Female Reproductive System

Question 1

What is endometriosis and how does it present histologically?

Answer 1

presence of endometrial glands and stroma outside the uterus

There are scattered endometrial type glands with surrounding endometrial type stroma.

Question 2

What are the common sites of endometriosis?

Answer 2

1) Ovaries
2) uterine ligaments
3) rectovaginal septum
4) cul de sac
5) pelvic peritoneum
6) serosa of the large and small bowel and appendix
7) mucosa of the cervix, vagina, and fallopian tubes, and
8) laparotomy scar

Question 3

What are the clinical features of endometriosis?

Answer 3

• Dysmenorrhea (painful menstruation)
• Dyspareunia (pain with intercourse)
• Pelvic pain - intrapelvic bleeding and periuterine adhesions.
• Menstrual irregularities
• Infertility - 30% to 40% of women

Question 4

What is the pathogenesis of endometriosis?

Answer 4

1) Regurgitation theory ( Retrograde menstruation)
2) “Benign” metastasis theory – spread through blood vessels and lymphatic channels
3) Metaplastic theory – coelomic epithelium (Mesothelium) – Mullerian ducts
4) Extrauterine stem/progenitor cell theory -stem/progenitor cells from the bone marrow differentiate into endometrial tissue

Question 5

What are the complications and risks of endometriosis?

Answer 5

• Periodic/cyclical bleeding - extrinsic cyclic (ovarian) + intrinsic hormonal stimulation - red-blue to yellow-brown appearance beneath the mucosal and/or serosal surfaces
• organizing hemorrhage -> extensive fibrous adhesions in tubes, ovaries, obliteration of pouch of Douglas.
• Ovaries - large cystic masses - contain brown fluid from previous
hemorrhage (chocolate cysts or endometriomas)
• Risk of malignancy – commonly endometrioid and clear cell carcinoma

Question 6

What is adenomyosis and how would it present histologically?

Answer 6

the presence of endometrial tissue within the uterine wall (myometrium)

Scattered islands of endometrial glands and stroma are seen scattered in the myometrium.

Question 7

What is the treatment of endometriosis?

Answer 7

• Hormonal treatments – supress oestrogen
(OCP/Progesterone/GNRH agonists)
• Surgery -preserve fertility – laproscopic diathermy/laser ablation
• Surgery – completed family – hysterectomy and bilateral salpingo-oophorectomy

Question 8

What is the cervical cancer screening programme, when is it offered and what are the steps?

Answer 8

NHS Cervical Screening Programme (NHSCSP)- available to women and people with a cervix aged 25 to 64 in England
25-49 years – every 3 years
50-64 years – every 5 years

STEP 1
Cervical Smear taking- detects changes in the squamous and glandular cells
STEP 2
HR HPV testing (PCR)
STEP 3
Cervical cytology- smear assess under microscope if positive for HR HPV
STEP 4
Colposcopy with biopsy +/- cervical loop

Question 9

What is the role of HPV?

Answer 9

• Human papilloma virus – DNA oncogenic virus - 99% of cervical cancers – strongest risk factor
• High risk HPV (HR HPV) subtypes -15 subtypes – HPV 16 accounts for 60% of the cervical carcinoma cases, HPV 18 another 10% of cases
• HR HPV – can cause cancers at other sites - vagina, vulva, penis, anus, tonsil, and other oropharyngeal locations.
• low oncogenic risk HPVs - sexually transmitted ano-genital warts (condyloma acuminatum)

Question 10

What is the transformation zone?

Answer 10

Question 11

What is colposcopy?

Answer 11

• binocular microscope
• acetic acid coagulates protein and the abnormal cells, which have more protein, appear ‘aceto-white’

Question 12

What is cervical intraepithelial neoplasia (CIN)?

Answer 12

• Squamous cervical precursor lesion/ Carcinoma in situ – precursor lesion to squamous cell carcinoma
• In UK 3 grades
CIN 1 (mild dysplasia)
CIN 2 (moderate dysplasia)
CIN 3 (severe dysplasia)
• CIN 2 and CIN 3 – high grade – risk of progression to invasive carcinoma – therefore require treatment

Image:
1- normal squamous epithelium
2- CIN1 nuclei enlarged, hyperchromatic nucleus, koilocytes
3- CIN2
4- CIN3

Question 13

What is the treatment of CIN?

