UP PGH 2019 Interns Review 3 Premalignant Cervix Endometrium

PREMALIGNANT LESIONS OF
THE CERVIX AND THE

ENDOMETRIUM
MARIA JULIETA V. GERMAR,MD,FPOGS,FSGOP,FPSCPC
THE ENDOMETRIUM
SGOP SGO
POGS ACOG
THE LINK
§ The precursor lesion of type I endometrial
cancer specifically the endometrioid type of
adenocarcinoma is endometrial
hyperplasia.
§ However, not every case of endometrial
hyperplasia proceeds to endometrial
carcinoma.
§ Accurate diagnosis and management of
true premalignant endometrial lesions
can reduce the likelihood of development of
invasive endometrial cancer .
Silverberg SG. Hyperplasia and carcinoma of the endometrium. Semin Diagn Pathol 1988; 5: 135–53.
CLINICAL PRESENTATION
of women with
90 %
endometrial hyperplasia
and cancer present with
abnormal vaginal
bleeding or abnormal
discharge.
2010 Society of Gynecologic Oncologists of the

Philippines (SGOP)Clinical Practice Guidelines for
Obstetrician Gynecologists.
Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol 2012; 120:1160
RISK FACTORS
ESTROGEN EXCESS
Unopposed estrogen lead to increased
mitotic activity of endometrial cells resulting
in more frequent errors in DNA replication
and somatic mutations.
Silverberg SG. Hyperplasia and carcinoma of the endometrium. Semin Diagn Pathol 1988; 5: 135–53.
Risk Factors Increase in Risk Pathophysiology
Increasing age Women 50- to 70-years-old Multifactorial, co-morbids
have a 1.4 percent risk of
endometrial cancer
Unopposed estrogen 10-30X increased mitotic activity of
therapy endometrial cells
Early menarche 1.5-2x Prolonged estrogen
exposure
Late menopause age >55 2-3x Prolonged estrogen
exposure
Nulliparity 3x Chronic anovulation
Infertility 3x Chronic anovulation
PCOS 3x Chronic anovulation
Obesity 2.5-4.5X Aromatization of
200-400% in those with BMI androstenedione to estrone
above 25
Type II Diabetes 2x Hyperinsulinemia and high
levels of Insulin Like
Growth Factor I
2010 Society of Gynecologic Oncologists of the Philippines (SGOP)Clinical Practice Guidelines for Obstetrician Gynecologists.
ACOG and SGO Practice Bulletin No. 149: Endometrial cancer.Obstet Gynecol. 2015 Apr;125(4):1006-26.
Di Saia and Creasman. Clinical Gynecologic Oncology. 9th edition. 2018
2018 UP-PGH Department of Obstetrics and Gynecology Annual Postgraduate Course

GERMAR 3 July 2018
Risk Factors Increase in Risk Pathophysiology
Tamoxifen 2-3 X Antiestrogenic to breast
but estrogenic to bone,
cardiovascular system and
UTERUS
Lynch syndrome 6-20X Autosomal dominant
(hereditary nonpolyposis 22 to 50 percent lifetime risk cancer susceptibility
RISK
colorectal cancer) syndrome
Cowden syndrome 13 to 19 percent lifetime risk Autosomal dominant PTEN
FACTORS Mutation

2010 Society of Gynecologic Oncologists of the Philippines (SGOP)Clinical Practice Guidelines for Obstetrician Gynecologists.
ACOG and SGO Practice Bulletin No. 149: Endometrial cancer.Obstet Gynecol. 2015 Apr;125(4):1006-26.

GERMAR 3 July 2018
Histopathogenic Type I Histopathogenic Type II
Precursor Lesion is Precursor Lesion is
Endometrial Hyperplasia Atrophic endometrium
Unopposed Estrogen Estrogen -independent
Endometrioid Non-Endometrioid: Serous, clear cell,

Well-differentiated mucinous
Poorly-differentiated
70% EARLY stage
60% ADVANCED stage
Younger, obese, nulliparous,
perimenopausal older,non- obese, parous,
postmenopausal
PTEN, microsatellite instability, B
catenin mutation, and K-ras alteration p53 mutations, human epidermal growth
factor receptor 2 (HER2)
overexpression/amplification, p16
Highly sensitive to progestins inactivation
Low sensitivity to progestins
9
POSTMENOPAUSAL BLEEDING
Postmenopausal Bleeding
Differentials
Conditions Incidence
MOST COMMON CAUSE 38%

Atrophy
MOST IMPORTANT TO RULE OUT 5-10%
Endometrial Carcinoma
Atypical hyperplasia 5-10%
Uterine sarcoma 3-5%

Not myoma
Ovarian cancer (Functioning ovarian 3-5%
tumor)
Fallopian tube cancer <3 %
Polyp
Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol
2012; 120:1160.
>50% diagnosed in women between
the ages of 50 and 69 years
ENDOMETRIAL
CANCER
>90% present with vaginal bleeding
100% Women presenting with

postmenopausal bleeding
must be evaluated
GERMAR 3 July 2018
POST
MENOPAUSAL
▪ What should be
BLEEDING the first step ?
Patient with POSTMENOPAUSAL BLEEDING
Thorough medical history and PE, IE

Risk
Assessment
PMB may be assessed initially with either

an endometrial biopsy or a transvaginal ultrasound
TRANSVAGINAL UTZ Endometrial Sampling
•Evaluation of the endometrium in symptomatic patients at risk is the critical

component in the diagnostic evaluation of women suspected of endometrial cancer
or a premalignant endometrial lesion.
•An endometrial sampling procedure is the gold standard for diagnostic
evaluation of women with abnormal uterine bleeding in whom endometrial
hyperplasia or carcinoma is a possibility.
ACOG and SGO Practice Bulletin No. 149: Endometrial Cancer. Obstet Gynecol. 2015 Apr;125(4):1006-26.
GERMAR 3 July 2018
ACOG Committee Opinion
Number 734 May 2018
The presence of a thin, distinct endometrial echo ≤4 mm is

associated with a risk of malignancy of 1 in 917
Sensitivity 95%, Specificity 55%
EMT ≤ 4mm
American College of Obstetricians and Gynecologists. Committee Opinion No.734: The role of transvaginal ultrasonography in
evaluating the endometrium of women with postmenopausal bleeding. Obstet Gynecol. May 2018;131(5) 124-129.

