Discrepancies in the diagnosis of intraductal proliferative lesions of the breast and its management implications: Results of a multinational survey

Yale University, New Haven, Connecticut, United States
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin (Impact Factor: 2.65). 12/2006; 449(6):609-16. DOI: 10.1007/s00428-006-0245-y
Source: PubMed
ABSTRACT
To measure discrepancies in diagnoses and recommendations impacting management of proliferative lesions of the breast, a questionnaire of five problem scenarios was distributed among over 300 practicing pathologists. Of the 230 respondents, 56.5% considered a partial cribriform proliferation within a duct adjacent to unequivocal ductal carcinoma in situ (DCIS) as atypical ductal hyperplasia (ADH), 37.7% of whom recommended reexcision if it were at a resection margin. Of the 43.5% who diagnosed the partially involved duct as DCIS, 28.0% would not recommend reexcision if the lesion were at a margin. When only five ducts had a partial cribriform proliferation, 35.7% considered it as DCIS, while if >or=20 ducts were so involved, this figure rose to 60.4%. When one duct with a complete cribriform pattern measured 0.5, 1.5, or 4 mm, a diagnosis of DCIS was made by 22.6, 31.3, and 94.8%, respectively. When multiple ducts with flat epithelial atypia were at a margin, 20.9% recommended reexcision. Much of these discrepancies arise from the artificial separation of ADH and low-grade DCIS and emphasize the need for combining these two under the umbrella designation of ductal intraepithelial neoplasia grade 1 (DIN 1) to diminish the impact of different terminologies applied to biologically similar lesions.

Full-text

Available from: Fattaneh A Tavassoli
ORIGINAL ARTICLE
Discrepancies in the diagnosis of intraductal proliferative
lesions of the breast and its management implications:
results of a multinational survey
Mohiedean Ghofrani & Beatriz Tapia &
Fattaneh A. Tavassoli
Received: 10 March 2006 / Accepted: 31 May 2006 / Published online: 13 October 2006
#
Springer-Verlag 2006
Abstract To measure discrepancies in diagnoses and
recommendations impacting management of proliferative
lesions of the breast, a questionnaire of five problem
scenarios was distributed among over 300 practicing
pathologists. Of the 230 respondents, 56.5% considered a
partial cribriform proliferation within a duct adjacent to
unequivocal ductal carcinoma in situ (DCIS) as atypical
ductal hyperplasia (ADH), 37.7% of whom recommended
reexcision if it were at a resection margin. Of the 43.5%
who diagnosed the partially involved duct as DCIS, 28.0%
would not recommend reexcision if the lesion were at a
margin. When only five ducts had a partial cribriform
proliferation, 35.7% considered it as DCIS, while if 20
ducts were so involved, this figure rose to 60.4%. When
one duct with a complete cribriform pattern measured 0.5,
1.5, or 4 mm, a diagnosis of DCIS was made by 22.6, 31.3,
and 94.8%, respectively. When multiple ducts with flat
epithelial atypia were at a margin, 20.9% recom mended
reexcision. Much of these discrepancies arise from the
artificial separation of ADH and low-grade DCIS and
emphasize the need for combining these two under the
umbrella designation of ductal intraepithelial neoplasia
grade 1 (DIN 1) to diminish the impact of different
terminologies applied to biologically similar lesions.
Keywords Breast
.
Ductal carcinoma in situ
.
Hyperplasia
.
Interobserver variability
.
Ductal intraepithelial neoplasia
Introduction
The concept of atypical hyperplasia was introduced decades
ago within the continuum of intraductal breast prolifer-
ations, a continuum which encompasses benign prolifer-
ations of usual ductal hyperplasia to high-grade ductal
carcinoma in situ (DCIS) [3 5 , 7, 15, 32]. The term atypical
ductal hyperplasia (ADH) was used initially for a vaguely
defined group lesions that had some but not all of the
requisite features of ductal carcinoma in situ [21].
