Breast Mark
A. Helvie,
MD
#{149} Christian
Hessler,
MD2
#{149} Thomas
S. Frank,
Atypical Hyperplasia of the Mainmographic Appearance Histologic Correlation’
W
The mammograms and histologic slides of 58 cases of atypical hyperplasia (AH) of the breast were retrospectively reviewed to determine the geographic correlation (direct, near, or remote) between mammographic abnormalities (if present) and the histologic findings. A direct mammographic-histologic correlation was found In 24 of the 58 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Clustered microcalcifications were the most common mammographic abnormality that was directly correlated with AH at histologic examination. Atypical ductal hyperplasia was much more frequently associated with a direct mammographichistologic correlation than was atypical lobular hyperplasia (48% vs 9%). The authors conclude that, although no pathognomonic appearance of AH was discovered, mammographic abnormalities similar to those of small cancers could be directly correlated with histologic findings in 41% of cases. Since AH has been shown to be associated with a fiveto tenfold increased risk of subsequent invasive carcinoma, frequent clinical and at least yearly ma.mmographic follow-up is suggested once AH is discovered.
OMEN
benign
shows
a diagnosis
Radiology
#{149} Breast,
00.31,
data
calcifica-
From
Medical
of Radiology
Center,
From the 1990 RSNA scientific 29; revision received December M.A.H. Current Switzerland. C RSNA, 2
address: 1991
Department
1500
(M.A.H.,
E Medical
performed
METHODS
able
for review.
mammography
C.H.,
D.M.I.)
during
and Pathology
even those
for palpable years.
(T.S.F.),
Since
University
A total
of 58 cases
(55
women) comprised our study population. The women ranged in age from 32 to 77 years (median, 49 years). The age distnibutions were as follows: 32-45 years (16 cases), 46-60 years (27 cases), and 61-77 years (15 cases). A positive family history of carcinoma in mother, sister, or daughten was obtained in 13 of 52 cases (25%) (the medical history for six cases was unknown). Oral contraceptive pills or supplcmcntab estrogen had been used in 19 of 50 cases (38%) (8 unknown). Eight of 55 (15%) women had had contralateral breast carcinoma, including six cases of invasive ductal carcinoma, one of invasive lobular carcinoma, and one of intraductal cardnoma. The histologic subtype of AR (ductal or lobular) was different than the carcinoma subtype (ductal or lobular) in four of those eight women. Thirty-two cases of AR were in the right breast and 26 in the left. Unlike previous pathologic series of AR
cases.
All breast biopsy samples obtained from January 1986 through April 1990 at our institution that contained AH were reviewed. This time period was chosen because most women underwent preoper-
00.32.
00.71,00.72
1991; 179:759-764
the Departments
We
AND
MD
the goal of this study was to correlate the mammographic features of AR with the histologic findings, we excluded all cases in which synchronous breast cancer and AR were contained within the same breast. Also excluded were cases in which a biopsy was performed without preoperative mammography or in which manmogmams were unavailable for review. Other cases were excluded because adequate histologic material was not avail-
(1,2,4),
mammographic-not
ated surgical
ative
I
(1-9).
M. Ikeda,
cal-findings
abnormalities
of Michigan
of
a retrospective study to determine the mammographic features of AR and to correlate those features with the histologic findings. PATIENTS
Index terms: Breast, biopsy tion, 00.81 #{149} Breast neoplasms, Breast, parenchymal pattern,
breast
atypical hyperplasia (AR) have a fivefold increased risk of subsequent invasive breast carcinoma developrnent in either breast (1-3). If theme is a positive family history for breast cancer, this risk doubles and becomes equal to the risk of carcinoma in situ (1). AH can be considered a “borderline” lesion between normal breast tissue and frank carcinoma in both histologic appearance and risk of subsequent invasive carcinoma. However, it is unknown whether AH is a necessary precursor to all carcinorna in situ and invasive breast carcinoma. At the very least, AH is a marker indicating women who arc at significantly higher risk for development of invasive breast carcinoma. If AH is a precursor to carcinoma, even in a minority of cases, its detection and removal become even more important. There is little known about the mammographic features of AH in spite of extensive pathologic and epiderniologic
#{149} Debra
Breast: and
in whom
biopsy
MD
Imaging
clini-
were the trigger that biopsy in the majority
Forty-one
of 58 cases
(71%)
initiof were
biopsy either on the basis of mammographic change (21 cases) or abnormalities on the initial mammogram (20 cases). Eight cases (14%) were sampled for biopsy primarily for a palpabbc finding with or without a mammographic correlate. Five cases (9%) were sampled for blind biopsy and four (7%) were sampled for biopsy for other rcasons. Dedicated screen film mammographic equipment was used, including a 500T or recommended
for
Dr. Rm TC-2910, Ann Arbor, MI 48109-0326. assembly. Received October 4, 1990; revision requested November 13; accepted February 22, 1991. Address reprint requests to of Radiology,
Center
Centre
Hospitalier
Univisitair
Vandois,
Lausanne,
Abbreviations: plasia, kM
ADH
atypical
ductal
hyper-
atypical hyperplasia, ALH atypical lobular hyperplasia, DCIS ductal carcinoma in situ, LCIS lobular carcinoma in situ.
