Histo: Gynaecological pathology Flashcards
List some gynaecological infections that cause discomfort but no serious complications.
- Candida
- Trichomonas vaginalis
- Gardnerella
List some gynaecological infections that cause serious complications.
- Chlamydia (infertility)
- Gonorrhoea (infertility)
- Mycoplasma (spontaneous abortion and chorioamnionitis)
- HPV (cancer)
What is pelvic inflammatory disease?
Ascending infection of the female genital tract that can affect the uterus, fallopian tubes and ovaries
What are the usual causes of pelvic inflammatory disease?
- Gonococci
- Chlamydia
- Enteric bacteria
List some complications of pelvic inflammatory disease.
- Peritonitis
- Intestinal obstruction due to adhesions
- Bacteraemia (sepsis)
- Infertility
What is salpingitis?
Infection of the fallopian tubes
List some complications of salpingitis.
- Infertility
- Ectopic pregnancy
- Plical fusion
- Adhesions to the ovary
- Tubo-ovarian abscess
- Peritonitis
- Hydrosalpinx
What is an ectopic pregnancy?
When the fertilised ovum implants outside the uterus (e.g. in the Fallopian tube)
What is the mean age of onset of cervical cancer?
45-50 years
List some risk factors for cervical cancer.
- Human papilloma virus (present in 95%)
- Many sexual partners
- Sexually active early
- Smoking
- Immunosuppression
Which HPV strains are considered low risk and what is infection associated with?
Types 6, 11
Associated with warts and low grade cervical dysplasia
Which HPV strains are considered high risk and what is infection associated with?
Types 16, 18, 31, 33
Associated with:
- Low and high grade cervical dysplasia
- Cervical cancer
- Vulval, vaginal, penile, and anal cancer
What epithelium type is the found in the cervix?
Endocervix - columnar epithelium
Ectocervix - stratified squamous epithelium
Sepearted by the transformation zone
What is the outcome of HPV infection in most people?
- Nothing - virus is eliminated by immune system and becomes undetectable within 2 years in 90% of people
- Persistent infection with high-risk HPV types is associated with dysplasia and cancerous changes
What are the two types of HPV infection? Describe them.
-
Latent (non-productive)
- HPV DNA continues to reside within basal cells
- Infectious virions are not produced
- Replication of viral DNA is coupled to replication of epithelial cells
- This means that complete viral particles are not produced
- Cellular effects of HPV are not seen
-
Productive
- Viral DNA replication occur independently of host chromosomal DNA synthesis
- Large amount of viral DNA and infectious virions are produced
- Characteristic cytological and histological featuers are seen (halo around the nucleus - koilocyte)
What components of high-risk HPV viruses are responsible for the carcinogenic effects of HPV?
Viral proteins can inactivate tumour suppressor genes
- E6 protein - inactivates p53 gene
- E7 protein - inactivates retinoblastoma (Rb) gene
What is cervical intraepithelial neoplasia?
Epithelial cells have undergone malignant changes but basement membrane is intact (no invasion)
Describe the classification of cervical intraepithelial neoplasia.
- CIN1 = lower 1/3 of the epithelium
- CIN2 = lower 2/3 of the epithelium
- CIN3 = entire epithelium
In which type of cervical epithelium does CIN occur?
Squamous epithelium is involved more often (CIN) than glandular epithelium (CGIN)
What is the term used to describe CIN occurring in columnar epithelium?
Cervical glandular intraepithelial neoplasia (CGIN)
What differentiates CIN from cervical cancer?
Invasion through the basement membrane defines change from CIN to invasive carcinoma
What are the two types of cervical cancer?
- Squamous cell carcinoma (most common)
- Adenocarcinoma (20%)
Which staging system is used for cervical cancer?
FIGO staging
Outline the screening intervals for cervical cancer screening.
- 25-49 = every 3 years
- 50-64 = every 5 years
- 65+ = if no screening since 50 or if abnormal test results
Describe the process of the cervical cancer screening
Women are first screened for high-risk HPV. If positive, sample then undergoes cytological analysis
How is HPV detected
Hybridisation assay
Signal amplification
Uses long synthetic RNA probes complementary to the DNA sequence of numerous low and high risk HPV strains
What vaccine is protect against HPV?
Gardasil 9
Protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58
At what age to children receive HPV vaccine?
12-13 years old:
- First dose in year 8
- Second dose 6-24 months later
Describe the structure of the uterine wall
List some diseases of the uterine body.
- Congenital anomalies
- Inflammation - endometritis
- Adenomyosis - endometrium present within muscle wall
- Dysfunctional uterine bleeding
- Enodetrial atrophy/hyperplasia
- Leiomyoma
- Endometrial polyp
- Tumours
What is endometrial hyperplasia?
Defined as irregular proliferation of the endometrial glands with an increase in the gland to stroma ratio when compared with proliferative endometrium.
- Usually driven by oestrogen
- Usually occurs in the perimenopausal period
- May be associated with atypia
List some causes of endometrial hyperplasia.
- Persistant anovulation (due to persistently raised oestrogen)
- PCOS
- Oestrogen therapy (without progesterone)
- Obesity
- Granuloma cell tumour of the ovary
List some risk factors for endometrial carcinoma.
- Nulliparity
- Early menarche, late menopause
- PCOS
- Obesity
- Diabetes mellitus
- Excessive oestrogen stimulation
List some prognostic factors in endometrial carcinoma.
- Histological type
- Grade
- Stage
- Lymphovascular invasion
What are the 2 subgroups of endometrial cancer and what differentiates them?
