Week 5 - Female Genital System

Question 1

Identify the common causes of vaginal bleeding/discharge.

Answer 1

Vaginal bleeding:
• Pre pubertal - trauma, foreign body, rare malignancy (sarcoma botryoides).
• Pregnancy - placenta praevia, miscarriage, ectopic pregnancy.
• Post-coital bleeding - lesions of cervix (carcinoma).
• Post-menopausal - uterine lesion (endometrial polyp/carcinoma).
• Abnormal menstruation - DUB - psychological, hormonal, dysfunction, haemostasis disorder. Local - infection, fibroids, polyps, endometriosis.
• Pain - uterine spasm, obstruction, adenomyosis, PID, tubal pregnancy, torsion.

Discharge:
• White, cheesy - Candida.
• Clear/watery - Trichomonas, gardnarella, Chlamydia, eczema.
• Pus/purulent - Gonococcal, bacterial.
• Haemorrhagic - Infections, trauma, malignancy.

Question 2

Describe the normal anatomy of the female genital system.

Answer 2

• Uterus and ovary come from 2 different embryonic structures - Müllerian duct and Mesonephric duct.
- Mesonephric duct gives rise to ovary.
- Müllerian duct gives rise to tubes, uterus, vagina, cervix.
• All people female by default.
• SRY gene on Y chromosome → male.
- If have Y chromosome and SRY gene not functioning → female.

Question 3

Outline the menstrual cycle.

Answer 3

• Hypothalamus → GnRH increases before ovulation (follicular phase).
• Pituitary → FSH and LH surge → follicles rupture and release ova at this point.
• Ovarian hormones
- Oestrogen gradually increases.
- Inhibin is the opposite of oestrogen.
- Following ovulation is the luteal phase.
• Endometrium goes through stages of proliferation and menstruation.
• Basal body temperature increases after ovulation.

Question 4

Describe the transformation zone.

Answer 4

• Transformation zone - site of cervical cancer
• Pre-pubertal - endocervix is inside, vagina and cervix covered by stratified squamous epithelium.
• During pubertal reproductive phase - the endocervix comes out - the columnar cells which are very sensitive cells are exposed. Also at this time, sexual activity exposes further infections to this zone.
• Exposed endocervical cells undergo metaplastic change to become stratified squamous epithelium from columnar epithelium. This zone is known as the transformation zone - site of cervical zone.

Question 5

Outline the normal cervix.

Answer 5

• Endocervix - columnar epithelium.
• Ectocervix - squamous epithelium.
• Abrupt transformation from endocervical columnar epithelium to squamous epithelium.
• High vaginal smear → infections.
• Cervical smear (transformation zone) → cancer.
• HPV, the causative agent of cervical cancer has an affinity for the immature squamous cells of the transformation zone.

Question 6

Outline vulva and vaginal disorders.

Answer 6

• Many different disorders.
• Commonest inflammations - sexually transmitted
• Cancers can also occur - less common.
• Young children can develop high grade sarcoma - CT tumour known as sarcoma botryoides.
• Bartholin cyst - obstruction and secondary infection of vaginal glands.
• Adenosis - chronic inflammation of vagina leading to increased mucous gland

Question 7

Outline vulvo-vaginitis - vaginal discharge

Answer 7

• Common - infection. Present as vaginal discharge. Can be simple inflammation (clear fluid), slighty turbid or cheesy discharge.

• Contact dermatitis:
- Urine, soaps, antiseptics, deodorants, creams, foreign body etc. oozing and crusting papules (children common).

• Infections:

• Chlamydia - asymptomatic, clear to pus discharge.
• Herpes - HSV 1 or 2, genital herpes - vesicles.
• Candida - Pregnancy/DM - thick, white cheesy discharge.
• Trichomonas - watery pale - yellow pus discharge.
• Syphilis - primary - chancre, secondary, tertiary.
• HPV - condyloma accuminata, wart.

• Inflammations and atrophy:
- Lichen sclerosis - atrophic, hyperplastic.

