3 dr mario sideri ais

COLPOSCOPY OF GLANDULAR LESIONS

Silvano Costa, Bologna, Italy

Mario Sideri, Milano, Italy

Adenocarcinoma in situ is the only known precursor to

cervical adenocarcinoma, and appropriate management

can prevent the occurrence of invasive disease in many

cases [1].

1 Alfsen GC,. Cancer 2000; 89:1291.

Adenocarcinoma in situ- AIS

http://www.uptodate.com/contents/invasive-cervical-adenocarcinoma/abstract/2








Adenocarcinoma in situ is the only known precursor to cervical

adenocarcinoma, and appropriate management can prevent the

occurrence of invasive disease in many cases [1].


2 Gien LT,. Gynecol Oncol 2010; 116:140.

The usual interval between clinically detectable

adenocarcinoma in situ and early invasion appears to

be at least five years, suggesting opportunity for

screening and intervention [2].


















Adenocarcinoma in situ is the only known precursor to cervical

adenocarcinoma, and appropriate management can prevent the

occurrence of invasive disease in many cases [2].


2 Gien LT,. Gynecol Oncol 2010; 116:140.

3 SEER data for 2003-2007: http://seer.cancer.gov/.

The usual interval between clinically detectable adenocarcinoma in

situ and early invasion appears to be at least five years, suggesting

opportunity for screening and intervention [2].


Glandular neoplasia of the uterine cervix comprises

25% of all annual cervical cancers diagnoses [3].


















From 1980 to 2000, epidemiological data show a six

fold increase of AIS (1) probably due to (2,3):

1) a better clarification of glandular findings by Bethesda

System cervical cytology classification

2) exposure to factors that cause or promote glandular

neoplasia as:

* prolonged infection with high risk HPV subtypes (mainly 16;18)

*oral contraceptives ?

3) less squamous neoplasia due to cytologic screening

1. SEER data for 2003-2007: http://seer.cancer.gov/.

2. Plaxe SC, Gynecol Oncol 1999; 75:55.

3. Tornesello ML, Gynecol Oncol 2011; 121:32.








• Between 2003 and 2009 forty-four cervical cancers were

diagnosed following at least one cyto -/ HPV+ result:

– 26 had one cyto-/HPV+ before diagnosis

– 15 had two

– 3 had three

• Cancer types:

– 16 squamous

– 1 small cell

– 24 adenocarcinomas

– 2 adenosquamous carcinomas

• Adenocarcinoma and adenosquamous CA usually

accounts for about 20% of cervical cancers

60% were adeno-

or adenosquamous

carcinomas

Kinney W, Fetterman B, Cox JT,Lorey T,Flanagan T,Castle PE..Gynecol Oncol. 2011 May 1;121(2):309-13.

Cytology is less effective at detecting AIS and adenocarcinoma

Characteristics of 44 cancers detected by cotesting

Cytology is less effective at detecting AIS and adenocarcinoma

Detection of CIN3, AIS, adenocarcinoma and SCC in the ATHENA Trial

Castle PE et al. Lancet Oncol. 2011 Sep;12(9):880-90. *25% difference

Sensitivity

Histology (number) CytologyHPV

testing

CIN3 (254)52%

(132)

92%

(254)

AIS (16) 63% (10) 88% (14)*

Adenocarcinoma and

AdenoSq Ca (1)100% (1) 100% (1)

Squamous cell cancer (3) 100% (3) 100% (3)

Cytology is less effective at detecting AIS and adenocarcinoma1,2

•Cytologic screening has been ineffective in reducing the incidence of adenocarcinoma1

•Incidence of adenoCA in women <40 has been increasing1

•Stage for stage survival for women with adenoCA is significantly less than for squamous cancer1

•85-90% of adenoCA is due to HPV 16,18, much higher than the approximately 70% for squamous cancers1

•In HPV-based screening, the numbers of women with screen-detected glandular disease are likely to increase2

1. Ault KA et al. Int. J. Cancer. 2011; 128, 1344–1353;2. Saslow d et al. CA Cancer J Clin. 2012 May-Jun;62(3):147-72;

3. Leeson SC et al J Low Genit Tract Dis.. 2013 Jun 14. [Epub ahead of print].

Reasons for moving from cytology to

HPV testing


•Age of onset : 35

•Location : upper limit of the SCJ, usually extending

up to 25 mm into the cervical canal

•Distribution: unifocal, multicentric, diffused or “skip

lesion”

•Co-exsistence with squamous lesion: ~ 50% (25-

90%) (1)

1) Costa S, et al., Gynecol Oncol, 2007 106:170-6.