GERMAR 3 July 2018
Ultrasound in the Evaluation of the Endometrium in the
Postmenopausal woman
ACOG Committee Opinion Number 734 May 2018
ACOG-SGO Practice Bulletin No. 149 April 2015
EMT ≤ 4mm EMT > 4mm
Endometrial sampling
Required:
Endometrial
sampling is not Office biopsy
required. Hysteroscopic guided D and C
D and C
American College of Obstetricians and Gynecologists. Committee Opinion No.734:The role of transvaginal ultrasonography in
GERMAR 3 July 2018
However if there’s persistent
EMT ≤ 4mm
Persistent
bleeding
or recurrent bleeding…
§ 11.5% of patients with recurrent
bleeding were found to have
Endometrial
cancer.
sampling § Recurrent bleeding requires further
evaluation with endometrial sampling
Gull B, Karlsson B, Milsom I, Granberg S. Can ultrasound replace dilation and curettage? A longitudinal evaluation of
postmenopausal bleeding and transvaginal sonographic measurement of the endometrium as predictors of
endometrial cancer. Am J Obstet Gynecol. 2003;188(2):401–408.
American College of Obstetricians and Gynecologists. Committee Opinion No.734:The role of transvaginal ultrasonography in
GERMAR 3 July 2018
Histopathogenic Type I Histopathogenic Type II
Precursor Lesion is Precursor Lesion is
Endometrial Hyperplasia Atrophic endometrium
Unopposed Estrogen
Estrogen -independent
Endometrioid Non-Endometrioid: Serous, clear cell,

Well-differentiated mucinous
70% EARLY stage Poorly-differentiated
60% ADVANCED stage
Younger, obese, nulliparous,
perimenopausal older,non- obese, parous,
PTEN, microsatellite instability, B postmenopausal
catenin mutation, and K-ras alteration p53 mutations, human epidermal growth
Highly sensitive to progestins
inactivation
19
Histopathogenic Type II
A thin or indistinct Precursor Lesion is

Atrophic endometrium
endometrial lining on
Estrogen -independent
transvaginal ultrasound
does not reliably exclude Non-Endometrioid: Serous, clear cell,
mucinous
type 2 endometrial cancer, Poorly-differentiated
which is not related to 60% ADVANCED stage
estrogen exposure or older,non- obese, parous,
endometrial hyperplasia postmenopausal
p53 mutations, human epidermal growth
inactivation
20
Initial episode of Risk
Assessment Persistent or recurrent bleeding
bleeding
Multiple risk
TRANSVAGINAL UTZ factors
Endometrial Sampling
Expectant Persistent or Endometrial Atypical

Management Recurrent Hyperplasia Endometrial Endometrial
Bleeding with no Hyperplasia Cancer
atypia
STAGING
Progestin THBSO SURGERY:
management EL, EHBSO,
PFC, BLND,
PALS
American College of Obstetricians and Gynecologists. Committee Opinion No.734: The role of transvaginal ultrasonography in evaluating the
endometrium of women with postmenopausal bleeding. Obstet Gynecol. May 2018;131(5) 124-129.
GERMAR 3 July 2018
What is the best

sampling method?
Hysteroscopy with targeted Endometrial biopsy (EMB)
Dilatation and Curettage
endometrial biopsy with a pipelle
• Factor risk level into decision-making

• EMB is a more cost-effective initial diagnostic test for populations
with an incidence of endometrial cancer ≥15%
• In the Philippines, incidence is 5-6 % however,
• It is considerably higher among women with polycystic ovarian
syndrome, obesity, diabetes, early menarche, late menopause,
nulliparity, a history of tamoxifen use, or hereditary nonpolyposis
colorectal cancer.
What is the best

sampling method?
Hysteroscopy with targeted Endometrial biopsy with a
endometrial biopsy pipelle
This is the GOLD STANDARD
Targeted Biopsy good for Focal, discrete

Lesions, lesions less than 50% of the
endometrium
Limitations: Availability and Cost
Di Saia and Creasman. Clinical Gynecologic Oncology. 9 edition. 2018 th
GERMAR 3 July 2018 ACOG and SGO Practice Bulletin No. 149: Endometrial Cancer. Obstet Gynecol. 2015 Apr;125(4):1006-26.
What is the best

sampling method?
This is the GOLD STANDARD Specificity 98-100%

May be done in the clinic, no anesthesia
Targeted Biopsy good for Focal, discrete needed
endometrium Low Cost, readily available
When the cancer occupies at least 50% of
Limitations: Availability and Cost the endometrial surface, this is 100%
accurate
Limitations: Blind biopsy, may miss focal
lesions
What is the best

sampling method?
This is the GOLD STANDARD Specificity 98-100% Only if under anesthesia and hysteroscopy
May be done in the clinic, no anesthesia not available
Targeted Biopsy good for Focal, discrete needed
Less likely to miss cancer than an
Low Cost, readily available endometrial biopsy
endometrium
When the cancer occupies at least 50% of Better in predicting definitive tumor grade
Limitations: Availability and Cost the endometrial surface, this is 100% in premenopause
accurate
Limitations: Blind biopsy, may miss focal
Limitations: Blind biopsy, may miss focal lesions
lesions
Case 1 ▪ Mrs. P, 58 G0 comes to see you because
of vaginal bleeding, which started 2
months ago. The patient reports that she
stopped menstruating about 4 years
ago and is not on hormone replacement
therapy or taking any medication.
▪ BMI is 30.She denies any vaginal

irritation, discharge, or dyspareunia. Her
uterus is intact and she had a Pap smear
about a year ago. Pelvic Exam is normal.
▪ What should be done?

Initial episode of Risk
bleeding Assessment
TRANSVAGINAL UTZ
Expectant Persistent or Endometrial Atypical

Management Recurrent Hyperplasia Endometrial Endometrial
Bleeding with no Hyperplasia Cancer
atypia
STAGING
Progestin THBSO SURGERY:
management EL, EHBSO,
PFC, BLND,
PALS

GERMAR 3 July 2018
TRANSVAGINAL ULTRASOUND
Endometrial biopsy with a

pipelle
Endometrial
adenocarcinoma well
differentiated
Endometrial Biopsy
Atypical Hyperplasia
The endometrial glands

