11.05 Pathology of Cervical Dysplasia and Malignancy Flashcards
What is dysplasia?
An abnormality of development (usually denotes a pre-cancerous lesion)
Can be defined as the enlargement of an organ or tissue by the proliferation of cells of an abnormal type, as a developmental disorder or an early stage in the development of cancer.
What are the histological gradings of dysplasia in the cervix?
- HPV infection
- Cervical intraepithelial neoplasia 1 (CIN 1)
- Cervical intraepithelial neoplasia 2 (CIN 2)
- Cervical intraepithelial neoplasia 3 (CIN 3)
CIN 1 is pretty much the same as HPV invasion while CIN2 and CIN3 are the pre-cancers and dysplasia
Describe what tissue HPV virus tends to infect
Potential to infect squamous epithelium (it is only able to complete its life cycle it in differentiating epithelium).
Many types of HPV serotypes exist causing different lesions.
What are the main two groups?
Common Warts (skin lesions): HPV1, 2, and 4
Genital Warts (can be divided into low risk and high risk)
High risk = HPV 16 and HPV 18 (… BUT other serotypes are associated with cervical cancer)
What two types of cervical cancers is HPV infection associated with?
High grade squamous intraepithelial lesion: proportion of HPV 16 and 18 is much higher
- Squamous Cell Carcinoma
- Adenocarcinoma
How common is infection with HPV and how is this infection aquired?
Infection is very common - estimated lifetime risk is 50-80%
Transmission is by sexual intercourse or anogenital contact
Describe the structure of the HPV virus
- Capsid proteins externally that encases viral DNA.
- Upstream regulatory region doesn’t code proteins and then a group of genes (E) early genes expressed early in the lifecycle of infection (often cell regulatory).
- L genes encode capsid proteins.
Early genes (E) of the HPV virus are expressed and their proteins interact with important aspects of the cell cycle. What are these?
E6 and E7 protein interacts with p53 and Rb gene respectively both important to cell cycle regulation.
Is the interaction of the proteins encoded by E6 and E7 enough to cause cancer?
Not sufficient in itself to cause cancer - high risk subtypes has their DNA that intergrates into the host DNA important for oncogenesis.
Why does the virus require fully differentiating squamous cells in order to complete its life cycle?
Uses machinery of the cell for replication
Proteins produced modify the cell cycle. Squamous infection reaching superficial layers is where capsid proteins are produced in abundance and the viral particles become active and shed off. Takes about 2-3 weeks for the cycle to occur.
Does every infection with HPV lead to cancer?
No
The majority of infections are subclinical.
We have a cell mediated immune response and a seroconversion response that is able to successfully eliminate HPV from a vast majority of people = clearance.
Only small % progress to dysplasia (and even smaller % to cancer)
Describe the basic timeline from infection to cancer.
Over what time frame does this occur?
- Virus particle replicates in infected epithelium
- HPV infection (low grade lesion - viral particles present in cells)
- Release and transmission through sexual activity
- Progression to high grade lesions (can still regress without medical intervention)
- Progression to cancer
This occurs of a number of years (up to 10 yrs and more)
What specific area of the cervix does this process of dysplasia occur?
Why?
The transformation zone
Transition between endocervical columnar and squamous epithelium on the ectocervix. Glandular epithelium pouts out to vaginal environment in puberty and undergoes metaplasia (the vulnerable epithelium to infection)
Because it is a high turnover and is undergoing metaplasia
What is the difference between a cervical chondyloma and a flat chondyloma?
Are these cancerous?
Cervical Chondyloma: Lesion that pokes out from the surface (uncommon).
- Epithelium is thickened with finger-like projections
Flat condyloma: Invisible to the naked eye (requires special stains).
- Cells of different size, less evenly distributed, cave of palor around nucleus (capsid proteins of HPV)
These could potentially be pre-neoplastic but not nessarily
Describe the histological changes seen in CIN1
CIN 1 is the same as HPV infection (morphological difference of dysplastic nuclear features in parabasal cells: larger, crowded and slightly disordered)
Describe the changes seen in CIN2
True pre-neoplastic lesion (Peak incidence in late 30s and associated with high risk subtypes of HPV)
Lack of maturation, disorder, croded, extend through 1/2 to 2/3 of epithelial surface
Describe the changes seen in CIN3
No maturation at all, dysplastic features through whole length of epithelium
What differentiates squamous cell carcinoma from CIN?
Invaded through basement membrane and lots of mess
Describe the clinical course following invasion through the basement membrane (ie of SCC)
Clinical course is determined by extent of invasion (into ureter or bladder and other local structures) wth metastasis to lymph nodes and distant sites
What is adenocarcinoma in situ (ACIS) of the cervix?
Pre-neoplastic condition: also related to HPV but serotype 18 has a bigger role than 16. May not be any macroscopic features to see.
- Epithelial cell crowding
- Variably enlarged nuclei are irregular
- Prominent nuclear hyperchromasia with coarse chromatin
- Mitotic figures are invariably present, easily visualized at luminal pole of cell, but can be as
- Apoptotic bodies at basal portion of gland in 70% of cases
- Conspicuous architectural alteration: papillary or cribriform intraglandular growth
- well demarcated appearance
- have abrupt transition to normal epithelium
What is adenocarcinoma of the cervix?
Invasive adenocarcinoma: papillary infolding, cribiform structures, high grade dysplasia, no maturation
What is cytology?
Used to obtain cells from cervix by scraping top layers off and spread to smear or into liquid medium
What are the cytological gradings of cervical pre-neoplasia?
- Low grade squamous intraepithelial lesion (corresponds to HPV and CIN1)
- High grade squamous intraepithelial lesion (corresponds to CIN2/3)
What is seen in mounts of Low grade squamous intraepithelial lesion (LSIL)?
Seeing HPV infected cells: binucleation and sharp nuclear cave and lacume around nucleus where proteins are proliferating
