1 & 2. Pathology of the female reproductive tract Flashcards
Microscopic anatomy
Normal anatomy informs pathology
Microscopic changes in cells and tissues are translated into clinical disease
Neoplasms originate from cellular components of tissues
What kind of tissue are the vulva and vagins
Stratified squamous epithelium
Vagina at puberty
Oestrogen secreted by the ovary stimulates maturation of squamous epithelial cells
Glycogen is formed within mature squamous epithelial cells
Glycogen in cells shed from the surface is a substrate for vaginal anaerobic organisms (dominated by lactobacilli)
Lactobacilli produce lactic acid keeping vaginal pH below 4.5
Cervix parts
Ectocervix
Endocervix
Transformation zone
Ectocervix
stratified squamous epithelium
Endocervix
Single layer of tall, mucin producing columnar cells
The endocervix has a deceptively large surface area
Columnar epithelium lines tiny blind ending channels (‘clefts’)
These radiate out from the endocervical canal into the surrounding stroma
Squamo-columnar junction
The ectocervix is covered by stratified squamous epithelium
The endocervix is lined by columnar epithelium
The junction between the two is called the ‘squamo-columnar junction
Formation of the transformation zone
During puberty the cervix changes shape
The lips of the cervix grow
The distal end of the endocervix opens
Endocervical mucosa becomes exposed to the vaginal environment
Metaplasia in the vagina
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
Metaplasia definition
a transformation of cell type from one kind of mature differentiated cell type to another kind of mature differentiated cell type
The transformation zone
Tissue from endocervical epithelium which has undergone metaplasia to become squamous like the ectocervix
What happens to the metaplastic squamous epithelium?
At first, the metaplastic squamous epithelium is thin and delicate (lots of proliferation & maturation is incomplete)
With time, the metaplastic epithelium comes to be as strong and well formed as that on the ectocervix
myometrium
bundles of smooth muscle, vasculature and nerves
Endometrium in proliferative phase
- Tubular glands
- Specialised stroma
- Blood vessels
Mitoses in glands
Endometrium in secretory phase
- Cork screw glands
- Specialised stroma
- Blood vessels
Secretions in glands
neoplasia
‘new growth’ – abnormal, uncoordinated and excessive cell growth.
persists following withdrawal of stimulus and associated with genetic alterations
Nomenclature of neoplasms
Different neoplasms have different behaviour
Accurate identification and naming therefore important for treating the patient
Neoplasms are classified according to their behaviour and histogenesis
Behaviour: Benign or Malignant Histogenesis: Recognising the cell of origin
behaviour of benign neoplasms
Benign:
Remains localised and doesn’t invade surrounding tissues
Generally grow slowly
Good resemblance of parent tissue
Consequences of benign neoplasms
Pressure on adjacent tissue Obstruction of lumen of a hollow organ Hormone production Transformation into a malignant neoplasm Symptoms for the patient
Leiomyoma of the myometrium
- A benign neoplasm of smooth muscle
- Localised
- Slow growing
benign neoplasms clinical problems
Pressure on adjacent tissue Bladder (frequency) Rectosigmoid (constipation) Obstruction to lumen of a hollow organ Adjacent (ureters) Blocking endocervix Hormone production ? Erythropoietin producing polycythaemia Transformation into a malignant neoplasm Probably malignancy arises de novo
Abnormal uterine bleeding, pain
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
How does malignant neoplastic tissue look different to normal tissue?
