PRE-CANCEROUS LESION

IN CERVIX:
GLANDULAR
INTRAEPITHELIAL LESION
 Pre-cancerous Lesion :
Squamous cell
Squamous Intraepithelial
carcinoma (90%)
Lesions (SIL)

Pre-cancerous Lesion :
Cervical Cancer Adenocarcinoma Glandular Intraepithelial
Lesions (GIL)

Mixed carcinomas and

others
  Almost always arises at the squamocolumnar junction
(transformation zone) , rarely it may develop in the upper
endocervix
 The exact reason behind the development GIL is still not
completely known
ETIOLOGY  Usualy associated with hrHPV infection ( HPV18 are identified
& SITES in a substantial number. HPV16 is also very commonly
identified, but is not in the majority as is noted in squamous
lesions )
 The type of HPV present has not been found to impact survival
of patient
RISK FACTOR (SIMILAR
TO
 SIL)
Typically occurs in young women in their reproductive years with an average age at
presentation of 38 years.
 Long term use of oral contraceptives. Exogenous hormone use also has been shown to be a
factor in the development of glandular cancers. History of diethylstilbestrol (DES, a synthetic
form of estrogen) use in mothers: Female children of women, who took this drug while pregnant
 Multiple sexual partners
 Young age at first intercourse
 History of cervical cancer in the family
 Unlike squamous cell carcinoma, cigarette smoking is not associated with increased risk of
endocervical adenocarcinoma.
 Unlike squamous cell carcinoma, endocervical adenocarcinoma appears to be less commonly
associated with high parity
 Has a greater association with obesity than squamous cell carcinoma (which is a known cause
of increased endogenous estrogen production)
 SCREENING
 Associated symptoms are quite uncommon and most patient diagnosed after
an abnormality has been detected on a Pap test (Cytology exam)
FLOWCHART
FOR
SCREENING :
IN GENERAL
 CLASSIFICATION
 Unlike cervical squamous epithelium, the cytologic features of precursor or
dysplastic glandular lesions of degrees have not been well defined much less
graded as to severity.

 The Bethesda System 2014 :

 Atypical glandular cells – endocervical (AEC/AGC)
 Recognize changes to endocervical glandular cells that did not meet
the criteria for AIS but that were sufficiently worrisome to require
reporting
 Divided into AGC-NOS and AGC-Favor Neoplasia
 Adenocarcinoma In Situ (AIS)
 ADENOCARCINOMA
IN SITU (AIS) -
CYTOLOGY
FEATURES
 Normal cervical glandular architecture
is preserved
 Hyperchromatic crowded groups
commonly noted initially at low
magnification (x10) (show nuclear
overlap on higher magnification)
 ADENOCARCINOMA IN
SITU (AIS) - CYTOLOGY
FEATURES

 Feathering at the periphery of groups

(At the margins of the groups, cells and
nuclei protrudes from the periphery of
the crowded cell groups may appear to
be falling off the edges of the crowded
cell groupings)
ADENOCARCINOMA
IN SITU (AIS)
- CYTOLOGY
FEATURES
Rosettes (gland-like formations) within
groups
ADENOCARCINOMA
IN SITU (AIS)
- CYTOLOGY
FEATURES
Pseudostratified strips of columnar cells
ADENOCARCINOMA
IN SITU (AIS)
- CYTOLOGY
FEATURES
Cellular disorganization—loss of rigid
“honeycombed” structure
 ADENOCARCINOMA IN SITU
(AIS) - CYTOLOGY FEATURES

 Enlarged nuclei, often elongate.

 Possible presence of small nucleoli
 Coarse chromatin which is generally
evenly distributed within the nucleus
 Increased nuclear to cytoplasmic ratio
 ADENOCARCINOMA IN SITU
(AIS) - CYTOLOGY FEATURES

 Mitoses (Presence of mitotic figures :

Instead of a nucleus, the chromosomes
are visible as tangled, dark-staining
threads.) and apoptotic debris are
common
 The presence of mitotic figures is
essential to the diagnosis
AEC/AGC, NOT OTHERWISE SPECIFIED (AEC/AGC-NOS)

 Applies when only some but not all of the features of AIS are
present, or the features present are qualitatively insufficient to
instill confidence in their application.

