Squamous cell lesions and cancer

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1 Squamous cell lesions and cancer

2 TBS 2001

3 Low-grade squamous intraepithelial lesion (LSIL) TBS 2001, BSCC: cellular changes associated with HPV (cytopathic thi effect) and mild dysplasia Muenchner Nomenklatur II Cytopathic effect: II Mild dysplasia: IIID together with moderate dysplasia

4 LSIL Mod. da Doorbar G.Negri, AP Bolzano

5 LSIL 85% are associated with HR-HPV HPV 70% regress spontaneously within 2 years 15-25% have a histology of CIN2+

6 Low-grade squamous intraepithelial lesion (LSIL) Histologically: Condyloma, mild dysplasia, CIN1 Lack of maturation in the lower third of the epithelium Koilocytes may be present in the upper epithelial layers G.Negri, Pathologie Bozen

7 Low-grade squamous intraepithelial lesion (LSIL) Large mature epithelial cells, single or in sheets Nuclear enlargement more than 3x; hyperchromasia is common, granular or smudged chromatin, nucleoli absent. Nuclear membrane usually smooth or slightly irregular. Multinucleation may be present. Koilocytosis: perinuclear cavitation may be present. Must be associated with nuclear atypia

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9 G.Negri, AP Bolzano

10 G.Negri, AP Bolzano

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14 G.Negri, AP Bolzano

15 ASC-US Superficial or intermediate cells DD LSIL Enlarged nuclei (2,5-3x) Minimal hyperchromasia and shape irregularity HPV test may be useful G.Negri, AP Bolzano

16 HSIL Mod. da Doorbar

17 High-grade squamous intraepithelial lesion (HSIL) Histologically: moderate and severe dysplasia, yp CIN2 and CIN3 Maturation completely lost or only evident in the upper third of the epithelium. Particularly l in CIN2, Koilocytes and parakeratosis on the surface may be present in the upper epithelial layers

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19 High-grade squamous intraepithelial lesion (HSIL) TBS 2001, BSCC: moderate and severe dysplasia, carcinoma in-situ it (CIN2-3) Muenchner Nomenklatur II Moderate dysplasia: IIID Severe dysplasia: IV

20 High-grade squamous intraepithelial lesion (HSIL) Medium-sized to small epithelial cells, single or in sheets, in CP occasionally with indian filing Variable nuclear enlargement, with increase of the n/c ratio. Variability of shape and size are typical. Deep indentations and grooves of the nuclear membrane are pathognomonic. Hyperchromasia is typical, however hypochromatic HSILs may occur. Chromatin may be fine or coarsely granular, nucleoli are usually absent Cytoplasm may have metaplastic features.

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24 G.Negri, AP Bolzano

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26 G.Negri, AP Bolzano

27 G.Negri, Pathologie Bozen

28 G.Negri, AP Bolzano

29 G.Negri, AP Bolzano

30 G.Negri, AP Bolzano

31 Pale HSIL

32 HSIL with metaplastic features

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35 ASC-H -usually few abnormal small cells with slightly enlarged nuclei - DD metaplastic cells G.Negri, AP Bolzano G.Negri, AP Bolzano

36 HSIL dd AIS

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39 SIL of indeterminate grade G.Negri, AP Bolzano

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44 Cervical carcinogenesis HPV infection Productive phase L1 Disregulation - proliferation p16, HPV RNA, proliferation markers

45 L1 P16/Ki67

46 Value of p16(ink4a) as a marker of progression/regression in cervical intraepithelial neoplasia grade 1. del Pino M, Garcia S, Fusté V, Alonso I, Fusté P, Torné A, Ordi J. Am J Obstet Gynecol Nov;201(5):488.e1-7. OBJECTIVE: The objective of this study was to evaluate the usefulness of p16(ink4a) staining to classify cervical intraepithelial neoplasia grade 1 according to its progression/regression risk. STUDY DESIGN: Patients with a histologic diagnosis of cervical intraepithelial neoplasia grade 1 were prospectively recruited (n = 138). Simultaneous detection of high-risk human papillomaviruses and p16(ink4a) evaluation were performed. Follow-up was conducted every 6 months by cytology and colposcopy and annually by high-risk human papillomavirus testing, for at least 12 months (mean, 29.0). Progression was defined d as a histologic i diagnosis i of cervical intraepithelial neoplasia grades 2-3, regression as a negative cytology and high-risk human papillomaviruses, and persistence as a cytologic result of low-grade squamous intraepithelial lesions and/or a positive test for high-risk human papillomaviruses. RESULTS: Progression was observed in 14 women (10.1%), 66 (47.6%) regressed, and 58 (42.0%) had a persistent disease. p16(ink4a) was positive in 77 (55.8%) initial biopsy specimens. Progression to cervical intraepithelial neoplasia grades 2-3 was identified d in 14 of 77 (18.2%) women with positive and none of 61 (0.00%) women with negative p16(ink4a) immunostaining (P <.001). CONCLUSION: p16(ink4a) negative cervical intraepithelial neoplasia grade 1 lesions rarely yprogress and may benefit from a less intensive follow-up.

47 HSIL with features suspicious for invasion HSIL with high atypia or keratinization without tumor diathesis Features suggesting g tumor diathesis in classical HSIL G.Negri, Pathologie Bozen

48 Squamous cell carcinoma Irregular aggregates g and atypical single cells Marked atypia with irregular cell and nuclear shape. Keratinization may be present. Irregular chromatin with nuclear clearing and nucleoli, li particularly l in nonkeratinizing cancer. Tumor diathesis particularly in non-keratinizing cancer. G.Negri, Pathologie Bozen

49 G.Negri, AP Bolzano

50 G.Negri, AP Bolzano

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52 G.Negri, AP Bolzano

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57 Tumor diathesis CP LBC G.Negri, Pathologie Bozen

58 G.Negri, Pathologie Bozen

59 G.Negri, Pathologie Bozen

60 G.Negri, AP Bolzano

61 G.Negri, AP Bolzano

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