Dr layla abdullah cytology & patholog
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Dr layla abdullah cytology & patholog







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Dr layla abdullah cytology & patholog Dr layla abdullah cytology & patholog Presentation Transcript

  •  Preinvasive lesions ( definition)  Historical review of terminologies  The latest cytological terminology : The 2001 Bethesda System for reporting of PAP smears .  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). View slide
  •  Definition: Derived from the Greek word DYS for ‘‘bad’’ and PLASIA for ‘‘molding’’ used in many areas of medicine to describe a nonmalignant process. View slide
  •  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
  •  HPV related ( Serotypes: High risk: 16, 18, 31, and 33)  Integration of viral genes into host genome inactivate p53 and retinoblastoma tumor suppressor genes.
  • 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) : 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 does.
  •  ( 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.
  • 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
  •  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
  • 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. 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%
  •  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 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
  •  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).
  • 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 participated  Clinicians, pathologists, cytopathologists, cytotechnologists, patient’s advocates, public organizations
  •  The Bethesda system recommends a specific format for cytology report including comments on : specimen adequacy general categorization interpretation/results
  •  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
  • 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
  •  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.
  • 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  Automated screening  recommendations
  • Histology reporting of preinvasive lesions
  •  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.
  • The Lower Anogenital Squamous Terminology
  • -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
  • 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)
  • 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.
  •  Literature review(> 1000 articles)  Inclusion & exclusion criteria.  Data extraction.  Member’s expert opinions  Draft recommendations  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 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
  • 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 communication  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.
  • The work is not yet done.
  •  Definition of dysplasia  Bethesda 2001 for PAP smear reporting  Pathological reporting of preinvasive cervical lesions.  The LAST terminology