03 Asc H Medicolegal Austin

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A potpourri of ASC-H and related interpretations-
(Part III)

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  • 03 Asc H Medicolegal Austin

    1. 1. ASC-H: Quality Improvement, Ancillary HPV testing, and Medicolegal aspects 1) Highlight blinded review quality improvement technique employed at MWH to enhance ASC-H detection 2) medicolegal ramifications of disputed retrospective ASC-H interpretations. 3) Unpublished data on the usefulness of HPV testing in the largest series reported to date from MWH
    2. 2. Multiple Slide Blinded Reviews as a Quality Improvement Tool <ul><li>Identify Pap tests screened as negative or equivocally abnormal preceding subsequent diagnoses of CIN2/3, AIS, or cervical cancer. </li></ul><ul><li>Insert Pap tests of interest into 10-20 slide cytology challenge sets. </li></ul><ul><li>Ask staff cytotechnologists to rescreen and interpret all cases on anonymous answer sheets. </li></ul><ul><li>Review rescreening findings with staff along with histologic and cytologic follow-up. </li></ul>
    3. 3. Paps #1 and 2 Two Negative Paps Preceding CIN2 Biopsy Result
    4. 4. Original Review Pap#1 <ul><li>Date: 4/7/03 </li></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Negative for intraepithelial lesion or malignancy. </li></ul></ul><ul><ul><li>Inflammatory changes. </li></ul></ul>
    5. 6. What do you think? <ul><li>Negative </li></ul><ul><li>Cancer </li></ul><ul><li>Suspicious for cancer </li></ul><ul><li>HSIL </li></ul><ul><li>AGC (Atypical glandular cells) </li></ul><ul><li>ASC-H </li></ul><ul><li>LSIL </li></ul><ul><li>ASCUS </li></ul>
    6. 7. Blinded Cytotechnologist Review Results <ul><li>Negative: 9 </li></ul><ul><li>LSIL: 1 </li></ul><ul><li>ASC-US: 4 </li></ul>Retro-review Diagnosis knowing outcome: Atypical Squamous Cells cannot exclude HSIL (ASC-H)
    7. 8. Original Review Pap #2 <ul><li>Date: 3/26/04 </li></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Negative for intraepithelial lesion or malignancy. </li></ul></ul><ul><ul><li>Inflammatory changes. </li></ul></ul>
    8. 15. What do you think? <ul><li>Negative </li></ul><ul><li>Cancer </li></ul><ul><li>Suspicious for cancer </li></ul><ul><li>HSIL </li></ul><ul><li>AGC (Atypical glandular cells) </li></ul><ul><li>ASC-H </li></ul><ul><li>LSIL </li></ul><ul><li>ASCUS </li></ul>
    9. 16. Blinded Cytotechnologist Review Results <ul><li>Negative: 9 </li></ul><ul><li>ASC-US: 4 </li></ul>Retro-review Diagnosis knowing outcome: Atypical Squamous Cells cannot exclude HSIL (ASC-H)
    10. 17. Subsequent Surgical Pathology Result <ul><li>Date: 1/4/07 </li></ul><ul><li>Diagnosis: </li></ul><ul><ul><li>Cervical intraepithelial neoplasia 2 (CIN 2) </li></ul></ul>
    11. 18. Paps #3 and 4 Two Negative Paps Preceding CIN2 Biopsy Result
    12. 19. Original Review Pap #3 <ul><li>Date: 4/21/05 </li></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Negative for intraepithelial lesion or malignancy. </li></ul></ul><ul><ul><li>Repair. </li></ul></ul>
    13. 23. What do you think? <ul><li>Negative </li></ul><ul><li>Cancer </li></ul><ul><li>Suspicious for cancer </li></ul><ul><li>HSIL </li></ul><ul><li>AGC (Atypical glandular cells) </li></ul><ul><li>ASC-H </li></ul><ul><li>LSIL </li></ul><ul><li>ASCUS </li></ul>
    14. 24. Blinded Cytotechnologist Review Results <ul><li>Negative: 8 </li></ul><ul><li>Atypical glandular cells: 1 </li></ul><ul><li>ASC-H: 2 </li></ul><ul><li>ASC-US: 2 </li></ul>Retro-review Diagnosis knowing outcome: Atypical Squamous Cells cannot exclude HSIL (ASC-H)
    15. 25. Original Review Pap #4 <ul><li>Date: 6/1/06 </li></ul><ul><li>Diagnosis </li></ul><ul><ul><li>Negative for intraepithelial lesion or malignancy. </li></ul></ul><ul><ul><li>Adequate with cocci partially obscuring 50-75% of epithelial cells. </li></ul></ul>
    16. 33. What do you think? <ul><li>Negative </li></ul><ul><li>Cancer </li></ul><ul><li>Suspicious for cancer </li></ul><ul><li>HSIL </li></ul><ul><li>AGC (Atypical glandular cells) </li></ul><ul><li>ASC-H </li></ul><ul><li>LSIL </li></ul><ul><li>ASCUS </li></ul>
    17. 34. Blinded Cytotechnologist Review Results <ul><li>Negative: 2 </li></ul><ul><li>HSIL: 4 </li></ul><ul><li>ASC-H: 5 </li></ul><ul><li>ASC-US: 2 </li></ul>Retro-review Diagnosis knowing outcome: High-grade squamous intraepithelial lesion (HSIL)
    18. 35. Subsequent Surgical Pathology Result <ul><li>Date: 1/4/07 </li></ul><ul><li>Diagnosis: </li></ul><ul><ul><li>Cervical intraepithelial neoplasia 2 (CIN 2) </li></ul></ul>
