Activate Windows

Go to Settings to activate Windows.

GY46 Gynaecology Toronto Notes 2023

Table 25. Ovarian Tumours

Type Description Presentation Ultrasound/Cytology Treatment

EPITHELIAL OVARIAN TUMOURS (malignant or borderline)

GeneralInformation Derived from mesoUielial cells lining

peritoneal cavity

Classified based on histologic type

80-85% of all ovarian neoplasms

(including malignant tumours)

Borderline

Cystectomy vs.unilateral salpingo-oopborectomy

Malignant

1.Early stage (stageI):Hysterectomyi 3S0 staging

(omentectomy.peritonealbiopsies,washings,pelvic and

para aortic lymphadenectomy). Depending on histology,

may require adjuvant chemotherapy

2.Advanced stage:Upfront cytoreductive (debulking)

followed by adjuvant chemotherapy consisting of IV

carboplalin/paditaxel vs.intraperitoneal chemotherapy

(stage III) neoadjuvant chemotherapy withIV carboplatin/

paditaxel,followed by delayed debuDcing with further

adjuvant IV chemotherapy

See above

Varies depending on

subtype

Serous 20-30'

» bilateral Lining similarto fallopian

tube epithelium

Often multilocular

Histologically contain

psammoma bodies (calcified

concentricconcretions)

Most common ovarian tumour histology

50% of allovariancancers

75% of epithelial tumours

70%benign

Mucinous 20% ol epithelial tumours Rarely complicated by

Pseudomyioma peritonei: epithelium

implants seed abdominal cavity Often multilocular

and produce largequantities May reach enormous size

ofmudn

Resembles endocervical Poor response to chemotherapy

If mucinous,remove appendix as well to rule out possible

source of primary disease

10% of epithelial tumours

Can be found adjacent to endometriosis

More commonin theAsian population

10% of epithelial tumours

Can be found adjacent to endometriosis

More likely to be detected at an Contains glycogen-rich cells

early stage

Clear Cell Poor responselo chemotherapy

with clear cytoplasm and

hobnail cells

Endometrioid Can beassociated with

endometrial neoplasm

Typically cystic or solid,

unilateral, and confined to

the ovary

lendto respondwell to chemotherapy

SEX CORD STROMAL OVARIAN TUMOURS

FibromaiThecoma

(benign)

From mature fibroblasts in ovarian stroma Non-functioning

Occasionally associated with

Meig's syndrome (triad of benign

ovarian tumour,ascites.and

pleural effusion)

Granulosa-Theca Cell

Tumours (benign or

malignant)

Estrogen-producing:feminizing Histologic hallmark of cancer Surgical resection of tumour

effects (precociouspuberty. is small groups of cells known Chemotherapy may be used for unresectable metastatic

menorrhagia,postmenopausal as Call-Exner bodies

bleeding)

Risk of endometrial cancer due

to estrogen

Androgen-producing:virilizing

effects (hirsutism,deep voice,

recession of front hairline)

Tumour marker is inhibin

disease

Sertoli-Leydig Cell

Tumour (benign or

malignant)

Can measure elevated androgens as

tumour markers

Surgical resection of tumour

Chemotherapy may be used for unresectable metastatic

disease

METASTATIC OVARIAN TUMOURS

From 61Tract.Breast, 4-8% of ovarianmalignancies

Endometrium. Lymphoma Krukenberg tumour:metastatic ovarian

tumour (usuallyGl tract commonly

stomach or colon,breast primary tumour)

80% bilateral Krukenberg tumours have

“signet-ring" cells

Investigation of Suspicious Ovarian Mass

• women with suspected ovarian cancer based on history, physical,or investigations should be referred

to a gynaecologic oncologist

bimanual examination

solid, irregular, or fixed pelvic mass is suggestive of ovarian cancer

RM1 (Risk of Malignancy Index) is best tool available to assesslikelihood of ovarian malignancy

and need for preoperative gynaecologic oncology referral (see sidebar)