Subsequently, the qualitative similarity to low-grade DCIS
(LG-DCIS) was stressed, and quantitative meas ures were
introduced to separate ADH from DCIS [21, 31].
Totally arbitrary boundaries were drawn to separate ADH
from LG-DCIS, a separation that resulted in drastically
different management approaches in the 1980si.e., mas-
tectomy for those diagnosed as DCIS and follow-up for those
with a diagnosis of ADH. Now, even with widespread use of
conservative surgery, patient management differs signifi-
cantly depending on whether a lesion is diagnosed as ADH
or DCIS. The two most notable approaches for this
separation have been based on: (a) the definition by Page et
al. [21] who defined the minimum requirement for LG-
DCIS as complete involvement of at least two spaces by a
proliferation that cytologically and architecturally resem-
bles DCIS and (b) the defin ition of Tavassoli and Norris
[31] who required complete involvement of one or more
ducts by a cribriform or micropapillary proliferation of
uniform cells with low-grade nuclei exceeding 2 mm in
aggregate diameter for a diagnosis of LG-DCIS. According
to either of these two definitions, any intraductal prolifer-
Virchows Arch (2006) 449:609616
DOI 10.1007/s00428-006-0245-y
M. Ghofrani
:
B. Tapia
:
F. A. Tavassoli (*)
Department of Pathology, Yale University School of Medicine,
Lauder Hall (LH) 222, 310 Cedar St.,
New Haven, CT 06510, USA
e-mail: Fattaneh.Tavassoli@Yale.edu
Present address:
B. Tapia
Department of Pathology and Immunology,
Washington University School of Medicine,
St. Louis, MO, USA
Page 1
ative lesion that demonstrated the qualitative cytologic and
architectural features of LG-DCIS but failed to pass the
defined quantitative threshold was to be designated as
ADH.
Since then, no objective molecular, ultrastructural,
immunohistochemical, or morphometric feature has been
identified to reliably distinguish ADH from LG-DCIS
[1, 11, 15, 16, 18, 25]. Therefore, the distinction of the two
continues to be based solely on application of the arbitrary
criteria mentioned above. Frequently cited studies in the
literature, which have attempted to calculate the relative
risk of various proliferative lesions, may have claimed to
adhere to the criteria of Page et al. have actual ly deviated
from the two-space rule and have accepted single-space
involvement as DCIS, th ereby blurring the distinction
between levels of hyperplasia and atypia and diminishing
the practical utility of such a distinct ion [8].
We conducted a survey 15 and 20 years postintroduction
of these two sets of criteria to determine how much
uniformity or discrepancy exists in the interpretation of
these lesions and how it would impact current patient
management.
Materials and methods
To investigate pathologists approach to selected problems
in the diagnosis and management of intraductal prolifera-
tive lesions of the breast, a questionnaire was prepared with
diagrammatic representations of five potentially problemat-
ic scenarios in breast pathology dealing with intraductal
proliferative lesions (Figs. 1, 2, 3, 4, 5). It was decided to
use diagrammatic representations rather than glass slides to
facilitate distribution of the survey among a greater number
of pathologists and to ensure that the participants focused
on the same diagnostic issue, given the presence of certain
lesions in the background. The questionnaire also inquired
whether the respondents considered breast pathology their
area of expertise, the average number of breast biopsies and
lumpectomies or mastectomies they signed out each week,
the practice setting in which they worked in (academic,
community, or private), and how long they had been in
practice.
The questionnaire was distributed among over 300
pathologists who were either known for their expertise
and specialization in breast pathology in various countries
or who were interested in the field as evidenced by their
participation in educational courses dedicated to breast
pathology. If a participant left a response in the question-
naire blank, that response was considered null and excluded
from calculations. Also, for all questions regarding diagno-
sis and management of lesions illustrated in the question-
naire, the respondents were given the option of choosing
one of the two answers (i.e., ADH vs DCIS, Yes vs No).
