Diagnosis problems in a case of minimal deviation adenocarcinoma of the cervix.
ABSTRACT We present the diagnostic problems in a case of minimal deviation adenocarcinoma of the cervix. Histopathologic exam of the tumor, made on serial sections, revealed a dense and profound proliferation of the glandular structures that were lined by endocervical type epithelia with minimal cellular and nuclear atypia. The aspect suggested the diagnosis of minimal deviation adenocarcinoma endocervical type; in order to confirm the diagnosis we immunohistochemical investigate the tumor for CEA, CA125, Ki67, ER and PR. The results indicated focal positivity for CEA, CA125 lack of immunostaining for ER and PR and Ki67 positivity with a low index of proliferation. We can conclude that all these markers are useful in the diagnosis, excluding the benign endocervical lesions.
Rom anian Journal of Morphology and Em bryology 2006, 47(3):245–249
O OR RI IG GI IN NA AL L P PA AP PE ER R
Diagnosis problems in a case of minimal
deviation adenocarcinoma of the cervix
CRISTIANA SIMIONESCU1), CLAUDIA VALENTINA GEORGESCU2),
CL. MĂRGĂRITESCU1), MIHAELA NICULESCU3)
1)Department of Pathology
2)Emergency County Hospital, Craiova
3)Department of Anatomy
University of Medicine and Pharmacy of Craiova
We present the diagnostic problem s in a case of m inim al deviation adenocarcinom a of the cervix. Histopathologic exam of the tum or,
m ade on serial sections, revealed a dense and profound proliferation of the glandular structures that were lined by endocervical type
epithelia with m inim al cellular and nuclear atypia. The aspect suggested the diagnosis of m inim al deviation adenocarcinom a endocervical
type; in order to confirm the diagnosis we im m unohistochem ical investigate the tum or for CEA, CA125, Ki67, ER and PR. The results
indicated focal positivity for CEA, CA125 lack of im m unostaining for ER and PR and Ki67 positivity with a low index of proliferation. We can
conclude that all these m arkers are useful in the diagnosis, excluding the benign endocervical lesions.
Keywords: minimal deviation adenocarcinoma, histopathology, immunohistochemistry.
Minimal deviation adenocarcinoma (MDA, malign
adenoma) is a well-differentiated variety of adeno-
carcinoma of the cervix, characterized by the fact that
the lining cells of the glands do not have malign
characteristics, resembling with the normal endocervical
cells. The term of minimal deviation adenocarcinoma
was proposed by Silverberg and Hurst , subsequently
being used and in other locations.
Minimal deviation adenocarcinomas are rare tumors,
representing 1–3% of the adenocarcinomas with this
localization and 18% from the differentiated forms of
them . In the literature it is mentioned the association
between these tumors and mucinous or sexual-stromal
ovarian tumors [3, 4].
Evolution of the tumors is difficult to appreciate,
majority being diagnosticated in advanced phases.
Despite the profound infiltrative growing, the cervical
aspect may remain unchanged favoring the tardy
detection of the tumor. In 40% of the cases in the
moment of diagnosis the parameters or/and miometrium
Some studies concerning this subject revealed a
unfavorable prognosis, other studies mention a
prognostic similar with
adenocarcinoma of the cervix, the five years rate of
surviving being of 54% [1, 5, 6].
? Material and methods
The material consists in fragments of cervix
obtained by cervical biopsy, 10% formalin fixed,
paraffin embedded and Haematoxylin–Eosin stained in
the Pathology Laboratory of the Emergency Hospital
from Craiova. Later were made serial sections
immunohistochemical processed by LSAB/HRP method
in the Laboratory of the Center for Microscopic
Morphology and Immunology study.
Tumor was investigated for CEA (polyclonal rabbit
anti-human CEA, code A0115, Ig fraction), CA 125
(monoclonal mouse anti-human CA125, clone M11,
isotype Ig1, kappa, code M3520), Ki67 (monoclonal
anti-human Ki67 antigen, clone MIB-1, code 724001,
DAKO Cytomation), ER (monoclonal anti-human
estrogen receptor, clone PPG5/10 code M7292, DAKO
Cytomation) and PR
progesteron receptor, clone 1A4, code A0098, DAKO
For CA125 and CEA was appreciate that the
distribution of the immunostaining was focal when
bellow 50% of the cells were positive, and diffuse when
over 50% of the cells were positive.
For Ki67 was calculated the positivity index the
number of positive cells being reported to 100 cells
(positive and negative) with ×40 objective.
The tumor belongs to a 32-years patient with
irregular vaginal leakage and bleedings, normal
cytological exam to which was performed profound
Histopathologic, on serial sections we noted glands
resembling with the normal one, but much more dense
with varied shapes and dimensions, distorted, irregular
aspect, exceeding in depth the inferior level of the
normal endocervical glands.
Cristiana Sim ionescu et al.
Together with small glands we noted the presence of
large glands with polyp like proliferations frequent
ramified and unregulated (Figure 1).
The glandular structures were delimited by a basal
membrane and lined by a single layer of columnar, well-
differentiated cells with abundant clear cytoplasm and
basally situated nuclei. On limited areas were present
aspects of pseudo-stratification and even epithelial
stratification. Some glands presented locally slight
enlarged nuclei, sometimes with eosinophilic nucleoli
and reduced mitotic activity (Figure 2).