• physical exam findingslargely dependent on stage of disease

• blood work:CBC, LF Ts, electrolytes,Cr, tumour markers as appropriate (CIA-125, inhibin, p-hCG,

LDH, AFP, androgens, CEA,Cai9-9, estrogen)

• biopsy not recommended due to tumour spillage into peritoneum, if extensive disease, can get

cytological diagnosis from paracentesisfrom ascites or tissue biopsy from peritoneal deposits or

omental cake

• radiology

transvaginal U/S best to visualize ovaries

CT abdomen and pelvis to look for metastatic disease

bone scan or PET scan not indicated

Causes of Elevated CA-125

• Age influences reliability of test as a

tumour marker

• 50% sensitivity in earty-stage ovarian

cancer (poor),thereforenot good for

screening

• Malignant

• Gynaecologic ovary,uterus

• Non-Gynaecologic pancreas,

stomach,colon,tectum

• Non-Malignant

• Gynaecologic benign ovarian

neoplasm,endometriosis,pregnancy,

fibroids.PID

• Non-Gynaecologic cirrhosis,

pancreatitis,renal failure

r T

t

_ J

+

Activate Windows

Go to Settings to activate-Windows:

GY-17 Gynaecology TorontoNotes 2023

• try to rule out other primary source (if suspected), based on:

occult blood per rectum:endoscopy ± barium enema

• gastric symptoms: gastroscopy ± upper G1 series

• abnormal vaginal bleeding: endometrial biopsy to rule out concurrent endometrial cancer;

abnormal cervix: need to biopsy cervix (not Pap smear); breast lesion identified or risk factors

present: mammogram

A Riskof Malignancy Incorporating CA-125,

Ultrasound,andMenopausal Status lor the

Accurate Preoperathre Diagnosis of Ovarian

Cancer

6J0G 890:97:922-929

RMI - U MiCA-125

Ultrasound Findings|1pt for each)

• Multilocular cyst

Evidence ol soldareas

Evidence of netattases

• Presence of asdles

|Mini Mm

U'1(for UfS scores of 0or 1)

U - 4|for IPS scoresof 2-5)

Menopausal Status

• Postmenopause'

:V - 4

Premenopausal:Mri

JfisohitE Zaire of CA-125 Serum Level

• For fill|j>200:gynaecoloi|icoacniogy referral is

recommended

Table 26. FIGO Staging for Primary Carcinoma of the Ovary (Surgical Staging) (2014)

Stage Description

Growth limited to the ovaries

t ovaiy,no ascites, no tumour on external surface,capsule intact, negative washings

2 ovaries,no ascites,no tumour on external surface,capsule intact

t oc 2ovaries with any of flic following: surgical spill|IC1). capsule ruptured|IC2), lumour on ovarian surface (IC2). or

malignant cells inascites (IC3)

I

IA

IB

IC

II Growth involving one or both ovaries with pelvic extension or primary peritoneal cancer

Extensioniimplants to uterus/tubes

Extension to other pelvic structures

IIA

lie

Tumour involving oncor both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal nodes

Positive retroperitoneal INs and/or microscopic metastasis beyond pelvis

Positive retroperitoneal INs

Microscopic, extrapelvic peritoneal involvement t positive retroperitoneal INs

Macroscopic peritoneal metastasis beyond pelvis 12 cm. tpositive retiopenloncal INs.Includes extension to capsule ol liver/

spleen

Same asabove but peritoneal metastasis »2 cm

III

IMA

IIIA1

OptimalPrimary Soigicil treatment lor Advanced

Epithelial Ovaciaa Cancer

Cochrane 08 Syst Ret 201l:(8|:CD00f56S

Summary During primary surgery Ini stage III or

IV epithelial ovarian cancer,all attempts should be

made toach.eve completecyloreduction.When this

is not achievable,optimal (<1cm)residual disease

should he the goal.

