Cervix
Premalignant / preinvasive lesions - cytology
ASCUS (cyto)
Authors: Joseph Reznicek, M.D., Bonnie Choy, M.D.
Editorial Board Members: David B. Chapel, M.D., Marc Pusztaszeri, M.D.
Last author update: 29 April 2022
Last staff update: 25 January 2023
Copyright: 2006-2023, PathologyOutlines.com, Inc.
PubMed search: ASCUS
Table of Contents
Definition / general | Essential features | CTP coding | Sites | Clinical features | Laboratory | Management | Diagrams / tables | Cytology description | Cytology images | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Reznicek J, Choy B. ASCUS (cyto). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixcytologyatypicalsquamouscells.html. Accessed September 22nd, 2023.
Definition / general
- Atypical squamous cells of undetermined significance (ASCUS) refers to cellular changes that are suggestive but not diagnostic of low grade squamous intraepithelial lesion (LSIL) (Nayar: The Bethesda System for Reporting Cervical Cytology, 3rd Edition, 2015)
Essential features
- Criteria based on the 2014 Bethesda System for Reporting Cervical Cytology (Nayar: The Bethesda System for Reporting Cervical Cytology, 3rd Edition, 2015)
- Nuclei are approximately 2.5 - 3.0x the area of the nucleus of a normal intermediate squamous cell
- Minimal nuclear hyperchromasia and irregularity in chromatin distribution or nuclear shape
- Differential diagnosis includes LSIL, as well as changes that are not related to HPV infection and neoplasia
CTP coding
- For screening Pap tests (routine and high risk): smear
- For screening Pap tests (routine and high risk): liquid based
- Manual screening only
- ThinPrep Imager assisted screening
- FocalPoint (instrument only)
- FocalPoint (with manual screening)
- For diagnostic Pap tests: smear
- For diagnostic Pap tests: liquid based
- Manual screening only
- ThinPrep Imager assisted screening
- FocalPoint (instrument only)
- FocalPoint (with manual screening)
Sites
- Cervix, vagina, anus
Clinical features
- Accounts for 4.3% (median) of all Pap test results (Arch Pathol Lab Med 2010;134:331)
- Accounts for > 90% of ASC interpretations in most cytopathology laboratories (while atypical squamous cells cannot exclude a high grade squamous intraepithelial lesion [ASC-H] accounts for < 10%)
- 40 - 50% rate of high risk HPV positivity in women with ASCUS interpretation (Am J Obstet Gynecol 2003;188:1383, Am J Clin Pathol 2007;128:1010)
- 10 - 20% of women with ASCUS are proven to have underlying high grade squamous intraepithelial lesion (HSIL) (Am J Obstet Gynecol 2003;188:1383)
- 5 year risks for HSIL and cancer: ASCUS with negative HPV, 1.1%; ASCUS with positive HPV, 18% (N Engl J Med 2013;369:2324)
Laboratory
- HPV testing may be used as part of screening, triage and surveillance (J Am Soc Cytopathol 2020;9:291)
- Initially endorsed as triage test for ASCUS cytologic result in 2001
- Approved for:
- Cotesting in 2003
- Postcolposcopic / posttreatment follow up and risk stratification using partial genotype (HPV 16 / 18) in 2006
- Primary screening option in 2014
- 5 FDA approved HPV testing platforms:
- Qiagen Hybrid Capture
- Hologic Cervista
- Hologic Aptima
- Roche Cobas: FDA approved for primary screening
- Becton Dickinson Onclarity: FDA approved for primary screening
- Note: HPV result plays no role in the cytologic examination or grading of squamous intraepithelial lesion (SIL)
Management
- 2019 American Society of Colposcopy and Cervical Pathology (ASCCP) risk based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors (J Low Genit Tract Dis 2020;24:102)
- Personalized risk based recommendations based on a patient's risk of CIN 3+, as determined by a combination of current results and past history (including unknown history)
- Unlike prior versions, the 2019 guidelines do not provide management algorithms for most screening and triage scenarios
- For patients < 25 years:
- Refer to the management algorithm in the Diagrams / tables section
- For patients ≥ 25 years:
- Management is now based on risk estimates
- Use the website or mobile app to calculate risk estimate and determine management recommendation for individual patient (ASCCP: ASCCP Management Guidelines Web Application [Accessed 25 April 2022], ASCCP: Mobile App - ASCCP Risk Based Management Consensus Guidelines [Accessed 25 April 2022])
- 5 year risks for histologic HSIL and cancer for cytology samples interpreted as ASCUS with high risk HPV testing (N Engl J Med 2013;369:2324):
- ASCUS with negative HPV, 1.1%
- ASCUS with positive HPV, 18%
- Reference: J Low Genit Tract Dis 2020;24:102
Cytology description
- Diagnostic criteria (Nayar: The Bethesda System for Reporting Cervical Cytology, 3rd Edition, 2015)
- Size of nuclei approximately 2.5 - 3.0x the area of the nucleus of a normal intermediate squamous cell (approximately 35 square microns) or 2.0x the size of a metaplastic squamous cell nucleus (approximately 50 square microns)
- Slight increase in nuclear to cytoplasmic ratio
- Minimal hyperchromasia and irregularity in chromatin distribution or shape
- Nuclear enlargement, hyperchromasia or irregular contours associated with dense orangeophilic cytoplasm (atypical parakeratosis)
- Cytoplasmic changes suggestive of HPV cytopathic effect (incomplete koilocytosis), such as ill defined cytoplasmic halos or cytoplasmic vacuoles resembling koilocytes but without or with minimal nuclear changes
- Cells that may be classified as ASCUS typically have the size and shape of superficial or intermediate squamous cells but can also be round or ovoid that are a third the size of superficial cells (resembling larger metaplastic or small intermediate cells)
- Common patterns
- Atypical parakeratosis: cells with dense orangeophilic cytoplasm with some degree of nuclear atypia or arranged in 3 dimensional clusters
- Atypical repair: reparative changes with some degree of cytology atypia, including cellular overlap, dyscohesion, anisonucleosis
- Postmenopausal atypia: atrophic cells with some nuclear enlargement and hyperchromasia
Cytology images
Contributed by Joseph Reznicek, M.D., Bonnie Choy, M.D. and Lucy Jager, M.D.
Enlarged nuclei
Slight hyperchromasia
Atypical parakeratosis
Radiation changes
LSIL
Pseudokoilocytes
Herpes cytopathic effect
Images hosted on other servers:
WHO digital atlas
Sample pathology report
- Statement of adequacy:
- Satisfactory for evaluation
- Transformation zone component present
- Final interpretation:
- Epithelial cell abnormality, squamous cell
- Atypical squamous cells of undetermined significance (ASCUS)
Differential diagnosis
- Low grade squamous intraepithelial lesion (LSIL):
- Nuclear atypia, including nuclear enlargement (> 3x the area of normal intermediate nuclei), hyperchromasia, anisonucleosis, coarsely granular, smudgy, densely opaque chromatin, variable nuclear membranes, binucleation and multinucleation
- Pseudokoilocytosis:
- Small perinuclear halo without any significant nuclear abnormality
- Seen in association with reactive, inflammatory conditions like Trichomonas infection
- Glycogen cytoplasmic vacuolization appears yellow, refractile and cracked
- Small perinuclear halo without any significant nuclear abnormality
- Herpes cytopathic effect:
- Early herpes cytopathic effect shows nuclear enlargement and degenerative chromatin but lacks other changes of the HPV cytopathic effect (koilocytosis)
- Cells with classic features of herpes (multinucleation, nuclear molding, margination of chromatin and clear, ground glass nuclei) will also be present
- Radiation changes:
- Large, bizarre cells with normal N/C ratio
- Binucleation and multinucleation common
- Cytoplasmic vacuolization and polychromasia (2 toned) without perinuclear clearing and peripheral condensation
- Reactive endocervical cells:
- Enlarged, polygonal shaped cell with prominent nucleolus and granular cytoplasm
- Usually seen with other more readily recognizable endocervical cells
Board review style question #1
What is the most likely interpretation of this cervical cytology specimen from a 25 year old woman?
- Atypical glandular cells, NOS
- Atypical squamous cells of undetermined significance (ASCUS)
- Benign reactive squamous cells
- High grade squamous intraepithelial lesion (HSIL)
Board review style answer #1
B. Atypical squamous cells of undetermined significance (ASCUS)
Comment Here
Reference: ASCUS cytology
Comment Here
Reference: ASCUS cytology
Board review style question #2
A cervical cytology specimen shows cells with some degree of nuclear atypia, concerning but not definitive for the diagnosis of low grade squamous intraepithelial lesion. What is the best interpretation?
- Atypical squamous cells - cannot exclude a high grade squamous intraepithelial lesion (ASC-H)
- Atypical squamous cells of undetermined significance (ASCUS)
- Benign reactive squamous cells
- Low grade squamous intraepithelial lesion (LSIL)
Board review style answer #2
B. Atypical squamous cells of undetermined significance (ASCUS)
Comment Here
Reference: ASCUS cytology
Comment Here
Reference: ASCUS cytology