Type 1 and type 2
- Type 1 are oestrogen-dependent, better prognosis
- Type 2 are oestrogen-independent, worse prognosis
What subgroup is endometroid carcinoma in and what are its key features
Endometrioid carcinoma is a type 1 endometrial cancer
Key features:
- MOST COMMON TYPE OF ENDOMETRIAL CANCER
- Oestrogen dependent
- Affects perimenopausal women
- Associated with atypical endometrial hyperplasia
Which endometrial cancers are classified as type 2?
Serous and clear cell carcinomas
What are the key features of type II endometrial carcinoma?
- Affect older, postmenopausal patients
- Oestrogen-independent
- Arise in atrophic endometrium
- High grade, deeper invasion and higher stage
Which genetic mutations are associated with the two types of type II endometrial carcinoma?
Endometrial Serous Carcinoma
- P53 (90%)
- P13KCA (15%) Her2 amplification
Clear Cell Carcinoma
- PTEN
- CTNNB1
- Her2 amplification
What criteria is the FIGO grading system based on?
3 tier system: grades 1,2, and 3 depending on
- Tissue architecture: % of gland formation
- Cytological atypia
Briefly describe the FIGO staging system
What is a leiomyoma? Outline its key features.
- A benign smooth muscle cell tumour in the uterus (MOST COMMON uterine tumour)
- aka. Fibroid
- Present in > 20% of women > 35 years
- Often multiple
- Usually asymptomatic
What are the three types of leiomyoma?
- Intramural
- Submucosal
- Subserosal
What is a leiomyosarcoma?
Malignant counterpart of leiomyoma
- Rare
- Usually solitary
- Affect mainly the postmenopausal
- Local invasion and bloodstream spread
- 20-30% 5 year survival
What is endometriosis? How common is it?
Presence of endometrial tissue outside the uterus
Common - affects 10% of premenopausal women
Outline the possible pathogenesis of endometriosis.
- Metaplasia of pelvic peritoneum
- Retrograde menstruation - endometrial lining travels up the fallopian tubes, into the peritoneal cavity and implants outside the uterus
Why is endometriosis an issue?
- It is functional and bleeds at the time of menstruation
- Can lead to pain, scarring and infertility
- May develop hyperplasia or malignancy
What is adenomyosis?
- Ectopic endometrial tissue deep within the myometrium
- Causes dysmenorrhoea (because it bleeds into the muscle layer and causes pain)
List two types of non-neoplastic ovarian cysts.
- Follicular and luteal cysts
- Endometriotic (chocolate) cyst
What are some manifestations of polycystic ovarian syndrome?
- Oligo/amenorrhoea
- Polycystic ovaries
- Hyperandrogenism
What three types of tissue do ovaries consist of?
- Surface epithelium
- Ovarian stroma
- Germ cells
List three types of primary specific ovarian tumour. Which is the most common
- Epithelial tumours - make up 60% of all ovarian tumours and 95% of malignant ovarian tumours
- Sex cord stromal tumours
- Germ cell tumours
Which age groups do epithelial, germ cell, and sex cord stromal tumours predominantly affect?
Epithelial: 45-65 years
Germ cell: bimodal, peak at 15-21, and 65-69
Sex cord stromal: mainly postmenopausal women but can also affect children
List some risk factors for ovarian cancer.
- Genetic predisposition (family history of breast/ovarian cancer)
- Nulliparity
- Early menarche
- Late menopause
- Infertility
- Endometriosis
- HRT
- Inflammation (PID)
List some benign epithelial ovarian tumours. Which is most common?
- Serous cystadenoma (most common)
- Cystadenofibroma
- Mucinous cystadenoma
- Brenner tumour
What are borderline tumours?
- Tumours where their biological behaviour cannot be predicted based on histology
- Low but definite malignant potential
What is the most common malignant ovarian tumour?
High grade serous carcinoma (cystadenocarcinoma) (80%)
- Aggressive
- Mutated p53
- Associated with BRCA1 and BRCA2
What proportion of ovarian cancers are familial?
Up to 10%
Which heritable mutations account for 90% of familial ovarian cancers
BRCA1 and BRCA2
Which 2 ovarian cancers are associated with endometrosis?
Endometroid carcinoma
Clear cell carcinoma
List four types of sex cord stromal tumours.
- Fibroma
- Granulosa cell tumour - may produce oestrogen
- Thecoma - may produce oestrogen (rarely androgens)
- Sertoli-Leydig cell tumour - may be androgenic
What syndrome are ovarian fibromas associated with?
Meigs’s sydrome
Triad of:
- Ovarian tumour
- Ascites
- Pleural effusion
(Also associated with Brenner’s tumour)
What are the key features of germ cell tumours?
- Account for 20% of ovarian tumours
- 95% are benign
- Mainly occur in < 20 years
What are the four main types of germ cell tumour?
- Dysgerminoma - no differentiation (female equivalent of male seminoma)
- Teratoma - from embryonic tissues
- Endodermal sinus tumour - from extraembryonic tissue (e.g. yolk sac)
- Choriocarcinoma - from trophoblastic cells which would form the placenta
What are the key features of a mature teratoma?
- Most common type of germ cell tumour
- Benign
- Can be solid or cystic
- May show numerous different mature tissue types
- Teeth and hair are common
What are the key features of an immature teratoma?
- Indicates presence of embryonic elements (most commonly neural tissue)
- Malignant tumour that grows rapidly, penetrates the capsule and forms adhesions
- Spreads within peritoneal cavity and metastasis to the lymph nodes, lungs, liver and other organs
What is a mature cystic teratoma with malignant transformation?
When any type of mature tissue within a teratoma becomes malignant (most commonly squamous cell carcinoma)
Name two secondary ovarian tumours.
Krukenberg Tumour
- Bilateral metastases composed of mucin-producing signet ring cells
- Usually of breast or gastric origin
Metastatic colorectal cancer
- 4-10% of CRC metatasise to ovaries
