Pathology of the Female Reproductive Tract Flashcards
Give an overview of what happens to the microscopic structure of the vagina at puberty
- 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
Describe the microstructure of the Ectocervix
- 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
Describe the microstructure of the Endocervix
- 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
Describe the formation of the transformation zone
- 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
What is the definition of metaplasia?
a transformation of cell type from one kind of mature differentiated cell type to another kind of mature differentiated cell type
Review the cervical transformation zone
- cells transform from columnar cells to squamous cells as it moves from the vagina to the cervix
What is this an image of
- identify 3 key parts in this image
Describe the myometrium
- Bundle of smooth muscle
- very good vasculature and nerve supply
Describe the Endometrium in the Proliferative phase
formed of
- Tubular glands
- Specialised stroma
- Blood vessels
Mitosis would be seen in the cells of the stroma and glands.
Describe the endometrium in the secretory phase
formed of
- corkscrew glands
- specialised stroma
- blood vessel
secretion/ shedding would be seen in the glands
Define neoplasia
‘new growth’ – abnormal, uncoordinated and excessive cell growth.
persists following withdrawal of stimulus and associated with genetic alterations
Explain the behaviour of benign neoplasms
- Remains localised and doesn’t invade surrounding tissues
- Generally grow slowly
- Good resemblance of parent tissue
What is the Leiomyoma of the myometrium?
- aka Fibroid
- a being neoplasm of the smooth muscle
- it is slow0growing and is often localised
What are the consequences of benign neoplasms?
- 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
Explain the behaviour of malignant neoplasms
- 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
What are the key differences between malignant neoplastic tissue and normal tissue
- loss of differentiation
- loss of cellular cohesion
- enlarged irregular dark nuclei
- increased numbers of mitoses
What are the consequences of malignant neoplasms?
- Destruction of adjacent tissue
- Metastasis
- Blood loss from ulcerated surfaces
- Obstruction of a hollow viscera
- Production of hormones
- Weight loss and debility
Explain is the terminology used for neoplasms?
- suffix?
- malignant names based on origin?
- 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
What is Dysplasia?
- 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
What is abnormal about this epithelium?
- 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
What are the different degrees of dysplasia that may be seen microscopically?
- 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
Where is dysplasia more likely to occur?
- 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
What are the normal constituent cells found in a pap smear?
What is the difference between normal surface cells of the cervix and dysplastic surface cells?
- 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
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
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
- high-risk HPV: 16, 18
- Double-stranded DNA virus 7.9Kbp
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
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
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
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
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.
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
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
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
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)
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?
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
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
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)
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)
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
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*
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
What are the tumour-specific parameters that inform behaviour and treatment?
- Tumour Type
- Tumour Grade
- Tumour Stage
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
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
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
What is the most common endometrial adenocarcinoma?
- Endometroid
- resembles the endometrial glands
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
Describe the anatomy of the cervix
- the uterus is ~ 4 cm long
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
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
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
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
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
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
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
What is this an image of?
- Gonorrhea infection of the cervix
What is this an image of?
- Trichomonas vaginalis infection
- strawberry cervix
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
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
