Pathology of the Female Reproductive Tract Flashcards
1
Q
Give an overview of what happens to the microscopic structure of the vagina at puberty
A
- oestrogen secreted by the ovary stimulates maturation of the squamous epithelial cells
- Glycogen is formed within mature squamous epithelial cells
- Glycogen in cells shed from the surface is a substrate for the vaginal anaerobic organism (lactobacilli)
- Lactobacilli produce lactic acid keeping vaginal pH below 4.5
- prevents infection
2
Q
Describe the microstructure of the Ectocervix
A
- made up of Stratified squamous epithelium
- as the cells move up the cervix they mature and are eventually shed from the surface of the epithelium
- multiple layers of cells on top of each other
3
Q
Describe the microstructure of the Endocervix
A
- made up of a single layer of tall mucin-producing columnar cells
- has a tiny blind-ending channel known as clefts
- these radiate out from the endocervical canal into the surrounding stroma
- increases the surface area of the endocervix
4
Q
Describe the formation of the transformation zone
A
- During puberty, the cervix changes shape
- The anterior and posterior lips of the cervix grow
- The distal end of the endocervix opens
- changes from a tubular shape to a funnel shape
- makes the Distal Endocervical mucosa becomes exposed to the vaginal environment
- The distal endocervical columnar epithelium is exposed to the acidic vaginal environment
- It is not suited to this, so undergoes an adaptive change called metaplasia
- Reserve cells in this area proliferate and mature to form squamous epithelium: This process is called squamous metaplasia
5
Q
What is the definition of metaplasia?
A
a transformation of cell type from one kind of mature differentiated cell type to another kind of mature differentiated cell type
6
Q
Review the cervical transformation zone
A
- cells transform from columnar cells to squamous cells as it moves from the vagina to the cervix
7
Q
What is this an image of
- identify 3 key parts in this image
A
8
Q
Describe the myometrium
A
- Bundle of smooth muscle
- very good vasculature and nerve supply
9
Q
Describe the Endometrium in the Proliferative phase
A
formed of
- Tubular glands
- Specialised stroma
- Blood vessels
Mitosis would be seen in the cells of the stroma and glands.
10
Q
Describe the endometrium in the secretory phase
A
formed of
- corkscrew glands
- specialised stroma
- blood vessel
secretion/ shedding would be seen in the glands
11
Q
Define neoplasia
A
‘new growth’ – abnormal, uncoordinated and excessive cell growth.
persists following withdrawal of stimulus and associated with genetic alterations
12
Q
Explain the behaviour of benign neoplasms
A
- Remains localised and doesn’t invade surrounding tissues
- Generally grow slowly
- Good resemblance of parent tissue
13
Q
What is the Leiomyoma of the myometrium?
A
- aka Fibroid
- a being neoplasm of the smooth muscle
- it is slow0growing and is often localised
14
Q
What are the consequences of benign neoplasms?
A
- Pressure on adjacent tissue
- bladder (frequency) Rectosigmoid (constipation)
- Obstruction of lumen of a hollow organ
- blocking endocervix
- Hormone production
- EPO producing polycythaemia
- Transformation into a malignant neoplasm
- Symptoms for the patient
- abnormal uterine bleeding pain
15
Q
Explain the behaviour of malignant neoplasms
A
- Invade into surrounding tissues
- Spread via lymphatics to lymph nodes and blood vessels to other sites (metastasis)
- Generally grow relatively quickly
- Variable resemblance to parent tissue
16
Q
What are the key differences between malignant neoplastic tissue and normal tissue
A
- loss of differentiation
- loss of cellular cohesion
- enlarged irregular dark nuclei
- increased numbers of mitoses
17
Q
What are the consequences of malignant neoplasms?
A
- Destruction of adjacent tissue
- Metastasis
- Blood loss from ulcerated surfaces
- Obstruction of a hollow viscera
- Production of hormones
- Weight loss and debility
18
Q
Explain is the terminology used for neoplasms?
- suffix?
- malignant names based on origin?
A
- Malignant epithelial tumours are carcinomas
- Carcinomas are named for the epithelial cell type which they resemble
- Carcinomas of glandular epithelium are called adenocarcinomas
- Malignant stromal tumours are sarcomas
19
Q
What is Dysplasia?
A
- disordered growth and differentiation characterised by increased proliferation (more mitoses), atypia of cells and decreased differentiation
- Dysplastic lesions may (but don’t always) progress to invasive malignancy
20
Q
What is abnormal about this epithelium?
A
- abnormal proliferation
- the nuclear division saw throughout the epithelium rather than just in the basal area
- abnormal differentiation
- the nuclear in the cells do not mature- the nucleus is still large as it moves to the apical end of the endothelium
- not very much accumulation of cytoplasm at the top where there should be
- nuclear atypia - abnormal size and shape of the nucleus itself
- the nucleus has angulated edges rather than smooth rounds
- the chromatin has a gritty appearances
21
Q
What are the different degrees of dysplasia that may be seen microscopically?
