Chapter 19: Vulva, Vagina and Cervix Flashcards
What is the most common uterine tumor? a) Leiomyoma b) Leiomyosarcoma c) Endometrial carcinoma d) Endometriosis
a) leimyoma (originates from myometrium)
Just know where to point out vulva, vagina, cervix, uterus, tuba falopii and ovaria.
Okay
What three structures can be found in the uterus?
Endometrium (lining of uterus), myometrium and serosa/peritoneum.
This picture is uterus tissue. Can you point out the glandular structures (epithelium) and stroma? And also point out the myometirum.
Glandular structures * Stroma ** Myometrium ***
What tumors originate from the myometrium?
Mesenchymal tumors -> leimyomas or leiosarcomyomas
What are (morphological) characterisations of Lichen Sclerosis? (and where can the disease exist)
Marked thinning of the epidermis, fibrosis of the superficial dermis and chronic inflammatory cells (T cells)in the deeper dermis. (the disease occurs in the vulva)
What are (morphological) characterisations of Lichen Simplex Chronicus? (and where can the disease exist)
Thickened epidermis and hyperkeratosis. (the disease occurs in the vulva)
What are condylomas and what two types exist?
Warty lesions of the vulva. Condylomata lata (flat, minimally elevated lesions) and condylomata acuminata (papillary and distincly elevated)
What are histological features of condylomas?
Koilocytosis, where perinuclear cytoplasmic vacuolization and a wrinkled nuclear contour occurs.
Just know that the most common type of carcinoma in the vulva is squamous cell carcinoma. Of this type, there are two distinct forms. One is high-risk HPV related and occurs in middleaged women. The other occurs in older women, sometimes following a long history of reactive epithelial changes.
Okay
How do vulvar carcinomas commonly manifest?
As areas of leukoplakia
What is Extramammary Paget Disease?
Paget disease is an intraepidermal proliferation of epithelial cells that can occur in the skin of the vulva or nipple of the breast. In the picture you can see large tumor cells with pale-pink cytoplasm that infiltrate the epidermis. Also chronic inflammatory cells are present in the underlying dermis.
Is squamous cell carcinoma of the vagina common?
No, it is extremely uncommon.
What was found in 1970 (for illustration)?
In 1970, clear cell adenocarcinoma, a very rare tumor, was identified in a cluster of young women whose mothers took diethylstilbestrol during pregnancy to prevent threatened abortion. Follow-up studies determined that the incidence of this tumor in persons exposed to diethylstilbestrol in utero is low.
Fill in: Most tumors of the cervix are of … (1) origin and are caused by oncogenic strains of … (2).
(1) = epithelial (2) = HPV
HPV has a tropism for …
the immature squamous cells of the transformation zone.
What is meant by the transformation zone of the cervic?
Colomnar mucus-secreting epithelium of the endocervix is joined to the squamous epithelial covering of the exocervix at the cervical os. During puberty eversion occurs, where the columnar epithelial cells become exposed. These cells undergo squamous metaplasia, forming a region called the transformation zone (typically place for tumors to arise).
What are precursors from which most invasive cervical carcinomas develop?
Squamous intraepithelial lesions (SILs)
Like most other DNA viruses, HPV uses host cell DNA polymerases to replicate its genome and produce virions. Virions must be shed from the surface of the squamous mucosa, yet under normal circumstances squamous cell maturation is accompanied by a cessation of DNA replication, which would prevent virus production. HPV “solves” this problem through the action of two viral oncoproteins, E6 and E7. What is the function of these proteins?
They inhibit p53 and RB
What is displayed in this picture?
Cervical transformation zone showing the transition from mature glycogenated squamous epithelium, to immature metaplastic squamous cells, to columnar endocervical glandular epithelium
What two factors of viral integration contribute to transformation of non-invasive cervical cancer to invasive cervical cancer?
Integration always disrupt an HPV gene that negatively regulates E6 and 7, which leads to their increased expression. Sometimes HPV integrates near a host cell oncogene, such as MYC, leading to its overexpression as well.
HPV-related carcinogenesis begins with the precancerous epithelial change termed SIL, which usually precedes the development of an overt cancer by many years, sometimes decades. What two types of SIL are there?
SIL is divided into low-grade squamous intraepithelial lesion (LSIL) and a high-grade intraepithelial neoplasia (HSIL).
What are characteristics of LSIL?
LSIL is associated with producitve HPV infection, but no invasion (they usually even regress).