The responses of the small minority who chose both were
similarly excluded from analyses. Also, if a participant
responded to the questions regarding average number of
biopsies or lumpectomies/mastectomies a week by provid-
ing a numeric range, the average value of the range was
considered for calculations. The collected responses were
anonymized and tabulated in a custom Microsoft Access
database (Microsoft Corporation, Redmond, WA, USA),
and custom queries were written for data analysis.
Statistical significance of the results was evaluated using
chi-square and t tests.
Results
A total of 230 completed questionnaires were received and
included in the study. Of the 230 respondents, 93 (40.4%)
considered breast patholog y their area of expertise, while
130 (56.5%) did not consider themselves experts but had
special interest or responsibility for signing out breast
pathology. The respondents signed out an average and
standard deviation of 10.1±9.5 biopsies and 7.5±7.8
lumpectomies or mastectomies a week. These figures were
14.4±11.4 biopsies and 10.3±9.0 lumpectomies or mastec-
tomies a week for the respo nding pathologists who
considered breast pathology their area of expertise and
6.9±6.0 biopsies and 5.3±6.0 lumpectom ies or mastecto-
mies a week for those who did not. T test showed the
differences between the means in these two groups to be
statistically significant (p <0.0001 for both biopsies and
lumpectomies/mastectomies).
Academic pathologists constituted 85 (37.0%) of the
respondents, while 11 3 (49.1%) of the respondents worked in
community hospitals and 20 (8.7%) in private laboratories.
Nine pathologists (3.9%) worked in more than one practice
setting. Sixty-five pathologists (28.3%) had been practicing
pathology for less than 5 years, 37 (16.1%) for 6 to 10 years,
and 125 (54.3%) had over 10 years of practice experience.
As shown in Fig. 1, the first question addressed whether
respondents considered a partially involved duct adjacent to
unequivocal cribriform DCIS as ADH or DCIS and, depend-
ing on their response, whether they would recommend
reexcision if this partially involved duct was less than
0.1 mm from the excision margin. Of the 230 respondents,
130 (56.5%) considered this partial cribriform proliferation as
ADH and, among these respondents, 49 (37.7%) recommend-
ed reexcision of the ADH if it were close to the excision
margin. On the other hand, of the 100 (43.5%) who diagnosed
this partially involved duct as DCIS, 28 (28.0%) would not
recommend reexcision if the lesion were close to the excision
margin. Although chi-square analysis showed that pathologists
who made a diagnosis of DCIS were significantly more likely
610 Virchows Arch (2006) 449:609616
Page 2
to recommend reexcision compared to those who made a
diagnosis of ADH (p<0.001), the final impact on patient
management was that, regardless of the diagnosis, 116
(50.4%) would recommend to have a reexcision while 108
(47.0%) would not.
Question 2 documented how respondents categorized a
partial cribriform proliferation involving a few (five) or
numerous (20 or more) ducts (Fig. 2). When only five ducts
had a partial cribriform proliferation, 82 (35.7%) of the
respondents considered it as DCIS. With 20 ducts so
involved, 139 (60.4%) of the respondents designated the
changes as DCIS. Chi-square testing showed this difference
to be statistically significant (p <0.001).
In Question 3, as shown in Fig. 3, the minimum size
requirement for diagnosis of LG-DCIS in a single duct was
addressed. When a single duct with a complete cribriform
pattern measured 0.5, 1.5, or 4 mm, a diagnosis of DCIS
was made by 52 (22.6%), 72 (31.3%), and 218 (94.8%) of
the respondents, respectively. Chi-square testing confirmed
that pathologists were significantly more likely to diagnose
DCIS if the single duct measured >2 mm (p<0.001).
Question 4 addressed the ap proach to management of
flat epithelial atypia when it was present in multiple ducts
located within less than 0.1 mm from the excision margin
(Fig. 4). In this scenario, when multiple ducts with flat
epithelial atypia were close to an excision margin, 48
respondents (20.9%) recommended reexcision .
“A” is a single duct with unequivocal cribriform grade 1 DCIS
“B” is a duct with partial involvement by a cribriform pattern located <0.1 mm from the
margin.