Methods:Idenbfiedll relrospecine studies

consisting of 4235 women using comprehensive

search strategy.

Results:

1. When subopbnul(margins >1 cm) was compared

with optimal|*tcm) cyioreduction.Ihesurvival

estimates were reducedbut remained statistically

in favour of the lower volume disease gruup.

2. No sign hunt difference in overall survival

between subopbmal and optimal cytoreduction.

3. Borderline difference in progression-free survival

when resxlual disease >2cm and <2 cm were

comparedlp'

0.05).

IIIA2

NIB

NIC

Distant metastasis beyond peritoneal cavity

Pleural effusion with positive cytology

Hepatic and/or splenic parenchymal metastasis or metastasis lo extra-abdominal organs (inguinal INs and LNsoutside of

abdominal cavity included)

IV

IVA

IVB

FIGO = International Federation of Gynaecology and Obstetrics

Cervix

MALIGNANT CERVICAL LESIONS

Epidemiology

• majority are SCC (90%);adenocarcinomas increasing (10%);rare subtypes include small cell,

adenosquamous

• 8000 deaths annually in North America

• average age at presentation: 50 yr; bimodal distribution (increased frequency in 40s and 60s)

Etiology

• at birth, vagina is lined with squamous epithelium; columnar epithelium lines only the endocervix

and the central area of the ectocervix (original squamocolumnar junction )

-Original squamous epithelium

-Squamous metaplasia

^

-Columnar

epithelium

Hand

opening

• during puberty, estrogen stimulates eversion of a single columnar layer (ectopy), thus exposing it to

the acidic pH of the vagina, leading to metaplasia (change of exposed epithelium from columnar to

/

X K

irA1’

squamous)

a new squamocolumnar junction forms as a result

• the TZ is the area located between the original and the current squamocolumnar junction

• the majority of dysplasias and cancers arise in theTZ of the cervix

• must have active metaplasia in presence of inducing agent (e.g. HPV ) to get dysplasia

• dysplasia progresses to carcinoma in situ (CIS), which further progresses to invasion of cervical tissues

• slow process (~10 yr on average)

• growth is by local extension

• metastasis occurs late

% External os

.1

5

-New squamocolumnar junction

-Original squamocolumnar

junction

a

*

<

Risk Figure 22. The cervix Factors

• HPV infection

see Sexually Transmitted Infections,GY47

high-risk of neoplasia associated with types 16, 18,31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and

82

low-risk of neoplasia associated with types 6, 11

>99% of cervical cancers contain one of the high-risk HPV types

• high-risk behaviours (risk factors for HPV infection)

multiple partners

« other STIs (HSV, trichomonas)

• early age at first intercourse

• high-risk male partner

r T

Cervical cancer is most prevalent in

developing countries and. therefore, is

the only gynaecologic cancer that uses

clinical staging:this facilitates consistent

international staging with countries that

do not have technologies such as CT

and MRI

L J

+

Activate Windows

Go toSettings to activate Windows.

GY‘I8 Gynaecology Toronto Notes 2023

• smoking

• poor screening uptake is the most important risk factor for cervical cancer in Canada

• at-risk groups include:

• immigrant Canadians

• Indigenous peoples in Canada

geographically-isolated Canadians

sex-trade workers

low socioeconomic status Canadians

immunocompromised individuals

Cervical Cancer Screening Guidelines (Pap Test)

• see family Medicine. TM5

Clinical Features

• SCC: exophytic, fungating tumour

• adenocarcinoma: endophytic or exophytic, with barrel-shaped cervix

• early

asymptomatic

discharge: initially watery, becoming brown or red

postcoital bleeding

• late

• 80-90% present with bleeding: either postcoital, postmenopausal, or irregular bleeding

pelvic or back pain (extension of tumour to pelvic walls)