are highly irregular in size
and shape and show
frequent outpouchings.
The atypia is
characterized by enlarged
round nuclei, irregular
chromatin distribution, and
prominent nucleoli.
Management of
1. Definitive management is an extrafascial
hysterectomy with bilateral salpingo-
oophorectomy (BSO).
2. A supracervical or subtotal hysterectomy is
unacceptable .
§ Removal of the cervix and lower uterine segment along
with the uterine corpus permits staging of any
incidentally discovered cancers and reduces the risk of
leaving behind residual disease.
Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol 2012;
120:1160.
COEXISTENT ADENOCARCINOMA
17 to 52 % percent of women
with atypical hyperplasia are found to
have coexistent endometrial carcinoma
on final histopathology of the definitive
specimen
Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A
long-term study of “untreated” hyperplasia in 170 patients. Cancer 1985;56:403-
12.
Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers.
Obstet Gynecol 2012; 120:1160.
Management of
3.An intraoperative assessment of the specimen should
be performed to evaluate for endometrial carcinoma.
§ gross examination with or without a frozen section .
Evidence is scarce with regard the value of an
intraoperative frozen section for atypical endometrial
hyperplasia to rule out a concurrent endometrial
adenocarcinoma.
§ It is therefore suggested that the patient be referred
preoperatively to a gynecologic oncologist so
intraoperative decisions may be individualized after
careful assessment in coordination with the attending
physician.
120:1160.
What is the histopathologic
diagnosis?
A. Serous
Adenocarcinoma
B. Sertoli-Leydig
C. Granulosa Cell Tumor
!
D. Brenner Tumor
!
What is the histopathologic
diagnosis?
A. Serous
Adenocarcinoma
B. Sertoli-Leydig
C. Granulosa Cell Tumor
!
D. Brenner Tumor
Call-Exner bodies In a postmenopausal woman
presenting with bleeding and
an adnexal mass ALWAYS
CONSIDER A
FUNCTIONING OVARIAN
TUMOR: GRANULOSA
! CELL TUMOR
Tumor marker : Inhibin
Who needs an ENDOMETRIAL BIOPSY?
PRE MENOPAUSAL WOMEN

§ Ultrasound measurement of endometrial
thickness in premenopausal women has no
diagnostic value.
§ The decision to histologically evaluate the
endometrium should be based on
symptomatology and clinical presentation.
ACOG and SGO Practice Bulletin No. 149: Endometrial Cancer. Obstet Gynecol. 2015
Apr;125(4):1006-26.
Age Cut off ?
§ 45 years-old is the threshold for increased
concern regarding endometrial neoplasia
§ Risk of endometrial hyperplasia and
carcinoma
§ 19 % of cases 45 to 54 years
§ This age threshold is also consistent with
American College of Obstetricians and
Gynecologists (ACOG) and Society of
45
Gynecologic Oncologists (SGO) guidelines
ACOG and SGO Practice Bulletin No. 149: Endometrial Cancer. Obstet Gynecol. 2015
Apr;125(4):1006-26.
Who needs an ENDOMETRIAL BIOPSY?
1. Postmenopausal
A. Women with postmenopausal bleeding
B. Asymptomatic women with endometrial thickening or
fluid
2. Premenopausal
A. Below 45 with Persistent abnormal bleeding with
history of chronic anovulation, with risk factors
B. 45 and above
3. Women on hormone therapy with bleeding
4. Women on tamoxifen with bleeding
5. Women above 35 with atypical endometrial
cells on Pap
Trimble CL, Method M, Leitao M, et al. Management of endometrial precancers. Obstet Gynecol 2012; 120:1160
Case ▪ A 38 year old single nulligravid consulted for
irregular periods at 2-3 months interval,
profuse, lasting 8-10 days which made her
2 missed work on several occasions. LMP was a
week ago. She is currently not sexually active.
▪ Normal Vital signs. BMI: 32.
▪ (+) acne on the face , lower back (+) facial
hair. (+) hirsutism
▪ Essentially normal speculum and internal
examination findings
▪ She was diagnosed with Polycystic Ovarian
Syndrome 5 years ago but was lost to follow
up.
39
Does she warrant
endometrial sampling?
Ultrasound measurement of
endometrial thickness in
premenopausal women has no
PRE diagnostic value and should not be
MENOPAUSAL performed.
WOMEN
The decision to histologically evaluate
the endometrium below 45 years old
should be based on symptomatology,
risk factors and clinical presentation.
Women with PCOS have 3-fold
increased risk and a 9% lifetime risk for
Endometrial Cancer
Women with PCOS have other risk factors
for endometrial cancer : chronic
POLYCYSTIC hyperinsulinemia, increased serum insulin-
OVARIAN like growth factor (IGF-1) concentrations,
SYNDROME hyperandrogenemia, and obesity
In oligoovulatory women with PCOS, an
endometrial thickness <7 mm on
transvaginal ultrasound was not associated
with histologic evidence of endometrial
hyperplasia
Gottschau M, Kjaer SK, Jensen A, et al. Risk of cancer among women with polycystic
ovary syndrome: a Danish cohort study. Gynecol Oncol 2015; 136:99.
Case
2 Transvaginal Ultrasound
Does she warrant
endometrial sampling?
Persistent abnormal bleeding with
history of chronic anovulation/ PCOS
Thickened endometrium on
ultrasound
Young Patient with HMB and PCOS,
thickened endometrium
What is the best

sampling method?
Hysteroscopy with targeted Endometrial biopsy (EMB)
endometrial biopsy with a pipelle
Hysteroscopy with targeted endometrial biopsy and Dilatation and

curettage is preferred over endometrial biopsy since the accuracy
of the endometrial biopsy in premenopausal women is lower and
the diagnosis of endometrial carcinoma may be misinterpreted as
endometrial hyperplasia in 15-25% of cases.
D&C may also be better at evaluating tumor grade than office

endometrial biopsy with significantly less cases being upgraded.
A 45-year-old G0 with a history of
Case 3 breast cancer is on her first year of
Tamoxifen. On history, she has no
vaginal bleeding .
On Transvaginal ultrasound however,
there was note of a thickened
endometrium ( EMT=0.6 mm) with
intact subendometrial halo . She was
referred to you by her medical
oncologist.
What’s the next step ?
Should an
endometrial sampling
be done ?
The primary therapeutic effect of tamoxifen is that
it is an antiestrogen, however ,it has modest
estrogenic activity to the endometrium.
Women on
Associated with endometrial proliferation,
Tamoxifen hyperplasia, polyp formation, invasive carcinoma,
and uterine sarcoma.
Increased relative risk is two to three times
higher than that of an age-matched population
American College of Obstetricians and Gynecologists. Committee Opinion No.601 June 2014
Tamoxifen and Uterine Cancer. Obstet Gynecol 2014;123:1394–7.
Correlation is poor between ultrasonographic
Women on measurements of endometrial thickness and
Tamoxifen abnormal pathology in asymptomatic
tamoxifen users because of tamoxifen-induced
subepithelial stromal hypertrophy
Tamoxifen and Uterine Cancer. Obstet Gynecol 2014;123:1394–7.
There is no role for routine screening
with endometrial biopsy or transvaginal
ultrasound in asymptomatic women on
Tamoxifen. (Level I, Grade A)
Women on Endometrial biopsy, with or without TV-
Tamoxifen UTZ, should be reserved only for patients
with abnormal vaginal bleeding or
discharge
2015 Society of Gynecologic Oncologists of the Philippines (SGOP)