1. What is your diagnosis for duct “B”?
____ DCIS
____ ADH
2. Would you recommend re-excision?
____ Yes
____ No
B
A
Fig. 1 The first scenario
assessed how pathologists
would diagnose a partially in-
volved duct adjacent to un-
equivocal cribriform DCIS, and
whether they would recommend
reexcision if it were less than
0.1 mm from a resection margin
There are multiple ducts (5) with partial cribriform proliferation; there is no necrosis.
1. What is your diagnosis?
____ DCIS
____ ADH
2. What would your diagnosis be if > 20 ducts showed the same finding?
____ DCIS
____ ADH
Fig. 2 In question 2, partici-
pants were asked whether
the number of partially involved
ducts affects their decision to
make a diagnosis of ADH
Virchows Arch (2006) 449:609616 611
Page 3
Finally, quest ion 5 evaluated how respondents measured
invasive carcinoma when two foci of stromal microinvasion
(measuring less than 1 mm each) emanated from two
opposite poles of a 1-cm duct with high-grade comedo-type
DCIS (Fig. 5). Of the 230 respondents, 185 (80.4%)
measured these as two separate foci of microinvasion (less
than 1 mm each), while 37 (16.1%) considered the total size
of invasive carcinoma as the aggregate diameter of the
high-grade DCIS plus the two microinvasive foci, namely,
1.19 cm.
Chi-square testing was perfor med t o com pare the
responses of exp ert breast pathologists and nonexperts to
all five questions. No statistically significant difference was
found between the two groups in the proportion of
responses to any of the questions.
Discussions
These results indicate that 15 and 20 years postintroduction
of criteria for separation of ADH from DCIS [21, 31],
interobserver variability in the diagnosis of intraductal
proliferative lesions of the breast has not diminished. Given
the significance of margin involvement or proximity in
current management of DCIS, this survey demonstrates an
There is a single 1.5 mm duct with classic cribriform nuclear grade 1 pattern; there is no
necrosis.
1. What is your diagnosis?
____ DCIS
____ ADH
2. What would your diagnosis be if the duct were 0.5mm?
____ DCIS
____ ADH
3. What would your diagnosis be if the duct were 4mm?
____ DCIS
____ ADH
Fig. 3 Responses to question 3
demonstrated what pathologists
thought was the lowest size
threshold required to make a
diagnosis of DCIS
The cribriform grade 1 DCIS (A) is more than 5mm from the inked margin.
Multiple ducts with flat epithelial atypia are within < 0.1 mm of the inked margin (B).
Would you recommend re-excision?
____ Yes
____ No
A
B
Fig. 4 Question 4 evaluated
how participants would manage
flat epithelial atypia close to a
resection margin
612 Virchows Arch (2006) 449:609616
Page 4
even wider variability that exists in the management of such
lesions and ultimately patient care.
In a survey done by Rosai in 1991, 17 ductal and lobular
proliferative breast lesions were distributed among five
experts in breast pathology [24]. The participants were
asked to catego rize such lesions, which had already been
circled on glass slides, as either hyperplasia, atypical
hyperplasia, carcinoma in situ, or other (to be specified)
based on the diagnostic criteria they used in their daily
practice. In that study, there was no a single case in which
all five pathologists agreed on the diagnosis, and there were
only three cases (18%) in which four of the five
pathologists agreed. Also, some pathologists tended to
make more malignant diagnoses than others. In his report,
Rosai considered this interobserver variability to be
unacceptably high and suggested the a doption of a
terminology such as mammary intraepithelial neoplasia
with a grading system similar to that which was being used
for the uterine cervix.
A poss ibl e e xp la na ti on for such a high degree o f
interobserver variability set forth in that report was that
the pathologists were not using a standard set of criteria.