Question 8

Identify the investigations for STIs.

Answer 8

• Tested for multiple STI organisms - Gonorrhea, Chlamydia trachomatis, Trichomonas vaginalis, Candida, syphilis and HIV infection. Mycoplasma genitalium (recurrent).
- Usually completed as a battery of multiple organisms - multiple organisms can occur together.
• Endocervical and high vaginal swab (in case of males - uretheral swab).
• Transport media UTM-RT (universal) sucrose phosphate. Minimal Transport time, store samples at low temp.
- Usually sent in transport media containing sucrose.
• Nucleic Acid Amplification test (NAAT) is now standard molecular genetic technique (PCR, RT-PCR etc.) detects pathogen earlier than antibody tests (window period).
- Another name for PCR, reverse transcriptase PCR.
- Now known as NAAT - standard.
- Detects pathogens much earlier than antibody tests as antibodies take time to develop (known as window period)
- Swab is rotated high in vagina fornix and sent in transport media.

Question 9

Outline cervicitis.

Answer 9

• Inflammation of cervix.
• Common - secondary to vaginal infections.
• STD - Gardnerella, Chlamydia, Trichomonas, Candida etc.
• Plenty of inflammatory cells in the PAP smear.

Question 10

Outline endocervical polyps - benign.

Answer 10

• Plenty of inflammatory cells in the PAP smear.
- Chronic inflammation usually produces polyps - mucosal gland hyperplasia with plenty of inflammatory cells (similar to chronic rhinitis producing nasal polyps).

Question 11

Outline Chlamydiasis.

Answer 11

• Common (developed world), asymptomatic 80%.
- Pus is not common presentation - can be clear fluid or pus.
• Common cause of long term complications - PID, infertility, ectopic pregnancy etc.
• No discharge or clear/pus discharge (less irritation/itching - more asymptomatic).
• Cytoplasmic reticulate bodies - seen within cytoplasm of epithelial cells.
- Clinically do NAAT test.

Question 12

Outline Mycoplasma Genitalium.

Answer 12

• Similar in clinical features.
- Asymptomatic.
• No cell wall → resistant to penicillin.
- Organisms have no cell wall → resistant penicillin - chronic/recurrent STDs common.
• Lab diagnosis - NAAT (nucleic acid amplification test).

Question 13

Outline Trichomonas vaginitis/cervicitis

Answer 13

• Flagellate protozoa - Trichomonas vaginalis (>50%).
- Cannot use antibiotics.
• Asymptomatic (<50%) to clear watery to white/yellow bubbly discharge, malodour, erythema, itching.
- Bubbles within the discharge is very typical.
• Increased pH → bacterial vaginosis. Strawberry cervix*
- Inflammation of cervix typical produces strawberry cervix - multiple erythematous spots.
• Produces proteolytic enzymes, complement, neutrophils.
- Breaks down mucosal defence → increased HIV and other STD infections in patients with Trichomonas.
• Increased HIV risk, PID and preterm birth.
- PID and preterm birth - long term complications.
• Urethra involvement common in males.
• Microscopy - parasites (protozoa) seen as flagellate leaf shaped cells → motile organisms.

Question 14

Outline Candida vulvovaginitis - Thrush.

Answer 14

• Fungus - Candia albicans
• Pregnancy, diabetes, immunodeficiency, HIV.
- Very common in pregnant women.
• Itching, sore, burning. Bright red rash.
• Heavy, white, curd/cheesy discharge.
- Thick cheesy discharge.
• Vaginal swab/PAP smear - diagnosis.
• Branching hyphae and budding yeast forms.
- Very characteristic of the fungus.

Question 15

Outline genital herpes.

