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Pathology · Additional topics

Atypical cells in cytology

Cervical Intraepithelial Neoplasia (CIN)

In cytological practice, atypical cells are a marker of impaired normal maturation, differentiation, and stratification of the stratified squamous epithelium. Most commonly, their appearance is associated with the development of cervical intraepithelial neoplasia (CIN) against the background of human papillomavirus infection, which is regarded as a precancerous condition of the cervix. The most critical criterion for intraepithelial neoplasia is the intactness of the basement membrane.

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Main causeIn 98% of cases, cellular atypia and cervical dysplasia are caused by the human papillomavirus (HPV).
Basement membraneAt any grade of CIN, atypical cells do not penetrate beyond the basement membrane of the epithelium.
SensitivityThe diagnostic yield of cytological screening is 60–90% and increases in severe lesions.
Screening regulationsAccording to the Russian Ministry of Health, preventive cytological screening is performed strictly once every 3 years.
4 min readFor medical studentsUpdated 10.10.2026
Material prepared by WhiteCoat Pro editorial team based on platform study guidesPending instructor review

Morphological manifestations of cellular atypia

The appearance of atypical cells is associated with proliferation disorders starting in the basal and parabasal layers of the epithelium. Immature elements migrate into the intermediate and superficial layers with varying intensity.

Key morphological signs of atypia include:

  • A significant increase in the nuclear-cytoplasmic ratio (the nucleus occupies an abnormally large space within the cell).
  • Hyperchromasia (intense staining) and pronounced nuclear polymorphism.
  • Uneven distribution of chromatin within the nucleus.
  • Loss of cellular polarity and general disorganization of the layers.
  • Increased mitotic activity, including the appearance of atypical mitoses.

Additionally, smears frequently reveal koilocytes—cells reflecting the cytopathic effect of HPV. They are characterized by a large hyperchromatic nucleus with coarse chromatin clumps, an irregular thickened nuclear membrane, and a wide clear zone around the nucleus (perinuclear halo).

Grades of intraepithelial neoplasia (CIN)

The histological grading of the severity of the process is based on the proportion of the epithelial layer occupied by immature undifferentiated cells. According to the WHO classification, three grades are distinguished:

  1. CIN I (mild dysplasia): atypical cells are restricted to the lower 1/3 of the epithelial layer. The upper layers remain mature, though isolated koilocytosis may be detected.
  2. CIN II (moderate dysplasia): immature cells involve the lower 2/3 of the epithelial thickness. Signs of koilocytosis become less pronounced.
  3. CIN III (severe dysplasia and in situ carcinoma): pathological changes involve more than 2/3 of the epithelial layer or its entire thickness. Koilocytosis is poorly expressed.

It is important to remember that when the virus transitions from the episomal form (viral particle assembly inside the cell) to the integrative form (integration of viral DNA into the human genome), tumor transformation is triggered, and the characteristic signs of koilocytosis gradually disappear.

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The Bethesda System (TBS) for reporting cervical cytology

In global practice, the Bethesda cytology reporting system is used to evaluate cervical disorders, dividing squamous lesions into two categories:

  • LSIL (Low-grade squamous intraepithelial lesion). This group includes mild dysplasia (CIN I), isolated koilocytosis, and condylomas.
  • HSIL (High-grade squamous intraepithelial lesion). Combines moderate dysplasia (CIN II) and severe dysplasia (CIN III), as well as carcinoma in situ.

HSIL conditions are classified as obligate precancer. The management strategy for such patients is uniform: they require mandatory surgical removal or laser ablation of the affected tissue area.

Screening and limitations of the cytological method

The development of invasive cancer from dysplastic foci is a slow process that can take over 10 years. Dysplasia itself is asymptomatic (contact bleeding occurs only on rare occasions). This is precisely why mass screening is of paramount importance. All women in the target group are subject to examination, even in the complete absence of complaints.

However, cytological examination is exclusively a screening tool. It does not allow for a definitive clinical diagnosis. Its sensitivity ranges from 60 to 90% and directly depends on the severity of the process: the more severe the dysplasia, the higher the likelihood of detecting atypical cells.

For accurate diagnosis, a comprehensive approach is used: visual inspection with a speculum, acetic acid test (VIA), HPV testing (PCR diagnostics actively implemented in screening), colposcopy, and directed biopsy followed by histological examination.

How to memorize

To easily remember the stages of CIN, use the "rule of thirds": CIN I—atypia in the lower third of the layer, CIN II—in two thirds, CIN III—all three thirds (the entire layer) are involved. The key point is that the basement membrane always remains intact.

Class and exam questions

What is the main difference between intraepithelial neoplasia and invasive cancer?

In intraepithelial neoplasia (up to carcinoma in situ), structural and cellular atypia occurs strictly within the epithelial layer without involving or destroying the basement membrane.

What does the appearance of koilocytes in a cytological smear signify?

Koilocytes are cells with specific alterations (a large nucleus and a perinuclear halo) indicating the direct cytopathic effect of the human papillomavirus (HPV) on the squamous epithelium.

Why are signs of koilocytosis weak or absent in severe dysplasia?

Koilocytes form when HPV is in the episomal form (replicating inside the cell). When the virus integrates into the epithelial cell genome and triggers active tumor transformation, the morphological signs of koilocytosis disappear.

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What else to study on this topic

  • Features of episomal and integrative forms of HPV infection
  • Histological structure of normal stratified squamous cervical epithelium
  • Principles of visual cervical assessment with acetic acid (VIA)
  • Morphological characteristics of carcinoma in situ (CIS)

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