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Atypia / premalignant / preinvasive lesions

Atypical squamous cells of undetermined significance (ASC)

Reviewer: Marilin Rosa, M.D., University of Florida (see Reviewers page)
Revised: 3 April 2014, last major update June 2011
Copyright: (c) 2006-2012, PathologyOutlines.com, Inc.


● May be neoplastic (HPV related, LSIL, HSIL) or reactive


● Formerly called ASCUS
● ASC is subdivided into atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot rule out a high grade lesion (ASC-H)

Clinical features

● In cervical smears, often related to SIL, now or at later biopsy (Mod Pathol 1994;7:920)
● Poor reproducibility for this diagnosis
● Typical ASC-US/SIL diagnostic ratio for a laboratory is 3:1; often lower for liquid based cytology
● HPV testing is recommended after ASC-US diagnosis (Gynecol Oncol 2005;99:S7, J Natl Cancer Inst 2002;94:102, Am J Clin Pathol 2011;135:468); may also be helpful for ASC-H diagnosis (Cancer 2005;108:32), particularly if result is negative (Cancer 2005;105:457)
● For liquid based cytology diagnoses of ASC-US, reprocessing of residual material often causes reclassification to LSIL or HSIL (Diagn Cytopathol 2005;33:434)
● Higher risk for SIL in HIV+ women (Clin Infect Dis 2006;42:855)


● Repeat cytology, colposcopy, or perform DNA testing for high risk HPV subtypes according to age group or previous history of dysplasia

Cytology description

● Nuclear changes are more marked than reactive, less than LSIL
● Nucleus is 2.5-3x size of intermediate cell nucleus or 1.5x size of mature metaplastic cell nucleus
● In perimenopausal women (40-55 years), cells with bland nuclear enlargement (2-3x size of intermediate cell nuclei), smooth nuclear membranes and fine chromatin are likely to be negative for SIL/malignancy (Am J Clin Pathol 2005;124:58)

Cytology images

Various images

Cytologic changes NOT typical of ASC-US

Mild nuclear enlargement

Nuclear enlargement with atrophy

Nuclear enlargement with hyperchromasia and irregular nuclear membranes

ASC-US possibly LSIL




Degenerative atypical cells

Additional references

Mod Pathol 2000;13:252

End of Cervix-cytology > Atypia / premalignant / preinvasive lesions > Atypical squamous cells of undetermined significance (ASC)

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