Answer 13

• CIN 1 (low grade) – surveillance as low grade lesions can spontaneously resolve
• CIN 2 and CIN 3 – Large loop excision of the transformation zone (LLETZ)
• Followed up post LLETZ – “Test of cure” – HR HPV

Question 14

What is cervical glandular intraepithelial neoplasia (GCIN)

Answer 14

• Precursor lesion to cervical adenocarcinoma
• High grade by definition and requires treatment

Question 15

What is the HPV vaccine for?

Answer 15

HPV vaccine protects against
• cervical cancer
• some mouth and throat cancers
• some cancers of the anus and genital areas
• In UK, Gardasil vaccine offered to all girls and boys in year 8

Question 16

What are the key histological features of squamous cell carcinoma?

Answer 16

High grade CIN which cases basement membrane invasion

Question 17

Type 1 vs type 2 endometrial cancers (age, clinical setting, morphology, precursor lesions and behaviour)

Answer 17

Question 18

What are the stages in development of type 1 endometrial cancers?

Answer 18

Question 19

What is endometrioid endometrial Adenocarcinoma?

Answer 19

• Closely resemble normal endometrium
• Gland forming tumour
• Usually express Oestrogen and progesterone receptors
• Grade 1 and 2 endometrioid adenocarcinoma generally have mild to moderate cytological atypia – low grade
• Grade 3 endometrioid adenocarcinoma is considered high grade

Question 20

What is serous endometrial Adenocarcinoma?

Answer 20

• Papillary architecture (may have glandular architecture)
• Display high grade cytological atypia
• Tumours have mutations in TP53 genes

Question 21

What is clear cell endometrial Adenocarcinoma?

Answer 21

• Can have solid, papillary and glandular architecture
• Characterised by the presence of “clear cells”
• Oestrogen receptor negative (ER-)
• High grade aggressive tumour

Question 22

What is the link between endometrial cancer and lynch syndrome?

Answer 22

• 2% to 5% of endometrial cancers - inherited susceptibility
• Lynch syndrome/hereditary nonpolyposis colorectal cancer (HNPCC) syndrome
• Autosomal-dominant inheritance -> germline mutation in one of the DNA mismatch repair genes
• Lynch syndrome – lifetime risk of developing endometrial cancer – 40-60%
• Other sites - colorectal, gastric, ovarian, pancreas, ureter, renal pelvis, biliary tract

Question 23

What is the treatment of endometrial cancer?

Answer 23

• Standard surgery - total hysterectomy with bilateral salpingo-oophorectomy
• High grade serous carcinoma – omentectomy
• High grade carcinomas – Sentinel lymph node biopsy/pelvic, para-aortic lymphadenectomy
• Post surgery – adjuvant radiotherapy or chemotherapy

Question 24

What are the 3 cell types in a normal ovary?

Answer 24

Three cell types in the normal ovary:
(1) EPITHELIAL majority of ovarian tumors (90% of ovarian cancers)
(2) GERM CELLS pluripotent germ cells
(3) SEX CORD STROMAL CELLS

Question 25

What are the 3 major histological epithelial ovarian tumour types?

Answer 25

Question 26

What are the High-grade serous ovarian cancer
(HGSOC)-risk factors?

Answer 26

• 80% of ovarian carcinomas
• germline BRCA1 and BRCA2 mutations - 5-15%
• Lynch syndrome (clear cell&endometrioid)
• Using Hormone replacement therapy (small risk)
• Smoking
• Obesity/overweight
• Asbestos exposure
• Early menarche & late menopause

Question 27

What are the signs ad symptoms of ovarian cancer?

Answer 27

• “Silent Killer”
• Bloating
• Abdominal pain
• Loss of appetite/feeling “full”
• Change in bowel habit
• Tiredness
• Weight loss

Question 28

How is ovarian cancer diagnosed?

Answer 28

• Tumour markers – CA- 125 – raised in 90% of advanced ovarian cancer
• Suspected germ cell tumour – Beta-HCG, AFP,LDH
• Imaging – Ultrasound/CT scan/PET scan – staging (FIGO)
• Biopsy

Question 29

What is the origin of HGSOC type 1 vs 2?

Answer 29

Question 30

What is the treatment of HGSOC?

Answer 30