759
600T
(General
Mamex
Electric
CGR,
Paris)
DC Mag (Technomed
shore,
NY).
formed known
A few
and
USA,
studies
were
a
Bay-
pen-
Table 1 Mammographlc
were neviewed by two nadiobogists (M.A.H., C.H.). Abnormalities, when present, were classified into the following broad categories: micnocalcifications, nodular masses, spiculated masses, areas of asymmetric opacity, and architectural
tions
distortions.
were
number,
further
Microcalcifications Ngdular opacity Spiculated mass
classified
distortion
and
was graded
as being
normal
while
high-suspicion
low-,
lesions
recommended since only
moderate-,
would
and
usually
classified (10,11).
Corresponding
slides ment
viewed firm
the
diagnosis
(T.S.F.)
of AH,
in cases
of small,
hyperchromatic
on the basis
clinical
findings)
amined moplasty
in
grossly,
and,
that
the
microscopically
than
(whether
760
#{149} Radiology
the
versus
Correlation
ALH
Direct
Near
Remote
Direct
Near
(n20)
(n11)
(n11)
(n=1)
(n=4)
Remote (n=6)
5
0
1
0
0
0
7 8 0
5 6 0
2 1 7
0 1 0
1 3 0
0 1 5
cases
of combined
processed
ALH
and
ADH
per
joint
pathologist
into
three
ities
cifications
man-
ab-
If abnor-
reading
sesthe
the
histo-
direct,
are not included.
corresponded
were
noted
to be
site
ductal
duct
calcifications
the
inti-
AH.
Near
correlations were classified as such when the mammographic abnormality was on the same microscopic slide as the area of
AH and appeared ty, but
not
to be in close
directly
related,
lesions
mammographically
occult
were
either from
the area of AH. Although most lesions could be readily classified with this systern, a few were difficult to classify. For example, an isolated cluster of rnicrocalcifications contained within a small spccimen from a wire localized biopsy would be classified as remote when the calcifications were not on the slide containing AH, even though these calcifications may
been
immediately
adjacent
to the
removal
of the
subjective,
was
a consensus
readily
reached
on all
correlations. classified as direct or had a specimen radio-
gle case of a 4-cm was also palpable
two included a sinasymmetric opacity that and a case in which a
large
also
obtained.
nodule
These
was
these cases, geographic could be established mens and histologic During the study biopsies
were
palpable.
of all
benign
performed
biopsy
In
both
of
relationships from the gross specislides. period, 2,664 breast or
our institution. There were noses of carcinoma. AH was
proximi-
or remote
the
All but two cases near correlations
reviewed
at
1,538 diagpresent in 7%
specimens.
RESULTS
to the actual
area of AH. Remote
have
somewhat
graph of
the microscopic focus in this category, even were not apparent containing
before
mammographic-histologic
AH at histologic examination, this was considered to be a geographic direct conrelation. Usually, the mammographic finding was at the exact site of the AH. A
case in which
of AH
specimen. In this case, we underestimated the correlation as remote rather than near. Hence, although this classification agreement
to the
at the
area
was
correlation abnormal-
of AH. For example, if discovered microcal-
exact
or
categories:
geographically
histologic area mammographically
in the
cx-
time
near, and remote. A direct meant that the mammographic
half
specimen
and
relations
which
mammograms were careWe classified the mamhistologic geographic con-
lu-
and
no visible
during
logic slides and fully reviewed. mographic and
surrounded was included calcifications
re-
examined.
during
at Mammography
Moderate Low
mately of AH though
malities were then discovered, additional sections were processed. After the diagnosis of AH was confirmed, the geographic relationship of the microscopic focus of AH was correlated to the mammographic abnormality. This
was determined
of Suspicion
High
radiologists,
did
acinar
in less
was
sections
at
Note-Five
included
of mammographic
if there
between
Level
.