• bladder/bowel symptoms

• signs

friable, raised, reddened, or ulcerated area visible on cervix

•Anyone with a cervix1

• Agei25 lor 21*)

• Asymptomatic:

Screening Pathway

I

Cytology Test

1

i i i

Normal/NILM ASCUS1 - LSIL£ High grade:

ASC-H. HSIL, AGC,AIS i i

Repeat cytology in6 mo Repeat cytology in 6 mo

I

i i 1

Normali'NILM >ASCUS Normal/NILM >ASCUS

I 1

Repeat cytology in 6 mo Repeat cytology m 6 mo

I

1 i i

Normat/NILM 2ASCUS Normol/NIIM >ASCUS

T v i jr

Return to cytology

screening everySyr3

Return to cytology

screening every Syr Refer 3

to colposcopy Refer to colposcopy

'Those guidelines apply to anyone with a cervix including women; prognant pooplo, transmen; non binary people; people who havo undergone a subtotal hysterectomy, and pooplo who have been

vaccinated with tho HPV vaccine

2Any visible corvicol abnormalities or abnormal symptoms must bo investigated Consider loforrol to e specialist (e g colposcopist, gynaecologist, gynoQoncologist)

]

Immunocompromised people may be at olovoted risk and should recoivo annual screening

J Ontario Health (Cancer Care Ontario) is aware that the Screening Activity Report is not yet aligned with this guidance and will be updated with HPV implementation. Criteria for preventive care

bonuses may not be updated during the interim period of changeover to HPV testing. Criteria for preventive care bonuses will be updated when HPV testing is implemented in screening

1

HPV testing is not currently funded by the Ministry of Health.Primary care providers can consider HPV testing for those with ASCUS results on a patient pay basis or wtvere available (i.e.in some

hospital settings!for people ages 30 and older

*Repeat cytology or colposcopy are acceptable management options after the first LSIL result Low grade abnormalities often regress on their own and may be best managed in surveillance,

however colposcopy may be considered

Figure 23. Decision making chart for Pap test (not applicable for adolescents)

Adapted from:Ontario Cervical Screening Program. June 2020.Cervical screening guidelines unique to each province

r t

L J

+

Activate Windows

Go to Settings to activate Windows,

GY49 Gynaecology Toronto Notes 2023

Diagnosis

• colposcopy is a clinical procedure that facilitates identification and biopsy ofsuspicious cells

• in colposcopy:

apply acetic acid and identify acetowhite lesions, punctation, mosaicism, and abnormal blood

vessels to guide cervical biopsy

ECC if entire lesion is not visible or no lesion visible

diagnostic excision ( LEEP) if:

unsatisfactory colposcopy (poor visualization/access to transformation zone )

discrepancy between cytology, colposcopy, and histological findings

positive findings/glandular abnormalities in endocervical curettage

suspicious for adenocarcinoma in situ (consider cold-knife conization)

recurrence of lesion post-ablation or excision

inability to rule out invasive disease, i.e. large lesions (lesions extending into endocervical

canal, extending widely on cervix, or onto vaginal epithelium)

• consider cold-knife conization (in OR) if glandular abnormality suspected based on cytology or

colposcopic findings due to concern for margin interpretation

• any imaging modality or pathological findings are permitted for E1GO clinical staging

The Bethesda Classification System

is based on cytological results of a Pap

test that permits the Examination of

cells but not tissue structure. LSIL. HSIL.

or cervical carcinoma is a histological

diagnosis, requiring a tissue sample via

biopsy of suspicious lesionsseen during

colposcopy

m

Cervical Camer Prognosis 5 yr Survival

Stage 0

Stage I

Stage II

Stage III

Stage IV

Overall

99%

75%

55%

30% Table 27. FIGO Staging Classification of Cervical Cancer (Clinical Staging) (2018)

