Week 4 Flashcards
1
Q
Cervical parts and types of cells
- ecto cervix
- junctional area
- endo cervix
A
- end of the cervix that forms a canal and connects the vaginal vault; stratified squamous epithelium
- (the transformation zone) Squamocolumnar junction –> where the squamous epithelium touches the columnar epithelium
- simple cuboidal
2
Q
endocervical gland
- cell type
- purpose
- Why do you need mucus in the endocervix?
A
- lined by columnar epithelium
- Secretion of mucus
- Protection against microbial and exogenous organisms, Helps with sperm motility, Lube for intercourse
3
Q
Transition Zone/Junctional Zone
- importance in cervical cancer
- relationship between HPV and mature squamous epithelial cells
- effects of puberty
A
- Where the cervix is vulnerable to HPV infection -> because they have potential to proliferate
- Can’t be infected by HPV
- endocervix protrudes into the vaginal vault and transition zone getting larger -> also common with sexual debut
4
Q
29 yr old female who is sexually active and is seen yearly, on OCPs for 10 yrs, pelvic exam normal, pap shows high grade squamous epithelial lesion
- why is she seen yearly
- risk factors would promote HPV infection
- what is concerning about the high grade lesion?
- how can we explain how it all of a sudden just appeared
A
- Overall gynecologic health, Sexual activity, Needs oral contraceptives
- Sexual activity, Multiple partners, Unprotected sex, Postcoital bleeding, Oral contraceptive use, Previous infection, Immunosuppression, Not vaccinated against HPV
- It is high grade and high grade cells are precursors to invasive cancer
- possible that a high grade lesion was missed (possible, but not probable) The cells can be very small and can be missed. Human error is also a possibility.
5
Q
Epidemiology of Cervical Cancer
- incidence -> why?
- what is a pap smear?
- how is it collected
- which type of CA comes from where?
- paps in other parts of the world -> issue
- used in US -> benefit?
- testing done
- discrepancy between the incidence of intraepithelial lesions and cervical cancer?
A
- Incidence has gone from 11 to 8. This is a significant decrease that can be attributed to screening (Pap Smear)
○ Vaccine was only recently developed - Examination of the cervical epithelium
- Exfoliative cytology –> we don’t have to pull it off, it is scraped off; During the pelvic exam, we use a brush which goes into the endocervical canal to obtain endocervical epithelium . A scraper scrapes the transitional zone
- squamous cell carcinoma which arises from the transitional zone and adenocarcinoma arises from the endocervical epithelium.
- a simple wooden spatula is used to scrape the transition zone which is then smeared on a slide and stained. The issue with scraping and smearing, you get a lot of cervical mucus and inflammatory cells which can obscure dysplastic cells.
- liquid based cytology where we utilize the brush in addition to the spatula. The brush is placed into a vial with fixative which is sent to a laboratory and spun down and put on a slide and stained. Benefits of this are that fixative allows for dissolving of mucus, inflammatory cells are removed, it is monolayer, and we have a smaller area to look at. This allows for greater sensitivity
- DNA testing to identify the HPV virus. There are 70+ types of HPV, but only a handful are significant. Their DNA sequences differ by a few nucleotides
- Intraepithelial lesions (aka precursor lesions, pre-carcinoma, intraepithelial neoplasia) –> neoplastic process is going on but it hasn’t become invasive yet
–> Not all precursor lesions develop into cancer
6
Q
HPV
- structure
- negative of being able to test for the
- Prevalence
- high risk?
- bad part?
A
- double stranded circular DNA virus
- can identify all of these different types but not everyone who is infected with HPV will develop cervical cancer
- Prevalence of HPV in sexually active young women is extremely high (9/10 will be positive)
- High risk HPVs: 16, 18 (16 is responsible for 70% of cervical carcinomas) 31, 33, 35, 45, 52, 58 are also high risk.
