplasm
Type 1 endometrial adenocarcinoma
Age: 50-60s
Obesity: common
Oestrogenic stimulation: common
Precursor lesion: EIN, atypical hyperplasia
Transition: slow
Type: endometrioid
Spread: lymph nodes
Concurrent ovarian: common
Prognosis: good
Type 2 endometrial adenocarcinoma
Age: 60-70
Obesity: uncommon
Oestrogenic stimulation: uncommon
Precursor lesion: EIC
Transition: unknown
Type: serous, mixed
Spread: peritoneum
Concurrent ovarian: uncommon
Prognosis: poor
Molecular pathology
The cancer genome atlas (TCGA) classified endometrial cancer in 4 groups
Based on integrated genomic, transcriptomic and proteomic characteristics of c370 endometrial carcinoma
TCGA endometrial cancers
Ultramutated cancer 7%
Hypermutated cancer 28%
Endometrial cancer with low frequency of DNA copy number alterations 39%
Endometrial cancers with high frequency of DNA copy number alterations 26%
Precursor lesion in the cervix
Cervical intra-epithelial neoplasia (CIN)
Process is dysplasia
Precursor lesion in the endometrium
Atypical hyperplasia
Supported by temporal, genetic and morphological continuity with endometrioid endometrial adenocarcinoma
Women at risk of endometrial adenocarcinoma
Most common invasive cancer of female genital tract in UK
Fourth most common cancer in women in UK (breast, lung, colorectal)
Lifetime risk 1/46
Usually arises in postmenopausal women
Peak incidence in 55-65 year olds
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
Smoking not a risk
Endogenous hormones
Excess exposure to oestrogen and 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 break from unopposed oestrogen during pregnancy and the removal of abnormal cells at delivery
Early menarche and later menopause increase risk
Excess body weight
34% endometrial cancers are linked to excess body weight
2-3 times increased risk in overweight women
Increased risk begins with a moderately elevated BMI
Central adiposity may be more important than BMI
Diabetes mellitus and insulin
Women with DM have 2x increased risk of endometrial cancer
Hard to separate effect of insulin from excess body weight but probably a direct effect
Insulin and IGF may increase the effects of oestrogen on the endometrium
Exogenous hormones and modulators
HRT- unopposed oestrogen
Tamoxifen
Ethnicity
Endometrial carcinoma less common in african american women
- group has higher mortality
Variable involved
- later stage at diagnosis
- unfavourable tumour type
- sociodemographic factors
- comborbidities
Three tumour specific parameters
Tumour type
Tumour grade
Tumour stage
