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The female genital system

28 important questions on The female genital system

From outside to inside, what are the layers of the uterus?

- Serosa/peritoneum
- Myometrium
- Endometrium
- Uterine cavity

What is the myometrium, and what type of tumors can arise there?

- The myometrium is the smooth muscle tissue between the serosa and the endometrium,
- and the type of tumor that can arise there are mesenchymal tumors:

leiomyomas
sarcomas

What kind of layer is the endometrium, and what type of tumor can arise there?

The endometrium has:
- glandular structures → epithelial tumors (endometrial polyp, endometrial carcinoma)
- (epithelium) and stroma → in the stroma: mesenchymal tumors (leiomyomas, sarcomas)

What is a leimyosacroma, and what are its histological characteristics?

- A malignant mass in the uterus,
- which has atypia, mitoses and necrosis

What are endometrial polyps?

- Outgrowths of endometrium,
- which can transform to a malignant tumor (endometrial carcinoma).

What is hyperplasia in the uterus?

- An overall thickening of the mucosa (endometrium) (looks like proliferative endometrium)
- which is due to long term estrogen stimulation,
- and gives a low risk to endometrial cancer.

What are risk factors for endomterial carcinoma?

- Obesitas
- Diabetes
- Hypertension
- Infertility
- Estrogen exposure
- Germline mutations
- PTEN (Crowden syndrome)

How is endometrial carcinoma diagnosed?

- Often discovered when the patient has postmenopausal bleeding, sometimes by cervical smear
- Curettage and histological examination

Endometrial carcinomas are often divided based on the 'grade' (from 1-3). What is this grading system based on?

- It is based on the level of 'solid growth',
- which means the amount of glands that still exist (like normal tissue), or whether there is a 'field of tumor cells' (like tumor tissue).
- Grade 1 = 1-5% solid growth = well differentiated (the tissue is relatvely normal)
- Grade 3 = >50% solid growth = poor differentiation.

Which gene is a marker for tumors of the genital tract?

PAX8 (is usually positive)

What two types of cancer are sometimes hard to distinguish?

Endometrial and cervical cancer.

What are some characteristics of serous carcinoma?

- Papillary (finger-like structures) and solid
- Nuclear pleomorphism
- Loss of polarity (disorganised)
- Hobnailing (bulging nuclei)
- Brisk mitotic activity
- A background of atrophy
- Immunohistochemistry: p53 (++ or loss), p16+

What can the human papillomavirus (HPV) cause?

Infection with HPV gives a high risk on getting cancers of the genital system, head-neck region and oropharynx.
The majority of genital cancers are caused by HPV infection.

What percentage of cervical cancer cases is caused by HPV?

>95%.

What are some characteristics of HPV?

It has a circular, double-stranded DNA genome, with 6 early ORFs, and 2 late ORFs.
HPV needs epithelial cells to replicate (epitheliotropic)

What is a transforming infection?

An infection that is transforming to cancer. The chance of clearance (restore of the epithelium) is lower.

Which part of the female genital system is in particular vulnerable for HPV infection?

The transformation zone, the transformation from the vagina to the cervix.
This is a transformation from squamous epithelium → glandular epithelium.

With what kind of grading system is the level of neoplasia in the cervix assessed?

With the CIN (cervical intraepithelial neoplasia) grading system:
CIN 1 = 1/3 abnormal cells (low grade)
CIN 2 = 2/3 abnormal cells (high grade)
CIN 3 = 3/3 abnormal cells (high grade)

In HPV-associated CIN lesions, which protein is expressed?

The p16 protein, which is also sometimes used as a marker for HPV-associated squamous neoplasia.

What is the difference between adenocarcinoma in situ, and adenocarcinoma?

- Adenocarcinoma in situ: pre-invasive/pre-malignant cancer
- Adenocarcinoma: invasive, outside the glands

What are the four FIGO stages of cervical cancer?

I. Microscopic tumor (<3 mm)
II. Involvement upper 2/3 vagina, tumor <4 cm
III. Lower 1/3 vagina
IV. Involvement of bladder or rectum

How is the screening for HPV and cervical cancer done in the Netherlands?

1. An HPV test (either by self-test or at GP)
2. Positive → cervical scrape for cytology
3. Test result based on cytology.

Based on what criteria is the cervical smear (cytology) examined, and what kind of 'grade' is connected to these criteria?

KOPAC-B coding:

Kompositie
Ontsteking
Plaveiselepitheel (Squamous epithelium)
Andere afwijkingen/endometrium
Cylinderepitheel endocervix (Glandular epithelium)
Beoordeelbaarheid

Based on these: a PAP code is given.

What does the Pap result tell about the cells of the cervix?

- Pap1 = normal cells
- Pap2/3a = viral/mild dyskaryosis (for example, some cells have multiple nuclei)
- Pap 3a = moderate dyskaryosis (very large nuclei)
- Pap 3b = severe dyskaryosis

In the national screening program, what action is taken based on the PAP test result?

Pap2/3a1 for HPV type 16/18, or Pap3a2+ → gynaecologist
Pap1 or Pap2/3a1 (for other HPV types) → control cervical scrape

What kind of test does the gynaecologist typically do when someone has been classified as Pap3a+?

A colposcopy (with acetic acid or jodium to visualise abnormal cells) and biopsy.

What is the difference between the Pap test and the CIN grading system?

Pap test: for cytological screening (based on the cervical smear)
CIN: histological screening (based on biopsy)

How does the Pap test correspond with the CIN (cervical intraepithelial neoplasia) grading system?

Pap1 =                         normal
Pap 3a mild =           CIN 1
Pap 3a moderate = CIN 2
Pap 3b/4 =                 CIN 3
Pap 5 =                       carcinoma

The question on the page originate from the summary of the following study material:

Pathology Part II

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