Normal/Benign
population
cells
were
0 0 0 13
to con-
their entirety. Reduction specimens were examined five
ALH:
and
of
Mammography
the cells
obliterate
moved
0
0 0 0 0
(ADH) and (ALH), with
in which
men or that did so only of the lobular unit. All biopsy specimens
1
1 1 1 0
ADH
of the
which
by a uniform
completely
normality,
of ADH Correlation
Level Suspicion
within the hyperplastic ducts fulfilled some, but not all, of the criteria of intraductal carcinoma, including rounded, uniform cells, regular cell placement of oval cells without streaming or onientation, and a cnibriform architectural arrangement. Cases in which ducts incompletely demonstrated these features or in which these features were limited to a single intraductal space were diagnosed as ADH. None of our cases had frank intraductal necrosis. The diagnosis of ALH was made in cases in which lobular acini
distended
1
Histologic
the criteria established by Page et al (1), Dupont and Page (2), and Cotran et al (12). Specifically, the diagnosis of ADH
were
1)
-
1)
-
Table 2 Comparison Histologic
from the Departfiles and were re-
ductal hyperplasia lobular hyperplasia
was made
(n
Normal(n13)
bemam-
by means
by a pathologist
atypical atypical
opacity
Distortion(n
hematoxylin-eosin
were retrieved of Pathology
4 2 0
be
knowledge has noted an association tween dense breasts and AH, each mogram was Wolfe system
12 2 0
and
for biopsy. Additionally, previous study to our
one
Remote (n19)
or
probably benign or having low suspicion, moderate suspicion, or high suspicion of carcinoma. A probably benign lesion would usually be recommended for inter-
val follow-up,
Near (n15)
11 4 5
2)
(n
nodule(n1) Asymmetric
geographic
27)
8) 5) and
Microcalcifications
by their
Correlation
Direct (n24)
(n (n (n
Microcalcifications
Microcalcifica-
morphology,
mabity
sions
Correlation
Mammographic Finding
distribution. A level of suspicion for hanboring malignancy was assigned to each mammographic abnormality. Each abnor-
were
and Histologic
Histologic
mammograms
not
Findings
at outside institutions with unbut dedicated equipment. All
Mammognaphic abnormalities were present in 45 cases (78%). included 27 cases of clustered
These micro-
calcifications, eight nodules, five spiculated masses, two calcifications with architectural distortion, one calcification with nodule, one asymmetric opacity, and one area of distomtion. 13
Mammograms (22%). The of suspicion
cases
levels
were normal mammognaphic were as follows:
June
in
1991
-
%-
2;-’
-
.
-
,
.
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.1’
-.
-
.
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.
a.’
_i
.
#{149}...sl:..,#{149}.)
,s...e . p
-
.-
‘:
, P
#{149}.?
#{149}
a..
#{149}
,., ,
#{149}_.,
. -
,
Microcalcifications
directly
.
.
_%._
.-
,
,..
#{149}f? i
,
‘
#{149}#{149}#{149}#{149}
#{248}#{149}
-
.
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-,
‘
:
#{149} s
: ‘
:#{149}Y0.,
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.
..
.
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*.-.
c.
b. 1.
.-_ .
./.
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-
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Figure
s;
‘:
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#{149}#{149}.
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.
.
.#{149}#{149}#{149}..
---
#{149}.
.;#{149}f.
. .
:
(
,.
.:.
correlated
with
AH in the left breast
and
intraductal
carcinoma
of the right
breast.
Microcalcifications
both breasts had developed in a 13-month period. (a) Specimen radiograph shows extensive punctate right breast microcalcifications, which were associated with pure intraductal cancer at histologic examination. Black bar indicates 5 mm. (b) Innumerable faint microcalcifications in the left breast were also present on the mammogram. These microcalcifications were directly related to an area of AH at histologic examination. Although fewer in number than those in the opposite breast, their morphology is very similar. Black bar indicates 5 mm. (c) Photomicrograph of left breast biopsy specimen shows microcalcifications (arrows) within an area of focal AH, which shows a direct conrelation (hematoxylin-eosin stain; original magnification, X200). in
ALH; 20)
the
rest
were
on contained
either
ADH
features (n 3).
ADH and ALH The microcalcifications bated directly number from
4
9,.
.‘
0.
r1
_.4L__
forms
j
V
‘
cluster
b.