7% Stage Description

50-60% I Confined lo cervix

Diagnosed only by microscopy

Stromal invasion not >3 mm deep

3mm to <5mm deep

Measured deepest invasion >5 mm (greater than stage IA).lesion limited to cervix

Stromal invasion >5mm deep and < 2 cm wide

Stromal invasion >5 mm deep and >2 cm and <4 cm wide

>4 cm in width

IA

IA1

IA2

final Effjcacy.lmmunogenicity. and Safety

Analyses ol a Nine-Valent Human Papillomavirus

Ifeccine in Women Aged 16-26 Years:A

Randomised. Double-Blind Trial

lancet 2017:390:2143-2159

Purpose: A nine-valent HPV vattine (9vHPV) was

developed which covers add ilionalstrainsol HPY

compared to the quadrivalent vaccme (qHPY).Ihis

study reported the efficacy ol the 9vHPV vatcine.

Methods A random ted double - hind efficacy trai

comparing thenine valent HPV vaccine (9vHW ) to

the quadrivalent HPYvacune (qHPY|in 14215 women ,

the primary outcomes weie incidence ol high-grade

cervical,vulvar, and vaginal diseases related to HPV31.33,45.52.and 58 ar.d non-inferiority of anti-HPY

6.It.16.and 18 mean litres.

Results:The incidence of high- grade cemcal.

vulrar, and vaginal disease was 0.5cases per WOOD

person-yrfor the 9vHPV group compared to19 cases

per 10000 persoo-yr loi the qHPV group. HPV 6,11.

K.and 18 titres were non-inferior in the 9vHPVgroup

compared to the qHPV group. There were noclwiica

-'fy

meaningful diHcrencesin severe adverse effects

between groups.

Conclusions: The 9 > HPV vaccine is elfectrve at

preventing infection, cytology! abnormalities, and

“ gh grade lesions and may offer broader protection

agaxist HPV and ceivical cancer compared to the

qHPV vaccine.

IB

IB1

IB2

IB3

Beyond uterus but not to the pelvic wall or lower1/3of vagina

Limited to upper 2/3 of vagina, no obvious parametria!involvement

Clinically visible lesion

-4 cm wide

Clinically visible lesion;4 cm wide

Obvious pniamelrial involvement, bul not up to pelvic wall

II

IIA

IIA1

IIA 2

IIB

III Extends to pelvic wall, and/or involveslower 1/3ol vagina,and/or causes hydronephrosisor non-functioning kidney, and/or

involves pelvic and/or para aortic lymph nodes

Involves lower1/3 vagina bul no extension into pelvic wall

Extension into pelvic side walland/or hydronephrosis or non-functioning kidney

Involvement of pelvic and/or para - aortic lymph nodes,irrespective of tumoursire and extent

Pelvic lymph nodes metastasis only

Paraaortic lymph node metastasis

MIA

NIG

me

IIIC1

IIIC2

Carcinoma has extended beyond true pelvis or hasInvolved (biopsy proven) the mucosa ol the bladdci or rectum (bullous

edema docs not permit a case lo he allotted lo stage IV)

Spread of the growth toadjacent oigans ( bladder or redum)

Distant metastases

IV

IVA

IV6

Treatment: Prevention and Management

Prevention: HPV Vaccine

• two vaccines currently approved (Gardasil*, Cervarix’)

Table 28. Comparison of Two Vaccines against Human Papillomavirus (HPV)

Gardasil • Cervarix

Viral Strains Covered

Route of Administration

Schedule of Dosing

6.11.16.18. 31.33, 45.52.and 58 16.18

IM IM

2 Dose:Second dose administered 6-12 mo after

first dose

3Oose:0.2.6 mo

Local:redness, pain,swelling

General:headache, lowgrade fever. Gl upset

females ages 9-45. males ages 9- 45

Pregnant women and women who are nursing (limited

data)

