AGC&AIS Setareh Akhavan M.D - PowerPoint Presentation

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AGC&AIS

Setareh Akhavan M.D

Gynecologist Oncologist

Tehran University of Medical Sciences

Slide3

Introduction

AGC on

cervical cytology usually originate from the glandular epithelium of the

endocervix

or endometrium.

AGC are

found less commonly than abnormal squamous cells (

incidence <1%

;

[0.1

to

2.1%]

) that is associated with

a high rate of clinically significant underlying pathology

, including malignancy

.

AGC are

found most commonly in women age 40 or older

.

ASC-US: 15-29

yrs

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Introduction

Women with

AGC require

further evaluation for premalignant conditions of the cervix, uterus, and rarely, ovary , fallopian tubes, and

even the UT or GIT.

Pathological findings

with

AGC

: squamous

or

glandular.

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Introduction

The terminology used to classify AGC is:

1)Endocervical,

2) endometrial, or

3) not otherwise specified (NOS) is noted as a subcategory.

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Introduction

(terminology ……)

●Atypical glandular cells,

favor

neoplasia

:

This designation is for specimens that show features suggestive of, but not sufficient for, an interpretation of adenocarcinoma.

●

Endocervical adenocarcinoma in situ (AIS

)

●

Adenocarcinoma

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RISK OF PREMALIGNANT OR MALIGNANT DISEASE

AGC

: premalignant

or malignant disease

in 30 % of

cases

.

Squamo

> Glandular

Two

literature reviews that included approximately 4300 women with

AGC: Findings

were

benign in 64

to 71

%

of women.

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Pre or malignant

in AGC

CIN–

20 to 28 percent, including:

- (

CIN 1) – 9 percent

- (

CIN 2,3) – 11 percent

SCC–

0.3 to 1 percent

AIS–

3 to 4 percent

Cervical

adenocarcinoma – 1 to 2 percent

Endometrial

hyperplasia – 1 percent

Endometrial

adenocarcinoma – 2 to 3 percent

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Abnormalities in AGC

Follow-up

of the AGC cytology specimen within six months

showed the following

prevalences

and

histologies

of cervical cancer

:

Squamous

cervical carcinoma – 0.3 percent

Cervical

adenocarcinoma – 0.99 percent

BMJ 2016; 352:i276.

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AGC subcategory

The

cytologic

subcategory is

predictive

of the histologic diagnosis.

AGC-NOS

(endometrial adenocarcinoma: 10.2 percent

),

AGC-

endocervical

(invasive cervical adenocarcinoma: 5.9 percent; adenocarcinoma in situ: 2.4 percent; and CIN 2,3: 5.3 percent),

and

AGC-endometrial (endometrial adenocarcinoma: 27.8 percent; and atypical complex endometrial hyperplasia: 22.2 percent) 

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Coexisting squamous

cytologic

abnormality

 

Approximately 50% of

women with AGC

have a coexisting squamous

cytologic

abnormality (ASC or a SIL).

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Human papillomavirus infection

 

 A positive test for HR-HPV types in women with AGC is associated with a histologic diagnosis of CIN, particularly those with AGC-NOS .

Testing

for HPV is not a reliable method of triaging follow-up of AGC cytology as it is for atypical squamous

cells.

However

,

it is useful in the further evaluation of women with AGC.

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Age

The risk of malignancy in women with AGC increases with

age.

T

he

rate of malignancy was

highest in women 50 years or older

(29-30%) compared

with those ages 40 to 49 years (2.8 percent) or younger than 40 years (2.0 percent

).

T

he

most common lesion in women younger than 40 years was squamous and premalignant,

ie

, CIN 2,3 (approximately 15.4 percent).

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Other factors

 Some data suggest that women with

persistent AGC-NOS (two or more cytology results)

are at especially high risk of significant glandular disease

(

60% women

had endometrial adenocarcinoma in one

study

).

Based

upon available data,

the incidence of AGC and of significant neoplasia appears to be similar or

higher in pregnancy

than in other women

 

.

