Squamous Cell Abnormalities (of Uterine Cervix)

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Squamous Cell Abnormalities (of Uterine Cervix)

By Mr. Tony Chan

The 2001 Bethesda System:
Atypical squamous cells

  • of undetermined significance (ASC-US)

  • cannot exclude HSIL (ASC-H)

Low-grade squamous intraepithelial lesion (LSIL)

High-grade squamous intraepithelial lesion (HSIL)
Squamous cell carcinoma

Cytology Criteria


  • Nuclei: approx. 2.5 to 3 times the area of the nucleus of a normal intermediate squamous cell.

  • Slightly increased N/C ratio.

  • Minimal nuclear hyperchromasia & irregularity in chromatin distribution or nuclear shape.

  • Nuclear abnormalities associated with dense orangeophilic cytoplasm (“atypical parakeratosis”).


“Atypical (Immature) Metaplasia”

  • Metaplastic cells occur singly or in small fragments of less than 10 cells.

  • Nuclei size 1.5 to 2.5 larger than normal.

  • N/C ratio may approximate that of HSIL.

  • Nuclear abnormalities: focal irregularities favour an interpretation of HSIL.

“Crowded Sheet Pattern”

  • A microbiopsy of crowded cells containing nuclei that may show loss of polarity or are difficult to visualize.

  • Dense cytoplasm, polygonal cell shape, and fragments with sharp linear edges that favour squamous over glandular differentiation.


  • Cells occur singly and in sheets.

  • Cytologic changes are usually confined to cells with “mature” or superficial type cytoplasm.

  • Overall cell size is large.

  • Nuclear enlargement more than 3 times the area of normal intermediate nuclei.

  • Slight increase in N/C ratio.

  • Variable degrees of nuclear hyperchromasia and variation in nuclear size, number and shape.

  • Binucleation and multinucleation

  • Chromatin is often uniformly distributed, but coarsely granular, alternatively the chromatin may appear smudged or densely opaque.

  • Nucleoli are generally absent or inconspicuous if present.

  • Contour of nuclear membranes is often slightly irregular, but may be smooth.

  • Cells have distinct cytoplasmic borders.

  • Perinuclear cavitation (koilocytosis) might present.


  • Cytologic changes affect cells that are smaller and less “mature” than the cells in LSIL.

  • Cells occur singly, in sheets, or in syncytial-like aggregates.

  • Overall cell size is variable, and ranges from cells that are similar in size to those in LSIL to quite small basal-type cells.

  • Nuclear hyperchromasia is accompanied by variations in nuclear size and shape

  • Degree of nuclear enlargement is more variable than in LSIL.

  • Chromatin may be fine or coarsely granular and evenly distributed.

  • Contour of nuclear membrane is quite irregular with frequently prominent indentations or grooves.

  • Nucleoli are generally absent, but may occasionally be seen, particularly when HSIL extends into endocervical gland spaces.

  • Appearance of cytoplasm is variable; it can appear “immature”, lacy, and delicate or densely metaplastic; occasionally the cytoplasm is “mature” and densely keratinised.

Keratinizing Squamous Cell Carcinoma

  • Relatively few cells may be present; often as isolated single cells and less commonly in aggregates.

  • Marked variation in cellular size and shape is typical, with caudate and spindle cells that frequently contain dense orangeophilic cytoplasm.

  • Nuclei vary markedly in size, nuclear membranes may be irregular in configuration, and numerous dense opaque nuclei are often present.

  • Chromatin pattern, when discernible, is coarsely granular and irregularly distributed with parachromatin clearing.

  • Macronucleoli may be seen but are less common than in nonkeratinizing squamous cell carcinoma.

  • Associated keratotic changes (“hyperkeratosis” or “pleomorphic parakeratosis”) may be present but are not sufficient for the interpretation of carcinoma in the absence of nuclear abnormalities.

  • A tumour diathesis may be present, but is usually less than that seen in nonkeratinizing squamous cell carcinomas.

Nonkeratinizing Squamous Cell Carcinoma

  • Cells occur singly or in syncytial aggregates with poorly defined cell borders.

  • Cells are frequently somewhat smaller than those of many HSIL, but display most of the features of HSIL.

  • Nuclei demonstrated markedly irregular distribution of coarsely clumped chromatin.

  • A tumor diathesis consisting of necrotic debris and old blood is often present.

  • Large cell variant tumors may show prominent macronucleoli and basophilic cytoplasm.

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