Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Cytology - normal | Cytology - nonneoplastic findings | Cytology images | Positive stains | Negative stains | Sample pathology report | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Ren S. Normal and nonneoplastic findings. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixcytologybenignfeatures.html. Accessed December 24th, 2024.
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
- Squamous cells:
- Nonneoplastic findings:
- Variations, reactive changes and inflammatory cells
Terminology
- 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
- Superficial cells:
- 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:
- Navicular cells:
- Variant of intermediate cells with boat-like appearance
- Incomplete maturation of the squamous epithelium associated with pregnancy, postpartum, contraceptive use, androgenic atrophy and estrogen in men (Diagn Cytopathol 2000;23:161, Cancer 2002;96:74)
- Ellipsoid (boat shaped) squamous epithelial cells with cyanophilic / eosinophilic cytoplasm due to intracytoplasmic glycogen (golden, refractile and granular)
- Eccentric nuclei and thickened folded cell borders
- Can form dense clusters
- Decidual cells (Diagn Cytopathol 2013;41:886):
- Present in pregnancy, during the postpartum period, oral contraceptives and progestin releasing intrauterine devices (IUDs)
- Derived from hormonally stimulated endocervical or endometrial stroma containing abundant glycogen and glycoprotein
- Singly and rarely small clusters, the size of mature squamous cells
- Ill defined cytoplasm is abundant, granular or finely vacuolated
- Nuclear with prominent basophilic nucleoli, fine granular evenly distributed chromatin and smooth membrane
- Cytotrophoblast and syncytiotrophoblast:
- Cytotrophoblastic cells:
- Derived from the placenta in late pregnancy and postpartum
- Typically single cells, occasionally in small clusters
- May resembling small squamous metaplastic or endometrial cells, as well as high grade squamous intraepithelial lesion cells
- Small cells with enlarged nuclei, high nuclear to cytoplasmic ratios, hyperchromasia with evenly distributed chromatin
- Scant dense cytoplasm with prominent vacuoles
- Syncytiotrophoblastic cells:
- Derived from fusion of cytotrophoblastic cells in late pregnancy and postpartum period
- Large multinucleated cells with up to 50 or more nuclei in the center
- Normal chromatic nuclei, even chromatin distribution and irregular nuclear membranes
- Tapering / tail of granular cytoplasm at one end of the cell
- Cytotrophoblastic cells:
- Arias-Stella reaction (Diagn Cytopathol 1996;14:349):
- In association with pregnancy or occasionally in nonpregnant hormonally stimulated individuals
- Reactive changes involving endocervical or endometrial glandular cells singly or in clusters in a clean background
- Large pleomorphic nuclei with irregular contour, granular to smudgy chromatin, multiple prominent nucleoli, no or very rare mitotic figures
- Variable cytoplasm, abundant, secretory
- Navicular cells:
- Reactive changes (Nayar: The Bethesda System for Reporting Cervical Cytology, 3rd Edition, 2015, DeMay: The Art & Science of Cytopathology, 2nd Edition, 2011, DeMay: The Pap Test, 1st Edition, 2005):
- See also actinomycosis, bacterial vaginosis, Candida / fungi, Chlamydia trachomatis
- Atrophy:
- Associated with lack of hormone stimulation, thin epithelium consisting of immature basal / parabasal cells
- Flat monolayer cells with preserved nuclear polarity and little nuclear overlap
- Slightly increased nuclear to cytoplasmic ratio, naked nuclei, mild hyperchromasia and elongated nuclei, evenly distributed chromatin and smooth nuclear contour
- Blue blobs
- Pseudoparakeratosis: degenerated orangeophilic eosinophilic parabasal cells with nuclear pyknosis
- Repair / regeneration with inflammation:
- Enlarged cohesive sheets of cells with "school of fish" architecture
- Variable nuclear enlargement, not overlapping, may be binucleation or multinucleation
- Smooth nuclear contour, vesicular and hyperchromatic nuclei, evenly distributed chromatin, prominent nucleoli or bare nuclei (loss of cytoplasm)
- Cytoplasm showing polychromasia, vacuolization, perinuclear halos and well defined cytoplasmic boundaries
- "Dirty" background with inflammatory cells, granular debris and fibrin (Arch Pathol Lab Med 2001;125:134)
- Radiation effect:
- Markedly enlarged cells, may be bizarre shaped, without increased nuclear to cytoplasmic ratio
- Variable nuclear size, common binucleation or multinucleation, degenerative nuclear changes with nuclear pallor, wrinkling or smudging chromatin, and nuclear vascularization, nucleoli
- Cytoplasmic vascularization (earliest effect), polychromatic and intracytoplasmic polymorphonuclear leukocytes
- Reactive changes with intrauterine contraceptive device:
- Reactive endometrial or endocervical columnar cells exfoliated singly or in clusters present in a clean background
- Cytoplasm with large vacuoles, displacing the nucleus
- Degenerated nuclei with wrinkled chromatin and cracking, prominent nucleoli
- Calcifications may resembling psammoma bodies
- Actinomyces-like organisms present in up to 25% of cases
- Perimenopausal (PM) cells:
- Squamous cells from perimenopausal women
- Significant cause of atypical squamous cell (ASC) overdiagnosis in women ages 40 - 55 years, may be attributable in part to air drying artifact and subtle atrophic changes (Cancer 2001;93:100, Am J Clin Pathol 2005;124:58)
- Squamous cells with enlarged, smooth, bland nuclei, no hypochromasia
- In early menopause, there is an intermediate cell maturation pattern (DeMay: The Pap Test, 1st Edition, 2005)
- Small blue cells (Nayar: The Bethesda System for Reporting Cervical Cytology, 3rd Edition, 2015):
- Mimic of exfoliated endometrial cells, increase with age
- Clusters of naked nuclei, likely of parabasal squamous or reserve cell origin
- Some loose nuclear contour, evenly distributed granular chromatin, sometimes molding
- Inflammatory cells:
- Present in different conditions
- Neutrophils, lymphocytes, plasma cells and histiocytes
- Artifact:
- Barr body: darkly stained body attached to nuclear membrane
- Inactive X chromosome, present on nuclear margin, formed by telomere association (Proc Natl Acad Sci USA 1991;88:6191)
- 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
- Barr body: darkly stained body attached to nuclear membrane
Cytology images
Contributed by Shuyue Ren, M.D., Ph.D.
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
Additional references
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?
- Basal cells
- Intermediate cells
- Parabasal cells
- Superficial layer cells
Board review style answer #1
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?
- Endocervical cells, not reported
- Endocervical cells, reported
- Exfoliated endometrial cells, not reported
- 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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