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INITIAL EVALUATION

For

pregnant women with AGC,

ECC and

endometrial sampling should 

NOT

 be performed,

the

endocervical canal may be sampled gently with a cytobrush

.

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All AGC categories (except endometrial)

Women

with cervical cytology with a finding of AGC-NOS or AGC-

endocervical

are

evaluated initially with

:

Cervical

colposcopy with directed cervical biopsies and sampling of the endocervical canal

Endometrial

sampling is performed for all women ≥35 years old and for younger women at risk for endometrial neoplasia (risk factors or symptoms are present)

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NEGATIVE OR LOW-GRADE FINDINGS ON INITIAL EVALUATION

 The management of women with

AGC

and negative or low-grade results on initial evaluation for

cervical or endometrial neoplasia

depends upon the AGC subcategory.

Glandular neoplasia of the cervix, in contrast with squamous disease, is often characterized

"

skip lesions

".

In

addition, some glandular disease may be located high in the cervical canal. Thus, some women will require cervical conization to detect disease.

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AGC-NOS or endocervical

Women with

AGC-NOS

or

AGC-

endocervical

are managed based on the findings of the initial evaluation

:

No (CIN2+),

no

(

AIS),

and no cancer

–

Cotest

at

12 and 24 months.

If co test :

negative –

Cotest

3

yrs

later.

If

cytology or HPV are abnormal – Perform colposcopy. If the

colposcopic

findings are

nondiagnostic

, endometrial sampling should be performed.

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Persistent abnormal cytology

 

 For women with

persistent findings of AGC-NOS or AGC-

endocervical

who have

nondiagnostic

findings with repeat colposcopy and endometrial biopsy, we suggest conization

.

In

addition,

vaginal colposcopy

should be performed in women with a history of

exposure to

diethylstilbestrol

.

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AGC favor neoplasia, AIS, adenocarcinoma

If

initial evaluation is negative in

women with

a

AGC,

favor

neoplasia; AIS; or adenocarcinoma

,

conization

followed

by an

ECC

of

the remaining

endocervix

is required

.

We suggest a

CKC rather

than a

LEEP .

A D&C is recommended at

the same time as the cone biopsy.

If

the results of the diagnostic

excisional procedure

and endometrial sampling are

negative TVS

is performed to look for a fallopian tube or ovarian lesion.

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AGC-endometrial

 

If

evaluation with endometrial biopsy and colposcopy are negative, the patient may resume routine screening for cervical cancer.

Some

experts advise that if the patient has a persistent finding of AGC-

endometrial

or has symptoms of other malignancies associated with AGC, the patient be

evaluated for disease at sites other than the cervix or uterus

 

and/or that endometrial sampling be repeated in 12 months.

 

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EVALUATION FOR OVARIAN CANCER OR OTHER MALIGNANCIES

 

The

first-line study is a

TVS.

Women

with no adnexal mass should be evaluated

for colon or other intra-abdominal malignancy with colonoscopy and abdominal CT or MRI

.

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AIS

The

usual interval between clinically detectable

AIS and

early invasion

appears to be at least

five

years

.The

average age

of diagnosis

of cervical

AIS =

36.9

years.

The incidences of both AIS and adenocarcinoma of the cervix have increased over the past several decades, particularly among young women.

(6 times)

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Why increase

I

ncreased

rates and efficacy of screening,

C

hanges

in the Bethesda cervical cytology classification

system and

Increased exposure to factors that cause or promote glandular neoplasia

(HR- HPV,

oral contraceptives)

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HISTOPATHOLOGY

.

Lesions usually originate at the

T- zone

with contiguous

extension proximally

within the endocervical canal

.

10%

to

15%of

patients with AIS

have multifocal disease

("skip" lesions)

with foci of AIS that are separated by

at least 2 mm of normal mucosa

.

AIS

lesions may also be located

high in the endocervical canal

and involve the deeper portions of the endocervical clefts.