Answer 15

• Commonly by HSV-2, HSV-1 increasing.
• Second common STI in Australia.
• Women, ~30 years, Indigenous.
- Women, reproductive age.
• Viral replication - peak in 3-4 days.
- Viral replications peaks 3-4 days after age.
• Large intranuclear inclusions (Cowdry A) and multinucleated giant cells.
- Large intranuclear inclusions - characteristic microscopy feature known as Cowdry A inclusions.
• Asymptomatic in majority → clusters of multiple, painful vesicles → ulcers.
• Tzanck smears of lesion simple (do not distinguish VZV and HSV infections).
- Scraping of lesions and taking fluid is known as Tzanck smears.
• NAAT test.
- Confirmatory test.

Question 16

Outline syphilis.

Answer 16

Primary syphilis:
• Primary chancre - painless hard.

Secondary syphilis:
• Condyloma Lata - knob/wart like.
• Rash (palmar/plantar) - Erythemat/pigmented.

Question 17

Outline Condyloma Accuminatum.

Answer 17

• Soft, moist, papillomatous/warty growth.
• STD - HPV serotypes 6 and 11.
• Low risk of malignancy.
• Microscopy - hyperkeratosis, papillary projections. Overgrowth of epithelium. Hyperview - perinuclear hallow known as koilocytes. Usually within basement membrane, do not spread (not a malignancy - benign tumour).

HPV cytologic features:
• Koilocytosis*
• Hyperkeratosis.
• Parakeratosis.
• Papillomatosis.
• Dyskeratosis & Dysplasia.
• Intact basement membrane.

Question 18

Outline vulval disorders.

Answer 18

Carcinoma (of the vulva) and Paget’s disease
• Rare, similar to cervical cancer, HPV 16.
• 3%, starts as dysplasia (VIN)
- Vulva intraepithelial neoplasia.
• Slow growth. Size: <2cm better.
• Paget’s disease - same as breast.
- Eczematous lesion due to malignant cells spreading to skin.

Lichen Sclerosus et.atrophicus
• Immune, T cell mediated.
- Epidermis undergoes marked thinning.
- Atrophy.

Lichen Simplex Chronicus
• Sq. Hyperplasia - Chronic irritation.
- Opposite - excess proliferation of skin.
- Both present as whitish scar like patches. 2 conditions of epithelial disorder but not cancer.
- Hyperplasia.

Question 19

Outline pelvic inflammatory disease.

Answer 19

• Chronic complication of many STDs (infections) - common being chlamydia.
• Organisms enter into the uterus and spreads through the fallopian tube into the peritoneal cavity → leads to chronic inflammation spreading to all the organs within the pelvis leading to chronic inflammation → pain, fever, mass (inflammatory granulation tissue), obstruction of fallopian tube leading to infertility.
• Inter organ adhesions due to chronic inflammations and scarring. Pelvic organs become one inflammatory mass.
• Can also occur secondary to endometriosis.

Question 20

Outline cervical cancer.

Answer 20

• 1st → 13th common cancer (PAP screening).
- Use to be most common cancer in females.
- PAP screening - early detection of cancer.
• First cancer to get vaccine*
• Pap screening → decreased incidence 99%*
• ‘Squamous cell carcinoma’
• It is an STD - Human Papilloma Virus (HPV 16, 18).
- STD due to HPV.
• Aetiology: HPV + oestrogens + others.
• Prolonged pre-cancer dysplasia ~ 10y CIN (cervical intraepithelial neoplasia).
- Characterised by long pre-cancer dysplasia phase - ~10 years - known as CIN.
• Present asymptomatic/post coital bleeding*
• Dysplastic cells in pap screen ~2y*
- Dysplastic cells can be seen in pap smears more than 2 years earlier than the clinical cancer.
• Not all CIN progress to invasive cancer.
• LSIL <5%, HSIL >70% → ca.
- Low grade lesions - approx. 5% become malignant.
- High grade - 70% become cancers.
• 5y survival stage 1 >80%, stage 4 ~10%.

• Normal transformation zone → leading onto whitish plaques (leukoplakia with HPV infection) → high grade lesions (erythematous areas) → cancer (period of nearly 10-15 years minimum for developing the cancer).

Question 21

Describe the aetiology of cervical cancer.

Answer 21

Aetiology (HPV + oestrogens + others)

• HPV - DNA virus (initiator - causes the mutation).