A
- go from normal to CIN III
- CIN 1 - 1 %
- CIN 2 - 5%
- CIN 3 - 40% likely to progress to SCC
- allows you to predict the likelihood of developing invasive malignancy
22
Q
Where is dysplasia more likely to occur?
A
- Often occurs in sites where there is metaplasia
- squamous metaplasia of the cervical transformation zone
- squamous metaplasia of the bronchial epithelium
- __increased in smoking to produce more resilient cells against the smoke
- glandular metaplasia of the distal oesophagus
- __gastric reflux leads to differentiation into cells that more resemble the gastric lining
23
Q
What are the normal constituent cells found in a pap smear?
A
24
Q
What is the difference between normal surface cells of the cervix and dysplastic surface cells?
A
- Normal surface cells have a small nucleus and lots of cytoplasm
- Dysplastic cells have a
- a higher ratio of nuclear size to cytoplasmic volume,
- the nuclei show the same features that we associate with malignancy
- still have a large nucleus,
- nuclear atypia,
- irregular nuclear margin
- gritty purple staining of the chromatin irregularly spread throughout the nucleus
25
What is the difference between dysplasia and carcinoma?
* a carcinoma invades into the basement membrane
* when an invasion is seen in the cell it moves from CIN to a carcinoma
26
What is HPV?
* Human Papillomaviruses (HPVs) infects the epithelium
* has to infect basal cells
* Confined to local site of infection without viraemia
* Over 130 HPV types, some of which infect the anogenital mucosa
* high-risk HPV: 16, 18
* CIN and carcinoma
* low-risk HPV: 6, 11
* benign anogenital warts
* Double-stranded DNA virus 7.9Kbp
27
Review the way in which HPV can infect the cervical region
* progress to a malignant stage when the HPV virus get's incorporated in with the normal cervical cells
28
What strategies are there to prevent cervical cancer?
* HPV Vaccination
* 16,18 then also 6, 11
* Population-based screening
* Cervical sample HPV test
* Cervical sample cytology, only 15% get investigated at this level
* Colposcopy
* Treatment of high-grade dysplasia
* **_Large Loop Excision of the Transformation Zone_**
29
What are the conditions that HPV infection can cause?
* genital warts (6,11)
* pre-malignant and malignant cervical disease (16,18,31)
* peri-anal cancers
* cancers of the oral-pharnyx
30
What is Endometrial cancer?
- common endometrial cancer symptom?
* Malignant neoplasm of glandular epithelium - **_adenocarcinoma_**
* most endometrial cancers occur in the glands of the endometrium
* 89% of women present with postmenopausal bleeding
* necrosis of the tumour --\> bleeding
31
Give an overview of adenocarcinomas from a single site of the body and from different sites in the body
* Adenocarcinomas arising at different sites in the body have different
* risk factors,
* pathogenesis,
* appearances, behaviour
* genetic abnormalities,
* 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.
32
What are the varying subtypes of endometrial adenocarcinoma by morphology?
* Endometrioid - differentiation that resembles endometrial glands
* Serous - resemble fallopian tube epithelium
* Clear cell - clear cytoplasm
* Mixed (components of the previous 3)
* Undifferentiated / Dedifferentiated
* not showing a normal pattern of glandular differentiation
* Carcinosarcomas
* can show some coexistent malignant mesenchymal differentiation
33
What are the two groups/ demographics that present with different types of endometrial adenocarcinoma?
- what distinguishes the two groups?
* Age
* Type 1: 50-60s
* Type 2: 60s-70s
* Cause
* Morphologic types of tumour
* T1: Endometroid
* T2: Serous, mixed
* Molecular genetic abnormalities
* T1: MSI, PTEN, PAX2 loss
* T2: P53mut, 1pdel., PAX2 loss
* Precursor lesions
* T1: EIN, atypical hyperplasia
* T2: EIC
* Prognosis and treatment
* T1: good
* T2: poor
34
What is the precursor lesion to invasive squamous cell carcinoma in the cervix?
* **Cervical Intra-Epithelian Neoplasia (CIN)**
* the disease process is caused by dysplasia
35
How can CIN be detected?
| (Cervical Intra-Epithelial Neoplasia)
* screening for HR HPV infection
* looking for abnormal cells
* examining the cervix by colposcopy
* treating by LLETZ (loop)
36
What is the precursor legion for endometrial carcinomas?
* assumed to come from **_Atypical hyperplasia_**
* closely packed glands that are enlarged
* more difficult to diagnose when investigating
* need better investigative methods?
37
What are the risk factors for endometrial adenocarcinoma?
* mostpenopausal women
* peak between 55-65 y/o
* the most common presenting feature is postmenopausal bleeding
* 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
38
Give an overview of the link between endogenous hormones and endometrial cancer
- what conditions may affect this?
