PART TWO
Diagnostic Cytology
Fig. 8.126 Dysplasia of metaplastic type. Positive-staining reaction
for keratin 18 in basal and parabasal cell layers indicating an increase in
cytoplasmic characteristics of simple (glandular) epithelium in this abnormal,
originally squamous metaplastic epithelium. Strong positive staining in
overlying columnar epithelium (immunoperoxidase method x MP).
Smedts and colleagues, in abnormal cervical epithelium, found
cytokeratins 10, 11, 13, and 16 to be irregularly distributed in CIN
grade 3.234,235 They noted a patchy pattern of distribution of posi-
tivity. Areas of positivity alternated with negative areas. They could
not demonstrate a consistent and progressive change in cytokera-
tin content from normal epithelium through CIN grades 1 and 2.
Their observations suggest that an abrupt change occurred at the
time of development of the lesion morphologically described as
CIN grade 3. CIN grade 2 lesions in invaginations of the endocer-
vical canal had a pattern identical to lesions on the surface of the
canal. The staining pattern in CIN grade 3 was comparable to that
found in invasive squamous cell carcinoma. Puts and associates
used anticytokeratin antibodies to keratins and found no quali-
tative differences in staining reactions between epithelial lesions
of various degrees of severity.236 They did find a variable number
of Langerhans cells in 32 dysplastic lesions but no specific pat-
tern in distribution between lesions of different severity.6 They
speculated that differences in the number of Langerhans cells
might be correlated to differences in the dysplastic processes, as
well as to differences in host response, and thus could potentially
be an indicator of a tendency to regression or progression.
Fig. 8.127 Severe dysplasia. Positive-staining reaction for keratin 4 in
intermediate cell layers. No staining reaction in basal, parabasal, and
superficial cell layers (immunoperoxidase method x MP).
Fig. 8.128 Severe dysplasia. Scattered areas of positive staining for
keratin 14 in basal and parabasal cell layers. No positivity in intermediate and
superficial cell layers (immunoperoxidase method x MP).
Smedts and co-workers investigated the expression of kerat-
ins in normal cervical epithelia, metaplastic epithelium, and
CIN grades 1, 2, and 3 with a panel of chain-specific mAbs.237,238
This allowed the detection of individual keratins 4, 5, 7, 8 , 10,
13, 14, 18, and 19 at the single-cell level. The results showed
that during the transformation of reserve cells into immature
squamous metaplasia, this epithelium acquired keratins typi-
cal of the ectocervical squamous epithelium, whereas keratins
typical of reserve cells and columnar cells were lost. This change
continued during further differentiation into mature squamous
metaplasia. Premalignant transformation resulted in a partial
loss of the keratins typical of squamous epithelium and acquisi-
tion of keratins atypical of simple epithelia.
In the course of increasing epithelial atypia through grades 1
to 3 of intraepithelial neoplasia, keratins characteristic of simple
epithelia appear in dysplastic lesions (Fig. 8.126). In CIN grade
1 approximately half and in CIN grade 2 (moderate dysplasia)
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