• Multiple partners - STI. Mucosal contact. Usually due to sexual exposure, mucosal contact is important.
• High risk - bind to cell DNA - 16, 18 (31, 33…). Many types of HPV - high risk types are where the viral DNA binds to cellular DNA to cause mutations (16 and 18). Many other subtypes - less common.
• Low risk free viral DNA - 6, 11 (42, 43, 44…)* Usually causes benign tumours because they don’t bind to the cellular DNA.

• Oestrogens - growth control hormones (promoter).

• Mutation (initiator) plus excess oestrogen (promoter) → cancer.
• Early menarche, late menopause, lack of pregnancy, hormone therapy obesity and hyper-oestrogenemia (endometrial polyps, hyperplasia etc.)

• Other factors

• Family history* - independent risk factor. Genetic factors less important compared to breast cancer.
• Smoking/other carcinogens (promoter)
• Other viral/mutations rarely.

Question 22

Describe the structure of HPV.

Answer 22

• DNA virus.
• Capsid contains many proteins - gp120 and gp41 important.
• HPV vaccine manufactured by taking the segment of the DNA which produces the viral capsid in fungus → produces capsid proteins and empty viral capsids (covering of the virus without its DNA) → extracted as vaccine → induces immunity.

Question 23

Describe the HPV vaccine.

Answer 23

• Since 1991 a series of research on papillomavirus. First anti cancer vaccine 2006. Australian of the year 2006.
• Vaccine has shown ~100% efficacy in the phase III human trial on over > 25,000 women.
• In 2006, FDA approved Merck’s vaccine, Gardasil a quadrivalent vaccine against strains 6, 11 (wart) and 16, 18 (Ca) of the HPV virus.
• HPV also causes cancer of oropharynx, vulva, vagina, penis, scrotum, rectum and perineum.
- Vaccine also prevents other HPV induced cancers.

Question 24

Explain the pathogenesis of cervical cancer.

Answer 24

• HPV (DNA virus) is found in >99.7% of Ca.Cx.
• >100 types, transmit by mucosal contact (STI).
• 6 and 11 - benign warts/condyloma accuminatum, LSIL.
- Low grade dysplasia.
• 16 and 18: 70% cancer/CIN2 and 3 (HSIL).
- Rarely by other types 31, 33, 35, 39, 52, 56, 69 (many other types but not important).
- High grade.
• Virus infects immature squamous cells of transformation zone.
- Transformation zone around external os gets transformed to metaplastic squamous cells.
• Pathogenesis - HPV proteins E6 (bind p53) and E7 (bind Rb) tumour suppressor genes → loss of growth suppression → cancer.
• Normal → low grade → high grade dysplasia → cancer.
- Dysplastic changes (initially low grade then high grade) leading to cancer.
• Not all CIN progress to invasive cancer.
- Not all dysplasia leads to cancer - low grade lesions can revert back to normal. High grade → 70% cancer
• LSIL <5%, HSIL >70% → cancer.

• 6 and 11 - free DNA - infect many areas (vulva, vagina, cervix, skin, oropharynx) → leads to benign wart or condyloma accuminatum with mild dysplasia.
• 16 and 18 - bind to cellular DNA → cause mutations. E6 and E7 protein suppress tumour suppressor genes Rb and p53 → leads to tumour formation through the stages of low grade dysplasia, high grade dysplasia to cancer.
• Occasionally, due to unknown reasons, benign warts can become malignant.
*See diagram.

Question 25

Identify the investigations for cervical cancer.

Answer 25

• Colposcopy - lack of epithelial maturation (glycogen).
- Based on the principle that metaplastic cells at the transformation zone lack epithelial maturation → cells do not have glycogen.
• PAP smear - nuclear irregularity.
- Based on nuclear shape/irregularity.
• Biopsy/excision - depth and infiltration.
- Tissue infiltration and depth of cancer.

Question 26

Outline colposcopy.