Therefore, a year later, Schnitt et al. [27] tried a different
approach to assess interobserver variability in the diagnosis
of intraductal proliferative lesions of the breast. In their
1992 survey, they asked six experts in breast pathology to
evaluate 24 proliferative ductal lesions. In this survey, the
participating pathologists agreed to use the criteria of Page
et al., and 15 teaching slides representing class ic examples
of usual ductal hyperplasia, atypical ductal hyperplasia, and
noncomedo DCIS were circulated among the six patholo-
gists to foster concordance before initiation of the study.
The specific area of interest on each study slide was
indicated by masking all the surrounding tissue so that all
the participants focused on the same lesion and to prevent
any bias that may result from assessment of changes in the
surrounding breast tissue. The participants in this survey
were asked to adhere to the provided criteria rather than the
ones they used in their daily practice. Despite all these
efforts, there was complete agreement among all six
pathologists in only 14 (58%) of the 24 cases and among
five or more pathologists in 17 cases (71%). The most
common diagnostic problem was the distinction of atypical
hyperplasia from DCIS in six cases. Although this study
showed a significant improvement in interobserver agree-
ment compared to Ro sais survey, the p ersistence of
significant differences among expert breast pathologists
even under optimal and highly artificial conditions con-
veyed a more widespread pro blem in the pathology
community with potential impact on patient management.
Responses to the current survey also demonstrate that
although criteria to distinguish ADH from DCIS have been
introduced over two decades ago, there is still no agreement
on how to categorize these two types of mammary intra-
ductal proliferation. While the sole partially involved duct
described in question 1 would not qualify as DCIS
according to the criteria set forth by either Page et al. or
Tavassoli and Norris, 43.5% of practicin g pathologists,
nevertheless, diagnosed it as DCIS. This might seem logical
because the partially involved duct probably reflects an
extension of the same process present in the nearby
unequivocal cribriform DCIS. However, the fact remains
that there is no consensus on what to designate a partially
involved duct adjacent to unequivocal LG-DCIS and how
to manage such a lesion when it is near or on the surgical
excision margin [10]. Even among the respondents who
considered the partially involved duct in question 1 as
ADH, more than a third recommended reexcision if it were
close to the margin of resection, and of those who
considered this partially involved duct as DCIS, close to
30% would not recommend reexcision even if the in situ
carcinoma were within 0.1 mm of the resection margin.
There is a single duct (B) with high grade DCIS and comedo-necrosis and two
unequivocal foci of stomal invasion, each <1mm, at opposite poles of the duct (A and C)
1. The size of the invasive carcinoma is:
_____ Two separate foci of microinvasion, <1mm each (A and C)
_____ The sum of A+B+C (a
pp
roximatel
y
1.2cm)
<1 mm
<1mm
1.2cm
A
CB
Fig. 5 Question 5 surveyed
how pathologists measured in-
vasive carcinoma in the pres-
ence of multifocal
microinvasion
Virchows Arch (2006) 449:609616 613
Page 5
This interobserver variability in diagnosis and management
was so high that, in the end, patients would have an almost
50:50 chance of having a reexcision or not, regardless of
the diagnosis of the partially involved duct as ADH or
DCIS. This w as due to a combination of the high
proportion diagnosing it as DCIS and the high proportion
of those who recommended reexcision even though they
interpreted it as ADH. Obviously, the impact of this issue
goes beyond simply margin involvement; it is also crucial
in the assessment of lesion size, resulting in widely varied
assessment of size/extent of LG-DCIS.
Question 2 addressed the concept of extensive ADH.
Cognizant of the fact that available criteria require complete
involvement of duct cross sections for a diagnosis of low-
grade (cribrif orm or micropapillary) varia nts of DCIS, it
was surprising to find that even when only five ducts were
involved by a partial cribriform proliferation, over 35% of
the respondents considered it as DCIS. Furthermore, when
greater than 20 ducts were partially involved by such a
cribriform proliferation, the proportion of respondents who
treated it as DCIS rose significantly to over 60%. Chi-
square testing showed that as the number of partially
involved ducts increased, the number of patients diagnosed
with cancer significantly increased. Nevertheless, even with
drastic differences in the number of involved ducts (5 vs
20), there was no unanimity in the diagnosis of carcinoma
in situ vs atypical hyperplasia.
