Reproductive Tract Cancers Flashcards by Katie Wilkinson

Define a tumour

Any clinically detectable lump or swelling

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Define neoplasm

An abnormal growth of cells that persists after the initial stimulus is removed

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What is a malignant neoplasm?

An abnormal growth of cells that persists after the initial stimulus is removed and invades surrounding tissue with potential to spread to distant sites

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In what demographic are vulval cancers most common?

Tend to arise in older patients

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What is the most common type of vulval cancer?

Squamous Cell Carcinoma (90%)

Note Atypical squamous cells - large nuclei, mitotic bodies, irregular borders and keratin formation (whirls and swirls)

Others are Basal Cell Carcinoma, Melanoma and Soft tissue tumours

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What is the main causative factor for vulval tumours in pre-menopausal women?

HPV (human papilloma virus)

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Which lymph nodes would vulval cancers predominantly metastasis to?

Inguinal lymph nodes

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What is vulval intraepithelial neoplasia?

An in situ precursor of vulval squamous cell carcinoma

Has not invaded through the basement membrane. May or may not develop into SCC

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Are VIN and Vulval SCC related to HPV?

Yes and No!

Yes:

30% of cases, usually HPV 16
Peak onset age 60s

No:

70% of cases
Usually associated with long term inflammatory conditions e.g. lichen scleosus
Peak onset age 80s

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Which direct extensions sites can vulval cancer spread to?

Anus
Bladder
Vagina

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Explain how the cell types of the cervix change in normal anatomy

The Transformation Zone is the area where the epithelium changes from columnar epithelium in the endocervix to squamous epithelium in the ectocervix

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How does the transformation zone change throughout the womans life?

Premenarche: Well defined ecto and endo cervix

Early reproductive age: Rises in oestrogen cause the endocervix to evert so columnar epithelium is exposed to the acidic environement of the vagina

In their 30s: Metaplasia from simple columnar to stratified squamous columnar in the transformation zone

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Which HPV strains are high risk?

HPV 16 & 18

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How does the HPV virus cause uncontrolled cellular proliferation?

HPV strains 16 &17 infect the transformation zone which is already at risk of dysplasia
Produces viral proteins E6 and E7
Viral proteins inactivate tumour suppressor genes p53 and Rb
Causes uncontrolled cellular proliferation

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What is cervical intraepithelial neoplasia?

Dysplasia of cells of the cervix confined to the cervical epithelium. Does not break through the basement membrane. Caused by HPV infection

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What are the main types of cancer of the cervix?

Squamous cell carinoma (80%)
Adenocarcinoma (15%)

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What factors increase risk of exposure to HPV?

Sexual partner with HPV
Multiple sexual partners
Early age of first intercourse

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What are some of the risk factors for CIN and Cervical Carcinoma?

Increased risk of exposure to HPV
Early 1st pregnancy
Multiple births
Smoking
Low socio-economic status
Immunosuppression

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How would you target the treatment of the different types of CIN?

CIN 1: often regresses spontaneously, follow up with smear 1 year later

CIN 2&3: need treatments, large loop excision of transformation zone

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Explain the principles of the cervical cancer screening programme

Brush used to scrape cells from the transformation zone and tested for HPV

If positive for HPV cells are looked at under microscope

Age 25-49: done every 3 years
Age 50-64: every 6 years
Over 65: only if recent abnormality

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What features of this histology slide indicate neoplasia?

Pleomorphism
Large nucleus size
Presence of nucleoli

Explain the basics of the HPV vaccination programme

Girls aged 12-13 offered vaccination against high risk HPV subtypes HPV 6/11/16/18
Protects aginst HPV infection for up to 10 years
Protects against cervical, vulval, oral and anal cancers

How would invasive cervical cancer present?

Bleeding
- Post coital
- Inter menstrual
- Post menopausal
Mass
Detected on screening

Which lymph nodes would carcinoma of the cervix spread to?

Iliac and then aortic lymph nodes

How can you treat invasive cervical cancer?

* Hysterectomy if advanced * Lymph node dissection * +/- Chemoradiotherapy

What is the main type of tumour of the endometrium and the two histological types?