Clinical Practice Guidelines for Obstetrician Gynecologists.
Barakat RR, Gilewski TA, Almadrones L, et al. Effect of adjuvant tamoxifen on the endometrium in women with
breast cancer: A prospective study using office endometrial biopsy. J Clin Oncol 2000;18:3459-3463.
PREMENOPAUS POSTMENOPAUSA
AL L
Women on Should be closely
Routine
Tamoxifen: gynecologic care monitored
The ability of
tamoxifen to
induce
endometrial
malignancy
differs between
premenopausal
and
postmenopausal
women.
Tamoxifen and Uterine Cancer. Obstet Gynecol 2014;123:1394–7
Wickerham DL, Fisher B, Wolmark N, Bryant J, Costantino J, Bernstein L, et al. Association of tamoxifen and uterine
sarcoma. J ClinOncol 2002;20:2758–60.
A 45-year-old G0 with a history of
Case 3 breast cancer is on her first year of
Tamoxifen. On history, she has no
vaginal bleeding .
On Transvaginal ultrasound however,
there was note of a thickened
endometrium ( EMT=0.6 mm) with
intact subendometrial halo . She was
referred to you by her medical
oncologist.
What’s the next step ?
No need to do an endometrial biopsy.
Case 3
Reassure patient
Advise her to continue Tamoxifen.
Follow up for any bleeding or spotting
Only do a biopsy if she bleeds

regardless of the endometrial
thickness.
SGOP CPG 2015
ENDOMETRIAL CANCER DIAGNOSIS
1.Endometrial cancer requires histologic confirmation and is
diagnosed by endometrial biopsy. Its accuracy in detecting
endometrial cancer is approximately 90%
2.Dilatation and curettage or hysteroscopy is generally reserved for
those women who continue to have symptoms that cannot be
explained by the results of the office biopsy.
The accuracy of Pipelle endometrial biopsy performed in an office
is comparable to dilatation and curettage in women with
postmenopausal bleeding
With the 2009 International Federation of Gynecology and
Obstetrics (FIGO) staging system, performance of
endocervical curettage (ECC) is no longer necessary.9
No need for a fractional curettage
Society of Gynecologic Oncologists of the Philippines Clinical Practice Guidelines 2015

2009 FIGO STAGING
FOR ENDOMETRIAL CANCER
STAGE II
Stage II:
Tumor invades
cervical
stroma, but
does not
extend beyond
the uterus**
** Endocervical glandular involvement

alone shoul be considered as Stage I
and no longer as Stage II

SGOP CPG 2015
ENDOMETRIAL CANCER DIAGNOSIS
3. D&C with hysteroscopic guidance is favored

over D&C alone because it has a higher
accuracy and superior diagnostic yield than
blind D&C. Directed biopsy thru hysteroscopic
guidance will afford confirmation of diagnosis of a
true premalignant endometrial lesion and exclude
endometrial carcinoma.

Evaluation of the
endometrium
§ Meta-analysis of 39 studies involving 7914 women compared the
results of endometrial sampling with histopathology at D&C,
hysteroscopy, and/or hysterectomy.
Sensitivity of the
Pipelle device
Diagnosis of atypical endometrial hyperplasia 81%
Diagnosis of endometrial cancer
premenopausal 91%
postmenopausal 99.6%
§ The Pipelle device was more sensitive for the detection of endometrial
cancer and atypical hyperplasia than all other sampling devices.
§ Fewer than 5 percent of patients had an insufficient or no sample.
Dijkhuizen FP, Mol BW, Brölmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of
.
patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 2000; 89:1765
DIAGNOSIS
Hysteroscopic guided
endometrial biopsy
ENDOMETRIAL BIOPSY § if a surgical approach is
favored, Hysteroscopic
Its accuracy in detecting endometrial guided D&C is
cancer is approximately 90% recommended over D&C
alone because it has
better accuracy
2014 WHO Classification of
Endometrial Hyperplasia
New term Synonyms Genetic changes Coexistent Progression
invasive to invasive
endometrial carcinoma
carcinoma
Hyperplasia Benign endometrial Low level of <!1 % RR: 1.01–

hyperplasia; simple non- somatic mutations
without atypia atypical endometrial in scattered glands
1.03
hyperplasia; complex with morphology
non-atypical endometrial on HE staining
hyperplasia; simple showing no
endometrial hyperplasia changes
without atypia; complex
endometrial hyperplasia
without atypia
Atypical Complex atypical Many of the 25–33 % RR: 14–45

endometrial hyperplasia; genetic changes (Zaino et al
hyperplasia/ simple atypical typical for
2014)
endometrioid endometrial hyperplasia; endometrioid
endometrial endometrial cancer 59 % (Owings
intraepithelial intraepithelial neoplasia are present,
neoplasia et al 2014)
(EIN) including: micro
satellite instability;
PAX2 inactivation;
mutation of PTEN,
KRAS and
CTNNB1 (β-
catenin)
! From Zaino R, Carinelli S G, Ellenson L H, Lyon: WHO Press; 2014.
Tumours of the uterine Corpus: epithelial Tumours and Precursors; pp. 125–126.
MANAGEMENT
Premenopausal and Postmenopausal Women
HYPERPLASIA WITHOUT ATYPIA
Levonorgestrel releasing IUD for 6 months
OR
Medroxyprogesterone Acetate(MPA)*
10 mg once a day for 6 months
ENDOMETRIAL
BIOPSY
NORMAL BIOPSY: PERSISTENT HYPERPLASIA:

Maintain Levonorgestrel releasing Levonorgestrel releasing IUD PLUS an
oral progestin
IUD OR
OR
Continue MPA 10 mg once daily for Increase MPA to 20 mg once daily for 3
12 months months then repeat biopsy
At any point during treatment that the vaginal bleeding recurs, another endometrial biopsy should
be performed
IF ATYPIA or ENDOMETRIAL CANCER IS DETECTED ON BIOPSY MANAGE THE PATIENT ACCORDINGLY
GERMAR PGHPGH
POST GRAD JUNE 2016
POSTGRADUATE COURSE MANAGEMENT OF PREMALIGNANT LESIONS GERMAR 29 JUNE 2016
Cyclic vs Continuous
§ Both continuous oral and local
intrauterine (levonorgestrel-
releasing intrauterine
system)progestogens are effective
in achieving regression of
endometrial hyperplasia without
atypia
Management of Endometrial Hyperplasia Green-top Guideline No. 67 RCOG/BSGE
Joint Guideline | February 2016
Progesterone Treatment for
Hyperplasia with NO atypia
PROGESTERONE DOSE AND DURATION Regression RCT
Rate % Author and year
Levonorgestrel This releases 15-20 mcg/day 92 Abu , 2015 27
and can be kept in place for 3
releasing IUD to 6 months . Endometrial
biopsy can be performed with
the IUD in place 25, 26,27
Medroxyprogesterone 10 mg OD for 3 to 6 months 97.5 Orbo et al 201428
acetate OR 10 mg OD for 12-14 days 96.6 Ozdegirmenci