This scenario has become increasingly more frequent
since the introduction of screening mammography. It was
not addressed in the criteria introduced by either Page et al.
or Tavassoli and Norris because both those retrospective
studies were based on predominantly premammographic
era biopsies. With the increasing number of such extensive
ADH cases (Q20 partially involved ducts) seen in her
consultation practice, Tavassoli suggested that even when
these are designated as extensive ADH due to strict
adherence to previously defined criteria, they should be
managed as DCIS and reexcised if close to or at the margin
of resection [29].
Question 3 demonstrated that the majority of respond-
ents used the 2-mm size criterion rather than the two spaces
in diagnosing DCIS. When the single duct described in the
question measured greater than 2 mm (4 mm), close to 95%
of the respondents considered it DCIS. However, if this
single duct measured less than 2 mm, i.e., 0.5 or 1.5 mm,
22.6 and 31.3% of the respondents considered it DCIS,
respectively. Although this difference in the probability of
diagnosing DCIS when the lesion measured less than or
greater than 2 mm was statistically significant, it is
interesting to note that over 30% of the respondents
considered a single duct measuring 1.5 mm as DCIS and
over 20% designated a single duct measuring only 0.5 mm
as carcinoma in situ despite the fact that these two scenarios
meet neither the criteria of Page et al., whi ch require two
completely involved spaces not otherwise specified as to
size [21], n or the criteria of Tavassoli and Norris, which
require one or more spaces greater than 2 mm in maximal
cross-sectional diameter [31]. Even with a substanti al 4 mm
duct, 5.2% did not designate the lesion as DCIS presumably
because of the two-space requirement of Page et al. These
responses demonstrate that in the current day to day
practice of pathology, some women with a 0.5-mm lesion
would be diagnosed as having DCIS, with a reexcision if it
were close to or at the resection margin, and most probably
radiation therapy, whereas some women with 4 mm lesions
interpreted as ADH would get no reexcision, would be
simply followed up, or at most would enter some form of
prevention trial with hormone therapy [2, 9].
Question 4 in our survey documented the confusion that
exists regarding the management of flat epithelial atypia,
with over 20% of respondents recommending reexcision if
the lesion were close to an excision margin. As a result,
over a fifth of the patients would have reexcision, while the
remaining 80% would not.
The last question showed the various approaches
pathologists take in measuring invasive carcinoma when
multifocal early invasion emanating from a single duct is
present. Although over 80% of respondents would consider
foci of invasion less than 1 mm emanating from opposite
poles of a duct with DCIS as microinvasion, slightly over
16% of responde nts would measure DCIS with its
associated microinvasion from opposite poles as one
continuous invasive carcinoma, which would entail a
drastically different treatment approach.
The results of this survey raise numerous questions
about studies performed in different countries and even
different institutions within the same country regarding
risk factors, treatment, prognosis, and outcom e of intra-
ductal proliferative lesions of the breast, which include
LG-DCIS and/or ADHa significant proportion of
mammographically detected noninvasive lesions. Even
when the criteria used are explicitly stated, application
of criteria varies remarkably among pathologists and
from one study to the next. Certainly, the issues raised in
this study are not uncommon but have not been
specifically addressed in any of the major single-,
multiinstitutional , or multinational studies on DCIS cases
that include LG-DCIS. Most if not all such studies lack a
central review of the diagnosis and even many rely on
multiple pathologists at sometimes mul tiple institutions.
This study also illustrates that 15 to 20 years of
education of pathologists at local, national, and interna-
tional courses has not helped much in increasing the
level of agreement and uniformity in the diagnosis and
interpretation of these common lesions using the criteria
available for separating ADH from LG-DCIS. Chi-square
614 Virchows Arch (2006) 449:609616
Page 6
testing failed to reveal any statistically significant
difference in the response behavior of expert breast
pathologists and pathologists who did not consider
themselves experts.