**Adenocarcinoma** 2 main histological types: **endometroid** and **serous**

What are the causes of endometrial hyperplasia?

Caused by **excessive oestrogen** * **Endogenous** * Obesity (androgens → oestrogens) * Early menarche/ late menopause * Oestrogen secreting tumours * **Exogenous** * Unopposed oestrogen hormone replacement therapy * Tamoxifen (breast cancer treatment) * **Irregular Cycles** * PCOS

What is the most common type of endometrial cancer?

**Endometrioid Adenocaricoma** Resembles **normal** endometrial glands just very close together with no stroma Commonly arises from hyperplasia

What is the less common form of endometrial cancer?

**Serous Adenocarcinoma** Less common but **more aggressive** Poorly differentiated cells, look nothing like normal endometrium

Where can serous adenocarcinoma spread to?

* Cervix * Bladder * Rectum * Desposits in the peritoneal cavity by transcolaemic spread

What histological feature is associated with exfoliates of serous adenocarcinoma?

Collections of Calcium - Psammoma bodies

How do you manage endometrial cancer?

* Hysterectomy * Bilateral salpingo-oophorectomy * +/- lymph node dissection * +/- chemo radiotherapy

What are fibroids?

Benign tumours of uterine smooth muscle Proper name = **leiomyomas** Pale, homogenous and well circimscribed mass

How may leiomyoma present?

* asymptomatic * pelvic pain * heavy periods * urinary frequency (if bladder compressed)

How does leiomyoma look histologically?

Whorled intersecting fasciles of beign smooth muscle cells

What is leiomyosarcoma?

* **Malignant** tumour of smooth muscle * Atypical cells * **Doesn't** arise from leiomyoma * Can metastsise to lung

What 3 types of tumour can develop in the ovary?

* epithelial tumours * germ cell tumours * sex cord stromal tumours

What are the histological subtypes of ovarian **epithelial** tumours?

* Serous * Mucinous * Endometrioid * All are types of **adenocarcinoma** Can all be further classified as benign, borderline or malignant

How do ovarian serous adenocarcinomas look histologically?

* highly atypical cells * Often show **Psammoma bodies**

How does ovarian mucinous adenocarcinoma look histologically?

How does ovarian endometroid adenocarinoma look histologically?

* glands resembling endometrium * may arise from endometriosis

Which markers exist for ovarian cancer?

**Ca-125** * Serum marker * For diagnosis / monitoring **BRCA 1/2** * tumour suppressor genes * assoicated with high grade serous cancers * would do a prophylactic salpingo-oophrectomy

What is a teratoma?

Most common germ cell tumour in women, also called a **dermoid cyst.** Can contai tissue from any of the 3 germ layers; skin, hair, teeth, muscle, cartilage etc 3 subtypes 1. mature (benign) 2. immature (malignant) 3. monodermal (highly specialised)

Other than teratoma, name some other germ cell tumours

* Dysgerminoma (seminoma of the testes) * Choriocarcinoma * Embryonal Carcinoma * Yolk Sac Tumour * **All are malignant**

What are the 2 types of sex cord stromal tumours that can arise in the ovary?

1. **Granulosa Cell Tumours** - resemble lining of ovary follicle, commonly produce oestrogen, from granulosa and theca cells 2. **Sertoli-Leydig cell tumours**- rare sex cord tumours that may produce androgen and cause defeminisation, masculation and amenorrhoea or infertility

What is a Krukenberg Tumour?

Metastatic spead of GI tumour Often **gastric** origin with **signet cell** sign

Which tumours commonly metastasise to the ovary?

* Breast cancer * Other gynae tumours * GI cancers

What is a key risk factor for testicular cancer?

**Cryptorchidism** i.e. **maldescended** testicle

What are some useful tumour markers for testicular cancer?

* **Beta hCG** - choriocarcinoma a type of germ cell tumour * **Alpha fetoprotein (AFP)** yolk sac tumours

What is a seminoma?

* Approx 50% of germ cell tumours are seminomas * Common in **young men** * **Fried egg** appearance on histology * Cancer confined to the testis for a long period * Common metastasis to **iliac** and **paraortic** lymph nodes

In which age group do yolk sac tumours usually present?

In young children Have good prognosis