Premalignant gynaecological conditions and their managment

1. Pre-malignant
Gynaecological
Conditions
Dr. Indunil Piyadigama

2. Endometrial
hyperplasia
• Irregular proliferation of the
endometrial glands with an
increased gland to stromal ratio
(more than 1:1)
• Lesions that mimic EH
• Disordered proliferation
• Secretory endometrium
• Benign polyps

3. Epidemiology
Rare in < 30yrs
Peak at 50-54
(common within
1st five years of
menopause)
Precursor of type 1
endometrial
cancer
3 times as
common as the
endometrial
cancer

4. Risk factors
Increased endogenous oestrogen
• Anovulation
• Obesity
• Diabetes
• PCOS
• Granulosa cell tumours
Exogenous oestrogen
• HRT - Cyclical use – Endometrial hyperplasia in 0.7%
• Tamoxifen
• Risk of hyperplasia 2-3 times higher than general population.
Currently restricted for 5 years use only
• Pretreatment screening, prophylactic hysterectomy or
endometrial sampling at a low threshold are suggested
interventions.
• Aromatase inhibitors – No increase in risk of cancer
Immunosuppression
Infection

5. Current classification -
WHO 2014
Hyperplasia
without
atypia
Atypical
hyperplasia

7. Risk of cancer
• Without atypia
• 5% risk of carcinoma over 20 years
• Majority (80%) regress without treatment
• Atypical hyperplasia
• Concurrent carcinomas can occur – 43%
• Progression to CA is 30% in 20 years

8. Clinical presentation
• AUB – 15% are diagnosed endometrial hyperplasia
• Intermenstrual bleeding
• Post menopausal bleeding
• Small number can be asymptomatic

9. Diagnosis
TVS
• In premenopausal is restricted to finding structural causes
• But for PCOS with absent withdrawal bleeding or AUB ET is
recommended
• <7mm unlikely to have endometrial hyperplasia

10. Pipelle biopsy
Despite negative biopsy 2% of women still can have endometrial
hyperplasia
Sensitivity
Premenopausal 80% Postmenopausal 75%

11. D&C
• Inpatient
• Up to 10% of endometrial pathologies missed

12. Hysteroscopy and biopsy
• Indications
• When EB fails
• Persistent AUB
• If intrauterine structural anomalies or
polyps suspected – Focal endometrial
pathology is seen in about 10% of
population
• Better at detecting rather than
excluding endometrial pathology
• 98% sensitive for hyperplasia

13. Treatment - Hyperplasia without atypia
Risk factor modification
• Weight
• Exogenous hormones

14. Progesterone
Indications
•Fail to regress following observation
•Symptomatic women
Type
•Continuous oral progesterone – MPA 10-20mg/day, NET 10-15mg/day
•LNG- IUS
Action
•Antimitotic on endometrial cells
•Modulating growth stimulatory signals of E2
•Reduces oestrogen secretion by HPO axis
•Reduces receptors
•Increases metabolism of E2
Higher disease regression rate (95%) compared to observation
alone (80%)
6 months use better than 3 months

15. Follow up
• EB with a minimum of 6 months treatment - 2 biopsies negative
shows cure and discharge. But on an off biopsies for 2 years
• High risk women (BMI>35 on oral progestogens) needs 6 monthly
assessment for 2 years and annual screening there after for follow up
• If bleeding needs further evaluation

16. Hysterectomy + BSO
• Indications
• Progression to atypical hyperplasia
• No regression following 12 months of treatment
• Recurrence
• Symptomatic
• If does not wish to have surveillance or treatment
• Premenopausal individualize oophorectomy, but B/L salpingectomy.
Oestrogen replacement therapy should be considered.
• Subtotal avoided

17. Endometrial ablation
• Not recommended
• Complete or persistent endometrial destruction cannot be ensured
and adhesion formation may preclude further histological surveillance

18. Atypical hyperplasia
• Total hysterectomy

19. Women who
have fertility
wishes
• MDT
• Counsel about the risk of underlying
malignancy
• Coexisting cancers
• Ovarian cancer – 4%
• Higher than stage1 ECa – 2%
• Metastatic disease – 0.5%
• Prior need
• Hysteroscopy
• MRI/CT
• Ca 125

20. LNG IUS or Oral progesterone
Follow up
• with 3 monthly EB
• Once 2 consecutive samples negative – Every
6monthly to 1year biopsies till hysterectomy
25% of live pregnancy rate
Results are better if
• Disease optimally suppressed
• Assisted reproduction techniques

21. Cervical
cancer
• Preventable
• Curable
• Long natural history
• Most common female malignancy in developing
countries
• 7th most common cancer in women worldwide
• Good screening had led to a dramatic reduction
in cervical cancer – 30% decrease from 1993-
2003 in UK