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CLINICAL FEATURES

 AIS

:

asymptomatic

,

not

visible

in

gross examination. Detected due to an abnormal

cervical

cytology.

Rarely,

AIS

present with cervical

bleeding.

The

cervix can only be identified as the site of bleeding with pelvic examination.

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DIAGNOSIS

 

Colposcopy, biopsy, and endocervical

curettage:

 

AIS

has no

colposcopic

features that differentiate it from other cervical lesions.

For women with

AGC ,

if

biopsy and ECC are negative

, further evaluation with

endometrial biopsy and conization

may be

warranted.

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Conization

indications

 

Cytology with AIS (or adenocarcinoma) and a negative biopsy and ECC

Cytology

with AGC-NOS, and a negative biopsy, ECC, and endometrial biopsy

P

ersistent

AGC, classified as endocervical or

NOS

,

and negative results after biopsy, ECC, and endometrial

biopsy

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MANAGEMENT

The management

: challenging

.

Because

of the pattern of disease distribution of AIS (

multifocal

,

high in

the

endocervical canal

, inside

endocervical clefts

):

negative

margins on a cone biopsy specimen or a negative

ECC

not

necessarily

: completely

excised.

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Clinical approach

 Hysterectomy

:

the standard treatment for AIS

;(Ovaries may be conserved

.)

Conization

: the

alternative

followed

by surveillance

.

C

onization

alone :

a high risk of residual AIS or adenocarcinoma, while the incidence of adenocarcinoma

after hysterectomy is limited to rare case reports

.

(a

positive conization margin

.)

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Clinical approach

We

recommend hysterectomy

for women with a positive conization margin

following two or more

conizations

.

These recommendations are consistent with guidelines from the

ASCCP, NCCN,

and

ACOG.

Based upon the complexity of managing AIS, treatment by a

gynecologic

oncologist is generally

preferred.

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Clinical approach

L

aparoscopic approach,

NO

morcellation

.

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Clinical approach

Prior to hysterectomy, for women who had positive margins on conization,

a

repeat

conization

to

exclude invasive disease.

(6 weeks prior to hysterectomy

.)

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Clinical approach

Women in whom adenocarcinoma is discovered at time of hysterectomy should be managed as appropriate

.

Further surgical staging and treatment with

radical

parametrectomy

and lymph node dissection may be required. In addition, chemotherapy and/or radiation may be indicated.

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surveillance

 Following hysterectomy for AIS, the optimal surveillance

= ????

Assuming

the hysterectomy specimen

did not show invasive cancer

,

the

following protocol:Vaginal

cytology and high-risk

HPV

testing of the vaginal fornix at 6 and 12 months after hysterectomy

If

normal, once a year indefinitely

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Clinical approach

If vaginal cytology results are abnormal

, vaginal

colposcopy

.

If colposcopy and biopsy are positive for high-grade dysplasia (glandular or squamous), the patient is treated either with

an ablative procedure

(eg

,

CO2

laser or ultrasonic surgical aspiration)

or excision.

 

If HPV testing is positive and vaginal cytology negative, the HPV test and cytology

repeat :

at the next surveillance visit.

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Conization margin status

Negative margin

 — 

Women with a negative conization have a risk of residual AIS or adenocarcinoma of 20 and 1 percent

, respectively, based upon data from hysterectomy or repeat

conisation.

C

onservative

management

:

counseled

about

the

risk of

 persistent/recurrent AIS or adenocarcinoma.

ECC is performed

at

the time of conization.

(

a positive ECC is a positive margin).

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Conization margin status

Positive margin

 — Women

who

desire to preserve fertility

: a

repeat conization

.

If the repeat conization margin is negative, we offer surveillance.

Women typically do not undergo more than two conization procedures

.

A third conization is

sometimes feasible

, but the risk of operative complications and preterm delivery in subsequent pregnancy increases with repeat procedures

.

We recommend hysterectomy for women with a positive conization margin following two or more

conizations

.

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