22
each month for 3 to 6 et al 2011 29
months 96.1 Dolapcioglu et al 2013
30
70.2
Orbo et al 201428
Norethisterone acetate 5 to 15 mg OD daily for 12 to 96.6 Ismail et al
14 days each month for 3 to 6 2013 31
months 96.3 Ozdegirmenci
et al 201129
Micronized 100-200 mg on Day10-25 each 91 Affinito, 1994 32

month for 3 to 6 months 24
progesterone
Depot MPA 150 mg intramuscularly every 91.8 Nooh 2016 33
three months
!
Important Considerations:
1. Endometrial sampling should be performed to
document regression to normal endometrium
every 3-6 months .
2. The endometrial sampling should be done after
the withdrawal bleed. This minimizes cytologic
and architectural effects of progesterone that could
otherwise interfere with accurate histologic
interpretation.
3. If regression to normal endometrium does not
occur after six months, the progestin dose may
be increased.
4. If atypia is noted or endometrial cancer develops
the patient should be managed appropriately
Endometrial Biopsy
The endometrial glands

are highly irregular in size
and shape and show
frequent outpouchings.
The atypia is
characterized by enlarged
round nuclei, irregular
chromatin distribution, and
prominent nucleoli.
MANAGEMENT
FACTORS TO CONSIDER
The choice of treatment of endometrial
hyperplasia is based on three factors:
1. Presence or absence of nuclear
atypia,
2. Age
3. The desire for fertility.
The interplay of the above factors
determines the primary treatment modality.
Management: POSTmenopausal Women
HYPERPLASIA WITH ATYPIA
EXTRAFASCIAL HYSTERECTOMY
with BSO
120:1160.
GERMAR PGHPGH
POST GRAD JUNE 2016
with BSO
120:1160.
GERMAR PGHPGH
POST GRAD JUNE 2016
Conservative Management
for Premenopausal Women
Desirous of Pregnancy
• The risk of progression to endometrial
cancer is high for hyperplasia with atypia
(29 percent).
The goals of treatment for these patients

are:
1. Complete clearance of disease,
2. reversion to normal endometrial
function,
3. prevention of invasive adenocarcinoma.
4. A successful pregnancy
Management of Endometrial Hyperplasia Green-top Guideline No. 67 RCOG/BSGE
Joint Guideline | February 2016
Factors to consider in the ConservativeTreatment
of Atypical hyperplasia.
FACTORS REQUIREMENTS IMPORTANT
CONSIDERATIONS
A robust informed consent Patient understands and Progression of disease is
accepts that this is not possible during treatment
standard of care
Patient is strongly Reasonable chance for Co manage with an infertility
desirous of pregnancy fertility specialist
Review fertility history of

patient and partner
No contraindications to No medical contraindications Thorough history, physical
medical management to progesterone examination and adequate
work-up
Histopathologic certainty Atypical hyperplasia D&C is better at evaluating
that only atypical
hyperplasia is present , not
adenocarcinoma
If available hysteroscopy
guided D and C may be done
Expert pathology review

Imaging No areas in the endometrium Expert sonologist
suspicious for carcinoma
Estrogen–progesterone Progesterone receptor Expert pathology review
receptor status, (optional) positivity
Management: Premenopausal Women
DESIROUS OF PREGNANCY:
NOT DESIROUS OF PREGNANCY:
Levonorgestrel releasing IUD for 3 months OR
Continuous Megestrol acetate
with or without BSO
80 mg BID FOR 3 months
ENDOMETRIAL
BIOPSY
PERSISTENT HYPERPLASIA:
NORMAL BIOPSY: Levonorgestrel releasing IUD plus
Continue
oral progestin for 3 months
Levonorgestrel releasing IUD for 3 OR
months
Increase megestrol acetate 160 mg BID
OR
for 3 months then repeat biopsy
Megestrol acetate ENDOMETRIAL
80 mg BID for 3 months BIOPSY
refer to infertility specialist for active
co-management PERSISTENT HYPERPLASIA
HYSTERECTOMY with or without BSO
At any point during treatment that the vaginal bleeding recurs, another endometrial biopsy should be performed
IF ENDOMETRIAL CANCER IS DETECTED ON BIOPSY MANAGE THE PATIENT ACCORDINGLY
PGH POSTGRADUATE COURSE MANAGEMENT OF PREMALIGNANT LESIONS GERMAR 29 JUNE 2016
Progesterone Treatment for
Hyperplasia with Atypia
PROGESTERONE DOSE AND DURATION
Megestrol acetate 80 mg BID continuously for 3 months
may increase to 160 mg BID if no regression
occurs after 3 months
Levonorgestrel releasing IUD This releases 15-20 mcg/day and can be kept in
place for 3 to 6 months . Endometrial biopsy can
be performed with the IUD in place 25, 26
Medroxyprogesterone acetate 10 mg OD continuously for 3 to 6 months
Norethisterone acetate 5 to 15 mg OD continuously for 3 to 6 months
Micronized progesterone 100-200 mg OD continuously for 3 to 6 months
24
Depot MPA 150 mg intramuscularly every three months

!
Abu Hashim H, Ghayaty E, El Rakhawy M. Levonorgestrel-releasing intrauterine system vs oral progestins for non-atypical
endometrial hyperplasia: a systematic review and metaanalysis of randomized trials. Am J Obstet Gynecol 2015; 213:469.
Orbo A, Vereide AB, Arnes M et al. Levonorgestrel-impregnated intrauterine device as treatment for endometrial
hyperplasia; a national multicenter randomized trial. BJOG 2014; 121: 477-486.
Management of Endometrial Hyperplasia Green-top Guideline No. 67 RCOG/BSGE Joint Guideline |

February 2016
Important Considerations:
1. Endometrial sampling should be performed to
document regression to normal endometrium
every 3 months .
2. The endometrial sampling should be done after
the withdrawal bleed. This minimizes cytologic
and architectural effects of progesterone that could
otherwise interfere with accurate histologic
interpretation.
3. If regression to normal endometrium does not
occur after three months, the progestin dose may
be increased.
4. If atypia is noted or endometrial cancer develops
the patient should be managed appropriately
PROGESTIN USE in
Atypical hyperplasia
§ Continuous treatment is superior to cyclic progestins .
§ The levonorgestrel releasing IUD is more effective
than oral progestins in treating women with
hyperplasia and complex atypical hyperplasia .
§ Once the endometrium reverts to normal the woman
must be co managed with an infertility specialist and
actively pursue all options to get pregnant. Once
childbearing is complete definitive management is
recommended
§ Extrafascial Hysterectomy is recommended for
treatment failures.
with BSO
120:1160.
GERMAR PGHPGH
POST GRAD JUNE 2016
THE CERVIX
SGOP PSCPC
POGS
Abnormal Pap Smear
Colposcopy with Biopsy , ECC
Biopsy Proven Cervical

