Pathology of the Female Reproductive Tract 3 Flashcards
Age standardised incidence rates of endometrial cancer (UK 1993-2016)
The predominant endometrial cancer arises in the … of the ….
The predominant endometrial cancer arises in the glands of the endometrium
Malignant neoplasm of glandular epithelium = …
Malignant neoplasm of glandular epithelium = adenocarcinoma
Over …% of women with endometrial cancer present with post menopausal bleeding
Over 80% of women with endometrial cancer present with post menopausal bleeding
Endometrium
- Composed of glands in a specialised … with a specialised blood supply
- Growth, maturation and regression of all three components is co-ordinated during each … cycle
- 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
… vs … (endometrium)
normal endometrium vs adenocarcinoma
What is shown here?
Uterus opened - can see a tumour on endometrium
Adenocarcinomas
- Adenocarcinomas arising at different sites in the body have different … factors, pathogenesis, appearances, … abnormalities, b…, p… and t….
- Among adenocarcinomas arising at a single site there are multiple …, initially divided by different appearances and increasingly supplemented by understanding molecular genetic pathogenesis.
- 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 (microscopic appearance)
- Endo…
- S…
- … cell
- … (components of the previous 3)
- Un… / De…
- Carcino…
- Endometrioid
- Serous
- Clear cell
- Mixed (components of the previous 3)
- Undifferentiated / Dedifferentiated
- Carcinosarcomas
Endometrioid Adenocarcinoma
- Endometrioid cancers show differentiation that resembles … …
Endometrioid cancers show differentiation that resembles endometrial glands
Serous cancers were thought to resemble .. … epithelium
Serous cancers were thought to resemble Fallopian tube epithelium
Clear cell cancers have clear …
Clear cell cancers have clear cytoplasm
Adenocarcinoma Subtypes
- Adenocarcinoma subtypes with similar appearance and the same names occur at other sites
- eg there is a clear cell carcinoma of the ovary
- They are NOT the … …
- If a tumour has spread to other sites it can be very difficult to work out which is the site of … and which is the site of …
- Adenocarcinoma subtypes with similar appearance and the same names occur at other sites
- eg 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 two groups of women with endometrial adenocarcinoma
- These 2 groups differ with respect to:
- C..
- A..
- M… types of …
- M… … …
- P… L…
- P and T
- These 2 groups differ with respect to:
- Cause
- Age
- Morphologic types of tumour
- Molecular genetic abnormalities
- Precursor lesions
- Prognosis and Treatment
Endometrial Adenocarcinoma - Type 1 and Type 2
Molecular Pathology - Endometrial Cancer
The cancer genome atlas (TCGA) published an integrated genomic classification of endometrial cancer in … groups
- The cancer genome atlas (TCGA) published an integrated genomic classification of endometrial cancer in 4 groups
TCGA Endometrial Cancers
-
4 groups…__
- … cancers (DNA pol epsilon mutations) 7%
- … cancers (defective mismatch repair and microsatelite instability) 28%
- Endometrial cancers with … frequency of DNA copy number alterations 39%
- Endometrial cancers with … frequency of DNA copy number alterations 26%
- Ultramutated cancers (DNA pol epsilon mutations) 7%
- Hypermutated cancers (defective mismatch repair and microsatelite 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 - Cervix
- In the cervix, the precursor lesion to invasive squamous cell carcinoma is
- … … …(CIN)
- The disease process is called …
- We detect CIN by
- screening for HR … infection,
- looking for … cells,
- examining the cervix by …
- … eg by LLETZ
- 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
We know much less about precursor lesions in the endometrium (compared to cervix - CIN)
- It is assumed that the common (endometrioid) form of endometrial carcinoma has its origin in a lesion called … …
- This is supported by temporal, genetic and morphologic continuity with endometrioid endometrial adenocarcinoma
- 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 woman at risk of endometrial adenocarcinoma
- … common … cancer of the female genital tract in UK
- … most common cancer in women in the UK (breast, lung, colorectum)
- Lifetime risk of 1 in …
- Usually arises in … women
- Peak incidence in the ..-.. y/o age group
- Most common presenting feature is … bleeding (c80%)
- 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%)
What is shown here? (endometrium??)
Atypical Hyperplasia - precursor lesion in endometrium
Lifetime risk of 1 in … (Endometrial adenocarcinoma)
Lifetime risk of 1 in 46 (Endometrial adenocarcinoma)
The most common presenting feature of endometrial adenocarcimoma is
postmenopausal bleeding (80%)
Endometrial adenocarcinoma is the … most common cancer in woman in the UK
fourth (after breast, lung, colorectum)
What is the most common invasive cancer of the female genital tract in UK?
Endometrial adenocarcinoma
Peak incidence of endometrial adenocarcinoma is … (Age group?)