Answer 26

1. Initially, saline wash and observation of blood vessel pattern. Mosaic is abnormal.
2. Application of acetic acid → whitens the dysplastic area (abnormal area becomes white patch - acetowhite lesion).
3. Iodine solution which stains normal tissue dark brown. Unstained areas = dysplastic tissue (appears pale - no glycogen).

Question 27

Describe the different appearances of pap smear test results.

Answer 27

• Normal pap smear - nuclei appear small and pyknotic.
• Low grade lesions - larger nucleus, smooth border.
• High grade lesions - very large, irregular. Clinically appears as acetowhite lesion.
• CIN I - mild dysplasia - low-grade SIL (LSIL).
• CIN II - moderate dysplasia - high-grade SIL (HSIL).
• CIN III - severe dysplasia - high-grade SIL (HSIL).
• CIN III - carcinoma in situ - high-grade SIL (HSIL).

Question 28

Outline the progression of cervical cancer.

Answer 28

CIN (stage 0)
• Both HPV 6, 11 and HPV 16, 18.
- Dysplasia with basement membrane still intact.

Stage 1: limited to cervix (has broken down basement membrane).
• 1a. Preclinical/microscopic.
- 1a-1 <3mm.
- 1a-2 <5mm.
• 1b. Larger >5mm - confined to cervix.

Stage 2: beyond cervix
• Upper 1/3 of vagina.

Stage 3: to pelvic wall/lower vagina.
• Lower 1/3 of vagina or up to pelvic wall.

Stage 4a: bladder, rectum.

Stage 4b: beyond pelvis.

LSIL/CIN-I is virtually a transient HPV infection and not a cancer precursor.

Question 29

Outline pap smear screening.

Answer 29

• Developed by George Papanicolaou (Gynaecologist).
• Screening prevents up to 90% of cervical cancer.
• Long pre-cancer stage (curable by simple excision).
- Dysplastic/in situ stage.
• Once leading cause of cancer death → after PAP → 8th cause.
• Best example of cancer prevention by early detection.
• Simple cytology (scrapping), easy, non invasive.

Technique:
• Cytology - scrapped cells from transformation zone.
• Good nucleus to cytoplasm differentiation.
• Superficial, mature pink cells (oestrogen effect).
- Pap stain shows hormonal effect.
- Superficial cells.
• Intermediate blue cells (progesterone effect).
• Increased neutrophils, basal cells → inflammation.
• Pleomorphic, hyperchromatic - ?Cancer*
- Irregular and hyperchromatic - suspect cancer.
- Pap smear cannot diagnose cancer (only suspect) - because just scrapping superficial surface. Irregular cells could be dysplasia or invasion.

Question 30

Identify the process of an abnormal pap smear.

Answer 30

• If LSIL and >30 - refer patient for immediate colposcopy.
• If <30 - yearly pap smears.
• Fluctuating repeat smear results - refer for colposcopy women with at least 2 low grade smear reports (at least 12 months apart) within a 3 year time frame.
• HSIL or any glandular abnormality → colposcopy.

• Not a diagnostic test*
• Cannot diagnose cancer.
• Only screening (normal pt).
• Abnormal → colposcopy/biopsy.
*See diagram/histology examples.

Question 31

Describe the normal anatomy and histology of the uterus.

Answer 31

• Myometrium - smooth muscle.
• Endometrium - glands in stroma.
• Section of myometrium - see plenty of bundles of smooth muscle lined internally by endometrium.
• During the proliferative phase, the glands will be small and round with plenty of stroma.
• In the secretory phase, the glands will be larger, less stroma and having secretions.
• Smooth muscle.

Question 32

Outline disorders of the uterus.

Answer 32

Myometrium (only tumours):
• Benign - Leiomyoma (Fibroid).
- Clinically known as fibroids.
• Malignant - Leiomyosarcoma.
- Very rare.

Endometrium:
• Endometritis - acute (STI), chronic (TB, fungal).
- Infections, STIs common.
• Endometrial hyperplasia - polypoid and diffuse.
- More common, hormone induced (oestrogen).
• Endometriosis and Adenomyosis.
- Endo - spread of endometrium outside uterus.
- Adeno - inside uterus (into myometrium).