What are characteristics of HSIL?
HSIL demonstrates increased proliferation, arrested epithelial maturation and lower levels of viral replication. HSIL is considered at high risk for progression to carcinoma.
What other name can be given to low-grade squamous intraepithelial lesion (LSIL)?
Cervical intraepithelial neoplasia I (CIN I).
What other names can be given to high-grade squamous intraepithelial lesion (HSIL)?
Cervical intraepithelial neoplasia II and III (CIN II and III)
What test can be used for early detection of SIL (and is the most succesful cancer-screening test)?
The Papanicolaou (Pap) test, in which cells are scraped from the transformation zone and examined microscopically (Pap 1=normal, Pap 3b=severe dyskaryosis)
This picture shows a low-grade squamous intraepithelial lesion (LSIL). What is typically shown here?
LSIL with koilocytotic atypia.
This picture shows a high-grade squamous intraepithelial lesion (HSIL). What is typically shown here?
HSIL with progressive atypica in all layers of the epithelium (CIN II) (it can also show diffuse atypia and loss of maturation (CIN III)).
(I can’t upload 2 pictures for comparison, so just know that normal squamous epithelial cells have a small nucleus and a lot of light cytoplasm. They usually stain light blue or pink). So with this in mind, what is different in this picture of HSILs?
The reduction in cytoplasm and increase in nucleus-to-cytoplasm ratio (reflects the progressive loss of cellular differentiation)
Fill in: Progression of SIL to invasive carcinoma is variable and unpredictable and requires … (1) infection as well as … (2) in tumor suppressor genes and … (3).
(1) = HPV (2) = mutations (3) = oncogenes
Just read
Invasive carcinomas of the cervix develop in the transformation zone and range from microscopic foci of stromal invasion to grossly conspicuous exophytic tumors. Microscopically, the invasive tumors often consist of tongues and nests of squamous cells that produce a desmoplastic stromal response.
What is a barrel cervix?
Tumors encircling the cervix and penetrating into the underlying stroma produce a barrel cervix.
What are high-risk HPV types that are associated with (pre)cancer?
Types 16, 18, 31, 33 and 45.
What is seen when immunohistochemistry is performed on cervical cancer?
It’s P16+ (tumor suppressor)
What is the primary test in the screenings program for cervical cancer a) Colposcopic examination b) HPV-test c) Cytology-test d) Histology-test
b) HPV-test
What are low-risk HPV types that are associated with condylomata?
Type 6 and 11
What is meant by productive infection of HPV?
The goal of the virus is to replicate itself. In order to do this it needs several proteins that accompany the process of genome maintenance, proliferation, genome amplification, pakaging and virus release.
What proteins are needed during the productive infection phase of HPV?
First proteins E6 and E7, followed by production of E4 and viral DNA, followed by production of L1 and L2 (capsid proteins).
What changes are made when a HPV infection transforms from a productive infection to CIN3 (invasive carcinoma)?
Slowly all proteins that are needed for reproduction of the virus (E6, E7, E4, viral DNA, L1 and L2) are upregulated.
What protein in immunohistochemistry can be used best for CIN grading?
P16, a protein expressed in HPV-associated CIN lesions. Here, no CIN/CIN1 is negative or patchy for P16 while CIN 3 will darkly stain P16.
What is done on woman aged 30-60 years each 5 years?
Cervical scrape –> PAP test
Based on what is a thin layer cytology judged?
On KOPAC-B coding:
- Kompositie (composition)
- Ontsteking (Inflammation)
- Plaveiselepitheel (squamous epithelium)
- Andere afwijkingen endometrium (other abnormalities endometrium)
- Cylinderepitheel endocervix (glandular epithelium)
- Beoordeelbaarheid (Adequacy of the specimen)
What happens after a Pap-test comes back abnormal?
Patient is referred to gynaecologist for colposcopy and biopsy.
What substances can be used to better visualize any lesions during colposcopy?
Acetic acid or jodium, dysplastic epithelium turns white.
There are two distinct forms of vulvar squamous cell carcinomas. One is related to high-risk HPV and the other one is related to Lichen Sclerosis. What lesions precede the one related to high-risk HPV and what lesions precede the one related to Lichen Sclerosis?
High-risk HPV -> vulvar intraepithelial neoplasia (VIN). Lichen Sclerosis -> differentiated vulvar intraepithelial neoplasia (dVIN)