ORIGIN & LOCATION

columnar or reserve

cells at T. Zone

Upper limit of T.

Zone

cervix

Detection of AIS

As preinvasive lesion AIS is asymptomatic

and detection occurs:

• By cytology

• By chance following Endocervical curettage, large

LOOP biopsy or conization for squamous lesion

G. Negri. Pap test tecnica e lettura. In Costa S, Syrjanen K. Gestione delle pazienti con pap test anormale. Athena

Ed., Modena, 2005

Detection of AIS: CYTOLOGY

AIS is detected in the majority of the women upon

evaluation of abnormal findings on cervical cytology

Either glandular or squamous cytologic abnormalities may

precede a diagnosis of AIS :

Glandular 40-60 %Squamous 40-50% Mixed squamous and glandular 15 %Negative findings 5 %

Detection of AIS

AIS is a histologic diagnosis made with a cervical

biopsy, which may include one or more of the

following techniques:

*colposcopy-directed biopsy,

*endocervical curettage,

*cone biopsy.

HISTOLOGY

Detection of AIS

COLPOSCOPY

COLPOSCOPY is poor at detecting glandular

lesions for two reasons:

1) The location within CC is out of view

2) Even within view there are not specific colposcopic

features of glandular lesions

Detection of AIS

COLPOSCOPY

Colposcopy In AIS:

50-70% prediction of squamous lesion

20-30% prediction of glandular lesion

15% Negative

55% Type 3 TZ

Detection of AIS

COLPOSCOPY

Colposcopic features of AIS may be associated

with:

• Elongated glandular villi

• Fused villi

• Acetowhitening of villi

COLPOSCOPY

Detection of AIS

COLPOSCOPY-Directed Biopsy

In AIS directed biopsy shows:

40-60% CIN 2+ or mixed (Squamous + Glandular)

25-40% Pure Glandular lesion

10-20% Negative-CIN 1

In case of cytologic finding of glandular abnormalities if

biopsy and ECC are negative, further evaluation with

conization may be warranted.

Detection of AIS

Endocervical Curettage ( EEC)

Even its use is questionable, ECC should be performed in all

women with a cytologic finding of glandular abnormalities

or a high grade squamous intraepithelial lesion extended

into CC (1,2)

In AIS patients ECC is positive in 35-65% of cases (3)

1.Wang SS,. Gynecol Oncol 2006; 103:541.

2. Costa S, Gynecol Oncol , 2012 ;124:490-5.

3. Zannoni G. Il Bethesda System in: Costa S, Syrjabnen K. Gestione delle pazienti con pap test anormale. Athena Ed., Modena, 2005









Conization is appropriate in cases with suspected

disease who have negative biopsy and ECC results

Detection of AIS

Conization

These include women with the following findings:

•Cytology with AIS or AdCa and a negative biopsy and ECC

•Cytology with AGC and a negative biopsy, ECC, or endometrial

biopsy

Conization may be performed using one of several

techniques, including:

•cold knife conization (CKC),

•loop electrosurgical excision procedure (LEEP)

•laser conization

Detection of AIS

Conization

Many women with AIS will undergo LEEP, because

there was no preoperative suspicion of glandular

disease [1]. These patients are managed the same way

as those who underwent CKC [2].

Detection of AIS

Conization

1. Kastritis E,. Gynecol Oncol 2005; 99:376.

2. Lee KB,. Int J Gynecol Cancer 2006; 16:1569.

http://www.uptodate.com/contents/cervical-adenocarcinoma-in-situ/abstract/17,24

http://www.uptodate.com/contents/cervical-adenocarcinoma-in-situ/abstract/24




















Many women with AIS will undergo LEEP because there was no preoperative

suspicion of glandular disease [1]. These patients are managed the same way

as those who underwent CKC.

