Diagnostic Cytology
Fig. 8.61 Moderate dysplasia of metaplastic type bordering
endocervical mucus-producing columnar cells. Disturbed maturation of
superficial layers. Nuclei show irregular sizes and shapes. Hyperchromasia of
nuclear chromatin (H&E x HP).
• Cytoplasm is cyanophilic, but more mature cells may
be eosinophilic with distinct cell borders;
• Nuclei enlarged, round to oval, with some irregular or
• Chromatin irregularly distributed with slight to
moderate hyperchromasia;
• Nucleoli usually not present; and
• Elevated nucleus-to-cytoplasmic ratio usually one-half
of cytoplasmic area.
According to Koss, virtually all lesions classified as moder-
ate dysplasia (CIN grade 2) must be considered as neoplastic
events in the squamous epithelium.64 Some of the abnormali-
ties may resemble flat condylomata, and in a proportion of
these moderately abnormal lesions HPV may be documented,
particularly with the application of recent highly sensitive in
situ hybridization techniques. Meisels and associates proposed
the term
atypical condylomata
for these lesions.108 Because of
their progressive potential, Koss advises eradicating all mod-
erately abnormal lesions under colposcopic control.64 This
also applies to the atypical condylomata associated with other
forms of CIN.
Severe Dysplasia and Carcinoma In Situ (CIN Grade 3,
High-Grade SIL)
In severe dysplasia, cells show a greatly disturbed arrangement
in all three layers of the epithelium (Fig. 8.67). Stratification is
present in only the most superficial layers (Fig. 8.68). Through-
out the entire epithelium, cells show a reduced maturation with
loss of cytoplasmic volume and an increased nuclear size. Cells
and nuclei vary in size and shape and often have irregular forms.
Differentiation in intermediate-type and superficial squamous-
type cells may be lost (Fig. 8.69). Nuclei have a hyperchromatic,
irregularly distributed, coarsely granular chromatin. Mitoses may
be found throughout all epithelial layers. The abnormal changes
often extend into the stromal invaginations of the endocervical
epithelium (Fig. 8.70).
The size of the cells in severely abnormal intraepithelial changes
is comparable with the parabasal cell type. Cytoplasm is usually
sparse, typically forming a small rim around the nucleus (Fig.
8.71). Cells are round to oval and often irregular or elongated
(Figs 8.72 and 8.73). The keratinizing squamous lesions some-
times contain large cells with plentiful, often eosinophilic, cyto-
plasm. Cells are seen singly as well as in aggregates. In the most
severe intraepithelial lesions, aggregates have a syncytial com-
position, with indistinct cell borders and irregularly arranged
nuclei (Fig. 8.74). The morphology of these aggregates is con-
sistent with the histologic evidence of the lack of cell maturation
and the irregular arrangement of nuclei in the most superficial
layers of severely abnormal epithelium (Figs 8.75 and 8.76). The
nucleus usually occupies at least two-thirds of the total area of
the cell. Nuclei have a hyperchromatic, irregularly distributed,
coarsely granular chromatin (Fig. 8.77). In actively proliferat-
ing lesions, eosinophilic-staining nucleoli may be observed,
but these more often are obscured by the dense hyperchromatic
chromatin. Some severe dysplasias show an extreme irregular-
ity in shape and size of the composing cells. In cervical smears,
these lesions may present with large, bizarre-shaped cells with
highly abnormal hyperchromatic nuclei. Differentiation from
invasive squamous cell cancer may at times be extremely dif-
ficult (Figs 8.78 and 8.79).
Key features of severe dysplasia (CIN 3, HSIL)
• Cells similar in appearance to parabasal cells;
• Sparse cytoplasm in rim around nucleus;
• Cells isolated or in syncytial groups with indistinct
cytoplasmic borders and loss of polarity;
• Enlarged nucleus occupies three-quarters of
cytoplasmic area;
• Dense hyperchromatic chromatin often with irregular
• Nucleoli usually absent; and
• Spindled, elongate, or bizarre forms may be present.
Biologic Significance Follow-up
The evolution of invasive squamous cell cancer involves a
number of stages with increasing intraepithelial abnormality
designated as dysplasia, carcinoma in situ, and microinvasive
carcinoma. Although it is not usually possible to predict the
malignant potential of an epithelial abnormality (prema-
lignant lesion), evidence suggests that mild dysplasias are
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