all

1. DR LAYLA S. ABDULLAH,MD,FRCPC
ASSOCIATE PROFESSOR/CONSULTANT
DEPARTMENT OF PATHOLOGY
FACULTY OF MEDICINE
KING ABDULAZIZ UNIVERSITY

2.  Preinvasive lesions ( definition)
 Historical review of terminologies
 The latest cytological terminology : The
2001 Bethesda System for reporting of PAP
smears .
 The LAST classification .

3.  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).

4.  Definition:
Derived from the Greek word DYS for ‘‘bad’’
and PLASIA for ‘‘molding’’
used in many areas of medicine to describe a
nonmalignant process.

5.  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
lesions
 Graded mild, moderate, or severe

9.  HPV related ( Serotypes: High risk: 16,
18, 31, and 33)
 Integration of viral genes into host genome
inactivate p53 and retinoblastoma tumor
suppressor genes.

10. Historical Review Of
Terminologies For
Cervical Preinvasive
Lesions

11.  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

12.  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
does.

13.  ( Koss and Durfee)
ballooned cytoplasm  koilocytes from the
Greek word for ‘‘empty space,’’
 similarity to descriptions of Reagan’s mild
dysplasia.
 In 1976, Meisels and Fortin linked
koilocytotic atypia with HPV.

15. proposed :
 cervical carcinogenesis was a continuum of
disease ranging from mild dysplasia to
cervical cancer
 He coined the term cervical intraepithelial
neoplasia (CIN) to emphasize its association
as a precursor to cancer

16.  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
biological continuum

17. CIN terminology was widely adopted for use
both in histology and cytology

19. CIN I CIN II CIN III/Ca
Insitu

20.  As our understanding of pathogenesis of
cervical cancer and its precursors improved
and increased.

21. Ostor AG. Natural history of cervical intraepithelial neoplasia :a critical
review. Int J Gynecol Pathol 1993;12:186-92.
regress persist Progress
to CIS
Progress
to
invasion
CIN 1 57% 32% 11% 1%
CIN 2 43% 35% 22% 5%
CIN 3 32% 56% >12%

22.  CIN biological classification as a spectrum
was questioned ???????

24.  Late 1980s : the biology of HPV and cervical
oncogenesis was increasingly understood.

25.  Human papillomavirus interacts with
squamous epithelia in 2 basic ways.

26.  The productive viral infection caused by Low
& high risk HPV  (self limited
spontaneously resolve)
and
 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
alteration

27.  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
(SIL)
 Subdivided only to 2 grades (Low & High).

29. Cervical
Cytology

30.  First Bethesda workshop in 1988
 Followed by another in 1991
 Latest was in 2001

31.  9 forums
 Internet based bulletin
 1000 comments regarding draft
recommendations
 Countries all over the world participated
 Clinicians, pathologists, cytopathologists,
cytotechnologists, patient’s advocates,
public organizations

32.  The Bethesda system recommends a specific
format for cytology report including
comments on :
specimen adequacy
general categorization
interpretation/results

34.  Within the two tiered terminology system
Controversy :
 Northern America  SIL/ASC
 BSCC system in UK Dyskaryosis/Borderline
 Modified Bethesda in Australia
 Europe and some other countries CIN
terminology

41. Satisfactory for evaluation
 A satisfactory squamous component must be
present
 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

42.  Specimen rejected/not processed because (specify
reason). Reasons may include:
• lack of patient identification
• unacceptable specimen (e.g. slide broken beyond
repair)
 Specimen processed and examined, but
unsatisfactory for evaluation of an epithelial
abnormality because (specify reason). Reasons may
include:
• insufficient squamous component.
• obscuring elements cover more than 75% of
epithelial cells.

50. LOW GRADE SQUAMOUS
INTRAEPITHELIAL LESION
(CIN I & HPV)

53. Moderate Dysplasia (CIN II)

58. Human Papilloma
Virus (HPV)
Ancillary
Tests

59.  Ancillary tests such as HPV testing
HPV Digene (+ or -)
Molecular PCR testing : Sub-typing
 P16 immunohistochemistry
 Automated screening
 recommendations

60. Histology
reporting of
preinvasive
lesions

61.  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
improved.

62. The Lower Anogenital Squamous Terminology

63. -Recommend terminology that is unified
across lower anogenital sites. (All sites,
both sex)
-Create a histopathological nomenclature
system that reflects current knowledge of
HPV biology
-Optimally uses available biomarkers
-Facilitates clear communication across
different medical specialties

65. The Lower Anogenital Squamous Terminology
(LAST) Project was cosponsored by
 the College of American Pathologists (CAP)
and
 the American Society for Colposcopy and
Cervical Pathology (ASCCP)

66. 5 working groups;
 WG 1 provided the historical background
 WG 2,3,4 performed comprehensive
literature reviews and developed draft
recommendations for SIL, SISCCA&
biomarkers .
 WG 5 will continue to foster implementation
of the LAST recommendations.

67.  Literature review(> 1000 articles)
 Inclusion & exclusion criteria.
 Data extraction.
 Member’s expert opinions
 Draft recommendations
 Open comment period (15 Jan-15 Feb 2012)

68.  Recommendations were finalized and voted
on at the consensus meeting (March 2012).

69.  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
sub categorization.
 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

71. HSIL vs. Immature
inflamed squamous
metaplasia

72. HSIL vs. Reparative atypia

73. P16 CIN 2

74.  Initiate action plans for implementation
of the recommendations.
 Disseminate, Implement & Monitor .
 Effective communication
 educational programs detailing the
recommendations and their appropriate
incorporation into practice

75.  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.

76. The work is not yet done.

77.  Definition of dysplasia
 Bethesda 2001 for PAP smear reporting
 Pathological reporting of preinvasive cervical
lesions.
 The LAST terminology

78. THANK YOU