Benign Proliferative Reactions, Intraepithelial Neoplasia, and Invasive cancer of the Uterine cervix
epithelial cells that lack the stimulus to mature. In such an aggre-
gate, the component cells are regularly arranged with relation to
one another. Less frequently, cells may be arranged in syncytial
masses. Here the component cells are irregularly arranged with
relation to one another and have indistinct cell borders. A syncy-
tial arrangement is more commonly associated with carcinoma
in situ and invasive cancer.
In almost all cases of dysplasia, sheet-like arrangements are
found. Syncytial masses are found in only 10% of specimens and
are always associated with a severe epithelial abnormality.8,12
The volume and the condition of the cytoplasm are a reflection
of the state of maturation and differentiation of the cells. Usually
found is an admixture of cells of various stages of maturity.
In view of the site of origin of dysplasias and the preceding
metaplastic process in the endocervical canal, the size of cells
involved in dysplastic changes may vary from almost the size of
a normal superficial squamous cell in minimal abnormalities to
the size of an immature basal cell or a very immature squamous
metaplastic cell in more severely abnormal changes.
Relating cell size to the severity of the histopathologic change
in dysplasias, those samples containing dysplastic cells with cell
areas predominantly in the range of normal squamous cells tend
to originate from a less atypical (less severe) dysplastic lesion.
These reactions are more frequently located on the portio vagi-
nalis or in relation to the external cervical os. Those samples
with dysplastic cells possessing cell characteristics more remi-
niscent of squamous metaplastic cells are more likely to have
arisen in the area of the distal portion of the endocervical canal
Most of the abnormal cells observed in the presence of dys-
plasia, carcinoma in situ, and invasive cancer possess cell sizes
as observed in cells from immature squamous metaplasia and
reserve cell hyperplasia. The relative nuclear area, nuclear shape,
and particularly intranuclear chromatin architecture should
then provide the basis for the right diagnosis.8
The shape of an abnormal cell in a sample may also reflect
the maturity of the parent tissue reaction. Dysplasia is char-
acterized by a predominance of polygonal cells accounting
for about 55% of the abnormal cell population (52.727 and
56%104). Round or oval forms, indicative of a less mature reac-
tion, represented about 40% of the abnormal cells in samples
studied (41.627 and 40% 104).
A predominance of polygonal forms, often found together
with eosinophilic staining of the cytoplasm, suggest an origin
from a dysplastic lesion, originating in original squamous strati-
fied epithelium. A predominance of oval forms is suggestive of a
dysplastic lesion in an area of squamous metaplasia, most likely
the transformation zone of the endocervical canal. The presence
of spindle-shaped or elongated cells may indicate the presence of
(abnormal) keratinization at the surface of the epithelium. The
elongated cells often show fibrillary structures in the cytoplasm.
The presence of these fibrils is indicative of keratinization in the
dysplastic process. Keratinization overlying a dysplastic lesion
most often occurs in the ectocervical epithelium, but a kerati-
nizing dysplasia may occasionally be found in the endocervical
canal in a metaplastic epithelium.
Anucleated squames, sometimes with pale yellow cytoplasm,
may also be found. When contamination from the vulvar mucosa
can be precluded, the presence of these squames should always
lead to an extra awareness on the part of the cytopathologist.
Severe dysplastic lesions or even keratinizing squamous cancer
may sometimes be covered by a thick layer of hyperkeratosis.
When making a scrape from this area, the cellular material
obtained may be restricted to keratinized squames. Owing to
the resistant cover, deeper layers have not been sampled and the
true lesion remains obscure.
When anucleated squames are diagnosed in a cell sample,
even without atypical cells being observed, a repeat smear
should be advised and the physician should be specifically
instructed to sample any area of leukoplakia (literally
very carefully, preferably by taking successive smears
from the same area, thus gradually uncovering the nonkerati-
nized part of the lesion.
N uclear M orphology
Nuclear characteristics are the main determinants for the grad-
ing of an epithelial abnormality. Although cytoplasmic features
may provide additional information about the origin and degree
of maturation of a cell, the main important denominator of the
severity of an epithelial abnormality remains nuclear changes.
Nuclear atypia should be classified as mild, moderate, or
severe. Cytoplasmic changes should be classified according to
quantity, density, staining quality, and shape.
The morphology of the cell nuclei in cases of epithelial changes
comprises a combination of any number of the following:71
• Disproportionate nuclear enlargement;
• Irregularity in form and outline;
• Irregular chromatin condensation;
• Abnormalities of the number, size, and form of the
Papanicolaou introduced the term
to designate cer-
tain cytologic patterns observed in vaginal and cervical smears
from cases of early carcinoma and some other pathologic lesions
of the uterine cervix.105,106 In these lesions, the exfoliated cells are
characterized by marked nuclear abnormalities consistent with
the generally accepted criteria of malignancy, although the cells
as a whole may show no significant deviation from their standard
normal type. He described the morphology of dyskaryosis cells
as follows: "The nuclei show distinct abnormal features such as
enlargement, hyperchromasia, anisokaryosis, bi- or multinuclea-
tion et cetera." Patten strongly advocates avoiding the use of sub-
jective terminology to describe morphologic changes and thus
rejects the use of the term dyskaryosis "which although useful
during the developmental stages of applied cytology, presently
has no place in the vocabulary of the diagnostic cytologist except
for historical reflection."12 The working party of the British Society
for Clinical Cytology,71 however, endorsed the recommendation
made by Spriggs and associates107 to use the terms dyskaryosis
and dyskaryotic in the description of nuclear abnormalities in
both squamous and endocervical cells in intraepithelial lesions
as well as in invasive carcinoma.
Relative N uclear Area
The relative nuclear area is an expression of nuclear area in rela-
tion to cytoplasmic area. The relative nuclear area increases with
the severity of the lesion from minimal dysplasia to carcinoma