2. Microcalcifications directly correlated with AH on screening mammograms. Specimen radiograph shows clustered innumerable minute punctate microcalcifications adjacent to the localization wire. Black bar indicates 5 mm. (b) Photomicrograph of biopsy specimen shows microcalcifications (arrows) within ducts involved with AH with focal cribriforming (hematoxylin-eosin stain; original magnification, X200).
(a)
normal on benign, 16 cases (28%); bow suspicion, 21 cases (36%); moderate suspicion, 15 cases (26%); and high suspicion, six cases (10%). A direct mammogmaphic-histologic comnclation was found in 24 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Table 1 companes the mammographic findings and the histologic correlation.
ADH
accounted
cases (72%) in 11 (19%), both trasts logic Note ADH only
Volume
for 42 of the
58
of AH. ALH was present and five (9%) cases had
ADH and ALH. Table 2 conthe mammognaphic and histocorrelation of ADH and ALH. that 20 of the 42 cases (48%) of had direct correlation, while one of the 1 1 cases (9%) of ALH
179
#{149} Number
3
were
median .
a. Figure
had
direct
seven
correlation.
of the
had normal mammography, cases (46%)
Conversely,
42 cases
(16%)
of ADH
on benign findings at while five of the 11 of ALH had normal or be-
nign findings. These differences flect, in large part, the absence case of calcification on spiculated mass
having
ALH. The
a direct
comein
meof any
correlation
with
mammographic-hisincluded
cases
of
(n 1 1), spicubated masses (n 5), nodular opacities (n 4), asymmetric opacities (n 1), distortion (n = 1), micmocalcifications and distortion (n = 1), and microcalcifications and nodule (n 1). Only of the
24 direct
correlates
was
noted
in three
diameter was
of the
5 mm
(range,
cases.
The
calcification 3-13
mm).
At histologic examination, the cabcifications were found to be located in mammary ducts within areas of AM in all
cases
earlier.
but
No cell
the
one
necrosis
mentioned
was
present
in any case with microcalcifications. Three of the five spiculated masses that were direct correlates had radial scbenosing lesions associated with AH (Fig 3). In the two remaining cases, the AM was surrounded by irregular fibrosis mimicking the appearance of
a small of the (mange, The
size 24 direct
tobogic correlates microcalcifications
one
that 1, 2) ranged to innumerable,
with a median of eight. In all but two cases, the individual cabcifications appeared irregular in form. The calcifications were variable in size and shape in all but one case. Linear
Si\
#{149}1
,
(Figs four
(n
of both
mm). duced
carcinoma.
The
median
size
spiculated masses was 10 mm 7-20 mm). four nodular masses ranged in
from
5 to 11 mm
Fibrosis surrounding the mammographic
(median,
10 AM profinding in
two of those cases. In the third case, the AH was associated with a papilboma that produced the mammogmaphic nodule, and in the fourth case, ductal hypcnplasia, AM, and fibrosis constituted the “nodule.” The single case of asymmetric
Radiology
#{149} 761
,
.
#{163}
a. 3. Spiculated sion shows an 8-mm power photomicrograph original
C.
mass directly correlated with AH and a radial sclerosing lesion. spiculated mass. Note calcifications associated with a degenerating shows focal AH X50). (c) High-power
magnification,
opacities produced taming
that directly by palpable AM. The single
(arrow) within a radial photomicrograph
21 as P2, Although
correlated was fibrosis condistortion
was also associated fibrosis. The single
with case
zero
extenof mi-
was
an unusual
case
ing this
fibroadenoma case, although
22 and agnosis
ADH
of a degencrat-
containing AH. the correlation
In
was geographically “direct,” the mammographic findings probably bated entirely to the fibroadenoma. The 15 cases of near correlation consisted
of 1 2 micnocalcifications,
two nodular calcification
masses, and one microwith distortion. Calcifi-
cations associated with sclcrosing adenosis near the area of AH were present in three of the 12 cases of micnocalcifications. In most cases, how-
the
calcifications
were
One of the two nodular caused by focal fibrosis The second nodule was immediately adjacent to nounced focus of AM case, it is possible that
the
duct,
producing
masses was near the AM. a small cyst a pro-
(Fig AH
the
5). In this obstructed
small
cyst.
