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DR LAYLA S. ABDULLAH,MD,FRCPC
ASSOCIATE PROFESSOR/CONSULTANT
DEPARTMENT OF PATHOLOGY
FACULTY OF MEDICINE
KING ABDULAZIZ UN...
 Preinvasive lesions ( definition)
 Historical review of terminologies
 The latest cytological terminology : The
2001 B...
 Cervical cancer was the most frequent form
of cancer around the world.
 Impact of cervical cancer screening:
Decrease i...
 Definition:
Derived from the Greek word DYS for ‘‘bad’’
and PLASIA for ‘‘molding’’
used in many areas of medicine to des...
 Dysplasia is an abnormal growth and
maturation of cervical squamous epithelium
 Cytological and architectural changes o...
 HPV related ( Serotypes: High risk: 16,
18, 31, and 33)
 Integration of viral genes into host genome
inactivate p53 an...
Historical Review Of
Terminologies For
Cervical Preinvasive
Lesions
 The earliest description of intraepithelial
pre-cancer was by Sir John Williams in 1888.
 carcinoma in situ (CIS) : cel...
 Surface lesions existed on the cervix that had
abnormal histological features that did not
fulfill the criteria for CIS....
 ( Koss and Durfee)
ballooned cytoplasm  koilocytes from the
Greek word for ‘‘empty space,’’
 similarity to description...
proposed :
 cervical carcinogenesis was a continuum of
disease ranging from mild dysplasia to
cervical cancer
 He coined...
 CIN : spectrum of cytological and
histological changes that shared a common
etiology, biology and natural history
 All ...
CIN terminology was widely adopted for use
both in histology and cytology
CIN I CIN II CIN III/Ca
Insitu
 As our understanding of pathogenesis of
cervical cancer and its precursors improved
and increased.
Ostor AG. Natural history of cervical intraepithelial neoplasia :a critical
review. Int J Gynecol Pathol 1993;12:186-92.
r...
 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
spontaneously resolve)
and
 The true neopl...
 In 1989 , Bethesda system was introduced to
standardize the reporting of cervical cytology
results and to incorporate ne...
Cervical
Cytology
 First Bethesda workshop in 1988
 Followed by another in 1991
 Latest was in 2001
 9 forums
 Internet based bulletin
 1000 comments regarding draft
recommendations
 Countries all over the world partic...
 The Bethesda system recommends a specific
format for cytology report including
comments on :
specimen adequacy
general c...
 Within the two tiered terminology system
Controversy :
 Northern America  SIL/ASC
 BSCC system in UK Dyskaryosis/Bor...
Satisfactory for evaluation
 A satisfactory squamous component must be
present
 Note the presence/absence of endocervica...
 Specimen rejected/not processed because (specify
reason). Reasons may include:
• lack of patient identification
• unacce...
LOW GRADE SQUAMOUS
INTRAEPITHELIAL LESION
(CIN I & HPV)
Moderate Dysplasia (CIN II)
Human Papilloma
Virus (HPV)
Ancillary
Tests
 Ancillary tests such as HPV testing
HPV Digene (+ or -)
Molecular PCR testing : Sub-typing
 P16 immunohistochemistry
 ...
Histology
reporting of
preinvasive
lesions
 Renewed debate about adopting a 2-tiered
low-grade and high-grade terminology for all
LAT HPV-associated intraepithelial...
The Lower Anogenital Squamous Terminology
-Recommend terminology that is unified
across lower anogenital sites. (All sites,
both sex)
-Create a histopathological no...
The Lower Anogenital Squamous Terminology
(LAST) Project was cosponsored by
 the College of American Pathologists (CAP)
a...
5 working groups;
 WG 1 provided the historical background
 WG 2,3,4 performed comprehensive
literature reviews and deve...
 Literature review(> 1000 articles)
 Inclusion & exclusion criteria.
 Data extraction.
 Member’s expert opinions
 Dra...
 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 recommend...
HSIL vs. Immature
inflamed squamous
metaplasia
HSIL vs. Reparative atypia
P16 CIN 2
 Initiate action plans for implementation
of the recommendations.
 Disseminate, Implement & Monitor .
 Effective commun...
 The LAST Project recommendations reflect
the participants’ consensus judgment for
best evidence-based pathology practice...
The work is not yet done.
 Definition of dysplasia
 Bethesda 2001 for PAP smear reporting
 Pathological reporting of preinvasive cervical
lesions...
THANK YOU
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
Dr layla abdullah cytology & patholog
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Dr layla abdullah cytology & patholog

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Dr layla abdullah cytology & patholog

  1. 1. DR LAYLA S. ABDULLAH,MD,FRCPC ASSOCIATE PROFESSOR/CONSULTANT DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE KING ABDULAZIZ UNIVERSITY
  2. 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. 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. 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. 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
  6. 6.  HPV related ( Serotypes: High risk: 16, 18, 31, and 33)  Integration of viral genes into host genome inactivate p53 and retinoblastoma tumor suppressor genes.
  7. 7. Historical Review Of Terminologies For Cervical Preinvasive Lesions
  8. 8.  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
  9. 9.  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.
  10. 10.  ( 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.
  11. 11. 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
  12. 12.  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
  13. 13. CIN terminology was widely adopted for use both in histology and cytology
  14. 14. CIN I CIN II CIN III/Ca Insitu
  15. 15.  As our understanding of pathogenesis of cervical cancer and its precursors improved and increased.
  16. 16. 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%
  17. 17.  CIN biological classification as a spectrum was questioned ???????
  18. 18.  Late 1980s : the biology of HPV and cervical oncogenesis was increasingly understood.
  19. 19.  Human papillomavirus interacts with squamous epithelia in 2 basic ways.
  20. 20.  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
  21. 21.  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).
  22. 22. Cervical Cytology
  23. 23.  First Bethesda workshop in 1988  Followed by another in 1991  Latest was in 2001
  24. 24.  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
  25. 25.  The Bethesda system recommends a specific format for cytology report including comments on : specimen adequacy general categorization interpretation/results
  26. 26.  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
  27. 27. 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
  28. 28.  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.
  29. 29. LOW GRADE SQUAMOUS INTRAEPITHELIAL LESION (CIN I & HPV)
  30. 30. Moderate Dysplasia (CIN II)
  31. 31. Human Papilloma Virus (HPV) Ancillary Tests
  32. 32.  Ancillary tests such as HPV testing HPV Digene (+ or -) Molecular PCR testing : Sub-typing  P16 immunohistochemistry  Automated screening  recommendations
  33. 33. Histology reporting of preinvasive lesions
  34. 34.  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.
  35. 35. The Lower Anogenital Squamous Terminology
  36. 36. -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
  37. 37. 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)
  38. 38. 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.
  39. 39.  Literature review(> 1000 articles)  Inclusion & exclusion criteria.  Data extraction.  Member’s expert opinions  Draft recommendations  Open comment period (15 Jan-15 Feb 2012)
  40. 40.  Recommendations were finalized and voted on at the consensus meeting (March 2012).
  41. 41.  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
  42. 42. HSIL vs. Immature inflamed squamous metaplasia
  43. 43. HSIL vs. Reparative atypia
  44. 44. P16 CIN 2
  45. 45.  Initiate action plans for implementation of the recommendations.  Disseminate, Implement & Monitor .  Effective communication  educational programs detailing the recommendations and their appropriate incorporation into practice
  46. 46.  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.
  47. 47. The work is not yet done.
  48. 48.  Definition of dysplasia  Bethesda 2001 for PAP smear reporting  Pathological reporting of preinvasive cervical lesions.  The LAST terminology
  49. 49. THANK YOU

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