SQUAMOUS CELLS: Atypical squamous cells (ASC) - of undetermined significance (ASC-US) - cannot exclude HSIL (ASC-H)

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2 SQUAMOUS CELLS: Atypical squamous cells (ASC) - of undetermined significance (ASC-US) - cannot exclude HSIL (ASC-H)

3 ASC refers to cytologic changes suggestive of SIL, which are qualitativley or quantitatively insufficinet for definitive interpretation Three essential features: - squamous differentation - increased N/C - minimal nuclear hyperchromasia, chromatin clumping, irregularity, smudging or multinucleation ASC category is developed to designate the interpretation of an entire specimen, not individual cells

4 ASC does not represent single biologic entity. It subsumes changes related to oncogenic HPV infection and neoplasia as well as findings that suggest the possible presence of CIN and rarely carcinoma In USA, 50% of women with ASC are infected with HR HPV, and the remaining noninfected woman are not at increased risk.

5 Numerous non-neoplastic conditions, unrelated to HPV infection may produce cytologic mimics classified as ASC; including inflammation, air-drying, atrophy with degeneratio and other artifacts

6 This reporting category should be used VERY carefully and sparingly. It is reserved for minority of ASC cases, expected to represent less then 10 % of ASC, in which cytologic changes are suggestive of HSIL It warrants immediate colposcopy to exclude the presence of HSIL

7 When cells have diameter N:C ratios of greater than 50% AND There are doubts over the correct interpretation of the chromatin of the cells in question; The differential diagnosis lies between normal reactive / inflammatory changes to HSIL

8 The need to use this category is likely to arise when dealing with equivocal nuclear changes in immature metaplastic cells or in three dimensional groups

9 Only a few cells present suggestive of HSIL Immature cytoplasm Larger nuclei than normal metaplastics Some degree of Anisonucleosis Nuclear membrane irregularity Mild hyperchromasia

10 Hyperchromatic crowded groups where density makes difficult for evaluation Cellular clusters of both repair and epithelial abnormality Benign reparative sheets: cohesive, flat, streaming from one pole to the other Abnormal reparative groups show clustering, over crowding, loose cohesion, anisonucleosis, uneven chromatin distribution

11 Reactive/ inflammatory conditions Reparative sheets Histiocytes Atrophic groups These can be difficult to distinguish from abnormal

12 Small cells with high N/C, Atypical ( immature) metaplasia Chrowded sheet pattern

13 Cell occur singly or in small fragments of less then 10 cells May stream in mucus Size of metaplastic cells with nuclei time larger then normal N/C more then 50 % Nuclear abnormalities

14 Interpretation: ASC-H Cytomorphologic Criteria: Loosely cohesive metaplastic cells with increased N:C ratio. Explanatory Notes: Differential includes reactive/reparative metaplastic cells, and HSIL. Follow-up: Repeat cytology was ASC-US; Colpo biopsy showed CIN2 and LEEP was CIN3

15 Interpretation: NILM vs ASC-H Cytomorphologic Criteria: Less mature squamous cells/metaplastic cells with polygonal shape, and slightly enlarged nuclei with occasional nuclear contour irregularities. Explanatory Notes: Boundary of ASC-US and ASC-H; differential includes CIN 2.

16 Interpretation: ASC-H Cytomorphologic Criteria: Metaplastic cells with enlarged nuclei and nuclear contour irregularities showing variation in size, shape, and ratio of nuclear to cytoplasmic area. Explanatory Notes: Differential includes reactive/reparative metaplastic cells and HSIL.

17 Interpretation: ASC-H versus HSIL Cytomorphologic Criteria: Metaplastic cells with increased N:C ratios and nuclear contour irregularities. Follow-up: HSIL on repeat Pap; CIN3 on LEEP

18 Interpretation: NILM vs. ASC-H Cytomorphologic Criteria: Metaplastic cells, some with enlarged or slightly irregular nuclei. Explanatory Notes: Differential includes reactive/reparative metaplastic cells, and HSIL. Follow-up: High grade CIN was found on biopsy

19 Interpretation: NILM vs. ASC-H Metaplastic cells with enlarged, hyperchromatic nuclei

20 Interpretation: ASC-H Cytomorphologic Criteria: Metaplastic cells with increased N:C ratios and some nuclear contour irregularities. Follow-up: HSIL on repeat Pap; CIN3 on LEEP

21 A microbiopsy of crowded cells containing nuclei that may show loss of polarity or are difficult to visualize Dense cytoplasm, polygonal cell shape and fragments with sharp linear edges generally favour squamous over glandular differentation

22 Interpretation: ASC-H Cytomorphologic Criteria: Thick aggregate of loosely cohesive, overlapping cells containing enlarged nuclei with even chromatin, variation in size and shape and obscured cell boundaries. The cluster demonstrates poor preservation/ staining. Explanatory Notes: Possible interpretations include reactive endocervical and / or metaplastic squamous cells, HSIL, and AIS.

23 Interpretation: ASC-H Cytomorphologic Criteria: A hyperchromatic cells cluster, the nature of which may be difficult to ascertain in this atrophic specimen. Follow-up: Severe dysplasia (CIN 3)

24 Few squamous cells suggestive of a high-grade lesion (H-SIL): use ASC-H when you feel not confident in diagnosing H-SIL

25 Clinical History: 50 year old postmenopausal woman, prior abnormal Pap elsewhere Interpretation: ASC-H Cytomorphologic Criteria: Atypical keratinized cells with smudged chromatin present in an atrophic background. Cells are suggestive of a high grade lesion however poor preservation precludes definitive interpretation. Follow-up: Moderate dysplasia on repeat Pap smear and cervical biopsy after topical estrogen therapy

26 Clinical history: Post-Menopausal Interpretation: ASC-H Cytomorphologic Criteria: Immature cells have high N:C ratios and irregular nuclear contours. Explanatory Notes: Such cells may be seen in atrophy, but the differential includes a high grade lesion. Repeat sampling following a course of estrogen may clarify the findings.

27 Interpretation: ASC-H Cytomorphologic Criteria: Single small cell with abnormal nuclear chromatin and high N:C ratio surrounded by mature squamous cells. Follow-up: Patient was subsequently found to have squamous cell carcinoma

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30 Smear containing basal cells, arranged in Indian files, with enlarged and irregular nuclei and a dense chromatin, suggesting high grade SIL:ASC-H vs HSIL. (obj. 20x)

31 Interpretation: ASC-H vs reactive endocervicals Cytomorphologic Criteria: Main panel shows columnar and polygonal cells with dense cytoplasm and high N/C. Nuclear chromatin is granular with small chromocenters or nucleoli. Occasional nuclear grooves are seen. The insert on the lower left corner contains cells from another specimen that appear similar, but possess cytoplasm that is scant and less dense. Explanatory Notes: Differential includes reactive endocervicals and/or repair and HSIL. Follow-up: HPV negative