0.1, 6 mo

Side Effects Local:redness, pain,swelling

General:headache, low grade fever. Gl upset

females ages 9-45

r m

L J

Approved Age

Contraindications

•Garda*H -9 cil\u cover*

type*

31, 33.45.52. and 58; also used to prevent genital wart* +

Activate Windows

Go to Settings to activate Windows^

GY50 Gynaecology Toronto Notes 2023

•should be administered before onset ofsexual activity (i.e. before exposure to virus) for optimal

benefit of vaccination

•may be given at the same time as hepatitis B or other vaccines using a different injection site

•not for treatment of active infections

•most women will not be infected with all four types of the virus at the same time, therefore vaccine is

still indicated for sexually active females or those with a history of previous HPV infection or HPVrelated disease

Abnormal Pap Tests in Pregnancy

•incidence: 1 in 2200

•Pap test at initial prenatal visit if overdue for routine Pap test

• if abnormal Pap or suspicious lesion, refer to colposcopy

• if diagnostic conization required,should be deferred until T2 to minimize risk of pregnancy loss

if invasive cancer ruled out, management of dysplasia deferred until completion of pregnancy

(may deliver vaginally)

if invasive cancer present, management depends on prognostic factors, degree of fetal maturity,

and patient wishes

general recommendations in Tl:consider pregnancy termination, management with either

radical surgery (hysterectomy vs. trachelectomv if desiresfuture fertility), or concurrent

chemoradiation therapy

recommendations in T2/T3: delay of therapy until viable fetus and (.

'

-section for delivery with

concurrent radical surgery or subsequent concurrent chemoradiation therapy

Table 29. Management of Abnormal Cervical Histology and Cervical Cancer

Histology Result from

Colposcopy

Management

If histology results normal and cytology > LSIL.then repeat colposcopy In 6 mo

Women «25 yr

If cytology is ISIl, ASCUS. or normal, then annual Paps by primary care provider « 3 years, followed by return

lo normal screening

It cytology is HSIL.then consider pathology review, and/or reassessment every 6-12 mo in colposcopy

Women *25 yr

If HPV •:routine Pap screening every 3yr

If HPV :follow- up colposcopy with cytology and HPV test (if 30 yr or older) in 1yr

Women »25 yr

Excisional procedures|e.g. cold knife.LEEP) or laser preferred

Those with positive marginsshould have follow-up with colposcopy and directed biopsies and/or endocervical

curettage

Women «25 yr

Colposcopy every 6 mo for 2 yr or treatment may be acceptable based on patient preference

Repeal colposcopy + treatment (e.g. LEEP. cold- knife cone) iendocervical curettage

LEEP if future fertility desired (and lesion'2 cm)

Simple hysterectomy il future fertility is not desired

Typically treated with radical hysterectomy and pelvic lymphadencdomy (sentinel nodes or pelvic lymph node

dissection)

If high chance of adjuvant radiation then consider primary chemoradiation as more morbidity occursfrom

double-modality treatment (surgery and radiation )

Equal cure rates may be obtained with primary radiation therapy:advantage of surgery: may accurately stage

and grade and more targeted adjuvant therapy

Advantage is that ovaries can be spared if premenopausal, better sexual functioning

For fertility preservation (if tumour «2cm),may have radical trachelectomy ( removal of cervix and parametria)

and nodes instead of radical hysterectomy for early-stage disease

Chemoradiation therapy il adverse high -risk prognostic factors on radicalsurgical specimen,such as: positive

pelvic lymph nodes, positive parametria, and/or positive margins or adverse cervical factors(2 or more):deep

stromal invasion,sice >4 cm.LVSI

Primary chemoradiation therapy

CT to assess extent of disease: evaluate pelvic and para aortic nodes

for positive nodes on PEI: primary chemoradiation with extended field Rl

Hysterectomy generally notsuggested following primary treatment with curative intent

Normal

LSIL

HSIL CINII/CIN III

AIS

Stage IA1(noLVSI)

Stage IA2.IB1. IB 2

Stages IB3 (»4 cm), II. III.IV

r *>

+