Pathology of the Female Reproductive Tract 3 Flashcards
Endometrial cancer
Over 80% of women with endometrial cancer present with post menopausal bleeding.
- It means that post menauposal bleeding must be investigated .
- the tip fo tumour has become ischemic and necrotic
- the dark discoloration is hwree it has been bleeding into the vascular space of the tumour
- the tumour fragments and the blood can break off and pass down through the endocervical canal
Normal lining endometrium
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
The endometrium is the epithelium of the uterus
•The predominant endometrial cancer arises in the glands of the endometrium
•Malignant neoplasm of glandular epithelium = adenocarcinoma
-so the most predominant type of endometrial cancer is adenocarcinoma
Compare normal endometrium and adenocarcinoma
On-Left-hand side we have some endometrium from the proliferative phase which is before ovulation.
- Abnormal differentiation here is reflected by the fact that we are not seeing this nice and today architecture with glandular formation.
- we are instead seeing this hint of these round structures forming in the middle of the tumour.
- we can see scatered mitotic figures which indicates that the figure is proliferating
- the nuclei are dark staining
Adenocarcinomas
Adenocarcinomas are malignant neoplasms arising in glandular epithelium.
- 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*
endometrial cancer/adenocarcinoma have different subtypes which can be identified by morphology (the appearance of the tumour under a microscope). they include;
•Endometrioid (most common) - the glands were though to resemble the original endometrial gland.
•Serous
•Clear cell
•Mixed (components of the previous 3)
•Undifferentiated / Dedifferentiated
•Carcinosarcomas (although they arise from the endometrial cells, they can show some coexistent in the mesenchymal differentiation).
*morphology means microscopic appearance
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
- Adenocarcinoma subtypes with similar appearance and the same names occur at other sites.
- eg there is a clear cell carcinoma of the ovary just as there is aclelar 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
adenocarcinoma contd
- We know that there are different microscopic morphologic types of endometrial adenocarcinoma.
- Does the appearance of the tumours reflect any biological difference in their cause and behaviour?
Demographic and histologic studies suggest two groups of women with endometrial adenocarcinoma
•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
Precursor lesions
•In the cervix, the precursor lesion to invasive squamous cell carcinoma is
•Cervical Intra-Epithelial Neoplasia (CIN)
•The disease process is called dysplasia
•We detect CIN by
–screening for HR HPV infection,
–looking for abnormal cells,
–examining the cervix by colposcopy
–Treating eg by LLETZ (Loop electrical excision procedure)
We know much less 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.
-TEMPORAL EVIDENCE (the lesion, if left untreated, will progress to something else).
Hyperplasia (from ancient Greek ὑπέρ huper, “over” + πλάσις plasis, “formation”), or hypergenesis, is an increase in the amount of organic tissue that results from cell proliferation. It may lead to the gross enlargement of an organ,
-the endometrium in the image is from a post-menopausal woman because its very thin and its not showing features of proliferation.
The woman 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 (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 (c80%)
Endometrial carcinoma by age of diagnosis
-it is peaking in women postmenopausal
Risk factors for endometrial cancer
•Endogenous hormones and reproductive factors
- Excess body weight
- Diabetes mellitus and insulin
- Exogenous hormones & modulators
- Ethnicity
- Familial (Cowden’s syndrome; HNPCC)
- Smoking not a risk
Endogenous hormones
- Excess exposure to estrogen unopposed by progestogens
- Overweight increases estrogen levels in post menopausal women
- Overweight can disrupt ovulation and progestogen production in pre menopausal women
•Polycystic ovarian disease
•Some rare ovarian neoplasms can produce estrogens
Reproduction
- Pregnancy and parity (often pregnancy) 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 overweight 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 estrogen on the endometrium.
Exogenous hormones & modulators
•Hormone replacement therapy
- Unopposed estrogen (RR 6.0)
•Tamoxifen (RR 2.0)
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men.
Ethnicity
•US studies show endometrial carcinoma is less common in African American women
–13 per 105 in African-American women
–23 per 105 in white
•BUT this group has higher mortality (x4)
•Many variables involved
–Later stage at diagnosis
–Unfavourable tumour type
–Sociodemographic factors and treatment
–Comorbidities
Evaluation of parameters informing behaviour and treatment of a tumour
There are three tumour-specific parameters
- Tumour type ✔
- Tumour grade
- Tumour stage
Grading of Neoplasms
Grading reflects how much a tumour resembles what we believe to be its parent tissue
Has to be done on tissue under a microscope
Many use a three-point system
Well differentiated (look a lot like the parent tissue) = Grade 1
Moderately differentiated = Grade 2
Poorly differentiated (doesn’t very much look like parent tissue)= Grade 3
Grading of endometrial carcinoma
tumour staging system
-A reflection of how far in the body a tumour has spread.
For all neoplasms, a T N M system exists
T for tumour: local spread (how far has it spread)
N for nodes: lymph node deposits (metastasis to the lymph node)
M for metastasis: metastatic deposits (metastasis to distant sites)
For gynaecological tumours a different system called _FIGO i_s usually used
FIGO Staging of Endometrial Carcinoma
- Stage 1: Confined to corpus
- Stage 2: Involving cervix
- Stage 3: Serosa/Adnexa/Vagina/Lymph Nodes
- Stage 4: Bladder, Bowel, Distant Metastasis
Key facts
- Over 80% of women with endometrial cancer present with post menopausal bleeding
- Most ‘endometrial cancers’ arise from endometrial glands and are adenocarcinomas
- There are several different types of adenocarcinoma – the most common is called endometrioid because it resembles endometrial glands
- Other types of endometrial adenocarcinoma can be recognized microscopically
- These may have distinct molecular abnormalities and behaviour
- Recognizing different types of adenocarcinoma benefits patients since it informs likely prognosis and treatment
more key facts
- Endometrioid cancer has a precursor lesion called atypical hyperplasia
- 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
more facts
•Incidence of endometrial cancer has been increasing in the last ten yearsRisk factors include
–Endogenous hormones and reproductive factors
–Excess body weight
–Diabetes mellitus and insulin
–Exogenous hormones & modulators
–Ethnicity
–Familial syndromes (Cowden’s syndrome; HNPCC)
•Mortality from endometrial cancer has been falling however, except for women over the age of 85