loss of differentiation
loss of cellular cohesion
enlarged irregular dark nuclei
increased numbers of mitoses
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 Anxiety and pain
Histogenesis of neoplasms
Classification by cell of origin
Determined by examining tissue under the microscope
Resemblance to parent tissue correlates with clinical behaviour
Terminology of neoplasia
Neoplasms have the suffix – oma
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
carcinoma
Malignant epithelial tumours are carcinomas
Carcinomas are named for the epithelial cell type which they resemble
Adenocarcinoma
Carcinomas of glandular epithelium
sarcomas
malignant stromal tumours
Squamous epithelium neoplasms
benign - squamous cell papilloma
malignant - squamous cell carcinoma
Glandular epithilial neoplasms
benign - adenoma
malignant - adenocarcinoma
Mesenchymal (stromal) cancer types
smooth muscle, striated muscle, adipose tissue, blood vessel, bone, cartilage
smooth muscle cancers
leiomyoma (benign), leiomyosarcoma (malignant)
striated muscle cancers
rhabdyomyoma (benign)
rhabdomyosarcoma (malignant)
Adipose tissue cancers
lipoma (benign), liposarcoma (malignant)
Blood vessel cancers
angioma (benign), angiosarcoma (malignant)
Bone cancers
Osteoma (benign), osteosarcoma (malignant)
Cartilage cancers
chondroma (benign), chondrosarcoma (malignant)
malignant vulva tumours
squamous - squamous cell carcinoma
malignant vagina tumours
squamous - squamous cell carcinoma
malignant cervical tumour
squamous - squamous cell carcinoma
glandular - adenocarcinoma
malignant endometrium tumour
glandular adenocarcinoma
stroma stromal sarcoma
malignant myometrium tumour
sm muscle leiomyosarcoma
Dysplasia
For some malignant neoplasms a ‘pre-malignant’ state is identified
This state is termed dysplasia
There is an accumulation of cells which look somewhat like malignant cells but do not invade the basement membrane
Dysplastic lesions may (but don’t always) progress to invasive malignancy
Recognising dysplastic lesions allows early treatment before invasion occurs
Dysplasia definition
disordered growth and differentiation characterised by increased proliferation (more mitoses), atypia of cells and decreased differentiation
Dysplasia terminology
Eg for the cervix:
Generic: Dysplasia
UK: Cervical intra-epithelial neoplasia (CIN)
US: Squamous intra-epithelial lesion (SIL)
How is degree of dysplasia relevant?
The degree of dysplasia may predict the likelihood of developing invasive malignancy
Grade % progress to CIN3 % progress to SCC
CIN1 11 1
CIN2 22 5
CIN3 - 40
Where does dysplasia often occur?
Dysplasia often occurs in sites where there is metaplasia
squamous metaplasia of the cervical transformation zone
squamous metaplasia of the bronchial epithelium
glandular metaplasia of the distal oesophagus
Normal constituents of a smear test
Endocervical cells in endocervix
Squamous cells in ectocervix
metaplastic cells in transformation cells
Normal cells vs dysplastic cells
Normal cells have a small nucleus and lots of cytoplasm
Dysplastic cells have a higher ratio of nuclear size to cytoplasmic volume, and the nuclei show the same features that we associate with malignancy
Difference between dysplasia and carcinoma
The difference between dysplasia and carcinoma is invasion through the basement membrane
What can cause CIN and cervical cancer?
human papillomavirus (HPV)
Human papillomavirus
Human Papillomaviruses (HPVs) infect epithelium
Confined to local site of infection without viraemia
Over 130 HPV types, some of which infect the anogenital mucosa
Double stranded DNA virus 7.9Kbp
High risk vs low risk HPVs
High Risk HPV 16,18,31,33,35,39,45,51,52,56,58,59,68
Low Risk HPV
6,11,40,42,43,44,54,61,72,81
Strategies to prevent cervical cancer
HPV Vaccination Population based screening Cervical sample cytology Cervical sample HPV test Colposcopy Treatment of high grade dysplasia Large Loop Excision of the Transformation Zone
Endometrial cancer vs cervical cancer epidemiology
Cervical cancer is predominantly a disease of the developing world.
The incidence of cervical cancer has been declining in Europe. The reduction in incidence of cervical cancer has been paralleled by reduced mortality
Endometrial cancer is presently most common in North America and Europe
What do seperate peaks in cervical cancer incidence indicate?
The separate peaks in cervical cancer incidence reflect a birth cohort effect
This happens when a group of people experience different circumstances to those born immediately before or after
An increase in cervical cancer incidence and mortality was seen in women reaching the age of sexual debut during WW1 and again in WW2
The incidence and mortality of cervical cancer in the UK have decreased, particularly since the early 1980s
In the UK this follows the introduction of the NHS cervical screening programme
A birth cohort effect exists, believed to reflect the different exposure to HPV at the time women reached the age of sexual debut
HPV vaccination is creating new birth cohorts