Intraepithelial Neoplasia
2014 Pap Smear Guidelines
Population Recommendation Comments
Less than 21 No screening Start screening 3 years
after sexual contact not
earlier than 21
21-29 If conventional cytology: Yearly
If Liquid based cytology :every 2 years
30-65 Conventional cytology every year or *If previous 3 consecutive
Liquid based cytology Every 3 years* smears normal
Co testing with HPV testing every 3
years
Above 65 Continue screening with yearly Local incidence rates of
conventional cytology or biennial LBC cervical cancer still high in
this age group
After No screening If surgery was for a
hysterectomy benign disease
Saslow,D, et al American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical
Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer. J Low Genit Tract Dis. 2012 Mar 13.
2010 Society of Gynecologic Oncologists of the Philippines (SGOP)Clinical Practice Guidelines for Obstetrician Gynecologists
2013 PSCPC CPG on Cervical Cancer Screening.
What to do with HPV positive
Cytology negative women?
HPV positive,
Cytology negative
Repeat cytology and Do HPV

HPV testing genotyping
after one year
HPV positive , HPV 16 or 18 HPV 16 or 18

Both negative Cytology negative positive negative
Repeat cytology
Rescreen in Colposcopy Colposcopy and co testing
3 years after one year
2012 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests and Cancer precursors Stewart Masad MD et al for
the 2012 ASCCP Consensus Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
Absolute Risk of CIN in women with
Normal Cytology
ATHENA Study: Women >30 Years
HPV Status CIN 2+ CIN 3+
High risk HPV (-) 0.9% 0.3%
High risk HPV (+) 6.3% 4.1%
16/18 (+) 11.7% 9.9%
Other 12 hr (+) 4.7% 2.5%
Wright et al. (2011) Am J Clin Path.

What to do with HPV positive
Cytology negative women?
HPV positive,
Cytology negative
Repeat cytology and Do HPV

HPV testing genotyping
after one year
HPV positive , HPV 16 or 18 HPV 16 or 18

Both negative Cytology negative positive negative
Repeat cytology
Rescreen in Colposcopy Colposcopy and co testing
3 years after one year
2012 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests and Cancer precursors Stewart Masad MD et al for
the 2012 ASCCP Consensus Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
Practical Points
§ HPV Genotyping availability
§ Agony of waiting for a year while
knowing one is HPV positive
§ If available in your area may refer for
colposcopy
§ If patient chooses to wait a year for
repeat co-testing : acceptable
Abnormal Pap Smear

CASE 2
§ A 36 year old G4P4 (4004) came
back with a pap smear result of
ASCUS . What’s next ?
Management of the Abnormal Pap Smear
ASC-US
Repeat Cytology* HPV DNA Testing
at 1 YEAR preferred
HPV Positive for

≥ ASC HPV Negative for
negative high risk types
on either result high risk types
/Manage as LSIL
ROUTINE COLPOSCOPY
SCREENING Repeat cytology
ECC preferred in women at 3 years
with no lesions or
inadequate colpo
Manage per ASCCP

Guideline
2012 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests and Cancer precursors Stewart Masad MD et al for the 2012
ASCCP Consensus Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
Germar PGHPGH
Post Grad June 2016COURSE MANAGEMENT OF PREMALIGNANT LESIONS GERMAR 29 JUNE 2016
POSTGRADUATE
CIN RISK AMONG WOMEN 30-64 years old
CIN2 CIN3
HPV POSITIVE ASCUS HPV POSITIVE ASCUS
ASCUS ASCUS
HPV - ASCUS HPV - ASCUS
Katki H et al. JLGTD 2013;17:S36-42

ASC-US
Repeat Cytology* HPV DNA Testing
at 1 YEAR preferred
HPV Positive for

≥ ASC HPV Negative for
negative high risk types
on either result high risk types
/Manage as LSIL
ROUTINE COLPOSCOPY
SCREENING Repeat cytology
ECC preferred in women at 3 years
with no lesions or
inadequate colpo
Manage per ASCCP

Guideline
Germar PGHPGH
Post Grad June 2016COURSE MANAGEMENT OF PREMALIGNANT LESIONS GERMAR 29 JUNE 2016
POSTGRADUATE
CASE 3
§ A 35 year old G3P3 (3003) with an
LSIL result. No HPV DNA was done
as patient could not afford it.
§ She’s a smoker 5 pack years, no
OCP use, two partners not known to
be promiscuous .
LSIL
LSIL with negative LSIL with no LSIL with positive
HPV test HPV test HPV test
Colposcopy
Repeat
No lesion identified must do an endocervical curettage
cotesting
must do an endocervical curettage
@1 year Inadequate colposcopy
PREFERRED
Adequate colposcopy and lesion +/- endocervical curettage
seen
Cytology
negative and
HPV negative No CIN/Cancer CIN/Cancer
Repeat Manage per Manage per

cotesting ASCCP Guideline ASCCP Guideline
@3 years
Germar PGH Post

PGH Grad June 2016COURSE MANAGEMENT OF PREMALIGNANT LESIONS GERMAR 29 JUNE 2016
POSTGRADUATE
CASE 4
§ A 42 year old G0 comes to your clinic
with a result of ASC-H . She is very
worried what will you advise her ?
ASC-H
Colposcopy
regardless of HPV status
No CIN/Cancer Biopsy confirmed CIN2,3
Manage per Manage per

ASCCP Guideline ASCCP Guideline
Germar PGH Post

POSTGRADUATE
CASE 5
§ A 54 year old G5P5 (5005) comes to
your clinic with a result of High grade
SIL what are the options ?
HSIL
Immediate Loop Colposcopy
electrosurgical with endocervical
Excision (LEEP) assessment
No CIN2,3 Biopsy confirmed

CIN2,3

Germar PGH Post

PGHGrad June 2016 COURSE MANAGEMENT OF PREMALIGNANT LESIONS GERMAR 29 JUNE 2016
POSTGRADUATE
HSIL
High Grade Squamous
Intraepithelial Lesion
5 yr Risk of 5 yr Risk of
CIN 3 invasive CA
HPV negative 29% 7%
HSIL
HPV POSITIVE 50% 7%

HSIL
Katki eta al Benchmarking CIN 3 risk Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
HSIL
Immediate Loop Colposcopy
electrosurgical with endocervical
Excision (LEEP) assessment
No CIN2,3 Biopsy confirmed