• Endometrial tumour

• Benign - endometrial polyp.
• Malignant - endometrial carcinoma.
• Stromal tumours - benign stromal nodule. Malignant - stromal sarcoma. Very rare.

Question 33

Outline leiomyoma (fibroid uterus).

Answer 33

• Multiple, benign, oestrogen responsive.
- Multiple benign tumours of smooth muscle.
- Can present internally (submucosal) or within the myometrium (intramural) or outside (subserosal).
• 70% have MED12 gene mutations.
- Now suspected to be neoplasms rather than hyperplasia.
• BPH 75% = FCD 50% + fibroids 25%
- Both males and females have hormone responsive tumours.
- BPH ~ fibrocystic disease breast and uterine fibroids.
• Submucosal, intramural, subserosal → regress after castration or menopause.
- Hormone responsive as regress after castration or menopause.
• Rapid increase during pregnancy.
• Bundles of smooth muscle, well demarcated (benign).
• Asymptomatic → DUB, abortion, malpresentation, PPH, torsion/strangulation etc.
- Asymptomatic when small but can cause uterine bleeding, post partum haemorrhage etc.
• Very rarely, benign metastasizing leiomyoma and peritoneal leiomyomatosis.
- Very rarely leiomyomas can spread - distant sites still appear benign. Known as benign metastasizing leiomyoma. Sometimes spreads to peritoneal cavity - peritoneal leiomyomatosis.

Question 34

Outline leiomyosarcoma.

Answer 34

• Rare.
• Single, malignant.
• Haemorrhagic.
• No capsule.
• Invasive.
• Haematogenous spread.
• Leiomyoma - well demarcated, round, capsulated. Well differentiated smooth muscle fibres.
• Leiomyosarcoma - very irregular. Very irregular with areas of haemorrhage and necrosis. Metastasis.

Question 35

Outline endometrial disorders.

Answer 35

• Functional abnormalities (hormonal, commonest)

• Most common, hormone induced.
• Irregular ripening or shedding (due to hormone) → clinically DUB.

• Inflammation - Endometritis (common STIs).

• Acute or chronic.
• Chlamydia - lymphocytic infiltration. Chlamydia most common, follow by gonorrhea.

• Excess proliferation (of endometrium due to hormone - excess oestrogen)

• Diffuse/polypoid - hyperplastic polyps. Can be diffuse or present as a polypoid structure (hyperplastic polyps).
• Endometriosis (spread outside).
• Adenomyosis (spread inside).

• Neoplasia

• Polyps - neoplastic polyps.
• Adenocarcinoma.

Question 36

Outline endometritis.

Answer 36

• Inflamed endometrium.
• Acute - sexually transmitted. STI neutrophilic.
- Chlamydia.
- Gonococci.
• Chronic - lymphocytic.
-TB
- PID.
• Complications:
- Bleeding (DUB), infertility, ectopic pregnancy.

Question 37

Outline endometrial hyperplasia & polyp.

Answer 37

• Hyper-oestrogenemia.
• Diffuse hyperplasia or polyp.
- Can be diffuse thickening of endometrium or a polypoid structure.
• Common cause of uterine bleeding.
• 3 types: simple, complex and atypical/dysplastic.
- Simple hyperplasia - glands are simple and cystic.
- Complex - branching.
- Atypical - irregular cells.
• Risk of malignancy - more with atypical.

Question 38

Outline endometriosis.

Answer 38

• Definition: endometrial spread beyond uterus (normal glands, not malignant).

• Regurgitation - via fallopian tube. More commonly it is a regurgitation of endometrial tissue through the fallopian tubes into the pelvic cavity.
• Vascular/lymphatic spread. Blood vessel and lymphatic spread. Spreading to lymph nodes, ovaries more common.

• Cause: hyper-estrogenemia, increased Pg E2.
- Excess proliferation of endometrium due to increased oestrogen. Prostaglandin E2 has also been seen in these patients.