22. Cervical pre-invasive
disease

23. Natural history of HPV
• Genital infection of HPV acquire only
through sexual contact
• Both high and low risk forms occur
commonly in 16-25 yr group (10-30%)
• But most virus clears in 2-3 year by cell
mediated immunity and CIN regresses
(60-80%)
• Rest, infection persists and within 2-4
years causes CIN lesions
• Progression rate of CIN is 5% per year

25. Likelihood of
regression
Invasive cancer in 20
years
CIN1 60% 10% will become high
grade lesions
CIN2 45%
CIN3 30% 36%

26. • Virus enters the epithelium through a breach in skin integrity caused
by microtrauma
• It remain in the cytoplasm as episomes and can be cleared
• But sometimes enter the nucleus and this is called integration
• The cell no longer undergo apoptosis after 40-60 cell cycles and
instead become immortal. E6 and E7 oncoproteins which binds to p53
and RB respectively are responsible for this

27. • Prevalence of HPV in cervical cancers - 99.7%
• HPV infection is necessary
• But persistence is important
• 70% of cancers have High risk 16 and 18
• Above 30 yrs HPV incidence decline to about 5% but the regression
rate is much lower
• In a woman over 30 years with high risk HPV positivity the risk of
developing CIN 3 is 116 times compared to a control
• The whole process of early lesion to invasive cancer may take 15-20
years

28. Risk factors
• early onset of sexual activity
• multiple sexual partners (of self or of the partner)
• low socioeconomic status
• Tobacco smoking (2-fold)
• oral contraceptives (2.5-fold)
• other sexually transmitted infections like herpes simplex virus,
Chlamydia and bacterial vaginosis might play a role in the
progression of HPV infection to dyskaryosis
• immuno-compromise, including human immunodeficiency virus (HIV)
(5-fold)

29. Screening
• Cytology based
• HPV based
• Histology to confirm –
colposcopy based

30. Routine
screening
Negative
Routine
recall
Inadequate
Rpt in 3/12
Borderline/
low grade
HPV
Negative Intermediate
Initial
borderline
Rpt Cytology
in 6/12
Initial LSIL
Colposcopy
Positive
Colposcopy
High grade
Colposcopy

31. Colposcopy
< CIN 1
Routine recall
CIN 1
Untreated
12/12
cytology
follow up
CIN 1/2/3
Treatment
Test of cure in
6/12

33. cGIN
• Associated particularly with HPV 18
• Cytology is unsatisfactory and no colposcopic features
• Diagnosis is by chance during treatment of squamous pre-invasive disease
• 90% of the lesions occur 1cm from SCJ. But can occur anywhere in the
endocervical canal
• Can have skip lesions higher up in the endocervical canal. Therefore even
after treatment 15% have recurrence.
• This is associated with 50% of CIN and 40% of adenocarcinoma
• Therefore cone biopsy is needed to exclude occult invasive
adenocarcinoma. Endometrial biopsy to rule out abnormality higher up

34. Management
• Colposcopy and biopsy – Because higher percentage has concomitant CIN
• Punch biopsy is inadequate since disease often occurs at the crypts of the
glands
• Therefore for diagnosis and treatment conization is used
• Endometrial sampling
• Local excision – excision margins should be clear
• Fertility sparing surgery is a possibility provided that the margins are clear
• These people are at higher risk of recurrence
• 15% when margins free
• 50% when margins involved
• Hysterectomy

35. Vulval intraepithelial
neoplasia
• Premalignant condition of the vulva
• Cellular changes are limited to the epithelium. Does not
breech the basement memebrane

36. Unifocal
• Postmenopausal
• Non HPV
• Differentiated histology
Multifocal
• Premenopausal
• HPV related
• Interlabial grooves, posterior
forchette, perineum

37. Clinical features
Pruritus
Perineal pain
Dysuria
50% asymptomatic
Mass, ulcer
Altered appearance
Most multifocal, non hairy part
raised/verrucous white, red, brown,
pink, gray, macular lesion

38. Investigations
Multiple biopsies needed - histology shows
loss of organisation of squamous epithelium
with a variable degree of cytological atypia
which is graded as undifferentiated or
differentiated and by depth
Colposcopy to exclude CIN and VIN
If perianal lesions anoscopy

39. Treatment
Conservative
• Supervision
• Some may regress
spontaneously
Medical
• 5% Imiquimod
cream – Regression
shown in small
studies. But limited
follow up
Unlicensed use
• 5FU – not reliable
Unlicensed use
Local destruction
• laser
• cryotherapy
• photodynamic
therapy
• USS surgical
aspiration
• Recurrence higher
But good cosmesis
Surgery
• Can be mutilating
when multifocal
• Local excision –
Treatment of
choice for small
well circumscribed.
Recurrence is
lowest with
excision
• Vulvectomy –
Effective but
recurrence can
occur

40. If not treated
80% can have invasive cancer in 10 years
If treated
10%

41. • Extramammary paget’s is a rare form of VIN. It is associated with
cancer of the apocrine gland
• Follow up - Specially for VIN 3

42. Thank you