55-65 yo
Endometrial carcinoma by age
- Peak in …
- Peak in postmenopausal women
Risk factors for endometrial cancer
- … hormones and … factors
- Excess … …
- … … and insulin
- … hormones & modulators
- E…
- F.. (Cowden’s syndrome; HNPCC)
- … not a risk
- 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
Is smoking a risk factor for endometrial cancer?
No
Endogenous hormones
- Excess exposure to estrogen unopposed by progestogens
- Overweight increases estrogen levels in … women
- Overweight can disrupt ovulation and progestogen production in … women
- … ovarian disease
- Some rare … … can produce estrogens
- 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 & Endometrial Cancer
- Pregnancy and parity … the risk of endometrial cancer
- Mechanism includes the … from unopposed … during pregnancy and the removal of … cells at delivery
- Early menarche and late menopause … risk (… by 7% for each year fewer)
- 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 & Endometrial Cancer
- c … % endometrial cancers are linked to excess body weight
- … - … times increased risk in overweight women
- Increased risk begins with a … elevated BMI
- Central … (waist circumference and waist:hip ratios) may be more important than …
- c 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 & Endometrial Cancer
- Women with diabetes mellitus have a …-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 … on the endometrium
- 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 - Endometrial Cancer
- Hormone replacement therapy
- Unopposed estrogen (RR is …)
- Tamoxifen (RR is ..)
- Hormone replacement therapy
- Unopposed estrogen (RR 6.0)
- Tamoxifen (RR 2.0)
Ethnicity & Endometrial Cancer
- US studies show endometrial carcinoma is … common in African American women
- 13 per 105 in African-American women
- 23 per 105 in white
- BUT this group has higher mortality (x…)
- Many variables involved
- Later stage at D…
- U… tumour type
- S… factors and treatment
- Co…
- 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 - Endometrial Cancer
- There are three tumour-specific parameters
- Tumour …
- Tumour …
- Tumour …
- There are three tumour-specific parameters
- Tumour type ✔
- Tumour grade
- Tumour stage
Grading of Neoplasms
- Grading reflects how much a tumour … its … tissue
- Has to be done on tissue under a …
- Many use a three-point system
- … differentiated Grade 1
- … differentiated Grade 2
- … differentiated Grade 3
- 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
- … also form glands
- The fraction of the tumour forming glands is estimated as a percentage
- (then divided into three groups)
- Tumour grade affects …
- Normal endometrial epithelium matures to form glands
- Adenocarcinomas also form glands
- The fraction of the tumour forming glands is estimated as a percentage
- (then divided into three groups)
- Tumour grade affects prognosis
Staging systems
- For all neoplasms a T N M system exists
- T for …: … spread
- N for …: … … deposits
- M for …: … deposits
- For gynaecological tumours a different system called … is usually used
- For all neoplasms 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
What staging system is usually used for gynaecological tumours?
FIGO (not usually TNM system)
FIGO Staging of Endometrial Carcinoma
- Stage 1: Confined to …
- Stage 2: Involving …
- Stage 3: S…/A…/V…/… …
- Stage 4: B.., B…, Distant …
- Stage 1: Confined to corpus
- Stage 2: Involving cervix
- Stage 3: Serosa/Adnexa/Vagina/Lymph Nodes
- Stage 4: Bladder, Bowel, Distant Metastasis
Most ‘endometrial cancers’ arise from endometrial … and are …
Most ‘endometrial cancers’ arise from endometrial glands and are adenocarcinomas
There are several different types of adenocarcinoma – the most common is called … because it resembles … glands
There are several different types of adenocarcinoma – the most common is called endometrioid because it resembles endometrial glands
Recognizing different types of adenocarcinoma benefits patients since it informs likely … and …
Recognizing different types of adenocarcinoma benefits patients since it informs likely prognosis and treatment
- Other types of endometrial adenocarcinoma can be recognized …
- These may have distinct molecular … and …
- Other types of endometrial adenocarcinoma can be recognized microscopically
- These may have distinct molecular abnormalities and behaviour
Endometrioid cancer has a precursor lesion called … …
Endometrioid cancer has a precursor lesion called atypical hyperplasia
Tumour … estimates the degree to which the neoplasm matures and informs prognosis and treatment
Tumour grading estimates the degree to which the neoplasm matures and informs prognosis and treatment
Tumour … demonstrates the extent to which a neoplasm has spread and informs prognosis and treatment
Tumour staging demonstrates the extent to which a neoplasm has spread and informs prognosis and treatment
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 (Cowden’s syndrome; HNPCC)
Mortality from endometrial cancer has been falling however, except for women over the age of …
Mortality from endometrial cancer has been falling however, except for women over the age of 85
Neoplasm Grade 1 = … differentiated
well differentiated
Neoplasm Grade 2 = … differentiated
moderately differentiated
Neoplasm Grade 3 = … differentiated
poorly differentiated
