DR LAYLA S. ABDULLAH,MD,FRCPC
DEPARTMENT OF PATHOLOGY
FACULTY OF MEDICINE
KING ABDULAZIZ UNIVERSITY
Preinvasive lesions ( definition)
Historical review of terminologies
The latest cytological terminology : The
2001 Bethesda System for reporting of PAP
The LAST classification .
Cervical cancer was the most frequent form
of cancer around the world.
Impact of cervical cancer screening:
Decrease incidence of invasive tumors and
increase incidence in the detection of
cervical preinvasive lesions (dysplasia).
Derived from the Greek word DYS for ‘‘bad’’
and PLASIA for ‘‘molding’’
used in many areas of medicine to describe a
Dysplasia is an abnormal growth and
maturation of cervical squamous epithelium
Cytological and architectural changes of
cervical cells/ loss of polarity
limited by the basement membrane
Pre-invasive, precancerous, Pre-malignant
Graded mild, moderate, or severe
HPV related ( Serotypes: High risk: 16,
18, 31, and 33)
Integration of viral genes into host genome
inactivate p53 and retinoblastoma tumor
Historical Review Of
The earliest description of intraepithelial
pre-cancer was by Sir John Williams in 1888.
carcinoma in situ (CIS) : cells that
morphologically looked like cancer but had
not invaded below the basement membrane
2-tiered clinical approach :
- Hysterectomy for women with CIS and
- No treatment for women without it
Surface lesions existed on the cervix that had
abnormal histological features that did not
fulfill the criteria for CIS.
Lower risk for progressing to cancer than CIS
( Koss and Durfee)
ballooned cytoplasm koilocytes from the
Greek word for ‘‘empty space,’’
similarity to descriptions of Reagan’s mild
In 1976, Meisels and Fortin linked
koilocytotic atypia with HPV.
cervical carcinogenesis was a continuum of
disease ranging from mild dysplasia to
He coined the term cervical intraepithelial
neoplasia (CIN) to emphasize its association
as a precursor to cancer
CIN : spectrum of cytological and
histological changes that shared a common
etiology, biology and natural history
All groups (CIN I ,II,III and ca insitu)
represented different stages of a single
CIN terminology was widely adopted for use
both in histology and cytology
As our understanding of pathogenesis of
cervical cancer and its precursors improved
Ostor AG. Natural history of cervical intraepithelial neoplasia :a critical
review. Int J Gynecol Pathol 1993;12:186-92.
regress persist Progress
CIN 1 57% 32% 11% 1%
CIN 2 43% 35% 22% 5%
CIN 3 32% 56% >12%
CIN biological classification as a spectrum
was questioned ???????
Late 1980s : the biology of HPV and cervical
oncogenesis was increasingly understood.
Human papillomavirus interacts with
squamous epithelia in 2 basic ways.
The productive viral infection caused by Low
& high risk HPV (self limited
The true neoplastic process confined to
epithelium but with the capacity to progress
to invasive cancer if not treated.
High grade, high risk HPV, desregulation of
E6&E7,monoclonal with chromosomal
In 1989 , Bethesda system was introduced to
standardize the reporting of cervical cytology
results and to incorporate new insights
gained from the discovery of HPV.
The name of pre-invasive lesions were
changed to squamous intraepithelial lesions
Subdivided only to 2 grades (Low & High).
First Bethesda workshop in 1988
Followed by another in 1991
Latest was in 2001
Internet based bulletin
1000 comments regarding draft
Countries all over the world participated
Clinicians, pathologists, cytopathologists,
cytotechnologists, patient’s advocates,
The Bethesda system recommends a specific
format for cytology report including
comments on :
Within the two tiered terminology system
Northern America SIL/ASC
BSCC system in UK Dyskaryosis/Borderline
Modified Bethesda in Australia
Europe and some other countries CIN
Satisfactory for evaluation
A satisfactory squamous component must be
Note the presence/absence of endocervical/
transformation zone component
Obscuring elements (inflammation, blood,
drying artifact, other) may be mentioned if
50–75% of epithelial cells are obscured
Specimen rejected/not processed because (specify
reason). Reasons may include:
• lack of patient identification
• unacceptable specimen (e.g. slide broken beyond
Specimen processed and examined, but
unsatisfactory for evaluation of an epithelial
abnormality because (specify reason). Reasons may
• insufficient squamous component.
• obscuring elements cover more than 75% of
LOW GRADE SQUAMOUS
(CIN I & HPV)
Renewed debate about adopting a 2-tiered
low-grade and high-grade terminology for all
LAT HPV-associated intraepithelial lesions.
Better reflects the known biology of HPV-
associated disease, diagnostic variability
is reduced, management & patient outcome
-Recommend terminology that is unified
across lower anogenital sites. (All sites,
-Create a histopathological nomenclature
system that reflects current knowledge of
-Optimally uses available biomarkers
-Facilitates clear communication across
different medical specialties
The Lower Anogenital Squamous Terminology
(LAST) Project was cosponsored by
the College of American Pathologists (CAP)
the American Society for Colposcopy and
Cervical Pathology (ASCCP)
5 working groups;
WG 1 provided the historical background
WG 2,3,4 performed comprehensive
literature reviews and developed draft
recommendations for SIL, SISCCA&
WG 5 will continue to foster implementation
of the LAST recommendations.
Literature review(> 1000 articles)
Inclusion & exclusion criteria.
Member’s expert opinions
Open comment period (15 Jan-15 Feb 2012)
Recommendations were finalized and voted
on at the consensus meeting (March 2012).
A unified histopathological nomenclature for
all HPV-associated of all LAT sites.
A 2-tiered nomenclature is recommended :
squamous intraepithelial lesion (SIL)
(LSIL) and (HSIL), which may be further
classified by the applicable IN
IN refers to intraepithelial neoplasia.
For a specific location : cervix = CIN 3,
vagina = VaIN 3, vulva = VIN 3, anus = AIN
3,perianus = PAIN 3, and penis = PeIN 3
HSIL vs. Immature
Initiate action plans for implementation
of the recommendations.
Disseminate, Implement & Monitor .
educational programs detailing the
recommendations and their appropriate
incorporation into practice
The LAST Project recommendations reflect
the participants’ consensus judgment for
best evidence-based pathology practice and
nomenclature for HPV-associated squamous
lesions of the LAT.