- If we know that she has one of these high risk ones, it is going to involve some really intensive workup on a young woman who is very likely going to eliminate the virus in six months-2 years (this is a negative)
7
Q
Pap Smears
- kind of cell
- A; classification of cells, explain what they look like
- B; classification of cells, explain what they look like
- C/D; classification of cells, explain what they look like
- what are koliocytes
A
• These are exfoliated cells (individual cells on a slide, nothing is holding them there)
• A: Mature squamous epithelial cells; these are normal, small nuclei, nuclear boarders are round and regular high amount of cytoplasm
• B: HPV low grade intraepithelial lesion; Nuclei are larger and the margins are irregular. They are hyperchromatic and have coarse chromatin.
• C and D are high grade –>. The nuclei become HUGE and are very ugly. When you get to really high grade (D), the cells start to get smaller and you have less cytoplasm.
- Koilocyte is a squamous epithelial cell that displays hairy nuclear halos that occur in the cytoplasm.
8
Q
Journey from normal epithelium to invasive carcinoma
- levels
- mutation
- how?
- replications
- next step?
- what do the cells look like?
A
- normal, low, high, invasive
- mutation from HPV 16
- The infection attacks the transition zone because they are immature cells and the virus can enter the parabasal (immature) cells to divide and mature, then it can infect the mucosa via damage to the epithelium of basal (mature) cells
- replicates using the basal/mature host cell’s machinery in the squamous epithelium, replication actually occurs at the surface, so inside of the nucleus we have replication of the viruses and the viral proteins are expressed & fill up the cytoplasm of these mature squamous epithelial cells, and that is what produces this phenomenon of endocytosis because we have now a viral protein (E5), which binds to the endoplasmic reticulum & forms little vesicles that fill up the cytoplasm & push the normal cytoplasmic components to the periphery or hemochromatosis
- infected cell replicates
- proliferation of the infected (abnormal or dysplastic, aka do not mature) cells & the nuclei become larger & hyperchromatic, borders become irregular, and N:C ratio increases
9
Q
categorization of the intraepithelial lesions
A
- CIN-I (or low-grade, aka only lower third of the squamous epithelium is dysplastic) & CIN-II (or high-grade, aka anything over a third) but no real distinction in the behavior of these two, so we combine them to make high-grade epithelial lesions
10
Q
significance of low-grade vs high-grade? What percentage will regress?
A
- 60-30-10 = low-grade lesion
- 30-60-10 = high-grade lesion, progression to high-grade lesion
- low-grade lesion = lower third
- high-grade lesion = nearly the entire surface
11
Q
HPV proteins E6 & E7
A
(E6 & E7) that prevent cell death or degradation & up-regulates telomerase or cell-immortalization of the infected cell & inhibition of p53 so lose p21 and mismatch-repair, resulting in cell proliferation or dysplastic process
12
Q
process that allows for these dysplastic cells to become invasive? What is the difference with HPV?
A
- they must integrate into the host cell DNA
- normally HPV can just sit in DNA and use hsot machinery to replicate but in order to become invasive it must integrate its genome into host DNA.
13
Q
Progression of HPV neoplasia histo
- Normal
- CIN-I
- CIN-II
A
- Normal or mucosa with maturation –> dysplastic in lower third & not much cytoplasm
- (CIN-I) –> immature & not as crowded & still dysplastic or disorganized cells in lower third
- (CIN-II) –> all or completely immature & dysplastic cells w/vertically-oriented nuclei & abundant glycogenation in cytoplasm & very crowded
14
Q
2 things seen in malignant cells
A
mitosis and apoptosis & little focus of invasion at the basement membrane
15
Q
Histo for invasive squamous cell carcinoma
A
- lots of invasion seen = viral DNA integrates into host DNA for event to occur = trying to replicate normal = hyperglandular cells
- In nests or islands & invade the stroma, which elicits a desmoplastic response, as the tumors invades the stroma, the stroma reacts & assists with invasion of the tumor & the stroma becomes bluer, which tells you there’s invasion