The only case of distortion and calcification was related to a radial sclcnosing lesion adjacent to a focus of
ALH. Overall by means
breast of the
demonstrated
density Wolfe
rather
as measured classification
equal
distnibu-
tion except for the breast density pattern Ni, which was undemnepresented. Actual distribution was as fobbows:
762
15 cases #{149} Radiology
were
classified
and
as DY,
ALH
patient
study, was only patients
12 have
carcinoma
after receiving One patient with
with
the
at a di-
a subsequent
initially
with
ADH
in
the lower inner quadrant of the breast developed a nonpalpable inregular 7-mm invasive ductab cancinoma in the upper outer quadrant. An additional patient had a concurrent diagnosis of intnaductal cancer in the might breast and ADH in the left (Fig 1). Both lesions were nonpalpable micnocabcifications.
in adja-
cent ducts on lobules often associated with areas of hypemplasia. One case of microcalcification was associated with sclerosis of a fibroadenoma.
in the period two
an ipsibatenal 9 months of AM.
five as Ni. ranged from
DISCUSSION The goal of screening mammography is the detection of small cancinomas before metastatic dissemination, resulting in improved survival mates in
women
mammography
who
undergo (13).
screening However,
in
with
use of coned
compres(b)
Lowstain;
X200).
diagnosed as AM are extremely close to frank carcinoma in situ, both momphobogically and biologically. Additionalby, it is known that once AM is diagnosed, the risk of subsequent invasive carcinoma occurring in either breast is approximately five times that of the general population, and the relative risk increases to approximately 10 times that of the general population if a positive family histo-
ry is present
(1,2,4,5,12)
and
equals
that of carcinoma in situ of the breast (3). Although it is established that AM is a high-risk lesion, a more uncertain issue is the relationship of AH to the pathogenesis of breast cancinoma. Whether AH is a necessary precursor for all carcinoma in situ and the frequency of eventual development of a frank carcinoma from a focus of AM are unknown (12). In one study (14), 51% of breast carcinomas had adjacent AM, which implies a close relationship between AH and carcinoma in at least some lesions. Therefore, although prognostic information can be obtained when AM is found,
it is not
necessarily
connect
that a premalignant condition has been surgically eradicated from the breast. With this information as background, we were interested to learn to
other organ systems at risk for cancem, intervention is directed at the histologic precursors of carcinoma as well as early carcinoma. For example, cervical dysplasia is often treated before the advent of frank carcinoma in situ. Can such logic be applied to treatment of the breast, and, in panticuban, to that of AM? Histologically, by definition, AM has some but not all of the momphologic features of carcinoma in situ. As such, the distinction between AH and carcinoma in situ is admittedly somewhat subjective, and some cases
obtained
in the upper right corner. adipose tissue (hematoxylin-eosin stain; original magnification,
by
negative mammognam had a lobular carcinoma in situ sampled for biopsy from a new palpable thickening. The
other mc-
years
follow-up Presently,
developed
(a) Mammogram fibroadenoma
sclerosing lesion surrounded of area of AH (hematoxylin-eosin
17 as P1, and follow-up
to four
mean months.
cmocalcification and distortion consisted of severe AH with microcalcifications and adjacent fibrosis (Fig 4). The case of calcification and nodule
even,
5-
b.
Figure
case sive
-
assume
whether
AM
had
a characteristic
appearance.
mammogmaphic some
pathologists
reaching
define
a maximum
(5), AM would visualized mammogram,
be expected
arc
they
histologic
to be
studies
histobogic-mammognaphic
Hence,
present
must findings
crocalcifications largest
as
of 2 mm
at mammography.
if abnormalities jacent
size
not
Since AM
on of
AM
fibrosis. do
on
relate
a
to ad-
such as miThe two not
include comrela-
June
1991
direct .
:
.
,
1’
.
I
: ,.
c
.
,
,
.
.
.
e-
.
9
b. AH.
4. Irregular distorted opacity This patient had had a contralateral
with
rare microcalcifications
directly
breast carcinoma. (a) Specimen strates an irregular opacity (arrows) at tip of localization needle associated crocalcifications. Note fatty tissue surrounding mass. (b) Photomicrograph men shows AH (arrows) with surrounding fibrosis and central calcifications eosin stain; original magnification, X50).
correlated
with
radiograph demonwith two tiny miof biopsy speci(hematoxylin-
t . .
1:.. -
C
..
/
j,
/.
,
.
,i:.
..
. .
.,.J__
,
.
.. ‘
.
mass
‘i;.. 8-
In our study of 58 cases, mammographic abnormalities, often similar to those of small carcinomas, were geographically directly correlated with the histologic findings of AM in 41% of cases. All but one of the cases with direct correlates were ADH. If
mabity
one postulates that theme some type of local effect
examination.