Detection of AIS

Conization

55 % of women with AIS are found to

have a coexisting squamous lesion

1. Macdonald OK, Am J Clin Oncol 2009; 32:411.










260 CIN2 on colpo directed biopsy were submitted to cervical conization; the pathology of cone revealed:Less than CIN2 = 25%CIN2 = 40%CIN3+ = 35%5 cases of AIS (5.4% out of the CIN3+)

CIN2: treatment Final diagnosis

362 CIN3 on colpo directed biopsy weresubmitted to cervical conization; the pathology of cone revealed:Less than CIN2 = 17% CIN2 = 13% CIN3+ = 70%7 cases of AIS

CIN2: treatment Final diagnosis

Many women with AIS will undergo LEEP because there was no preoperative

suspicion of glandular disease [1]. These patients are managed the same way

as those who underwent CKC.

Detection of AIS

Conization

55 % of women with AIS are found to have a coexisting squamous lesion

Although there are conflict data regarding

information on residual disease, some

surgeons perform ECC at the time of

conization

1. Macdonald OK, Am J Clin Oncol 2009; 32:411.










AIS MANAGEMENT

The management of AIS is challenging :

Negative margins on a cone biopsy specimen or a

negative EEC do not necessarily ensure that the lesion

has been completely excised.

RESIDUAL LESION

Initial conization positive margin : AIS: 52 %; AdCa: 6%

Initial conization negative margin: AIS 20% ; AdCa: 1.5%

AIS MANAGEMENT

Since many women treated with conization have a

high risk of residual AIS or adenocarcinoma (AdCa)

Hysterectomy remains the standard

treatment for AIS

AIS MANAGEMENT

For women who wish to preserve fertility,

conization followed by surveillance is a

reasonable option in case of negative

margins and negative endocervical curettage

AIS MANAGEMENT

Pap smear : low sensitivity

Colposcopy : not appropriate

Follow Up Problems

AIS MANAGEMENT

Follow Up Problems

Recent observations (1) suggested that

HR-HPV test in conjunction with cervical

cytology offers clear advantages in monitoring

the women conservatively treated for cervical

glandular intraepithelial neoplasia

Pap smear : low sensitivity Colposcopy : not appropriate


HPV testing after

conservative treatment for

AIS

HPV testing has been shown to be useful also

in the follow up of conservatively treated

cervical AIS by our group.

Gynecologic Oncology 2007, 106, 170-176

HPV testing after conservative treatment for AIS

When both PAP smear and HPV test are used together, such a combined test detectspersistent lesions at the 1st FU visit with OR=9.0 (95% 0.91–88.57) and givessensitivity (SE) of 90.0%, specificity (SP) 50.0%, PPV 52.9%, and NPV 88.9%. Atthe 2nd FU visit, this combination gives SE 100%, SP 52.6%, PPV 40.0%, and NPV100% (OR not computable). At the 3rd FU visit, when most of the disease hasdisappeared, SE is 0%, SP 91.7%, PPV 0%, and NPV 91.7%.

Costa S, et al. Gynecologic Oncology 2007, 106, 170-176

Positive HR-HPV test was the only independent

predictor of disease recurrence (OR=2.72),

and with free cone margins,

was also the most powerful predictor of disease

progression to AdCa (OR=3.7).

AIS MANAGEMENT

Performance of Pap smear, colposcopy, cone

margins and HR-HPV DNA test


Thank you

Invasive adenocarcinoma, negative pap and HPV test positive type 16

Nulliparous, 37 years old,

2010 negative smear and cervical cauterization of an ectopy;

april 2013 negative smear;

because of postcoital bleeding cytology again and report of

adenocarcinoma, HPV16;

colposcopy positive, TZ type 2, suspicion of invasion,

biopsy adenocarcinoma endocervical type, well differentiated, villoglandular.

Lasercone pathology report endocervical adenocarcinoma, well differentiated

innvasive (max depth 5 mm; max lenght 8 mm) FIGO stage IB1.

Science

3 dr mario sideri ais