CIN2,3

Germar PGH Post

PGHGrad June 2016 COURSE MANAGEMENT OF PREMALIGNANT LESIONS GERMAR 29 JUNE 2016
POSTGRADUATE
Case 6
§ A 50 year old G1P0 (0010) comes
back to you with a pap smear result
of AGC atypical glandular cells
Atypical Glandular Cells
DIFFERENTIALS:
inflammation
Hyperplasia
dysplasia
endometrial or cervical adenocarcinoma
9-38% with a precancer
3-17 % with a cancer
MUST THEREFORE BE TAKEN
SERIOUSLY Sharpless. Dysplasia associated with glandular cells on
cervical cytology. Obstet Gynecol 2012;105:501-506.
AGC:Atypical Glandular Cells

All subcategories:
endocervical, glandular cells Atypical Endometrial Cells
Endometrial and
Colposcopy with endocervical
ECC sampling
and for
women ≥35 y/o or
at risk for No endometrial pathology
endometrial
neoplasia do an
endometrial biopsy
Colposcopy
2012 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests and Cancer precursors Stewart Masad MD et al for the
2012 ASCCP Consensus Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
PGH POSTGRADUATE COURSE MANAGEMENT OF PREMALIGNANT LESIONS GERMAR 29 JUNE 2016

Summary: Management of the
Abnormal Pap Smear
HPV DNA testing
ASC-US
or repeat cytology
LSIL Colposcopy +/-biopsy and ECC
, HPV positive or status unknown
If
ASC-H Colposcopy + biopsy and ECC
Regardless of HPV status
Immediate LEEP or
HSIL
Colposcopy + biopsy and ECC
Colposcopy with ECC
AGC Endometrial sampling in
women 35 years of age and older
ABNORMAL WOMEN WOMEN 21-24 PREGNANT POST
CYTOLOGY ABOVE 25 YEARS OLD MENOPAUSAL
General General Population Management is Manage as in not Manage the same as
remarks more conservative pregnant except in the general
that an ECC is not population
done deferring
colposcopy until 6
weeks postpartum
is acceptable for
low grade lesions
ASCUS HPV testing Repeat Cytology HPV testing HPV testing
preferred at 1 year preferred preferred
preferred
Repeat Cytology Repeat Cytology Repeat Cytology
at 1 year HPV testing at 1 year at 1 year
acceptable acceptable acceptable acceptable
ASC-H Colposcopy Colposcopy Colposcopy Colposcopy
LSIL Colposcopy Repeat Cytology Colposcopy Colposcopy

@ 1 year
HPV(-) repeat HPV(-) repeat
cytology at 1 year cytology at 1 year
HSIL Immediate LEEP Colposcopy with Colposcopy Immediate LEEP

OR colposcopy ECC OR colposcopy
with ECC with ECC
AGC Colposcopy with Colposcopy with Colposcopy Colposcopy with

ECC ECC ECC
Endometrial Endometrial
sampling in sampling
women 35 years
of age and older
!
For Women 21-24 years old
ASC-US Annual cytologic follow up or HPV testing
LSIL Annual cytologic follow up
ASC-H Colposcopy
HSIL Colposcopy + biopsy and ECC
AGC Colposcopy + biopsy & ECC

What about an Abnormal pap
smear in Pregnancy ?
Expert colposcopy
Biopsy may be done
ECC is UNACCEPTABLE
A diagnostic excisional procedure
(LEEP/CONE) ONLY IF invasion is
suspected
Reevaluation with cytology and colposcopy
no sooner than 6 weeks postpartum
2012 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests and Cancer precursors Stewart Masad MD
et al for the 2012 ASCCP Consensus Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
For a pregnant patient
ASC-US* HPV DNA testing or Rpt Paps
ASC-H* Colposcopy +/-biopsy NO ECC

LSIL* Colposcopy +/-biopsy NO ECC
HSIL Colposcopy + biopsy NO ECC
* Except for cases of HSIL colposcopy may be deferred

until at least 6 weeks postpartum
Abnormal Pap Smear

CERVICAL INTRAEPITHELIAL NEOPLASIA
HISTOLOGIC BETHESDA TERMINOLOGY LAST TERMINOLOGY

IMAGES
CIN 1 Low-grade squamous
intraepithelial lesion (LSIL)
CIN 2 P16 NEGATIVE

Poor reproducibility and is likely Low-grade squamous
a heterogeneous mix that intraepithelial lesion (LSIL)
includes lesions that could be
called CIN 1 or 3 P16 POSITIVE
High-grade squamous
intraepithelial lesions (HSIL).
CIN 3 High-grade squamous

intraepithelial lesions (HSIL).
CIN terminology is used because that
terminology is used in the
2012 American Society of Colposcopy
and Cervical Pathology guidelines for
the evaluation and management of
cervical cytologic and histologic
abnormalities
Cervical Intraepithelial Neoplasia 1
CIN 1 : Natural History
§ High rate of regression & low rate of

progression
Ostor et al, Melnikow et al,
1993 1998
Spontaneous regression 57 47.4
Progression to CIN 2/3 11 20.8
Progression to cancer 0.3 0.15

§ The management of women with CIN
1 depends upon the preceding
cytology
Management of CIN 1
preceded by LESSER ABNORMALITIES:
ASC-US or LSIL Cytology,
Follow up without treatment
Co-testing with cervical

ASCUS or worse
cytology and HPV testing in
or HPV positive
12 months.
HPV negative
cytology negative
Colposcopy
Age appropriate
retesting @ 3years
No CIN2,3 Biopsy confirmed CIN 1
CIN2,3
HPV negative
cytology negative
If persistent for at
Manage per Manage per least 2 years
ASCCP ASCCP Follow up or treat
Routine Screening Guideline Guideline Ablative or
excisional
PGH POSTGRADUATE 2012 ASCCP Consensus Conference Journal
COURSE MANAGEMENT OFof Lower Genital
PREMALIGNANT Tract Disease Vol
LESIONS17 Number 5, 2013
GERMAR 29 JUNE 2016
Germar PGH Post Grad June 2016
Management of CIN 1
preceded by
HSIL or AGC-NOS Cytology
If adequate colposcopy,
ECC negative
Diagnostic Excisional
Cotesting @12 and 24 Slide review of pap
procedure
months smear, clinical findings
LEEP/Cone
HPV negative HPV POSITIVE or HSIL

cytology negative any cyto abnormality
at both visits except HSIL
Manage per
ASCCP
Age appropriate Colposcopy Guidelines
retesting @ 3years
2012 ASCCP Consensus Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
Germar PGH Post

