New Diagnoses Need New Approaches: A Glimpse into the Near Future of Gynecologic Pathology

Transcription

1 New Diagnoses Need New Approaches: A Glimpse into the Near Future of Gynecologic Pathology United States and Canadian Academy of Pathology 102 nd Annual Meeting Baltimore, Maryland Christina S. Kong, M.D. Associate Professor & Director of Cytopathology Stanford University Department of Pathology Stanford, CA

2 Case 1: Clinical History 41 year old woman with ASC-US on recent cervical cytology and positive high-risk HPV test. Colposcopy with cervical biopsy performed

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9 p16 immunostain

10 Differential Diagnosis Reactive metaplasia Immature squamous metaplasia Transitional metaplasia High grade squamous intraepithelial lesion (HSIL) with metaplastic changes HSIL (CIN2) HSIL (CIN3)

11 Immature Squamous Metaplasia Proliferation of reserve (basal-type) cells High N:C ratios but uniform, round to oval nuclei and often prominent nucleoli Replaces and may undermine endocervical columnar mucosa No cellular crowding or disorganization Can have high mitotic figures but not abnormal

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15 Transitional Metaplasia Associated with atrophy but can be seen in premenopausal women Occurs in transformation zone; may extend into endocervical glands Hyperplastic mucosa, resembling urothelium Weir 1997; Duggan 2000

16 Transitional Metaplasia Uniform, oval nuclei with longitudinal grooves Vertically oriented nuclei (deep)or streaming (superficial) Mitotic figures rare Perinuclear halos common

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20 High-grade SIL Atypical high N:C cells CIN2: Involves 1/3-2/3 epithelium CIN3: Involves >2/3 epithelium High mitotic figures Architecture Crowding, disorderly arrangement Loss of maturation Loss of polarity

21 HSIL (CIN3) severe dysplasia

22 HSIL (CIN2) moderate dysplasia Figure C2: CIN2

23 Reproducibility Poor reproducibility for diagnosis of CIN2 ALT Study: CIN2: 43.4% CIN3: HSIL: 77-80% Guanacaste, Costa Rica study: CIN2: 13-31% agreement CIN3: 81-84% agreement CIN2 equivocal diagnosis that encompasses both CIN1 and CIN3 Stoler 2001; Carreon 2007

24 HSIL with Metaplastic Changes Difficult to distinguish from reactive metaplasias - may undermine columnar mucosa Helpful features: Hyperchromasia Nuclear pleomorphism Mitotic figures in upper half of mucosa Loss of polarity

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26 Figure 1-6

27 The LAST Project The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions sponsored by CAP & ASCCP Recommendations for use of biomarkers in HPV-associated squamous lesions Recommendations for unified terminology for preinvasive squamous lesions and superficially invasive SCC across the lower anogenital tract Darragh 2012

28 LAST: HPV-related Biomarkers Multiple markers and methodologies p16 only marker with sufficient data for analysis of utility ProEx C and Ki67 showed similar results to p16 but with insufficient data for independent analysis Data does not support use of multiple markers

29 p16 Recommendations USE: HSIL vs. benign mimic Confirm diagnosis of CIN2 Disagreement about diagnosis of HSIL Negative biopsy with prior high-risk cytology (HSIL, ASC-H, AGC-NOS, ASC- US/HPV16+)

30 p16 Immunohistochemistry Positive stain = strong and diffuse block positive nuclear or nuclear and cytoplasmic staining of basal layer and extending up at least 1/3 of epithelial thickness Correlates with presence of HR-HPV and diagnosis of dysplasia Grading of dysplasia based primarily on H&E morphology

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32 HSIL (CIN2) p16+

33 Figure 1-4

34 HSIL (CIN2) p16+

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36 Transitional metaplasia p16(-)

37 p16 Recommendations DO NOT USE: LSIL vs. benign mimic Morphology unequivocally diagnostic of LSIL (CIN1), HSIL (CIN3), or negative for dysplasia

38 LAST Terminology Low-grade Squamous Intraepithelial Lesion (CIN 1) High-grade Squamous Intraepithelial Lesion (CIN 2) or (CIN 3) or (CIN 2-3) Squamous Intraepithelial Lesion, indeterminate grade (CIN 1-2)

39 Figure 1-3

40 High-grade Squamous Intraepithelial Lesion (CIN2) with metaplastic changes FINAL DIAGNOSIS