    19. 36. Multiple Slide Blinded Review (MSBR) Conclusions <ul><li>Difficult to diagnose ASC-H cases may be best recognized only with the hindsight bias of later known histologic outcome. </li></ul><ul><li>Standard of practice- what a reasonable peer who do under similar circumstances- is different from hindsight bias-influenced retrospective review. </li></ul><ul><li>ASC Pap Litigation Guidelines state that a violation of the standard of practice can ONLY be confirmed with MSBR. </li></ul>
    20. 37. ASC-H and HPV Testing MWH Experience
    21. 38. <ul><li>Atypical squamous cells, cannot exclude HSIL ( ASC-H ) subcategory was introduced in the 2001 Bethesda System. </li></ul><ul><li>“ Atypical (immature) Metaplasia” : small cells with high N/C ratios. </li></ul><ul><li>“ Crowded Sheet Pattern” </li></ul>
    22. 39. Background <ul><li>Mimics : </li></ul><ul><ul><ul><li>Atrophy </li></ul></ul></ul><ul><ul><ul><li>Reactive/reparative change </li></ul></ul></ul><ul><ul><ul><li>Naked nuclei </li></ul></ul></ul><ul><ul><ul><li>Parakeratosis </li></ul></ul></ul><ul><ul><ul><li>Immature metaplastic cells </li></ul></ul></ul>
    23. 40. Background <ul><li>Incidence of ASC-H: 0.22% - 1.09% </li></ul><ul><li>Reported rate of CIN 2/3 on histologic follow-up: 12.2% - 68.2% </li></ul><ul><li>Reported rates of high-risk HPV + in ASC-H: 33.3% - 85.6% </li></ul>
    24. 41. Background <ul><li>2006 Consensus Follow-up Guidelines from the American Society for Colposcopy and Cervical Pathology (ASCCP) </li></ul><ul><ul><li>ASC-H go to colposcopy </li></ul></ul><ul><ul><li>Based on data from the ASCUS / LSIL Triage Study (ALTS) </li></ul></ul>
    25. 42. Background on ALTS <ul><li>All patients had previous ASC-US or LSIL pap on conventional smears based on 1991 Bethesda terminology. </li></ul><ul><li>Participants had liquid-based Pap and HPV testing. </li></ul><ul><li>Diagnosis was made by 4 pathologists </li></ul><ul><ul><ul><li>110 ASC-H cases; 84% + hrHPV </li></ul></ul></ul><ul><li>Younger than average patient population. - Median age 24 years old. </li></ul>
    26. 43. Background <ul><li>2001 ASCCP guidelines for ASC-US recommend “reflex” HPV DNA testing when liquid-based cytology is used. </li></ul><ul><ul><li>~ 85% of ASC-US paps get reflex HPV testing . </li></ul></ul><ul><li>Some studies suggest that HPV testing may help triage ASC-H patients and reduce the number of colposcopies. </li></ul>
    27. 44. GOALS <ul><li>Evaluate: </li></ul><ul><ul><li>ASC-H paps </li></ul></ul><ul><ul><li>High-risk HPV (hrHPV) DNA test results </li></ul></ul><ul><ul><li>Histologic follow-up </li></ul></ul><ul><ul><li>Presence or absence of endocervical/ transformation zone (EC / TZ) </li></ul></ul><ul><ul><ul><li>Affect on detection of CIN </li></ul></ul></ul><ul><ul><ul><li>Affect on hrHPV detection </li></ul></ul></ul>
    28. 45. Materials and Methods <ul><li>July 1, 2005 – December 31, 2007 </li></ul><ul><li>ThinPrep Imaging System (TIS) was used </li></ul><ul><ul><li>ASC-H called when small, rounded, squamous cells with dense limited cytoplasm, enlarged and euchromatic or hyperchromatic nuclei and some degree of nuclear membrane irregularities were identified </li></ul></ul><ul><ul><li>EC/TZ status based on Bethesda 2001. </li></ul></ul><ul><li>High-risk HPV DNA testing via Hybrid Capture II (HC2) </li></ul><ul><ul><li>Ordered by clinicians as reflex for ASC pap, women > 30 y.o., or HPV regardless. </li></ul></ul>
    29. 46. Materials and Methods <ul><li>Histologic follow-up </li></ul><ul><ul><li>Endocervical curettage </li></ul></ul><ul><ul><li>Cervical biopsy </li></ul></ul><ul><ul><li>Cervical conization (loop or cold knife cone) </li></ul></ul><ul><li>Two surgical pathologists confirmed CIN diagnoses. </li></ul><ul><ul><li>CIN1 </li></ul></ul><ul><ul><li>CIN 2 or higher (CIN2/3) </li></ul></ul><ul><li>Stratified according to age and EC/TZ status. </li></ul>
    30. 47. Results <ul><li>ASC-H interpretations </li></ul><ul><ul><li>1646 (1619 ThinPrep, 27 conventional) </li></ul></ul><ul><ul><li>0.59% of all paps </li></ul></ul><ul><ul><ul><li>0.60% in TP, 0.38% in conv. </li></ul></ul></ul><ul><ul><li>1187 (of TP) 73.3% had hrHPV testing done </li></ul></ul><ul><li>Presence or absence of EC/TZ made no difference with regard to hrHPV DNA detection or detection of CIN 2/3 </li></ul>
    31. 49. Results The difference in hrHPV + was significant between women <40 y.o. and women > 40 y.o.