* Excess exposure to estrogen unopposed by progestogens
* increased neoplastic growth in the endometrium
* Being overweight increases estrogen levels in postmenopausal women
* Overweight can disrupt ovulation and progestogen production in premenopausal women
* Polycystic ovarian disease
* prolonged exposure of the endometrium to unopposed estrogen that results from anovulation
* Some rare ovarian neoplasms can produce estrogens
39
Give an overview of the link between reproduction and 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)
40
Give an overview of the link between excess body weight and endometrial cancer
* 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
( links with DM and Insulin)
41
Give an overview of the link between Diabetes mellitus and insulin, and endometrial cancer
* Women with diabetes mellitus have a two-fold increased risk of endometrial cancer
* Insulin and insulin-like growth factors may increase the effects of estrogen on the endometrium
Hard to separate the effect of insulin from excess body weight but a probably direct effect
42
Give an overview of the link between exogenous hormones & modulators, and endometrial cancer
* Hormone replacement therapy
* unopposed estrogen (RR 6.0)
* Tamoxifen (RR 2.0)
\*relative risk\*
43
Give an overview of the link between ethnicity, and endometrial cancer
* 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 ( less access to health)
* Unfavourable tumour type
* Sociodemographic factors and treatment
* Comorbidities
44
What are the tumour-specific parameters that inform behaviour and treatment?
* Tumour Type
* Tumour Grade
* Tumour Stage
45
What are the gradings for a neoplasm?
* Well differentiated - Grade 1
* Moderately differentiated - Grade 2
* Poorly differentiated - Grade 3
* grading reflected how much he tumour resembles its parent tissue
* has to be done under the microscope
* 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
46
What is the staging 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
47
What is the grading system used in gynaecological tumours?
- what is the system for **Endometrial carcinoma**
a FIGO system is used (Fédération Internationale de Gynécologie et d’Obstétrique)
* Stage 1: Confined to corpus
* Stage 2: Involving cervix
* Stage 3: Serosa/Adnexa/Vagina/Lymph Nodes
* Stage 4: Bladder, Bowel, Distant Metastasis
48
What is the most common endometrial adenocarcinoma?
* Endometroid
* resembles the endometrial glands
49
What congenital abnormalities are there of the cervix?
* agenesis of the cervix
* nor formation of the cervix
* dysgenesis of the cervix
* only part of the cervix has formed
* no connection with the vagina
50
Describe the anatomy of the cervix
* the uterus is ~ 4 cm long
51
Describe the appearance of the cervix in women
* size and shape varies with age, hormonal state and parity
* in nulliparous females it is barrel shaped with a small pinhole/ circular shaped external os
* in parous women the cervix is bulky and the external os is slit-like
52
Explain the histology of the normal cervix
* **Ectocervix:** covered by non-keratinising, stratified squamous epithelium
* **Endocervix:** lined by simple columnar epithelium that secrete mucus
* **Transformation zone**: undergoes continuous metaplastic change as the squamous epithelium from the vagina changes to columnar epithelium
53
What happens to the cervix after the Menopause?
* the SCJ moves from outside the cervix into the canal due to a lack of oestrogen
* so the transformation zone is now inside the endocervix rather than on the ectocervix
* may require a profolactive loop during smear tests to check for any precancerous changes
54
Describe the structure of the Cervix
- stroma structure
- blood supply
- lymphatic drainage
- nerve supply
* the stroma of the cervix is made of collagenous connective tissue and is mad of approx 15% smooth muscle fibre
* It's blood supply is the descending branch of the uterine artery, and the venous drainage is the uterine veins
* the lymphatic drainage is via
* parametrium
* obturator
* int. ext, common illiacs towards the aorta
* the nerve supply
* pain with the parasympathetic nerves to S2-S4
55
What is the function of the cervix?
* produces mucus to facilitate sperm migration
* acts as a barrier to ascending infection - mucus plug during pregnancy
* holds a developing pregnancy in place
* effaces and dilates to enable vaginal bith
56
What physiological changes happen to the cervix during pregnancy?
* hypertrophies
* becomes softer due to increased vasculature
* increased vascularity/ venous congestion (purple tinge)
* glands are destined with mucus forming a mucus plug
* prominent ectropion
* migration of the columnar epithelium onto the ectocervix
* remains elongated until the onset of labour when it begins to thin and dilate
57
What normal physiological presentations of the cervix are there?
* Cervical ectopy (ectropion) "erosion"
* caused by oestrogen usually found in women on the COCP
* Atrophic "cervicitis"
* due to a lack of oestrogen usually found in postmenopausal women
58
What is this an image of?
* Gonorrhea infection of the cervix
59
What is this an image of?
* Trichomonas vaginalis infection
* strawberry cervix
60
What are risk factors that increase HPV related changes that lead to pre-cancer or cancer of the cervix?
* smoking
* multiple sexual partners
* immune compromise
* low socioeconomic status
61
What is the treatment for cervical cancer?
* for low-grade cancers 1a, there is a cone biopsy/excision
* more severe cancers 1b: radical hysterectomy/ radical trachelectomy
* if they are of child-bearing age and would like to have children, the radical trachelectomy surgery can be done where the uterus is attached to the vagina
* if it's grade \>1b2 chemotherapy is advised