Since the institution of widespread screening mammog-
raphy, the number of early, LG-DCIS lesions that are
diagnosed has dramatically increased [13, 14, 19]. How
partially involved ducts, often spread around completely
involved ducts, are interpreted could change the size/extent
of the l esion by several centimeters. This potentially
undermines the internal consistency and comparability of
epidemiological studies and clinical trials regarding such
lesions.
In his 1991 survey, Rosai lamented the fact that there
were no known morphometric, ultrastructural, immunohis-
tochemical, or molecular features to distinguish ADH from
LG-DCIS [24]. Unfortunately, this issue continues to be the
case [1, 11, 15, 16, 18, 25]. Pathol ogists must assign lesions
within the ADHDCIS continuum to one end of the
spectrum or the other based on the morphologic features
present on an H&E-stained slide and an arbitrary set of
quantitative criteria that cannot be applied to every lesion
encountered. Not only the subjective nature of interpreting
the morphologic findings but also the existence of different
and in some cases conflicting diagnostic criteria create
considerable interobserver variability in distinguishing
ADH from LG-DCIS.
This diagnostic variability in turn leads to confusion
regarding the optimal mana gement ap proach to such
intraductal proliferative lesions because a diagnosis of
LG-DCIS is automatically associated with a significantly
worse prognosis and usually requires a more drastic
surgical approach compared to ADH. Furthermore, the
negative imp act of the diagnosis of carcinoma, albeit an
in situ one, on patients psychological well-being (depres-
sion and anxiety) has been well documented [12, 23] and
should be a consideration in the choice of optimal
terminology.
Molecular, immunohistochemical, and morpholog ic
similarities indicate that the only difference between
ADH and LG-DC IS is a quantitative one [1, 11, 15, 16,
18, 25]. The claim that separation of ADH from LG-DCIS
is justified based on the development of carcinomas post-
ADH in either breast while those that develop after LG-
DCIS occur in the same breast is questionable [20, 22, 26].
Over a period of 23 years, three papers have appeared on
this topic based on a group of 28 women with a median
follow-up of 31 years, noting that the invasive carcinomas
that occur after LG-D CIS treated by biopsy alone develop
in the same breast and in the same quadrant from which the
original biopsy with DCIS was taken. Seven of the 11
women who developed subsequent invasive carcinoma
were diagnosed within 10 years of the DCIS biopsy, 1
was diagnosed within 12 years, and the remaining 3
developed infiltrating carcinomas over 2342 years. The
authors conclude that these results indicate a striking
dividing point biologically and histopathologically between
LG-DCIS lesions and the cytologically similar but lesser
lesions of ADH
[26]. When 7 of the 28 women developed
invasive carcinoma within 10 years, one wonders why the
remaining patients were not contacted to receive appropri-
ate therapy for their disease rathe r than continuing the study
for another 20 years.
Judging from the microscopic description and the
sampling documented for these 28 cases, a substantial
number of these lesions were probably not low grade
because they had some atypia and/or necrosis, albeit not
diffusely, suggesting that those who died within 10 years
most likely had substantial amount of residual disease
and/or higher grade DCIS lesions [ 6 ]. The gross and
pathologic features of these 28 cases are described in detail
in the initial paper published in 1982, which did not refer to
them as low grade [20]. Therefore, it is more likely that this
study reflects the natural history of a wide variety of
intraductal carcinomas, only some of which were LG-
DCIS. A more simple explanation for any differences that
might exist between ADH and LG-DCIS in the frequency
of subsequent progression would be that a min uscule
lesion, once totally removed, results in near equalization
of the risk for subsequent development of carcinoma in the
two breasts of that individual patient. A more extensive
process, however, is less likely to be completely eliminated
by conservative surgical excision alone, leading to the
development of recurrences at the same site due to residual
disease [6].
