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
ASC-US
 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”).
ASC-H
“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.
LSIL
 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.
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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.
HSIL
 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.
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A tumor diathesis consisting of necrotic debris and old blood is often present.
Large cell variant tumors may show prominent macronucleoli and basophilic
cytoplasm.