POSTGRADUATE
Adequate or Satisfactory
Colposcopy
Biopsy Confirmed
Cervical Intraepithelial Neoplasia 2 & 3
CIN 2 & CIN 3
§ Lesions more likely to persist or progress than to regress
Regression Persistence Progression

(%) (%) (%)
CIN 2 43 35 22 57
CIN 3 32 56 14 70
Mitchell et al, J Natl Cancer Inst Monogr, 1996

Management of CIN 2 and 3
Inadequate Colposcopy
Adequate
Recurrent CIN 2,3 or
Colposcopy
entire squamocolumnar junction is visible circumferentially
ECC is CIN 2,3
around the external cervical os
Excisional Methods Ablational Methods Diagnostic Excisional

Acceptable Acceptable Procedure
Cotesting @12 and 24

months
HPV negative
cytology negative Any test abnormal
at both visits
Repeat cotesting @ Colposcopy

3years with ECC
Germar PGH Post Grad June2012 ASCCP Consensus
2016 Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
§ 7 percent of women with CIN 2,3 and
an inadequate colposcopic
examination had occult invasive
cervical cancer
Duggan BD, Felix JC, Muderspach LI, et al. Cold-knife conization versus conization by the loop electrosurgical excision
procedure: a randomized, prospective study. Am J Obstet Gynecol 1999; 180:276.
Fine BA, Feinstein GI, Sabella V. The pre- and postoperative value of endocervical curettage in the detection of cervical
intraepithelial neoplasia and invasive cervical cancer. Gynecol Oncol 1998; 71:46.
Ablative Modality :
Cryotherapy
Excisional Modalities
LEEP CONIZATION
LEEP and Cold-Knife

Conization
§ Removal of affected
tissue allowing pathologic
examination
Management of CIN 2 and 3
Inadequate Colposcopy
Adequate
Recurrent CIN 2,3 or
Colposcopy
entire squamocolumnar junction is visible circumferentially
ECC is CIN 2,3
around the external cervical os
Excisional Methods Ablational Methods Diagnostic Excisional

Acceptable Acceptable Procedure
Cotesting @12 and 24

months
HPV negative
cytology negative Any test abnormal
at both visits
Repeat cotesting @ Colposcopy

3years with ECC
Germar PGH Post Grad June2012 ASCCP Consensus
2016 Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
Summary
PATHOLOGY MANAGEMENT
CIN 1 preceded by FOLLOW-UP WITHOUT
ASC-US,LSIL TREATMENT
Co-testing with cervical cytology
and HPV testing in 12 months
CIN 1 preceded by ADEQUATE COLPO
HSIL, , ASC-H Observation with colposcopy and
cytology at 6 month intervals
Diagnostic excisional procedures
Slide review/ review of all findings

Summary
PATHOLOGY MANAGEMENT
CIN 2,3 Ablate (cryotherapy) or Excise
ADEQUATE COLPOSCOPY (LEEP or Cone)
CIN 2,3 Must excise (LEEP or Cone)

INADEQUATE
COLPOSCOPY
UNACCEPTABLE
Treatment Approaches
§ Observation of primary CIN 2/3 with serial

cytology and colposcopy
§ Hysterectomy as primary therapy for CIN
2/3 ê
2012 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests and Cancer precursors Stewart Masad MD
et al for the 2012 ASCCP Consensus Conference Journal of Lower Genital Tract Disease Vol 17 Number 5, 2013
THE CERVIX AND THE
ENDOMETRIUM
MARIA JULIETA V. GERMAR,MD,FPOGS,FSGOP,FPSCPC

UP PGH 2019 Interns Review 3 Premalignant Cervix Endometrium

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PREMALIGNANT LESIONS OF

THE CERVIX AND THE

2010 Society of Gynecologic Oncologists of the

2018 UP-PGH Department of Obstetrics and Gynecology Annual Postgraduate Course

2018 UP-PGH Department of Obstetrics and Gynecology Annual Postgraduate Course

Endometrioid Non-Endometrioid: Serous, clear cell,

MOST COMMON CAUSE 38%

Uterine sarcoma 3-5%

>90% present with vaginal bleeding

100% Women presenting with

Thorough medical history and PE, IE

PMB may be assessed initially with either

•Evaluation of the endometrium in symptomatic patients at risk is the critical

The presence of a thin, distinct endometrial echo ≤4 mm is

Sensitivity 95%, Specificity 55%

2018 UP-PGH Department of Obstetrics and Gynecology Annual Postgraduate Course

EMT ≤ 4mm EMT > 4mm

Endometrioid Non-Endometrioid: Serous, clear cell,

A thin or indistinct Precursor Lesion is

Expectant Persistent or Endometrial Atypical

What is the best

• Factor risk level into decision-making

What is the best

This is the GOLD STANDARD

Targeted Biopsy good for Focal, discrete

What is the best

This is the GOLD STANDARD Specificity 98-100%

What is the best

▪ BMI is 30.She denies any vaginal

▪ What should be done?

Expectant Persistent or Endometrial Atypical

2018 UP-PGH Department of Obstetrics and Gynecology Annual Postgraduate Course

Endometrial biopsy with a

The endometrial glands

PRE MENOPAUSAL WOMEN

What is the best

Hysteroscopy with targeted endometrial biopsy and Dilatation and

D&C may also be better at evaluating tumor grade than office

2015 Society of Gynecologic Oncologists of the Philippines (SGOP)

Only do a biopsy if she bleeds

Society of Gynecologic Oncologists of the Philippines Clinical Practice Guidelines 2015

** Endocervical glandular involvement

Society of Gynecologic Oncologists of the Philippines Clinical Practice Guidelines 2015

3. D&C with hysteroscopic guidance is favored

Society of Gynecologic Oncologists of the Philippines Clinical Practice Guidelines 2015

Hyperplasia Benign endometrial Low level of <!1 % RR: 1.01–

Atypical Complex atypical Many of the 25–33 % RR: 14–45

NORMAL BIOPSY: PERSISTENT HYPERPLASIA:

acetate OR 10 mg OD for 12-14 days 96.6 Ozdegirmenci

Micronized 100-200 mg on Day10-25 each 91 Affinito, 1994 32

The endometrial glands

HYPERPLASIA WITH ATYPIA

HYPERPLASIA WITH ATYPIA

The goals of treatment for these patients

Review fertility history of

Expert pathology review

Depot MPA 150 mg intramuscularly every three months

Management of Endometrial Hyperplasia Green-top Guideline No. 67 RCOG/BSGE Joint Guideline |

HYPERPLASIA WITH ATYPIA

Colposcopy with Biopsy , ECC

Biopsy Proven Cervical

Repeat cytology and Do HPV

HPV positive , HPV 16 or 18 HPV 16 or 18

Only do a biopsy if she bleeds