    32. 50. Results 926 with ASC-H & hrHPV testing 421 No histology 505 w/ at least 1 cervical bx * 257 (50.9%) hrHPV + 248 (49.1%) hrHPV - * 101 women had two or more biopsies
    33. 51. Results 257 (50.9%) HPV + 248 (49.1%) HPV - 160 (62.3%) CIN 35 (14.1%) CIN
    34. 52. Results <ul><li>Cumulative CIN detection rate was 38.6% (195/505) </li></ul><ul><li>CIN 2/3 in 87 (17.2%) of 505 ASC-H & hrHPV tested patients </li></ul>
    35. 53. Results <ul><li>Statistical difference (P < .001) between hrHPV+ w/ CIN 2/3 and hrHPV – w/ CIN 2/3. </li></ul><ul><li>Women 30 -39 y.o. w/ + hrHPV had the greatest risk. </li></ul><ul><li>4 women had AIS; all were hrHPV + </li></ul>
    36. 54. Results (Table 4) <ul><li>35.8% of HPV+ women < 40 y.o. had CIN 2/3; </li></ul><ul><li>20.8% of HPV+ women > 40 y.o. had CIN 2/3 </li></ul>
    37. 55. Results <ul><li>ASC-H PPV of CIN2/3 = 17.2% </li></ul><ul><li>ASC-H and + hrHPV PPV of CIN2/3 = 32.7% </li></ul><ul><li>ASC-H and – hrHPV NPV of no CIN2/3 = 98.8% </li></ul>
    38. 56. ASC-H w/ reflex hrHPV Testing <ul><li>< 40 y.o. </li></ul><ul><li>Sensitivity 96.1% </li></ul><ul><li>Specificity 54% </li></ul><ul><li>PPV 35.8% </li></ul><ul><li>NPV 98.1% </li></ul><ul><li>< 40 y.o . </li></ul><ul><li>100% </li></ul><ul><li>68.4% </li></ul><ul><li>20.8% </li></ul><ul><li>100% </li></ul>
    39. 57. Comment CAP interlaboratory comparison program
    40. 58. Comment <ul><li>Some abstracts report increased ASC-H reporting with the use of the ThinPrep Imaging System (TIS) </li></ul><ul><ul><li>Decreased detection of hr HPV </li></ul></ul><ul><ul><li>Decreased detection of CIN 2/3 </li></ul></ul>
    41. 59. Comment ALTS
    42. 60. Why so much variability in hrHPV detection rates? <ul><li>Differences in cytologic interpretation threshold for ASC-H </li></ul><ul><li>Undercalling of HSIL </li></ul><ul><li>Overcalling of ASC-H as HSIL </li></ul><ul><li>Overcalling metaplastic cells as ASC-H </li></ul><ul><li>Different patient populations </li></ul><ul><ul><li>Rate of hrHPV + varies from 2.9% (current study) - 32.7% (ALTS) </li></ul></ul><ul><ul><li>ALTS median age 24 y.o.; this study median age 30 y.o. </li></ul></ul>
    43. 61. Summary of this study <ul><li>Significant difference in detection of CIN in + hrHPV than negative. </li></ul><ul><li>The negative predictive value of – hrHPV in ASC-H was 100% in women > 40 y.o. </li></ul><ul><li>Highest CIN 2/3 detection rate was in women 30-39 y.o. with ASC-H and + hrHPV </li></ul>
    44. 62. Conclusions <ul><li>Using both Pap test and high-risk HPV DNA testing allows for effective risk stratification of patients: </li></ul><ul><ul><li>HPV + to colposcopy </li></ul></ul><ul><ul><li>HPV – to follow-up with regular Pap and hrHPV testing. </li></ul></ul>

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