Benign Proliferative Reactions, Intraepithelial Neoplasia, and Invasive cancer of the Uterine cervix
more severe abnormalities, the nuclear chromatin is increased
and often irregularly distributed. Cellular changes originate in
preexistent squamous epithelium or more often in squamous
metaplastic epithelium.
Key features of condylomatous lesions (CIN 1, LSIL)
• Koilocyte is the classic cell—superficial or intermediate
type cell with large clear-cut perinuclear halo;
• Cytoplasm is densely cyanophilic and often
• Nuclei may be degenerated with poorly defined,
clumped chromatin and indistinct nuclear
• Chromatin is normochromic to slightly hyperchro-
matic unevenly distributed;
• Nucleoli are absent;
• Multinucleation is common; and
• Non-koilocytes may show markedly enlarged nuclei
with increased nucleus to cytoplasmic ratio.
Cytology may detect the majority of lesions with koilocytotic
features but may not detect focal CIN grades I, II, and III lesions
associated with these condylomatous changes.68
Cellular changes due to low-risk HPV infection may mimic
the changes found in cases of well-differentiated squamous
cell carcinoma. The right diagnosis may usually be made on
the basis of the less apparent nuclear abnormalities in low-risk
HPV-induced epithelial lesions.
Neither cytology nor histology can detect an asympto-
matic, colposcopically negative, latent HPV infection, which
can be detected by in situ hybridization tests only. The great
intraobserver and interobserver variability in the cytologic and
histologic diagnosis of condyloma and CIN reflects the great
amount of subjectivity in evaluating the morphologic char-
acteristics of a lesion. The correlation between morphologic
signs of HPV infection and the results of HPV-DNA hybridiza-
tion indicates that the sensitivity of the cytologic and histo-
logic features of HPV infection are in the range of 15 to 36%.69
Future diagnosis of HPV by PCR should include also in situ
Squamous Intraepithelial Neoplasia
The primary function of a diagnostic terminology is to
communicate to the referring physician the interpretation of a
specimen in descriptive terms that will have clear implications
for appropriate patient management. Many practicing
physicians do not have detailed knowledge of cytopathology.
Thus the cytologic report should not only be scientifically
accurate but also easily understood.40
The terminology currently used in cytopathology is variable,
inconsistent, and sometimes ambiguous. Many cytopathologists
and clinicians are thus confused and uncertain about the mean-
ing of some terms. Failure to understand the clinical meaning
of a cytopathologic evaluation may lead to inappropriate treat-
ment of patients.
The cytology report should consist of a concise description
of abnormal cellular findings in well-defined and generally
accepted terms, followed, if appropriate, by a prediction of the
histologic condition, and should also include a recommenda-
tion for the further treatment of the patient.21,26,70-72
In pathology, the basis for any system of classification is
However, where
should relate to the biologic significance or potential of the
Papanicolaou classification
The Papanicolaou classification of cytologic findings in epi-
thelial lesions has led to different interpretations. Also, the
Papanicolaou system does not provide for the diagnosis of non-
cancerous lesions.
"The groups of the Papanicolaou system do not reflect the
current understanding of cervical neoplasia and the Papanico-
laou classes do not have an equivalent in tissue diagnostic termi-
nology."74,75 Epithelial abnormalities of the uterine cervix form a
morphologic and most likely also a biologic continuum.
The rationale for distinguishing between dysplasia and carci-
noma in situ on a cytomorphologic basis is to permit the best
possible correlation between the cellular and tissue sample and
the final clinical outcome of the epithelial change.
Years of experience have demonstrated the difficulty of cat-
egorizing dysplastic cervical lesions into the diagnostic triad of
mild, moderate, and severe dysplasia. In our own experience,
cytologic diagnoses of mild or severe dysplasia and carcinoma
in situ proved to be fairly accurate. The cytologic diagnoses of
moderate dysplasia were less accurate. A large proportion (57%)
of moderate dysplasias were absent or had regressed to a less
severe lesion at follow-up 6 months after primary diagnosis. On
the other hand, in about 20% of cases, during follow-up a more
severe lesion was found.76,77
In the USA a National Cancer Institute (NCI) working group
(aka Bethesda 1988 and Bethesda 1991) recommended discon-
tinuing the use of the Papanicolaou classification as a means for
reporting. The Papanicolaou classification is deficient in advis-
ing about the true nature of abnormalities unless it is accompa-
nied by a verbal description of the cytologic findings.
In order to establish some order, all lesions known to be
reactions to infections, inflammation, or reparative reactions
(regeneration) should be excluded, as well as benign prolif-
erative reactions in the endocervical canal such as reserve cell
hyperplasia and squamous metaplasia, because these in them-
selves are not considered to be stages in the process of carcino-
genesis.74,75 In the Bethesda System the inflammatory diseases,
the infectious conditions, and other reactive cellular changes
such as repair (due to trauma, infection, IUCD), radiation, and
atrophy are classified as "negative for intraepithelial lesion or
The NCI working group adopted a new classification based on
only two main categories for intraepithelial cell abnormalities:
Low-grade squamous intraepithelial lesions (LSIL)
• Changes consistent with HPV infection: multinuclea-
tion, perinuclear halos, and slight nuclear atypia; and
• Mild dysplasia (CIN grade 1).
High-grade squamous intraepithelial lesion (HSIL)
• Moderate dysplasia (CIN grade 2);
• Severe dysplasia (CIN grade 3); and
• Carcinoma in situ (CIN grade 3).
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