 These features may include :

 Nuclear enlargement
 degrees of hyperchromasia
 nucleoli formation
 size variability
 cell crowding and nuclear overlap
 incomplete rosette formation
 partial pseudostratification.
 Mitotic figures may be found but should not be numerous,
and apoptotic breakdown fragments should not be prominent
AEC/ AGC, FAVOR NEOPLASIA ( SUSPICIOUS FOR
AIS OR CANCER)

 Used when more pronounced or more numerous

abnormalities are present in the endocervical
cells, which may include :
 Rosettes
 Feathering
 Pseudostratified strips and
 Intermediate numbers of mitoses but of
insufficient extent to allow confidence in an
outright interpretation
 DIAGNOSIS

Possible symptoms : Abnormal

vaginal bleeding, Pain during and
Associated symptoms are quite
bleeding after intercourse,
uncommon (though if present, the
Menstrual cycle disturbances,
most common is abnormal vaginal
Abnormal vaginal discharge,
bleeding )
Anemia (due to bleeding), Loss of
weight, loss of appetite
DIAGNOSI
S  It is recommended that all women with AGC in cystology undergo colposcopy
with endocervical sampling (obtaining a histologic specimen by endocervical
curettage or cytobrush or obtaining a cytologic sample with a cytobrush.)

 In women aged 35 and older or in younger women with risk factors for
endometrial adenocarcinoma, sampling of the endometrium should be performed
along with colposcopy and sampling of the endocervical canal.
 Risk factors for endometrial adenocarcinoma in younger women include
abnormal vaginal bleeding and chronic anovulation
DIAGNOSIS –
HISTOLOGY  Histologically, normal cervical glandular architecture is preserved, with the
glands lined by crowded cells with enlarged, hyperchromatic, stratified, or
pseudostratified nuclei.
 Adenocarcinoma in situ may sometimes have a more complex growth
pattern, with intraluminal papillary infolding or cribriform growth
 In 30 to 50% of cases, adenocarcinoma in situ is associated with SIL
  If the initial colposcopic work-up for women with AGC—
MANAGEMEN favor neoplasia or endocervical AIS on cytology reveals no
evidence of invasive tumor, a diagnostic excisional procedure.
T Also, endocervical sampling after the excision should be
performed.
 MANAGEMENT – DIAGNOSTIC EXCISIONAL
PROCEDURE

 Diagnostic excisional procedure: obtaining a histologic

sample of the transformation zone and endocervical
canalusing using two method :
 LEEP ( loop electrosurgical excision procedure ) : uses a
wire loop heated by electric current to remove cells and
tissue in a woman's lower genital tract
 CCK (cold knife conization) : A procedure in which a
cone-shaped piece of abnormal tissue is removed from the
cervix using a scalpel or laser knife
 LEEP excises the cervical transformation zone

MANAGEMEN
and a small amount of stroma.Compared with
cold knife conization, LEEP can be performed
in the office under local anesthesia and
removes less tissue. T–
 Because LEEP can cause cautery heat artifact
at the margins, cold knife conization is
DIAGNOSTIC
preferable when margin status is critical for
determining residual disease and clinical
EXCISIONAL
management, as in adenocarcinoma in situ and
suspected squamous microinvasion.
PROCEDURE
 MANAGEMENT –
AFTER DIAGNOSTIC
EXCISIONAL PROCEDURE

 Endocervical sampling after the

excision should be performed.
 Tissue sample from excision should be
analyzed for intraepithelial neoplasia
 When the endocervical margin or
endocervical curettage (ECC) are
positive for intraepithelial neoplasia at
the time of excision, there is an
increased risk of residual disease
FURTHER MANAGEMENT
 SOURCES
 Fletcher's Diagnostic Histopathology of Tumors, 4th Edition
 Rosemary H. Tambouret; David C. Wilbur.Glandular Lesions of the Uterine
Cervix: Cytopathology with Histologic Correlates (Essentials in Cytopathology)

 WHO guidelines for screening and treatment of precancerous lesions for cervical cancer
prevention

THANK  WHO guidelines for treatment of cervical intraepithelial neoplasia 2–3 and
adenocarcinoma in situ

YOU
 ASCCP Updated Consensus Guidelines for Managing Abnormal Cervical Cancer
Screening Tests and Cancer Precursors

 Gynecologic Procedures: Colposcopy, Treatment of Cervical Intraepithelial

Neoplasia, and Endometrial Assessment https://www.aafp.org/afp/2013/0615/
p836.html

 https://www.sciencedirect.com/science/article/pii/B9781416042082100090
 https://www.sciencedirect.com/science/article/pii/B9780323065160100220
 https://screening.iarc.fr/atlascyto.php