A recent epidemiological study has shown a nearly equal
incidence rate (5.4 vs 4.5/1,000 person-years) for develop-
ment of subsequent invasive carcinoma in either breast after
a diagnosis o f DCIS among close to 37,700 patients
diagnosed between January 1988 and December 2002,
many of whom wer e treated by surgery and radiation
therapy [17]. This confirms the fact that once a DCIS is
adequately treated, it results in equalization of risk for
either breast. Furthermore, it indicates that complete
excision is an adequate therapy for smal l lesions. Therefore,
complete excision with adequate margins should be
explored further as the only therapy for small DIN 1 (DCIS
grade 1) lesions that do not exceed 34 mm in maximum
extent, particularly when there is no evidence of even any
flat epithelial atypia around the DCIS.
It seem s only logical to adopt a terminology in which
two morpho logically ide ntical lesions are not given
diagnostic designations as different as hyperplasia and
carcinoma. The use of the DIN terminology may help
solve this problem [28, 30]. Although the DIN terminology
does not claim to reduce interobserver variability, it
Virchows Arch (2006) 449:609616 615
Page 7
diminishes the effect of drastically different designations
for similar lesions by including the spectrum of atypical
ductal hyperplasia and LG-DCIS under the umbrella
designation of grade 1 DIN.
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    • "Another questionnaire study involving 200 breast surgeons in the United Kingdom showed less variation in surgeon practices with 91% of respondents favoring no further surgery if there was ADH at the margin of excision, but both invasive and in situ disease were 10 mm clear of the margin [20]. There is a large practice variation amongst American pathologists as well as demonstrated in the study conducted by Ghofrani et al. [18], which was described earlier in our paper. In addition to classifying the proliferative lesion adjacent to DCIS as ADH or DCIS, the pathologists were also asked what to do with the lesion if it involved the margin of a BCS specimen. "
    [Show abstract] [Hide abstract] ABSTRACT: Background. Negative margins are associated with a reduced risk of ipsilateral breast tumor recurrence (IBTR) in women with early stage breast cancer treated with breast conserving surgery (BCS). Not infrequently, atypical ductal hyperplasia (ADH) is reported as involving the margin of a BCS specimen, and there is no consensus among surgeons or pathologists on how to approach this diagnosis resulting in varied reexcision practices among breast surgeons. The purpose of this paper is to establish a reasonable approach to guide the treatment of ADH involving the margin after BCS for early stage breast cancer. Methods. the published literature was reviewed using the PubMed site from the US National Library of Medicine. Conclusions. ADH at the margin of a BCS specimen performed for early stage breast cancer is a controversial pathological diagnosis subject to large interobserver variability. There is not enough data evaluating this diagnosis to change current practice patterns; however, it is reasonable to consider reexcision for ADH involving a surgical margin, especially if it coexists with low grade DCIS. Further studies with longer followup and closer attention to ADH at the margin are needed to formulate treatment guidelines.
    Full-text · Article · Dec 2012 · International Journal of Surgical Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Implantable cardioverter/defibrillator devices use different algorithms to recognize ventricular tachycardia and ventricular fibrillation from sinus rhythm. However problems remain, especially differentiating physiologic high rhythms from life threatening situations. In order to test detection abilities of different methods, off-line analysis was performed in time (rate counting, autocorrelation function, statistical methods) and in frequency (digital fast Fourier transform) domains on bipolar electrograms that were obtained in 28 patients during the implantation of an automatic defibrillator. Tachycardia and fibrillation were induced and recordings made of the ECG, right ventricular electrogram and aortic pressure. Results showed that even simple methods perform equally well compared to calculation intensive methods
    No preview · Conference Paper · Oct 1994
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Columnar cell lesions of the breast represent a spectrum of lesions which have in common the presence of columnar epithelial cells lining variably dilated terminal duct lobular units, ranging from those that show little or no cytologic or architectural atypia to those that show sufficient cytologic and architectural features to warrant a diagnosis of atypical ductal hyperplasia or ductal carcinoma in situ. Recent studies have begun to provide insights into the biological nature and clinical significance of these lesions. In this article, we review the current state of knowledge and propose a simplified scheme for their classification.
    Full-text · Article · Jun 2003 · Advances in Anatomic Pathology
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