The neoplastic glands were separated each by other
by fibrous stroma with low intensity desmoplastic
reaction and areas of peri-glandular edema.
The microscopic aspect of the lesion concerning the
density and the deepness of the glandular proliferation,
correlated with the minimum cellular and nuclear atypia
suggested the diagnosis
adenocarcinoma endocervical type. In order to confirm
this diagnostic, we immunohistochemical investigated
the tumor for CEA, Ki67, ER and PR.
The immunoreactions for hormonal receptors
(ER and PR) were negative. CA125 reaction was focal
positive, staining being cytoplasmatic with increase
apical intensity (Figures 3 and 4).
CEA staining was apical limited positive with focal
distribution (Figures 5 and 6).
The CEA immunoexpression was slight intense
comparative with CA125 expression. The investigation
of the cellular proliferation made by calculation
of the index of positivity for Ki67 indicated reduced
values, 1% (Figure 7).
of minimal deviation
Minimal deviation adenocarcinoma is a rare variety
of invasive cervical adenocarcinoma considered unique
by the diagnostic difficulties because the benign
mystifying aspect of the neoplastic cells. This tumor
occurs between 25 and 72 years with a media of
42 years .
The differential diagnosis of the minimal deviation
adenocarcinoma covers a large spectrum of proliferative
lesions of the endocervical epithelia. The entire area of
the endocervical glandular proliferations, in which the
minimal deviation adenocarcinoma represents only a
lesional subset, is additionally complicated by the
existence of a large number of benign proliferative
lesions of the cervix that can be occasionally wrong,
interpreted as adenocarcinoma.
discordances suggest the absence of a consensus of the
diagnostic criteria between benign hyperplasic lesions,
minimal deviation adenocarcinoma and common
differences of interpretations concerning cellular atypia
and invasion [6–8].
The benign histopathologic
proliferation in minimal deviation adenocarcinoma can
determine diagnosis confusions with a set of reactive
proliferations of the endocervical epithelia.
Between the benign glandular proliferations that can
be over evaluated and wrong interpreted is micro-
consequence of the
aspect of the
glandular lobular hyperplasia, diffuse laminar glandular
hyperplasia of the endocervix, infiltrative-like tubal
metaplasia [9, 10, 15].
These possible confusions impose the necessity
of additional investigations
For the investigated
immunostainings for: CA125, CEA, Ki67, ER and PR.
The tumor was ER and PR negative, aspect mentioned
and in other studies that followed the differentiation
MDA from the normal endocervical epithelia or
benign reactive glandular proliferations of the
endocervix [11, 12].
CA125 was focal positive with cytoplasmic
distribution, predominant apical. The tumor was focal
CEA positive, with luminal localization and with a
slight intensely expression
CA125 expression. The focal positivity for CEA
and CA125 mentioned and by other authors is
considered useful in differentiation of the tumor
from the normal endocervical epithelium that is CEA
negative [11, 13–17].
Ki67 indicated a reduced index of proliferation, 1%,
confirming the mitotic activity noted in usual staining.
comparatively for minimal deviation adenocarcinoma
endometrioid type and typical endometrial adeno-
carcinoma indicate similar results.
In the case of minimal deviation adenocarcinoma the
authors communicate focal positivity for CEA and
values of the Ki67 index between 0 and 1%,
comparative to the diffuse positivity for CEA and Ki67
between 20 and 30% for the typical endometrioid
that exclude such
lesion, we made
Minimal deviation adenocarcinoma represents a
diagnostic problem because of the benign aspect of the
proliferation, which frequent delayed the diagnostic and
aggravates the prognostic of neoplasia.
Useful in the diagnosis are immunohistochemical
investigations that can decide the diagnostic.
The focal positivity for CEA and CA125, the lack of
immunostaining for ER and PR, together with a reduce
index of proliferation for Ki67 represents useful
diagnostic markers for minimal deviation adeno-
carcinoma, differentiating it for benign glandular
proliferations of the cervix.
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Diagnosis problems in a case of minimal deviation adenocarcinoma of the cervix
Figure 1 – Minimal deviation adenocarcinoma
(HE stain, ob. ×10)
Figure 2 – Minimal deviation adenocarcinoma
(HE stain, ob. ×20)
Figure 3 – Minimal deviation adenocarcinoma
(Ca125, ob. ×10)
Figure 4 – Minimal deviation adenocarcinoma
(Ca125, ob. ×20)
Cristiana Simionescu et al.
Figure 5 – Minimal deviation adenocarcinoma
(CEA, ob. ×10)
Figure 7 – Minimal deviation adenocarcinoma
(Ki67, ob. ×20)
Figure 6 – Minimal deviation adenocarcinoma
(CEA, ob. ×20)
Figure 8 – Minimal deviation adenocarcinoma
(Ki67, ob. ×40)
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Cristiana Simionescu, Professor, MD, PhD, Department of Pathology, University of Medicine and
Pharmacy of Craiova, 66 1 May Avenue, 200 628 Craiova, Romania; Phone/Fax +40251–599 228,
Received: August 30th, 2006
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staining for carcino-
Accepted: November 20th, 2006