Calci-
Volume
179
#{149} Number
3
area
of AM that
is associated
cification deposition tion, an even higher our mammognaphic
related (66%)
Of
considerable
difference
noted
inbe-
of microcalcifications
in
DCIS,
but not in lobular carcinoma in situ (LCIS). Microcalcifications are frequently seen in association with DCIS at the site of the carcinoma and,
to the
mammographic
ap-
with AM, were either
rebates. Microcalcifications common indication opsy and had the
may be around an
with
not
could dealing
all
the
cal-
on fibrotic neacpercentage of findings arc con-
as 39 of the 58 cases near on direct cor-
of DCIS).
It
is gen-
mect or near correlation was found and the marked differences in mammographic correlations between ADH and ALH, we do not believe this to be true. Fibrosis associated with AM produced mammognaphic nodular opacities, spiculations, and asymmetric opacities. Whether AM caused the fibrosis in these cases on was merely coincidental is speculative. Altemnativeby, an outside stimulus may induce both the AH and fibrosis.
We conclude
were the most a surgical binumber of
that
pathognomonic
was
discovered,
cancers with the of cases.
although
appearance
normabities for highest
features
be argued that, since one with a histologic entity
crabby under 2 mm without a macroscopic correlate, the discovery of AM is always fortuitous. Because of the high percentage of cases in which di-
tion (1,2). Mammograms were obtamed in about half of the women with AH in the study by Ashikami et al from 1960 to 1972 (4). Thirty-one percent of those mammograms were “suspicious,” although nearly all patients had a coexistent breast abnomfications were the most frequent mammognaphic abnormality, although mammographic-histobogic correlation was not discussed. In the study by Rubin et al, among 10 patients with lesions of AM, eight had microcalcifications at wire-localized biopsy and two had steblate masses; no correlation between the mammographic and histologic findings was offered (10).
presence
but
with
near correlation to AH. (a) Mammogram shows an isolated mm benign-appearing nodule that developed over a 24-month period (arrow). This nodule did not meet all sonographic criteria for a simple cyst. (b) Photomicrograph of the biopsy specimen demonstrates the nodule to be a simple cyst (c). AH (arrows) is located immediately adjacent to the cyst, a near correlation (hematoxylin-eosin stain; original magnification, X50).
at physical
lesion.
pearances of DCIS and LCIS. This mcbationship would not be unexpected if the mammographic features parabbel the histologic features (ic, if ADH contains most but not all features of DCIS at histologic examination, then the mammognaphic features of ADH might be expected to contain some
b. Nodular
(15).
is the
is parallel
t,
.1
.
5.
in with-
itous finding (15,17). The overall difference in direct correlation between ADH and ALH was striking (48% vs 9%) and, again,
./. .
Figure
masses of direct
in fact, may be the sole mammographic abnormality (16). In contrast, microcalcifications in LCIS arc often in adjacent tissue and may be a fontu-
...,d
.
at histo-
tween directly correlating cases of ADM and ALH in regard to microcalcifications. In our study, micmocabcifications were frequently directly associated with ADH, but never with ALH. This finding is parallel to the
;.
: Figure
sclemosing
(DCIS)
tenest -
AH
Spicubated percentage
The pathogenesis of micmocalcification in association with ADM is unknown, but it does not appear to melate to cell necrosis, as is believed to occur in some ductal carcinoma in situ
.
with
correlations with AM, although three of these cases the AM was in a radial
.,
amu#{216}
:‘
correlations
logic examination. had the highest
#{149}1.
.
mammographic similar
could
no of AM
to those
be directly
abof small
correlated
histologic findings in 41% This correlation with ADH
Radiology
#{149} 763
occurred
much
more
frequently
Page
DL,
MS.
Atypical
female
study. 2.
Dupont breast
11.
Pathol Lab Med 1986; 110:171-173. Ashikari R, Huvos AG, Snyder RE, et al.
12.
4.
5.
A clinicopathologic sions of the breast. 317. Tavassoli FA, Norris
3.
the results atypical
6.
Dupont
breast:
WD, Rogers LW, hyperplastic lesions a long-term
cancer
in women
with
for proliferative
#{149} Radiology
of atypical le1974; 33:310A comparison
follow-up
hyperplasia
hyperplasia
of the
breast.
of
13.
for and
intra-
14.
Cancer
1990; 65:518-529. Hutchinson WB, Thomas DB, Hamlin WB, Roth GJ, Peterson AV, Williams B. