Cytologic features
Normal and nonneoplastic findings

Minor changes: 4 August 2020

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PubMed search: Benign cytologic features cervix

Shuyue Ren, M.D., Ph.D.
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Cite this page: Ren S. Normal and nonneoplastic findings. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixcytologybenignfeatures.html. Accessed January 17th, 2021.
Definition / general
  • Normal and nonneoplastic findings in cervical components of Pap test for routine screening for cervical cancer
  • Preparations: conventional and liquid based (ThinPrep and SurePath)
Essential features
  • Normal cellular elements:
    • Squamous cells:
      • Superficial cells
      • Intermediate cells
      • Parabasal and basal cells
    • Endocervical cells, endometrial cells and lower uterine segment cells
  • Nonneoplastic findings:
    • Variations, reactive changes and inflammatory cells
  • Pap smear / test
ICD coding
  • ICD-10: Z01.419 - encounter for gynecological examination (general) (routine) without abnormal findings
Cytology - normal
  • Squamous cells: ectocervical stratified epithelium
    • Superficial cells:
      • Outermost layer
      • Small highly condensed / pyknotic nucleus
      • Abundant, usually eosinophilic cytoplasm
    • Intermediate cells:
      • Middle layer
      • Larger nucleus with finely granular chromatin and often longitudinal groove
      • Abundant cytoplasm
    • Parabasal and basal cells:
      • Also called immature squamous metaplastic cells
      • Least mature cells
      • Deep layer
      • Nucleus larger than intermediate cells
      • Scant cytoplasm, more granular and dense
      • High nuclear to cytoplasmic ratio
      • Hallmark of atrophy:
        • Low estrogen state: premenarche, postpartum, postmenopause, Turner syndrome and postoophorectomy
  • Endocervical cells:
    • Picket fence or honeycomb configuration
    • Mucin producing glandular cells with polarity, nuclei at one end and mucus at the opposite end
    • Nucleus slightly larger than intermediate cell nucleus
    • Nucleus with finely granular and even chromatin and small nucleoli
    • Vacuolated or granular cytoplasm
  • Endometrial cells and lower uterine segment cells:
    • Glandular cells, tight clusters or isolated
    • Smaller than endocervical cells
    • Nucleus equal or slightly smaller than intermediate cell nucleus, dense heterogeneous chromatin
    • Scant cytoplasm, dense or vacuolated
    • Exodus: exfoliated dense aggregates of endometrial stroma cells with a surrounding layer of glandular epithelium
Cytology - nonneoplastic findings
  • Variations:
    • Bland nuclear enlargement
    • Squamous metaplasia: replacement of endocervical cells
      • Stimulated by trauma, infection or inflammation
      • Spectrum of morphologic changes
      • Immature parabasal-like cells
      • Intermediate / superficial cells-like squamous cells
    • Hyperkeratosis:
      • Anucleate mature polygonal squamous cells
      • Empty spaces or ghost nuclei
    • Parakeratosis:
      • Miniature superficial squamous cells with dense eosinophilic cytoplasm
      • Small and dense nuclei
    • Tubal metaplasia (Diagn Cytopathol 1993;9:98):
      • Replacement of endocervical epithelium by fallopian tube-like epithelium with cilia and terminal bar
    • Pregnancy related changes:
  • Reactive changes:
    • Associated with inflammation, radiation therapy and intrauterine contraceptive device
    • Glandular cells status post hysterectomy
  • Inflammatory cells:
    • Present in different conditions
    • Neutrophils, lymphocytes, plasma cells and histiocytes
  • Artifact:
    • Barr body: darkly stained body attached to nuclear membrane
    • Blue blobs: dark blue, rounded, amorphous masses
      • Condensed mucus, degenerated bare nuclei or precipitating hematoxylin
      • In postmenopausal women, represent parabasal / intermediate squamous cells with various degrees of degeneration (Acta Cytol 2000;44:547)
      • May have string of pearls appearance on ThinPrep in postmenopausal atrophy (Diagn Cytopathol 2010;38:233)
    • Cornflakes:
      • Brown artifact of air bubbles trapped on superficial squamous cells resulting in obscuring of nuclei
      • More common on conventional than liquid based preparations
      • It can be reversed by returning the slides through xylene and alcohol to water then restaining and recoverslipping
    • Degeneration / air drying artifact:
      • Degenerative type changes due to delay in transfer of cells to the slide, inflammation or atrophy
      • Cytoplasm is lost and moth eaten with vacuolization
      • Chromatin is clumped, hazy, smudged or indistinct
      • Chromatin rim has variable thickness and irregular contours but no sharp angles of malignancy
Cytology images

Contributed by Shuyue Ren, M.D., Ph.D.

Squamous cells, superficial

Squamous cells, intermediate

Squamous cells, parabasal and basal cells

Endocervical glandular cells

Endometrial cells

Endometrial cells: exodus

Squamous cells: bland enlargement



Tubal metaplasia

Squamous metaplasia


Abundant blood

Glandular cells status posthysterectomy

Reactive changes
associated with

Positive stains
Negative stains
  • Benign squamous cells: p16
Sample pathology report
  • Specimen adequacy:
    • Satisfactory for evaluation; endocervical cells / transformation zone component present
  • General categorization:
    • Negative for intraepithelial lesion or malignancy
Board review style question #1
A 35 year old woman presents for routine gynecological examination and Pap test is performed. What kind of squamous cells are predominantly present?

  1. Basal cells
  2. Intermediate cells
  3. Parabasal cells
  4. Superficial layer cells
Board review style answer #1
D. Superficial layer cells

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Reference: Normal and nonneoplastic findings
Board review style question #2

A 40 year old woman presents for routine gynecological examination and Pap test is performed. A tight cluster of cells is noted. By 2014 Bethesda System, how do you report the cluster of cells?

  1. Endocervical cells, not reported
  2. Endocervical cells, reported
  3. Exfoliated endometrial cells, not reported
  4. Exfoliated endometrial cells, reported
Board review style answer #2
C. Exfoliated endometrial cells, not reported. By 2014 Bethesda System, exfoliated endometrial cells should be reported in a woman 45 years of age or older.

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Reference: Normal and nonneoplastic findings
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