• Sites:

• Endometriosis Interna - Adenomyosis. When the endometrial glands spread to the myometrium.
• Endometriosis Externa. Normal endometriosis.

• Common to ovary → chocolate cyst →

• More common site is to ovary.
• In the ovary, it produces a chocolate cyst. Due to bleeding and gradually increasing tumour.
• Clinical: severe cyclic pain, pelvic inflammation → fibrosis.
• Complications: PID, infertility.
• Therapy: COX2 inhibitors.

• Endometriosis can be very small/microscopic like petechial haemorrhages or can be a huge cyst filled with blood (chocolate cyst).

Question 39

Outline uterus adenomyosis.

Answer 39

• Myometrial invasion by endometrium (internal endometriosis) → hyperplasia.
- Result of hyperplasia. Hyperplasia of myometrium in response to endometrial spread → results in rounded uterus, multiple haemorrhagic parts.
• Aetiology - hyper-estrogenemia (+/- polyps*)
- Related to hyperestrogenemia so patients may have endometrial polyps/hyperplasia with adenomyosis.
• Cyclic pain, DUB, uterine hypertrophy.
• Normal basal glands - not malignant.

Question 40

Outline endometrial carcinoma.

Answer 40

• Elderly 55-65y, post menopausal. Increasing incidence (due to decreasing cervical cancer).
• Adenocarcinoma (oestrogen, not HPV).
- Cervical cancer is squamous cell carcinoma.
- Cervical cancer is virus related. Adenocarcinoma is oestrogen related.
• Presents with post-menopausal bleeding - early detection.
- Unlike cervical cancer - delayed detection.
• Irregular, polypoid, tumour - bleeding.
- Bleeding within endometrial cavity.
• Plenty of dysplastic glands, little stroma

• Type 1 - obese, DM, increased oestrogen. 80%.
- Associated with oestrogen, obesity, DM and HTN.
• Type 2 - thin, atrophic uterus, serous Ca. 15%.
- Occasionally familial type usually seen in atrophic uterus. Serous carcinoma.

Microscopy:
• Endometrial hyperplasia will have uniform glands.
• Adenocarcinoma - pleomorphic, closely packed back to back glands (very irregular).

Question 41

Outline abnormal/dysfunctional uterine bleeding (DUB).

Answer 41

• Most common cause of patients coming to attention clinically → DUB (usually during reproductive age).
• DUB - after excluding any lesion (infections, inflammation, polyps, cancer).
- Diagnosis by exclusion - bleeding without any other pathology.
• Menorrhagia (excess blood during cycle), metorrhagia (irregular between periods).

Aetiology:
• Ovulation failure (commonest) - ends of reproductive period, increased oestrogen, endocrine disorders (e.g. thyroid), nutrition, obesity, psychological, stress etc.
- Common in early menarche and later peri-menopausal.
- Causes of ovulation failure → leads to DUB.
• Luteal phase failure, contraceptive induced bleeding etc.
- Also can be causes.

• Pathology - proliferative, abnormal cystic glands, no secretary phase, scanty stroma → breakdown → bleeding.
- Breakdown of endometrial tissue causing bleeding.

• Microscopy - smaller/bigger glands, less stroma.

• Management - rule out any pathology, then D&C (dilation and curettage)
- Take out endometrium (so fresh endometrium starts).

Question 42

Uterine disorders summary.

Answer 42

Myometrial Disorders:
• Leiomyoma - hormone induced hyperplasia, DUB, mass, infertility.
• Leiomyosarcoma - rare.

Endometrial disorders:
• Endometritis - acute, chronic, STI chlamydia, gonorrhea etc. TB.
• Endometrial hyperplasia - oestrogenic, diffuse/polypoid.
• Endometrial carcinoma - adenocarcinoma, oestrogen, old age, post menopausal bleeding, early diagnosis.
• DUB - dysfunctional uterine bleeding* commonest.
- Commonest hormonal balance due to normal ovulation.