PART TWO
Diagnostic Cytology
Fig. 9.32 In these examples of directly sampled endometrium, the most common presentations are as flat honeycombed 2-dimensional sheets (A) and
pseudostratified strips (B). Other groups show typical wispy and elongated marginal cytoplasm (C). Occasionally the pseudostratified strips of cells may become
tall and mimic the appearance of endocervical AIS (D). The key to the distinction is the small average size of the endometrial cells (liquid-based preparation,
Papanicolaou x (A, C) MP, (B, D) HP).
proportions of benign tubal metaplasia, normal endocervical
glands, and Nabothian cysts; however, the pattern of staining
in these benign/normal processes is heterogeneous and not of
the diffuse, strong staining pattern seen in the high proportion
of true endocervical glandular neoplastic lesions.103,107 Yet other
reports have shown only occasional cases of tubal metaplasia
and endometrial tissue with strong p16 immunoreactivity in a
small percentage of cells,105 while others have shown no benign
endocervical cell staining.106 Conflicting immunohistochemi-
cal data at present most likely are related to differing antibody
and technique utilization. Careful validation studies should be
performed in each laboratory prior to making definitive conclu-
sions about the results of such marker assays. This finding of
non-specificity for true glandular neoplasias makes evaluation
of such important differentials on cytologic preparation even
more problematic. The use of p16 immunostaining in cervical
cytology has been shown to be of utility in squamous lesion
triage.108-111 Studies of the use of p16 for the detection of endocer-
vical glandular lesions in cervical cytology samples have been
few at present, with two such studies performed on ThinPrep
cervical cytology slides showing strong immunoreactivity in 8
of 10 examples of AIS and invasive adenocarcinoma with weak
staining in the remaining 2 cases,104 and in 12 of 14 adenocar-
cinomas,112 respectively. Negri et al. did note a weaker positive
reaction in occasional normal endocervical cells, but reported
that this did not influence the overall interpretation.104 Ishikawa
et al. reported no p16 staining in benign endocervical cells.112 If
the issue of non-neoplastic glandular cell staining can be further
characterized, use of p16 may be of value in the evaluation of
glandular lesions in cervical cytology specimens. Interestingly, in
the so-called minimal deviation endocervical adenocarcinoma,
investigators have shown low associations with p16 immuno-
reactivity, providing further evidence that in this rare type of
endocervical
adenocarcinoma,
HPV-associated
mechanisms
may not be operant as in the more common types of endocervi-
cal adenocarcinoma.113 Use of p16 in combination with other
immunostaining markers may improve the overall accuracy for
detection of cervical glandular neoplasia. The use of Ki-67 (Mib-1),
a marker of cellular proliferation, was shown to have either a
high or moderate index in endocervical neoplastic processes
and had a low to moderate index in benign processes; how-
ever, a small number of tubal metaplasia showed high levels of
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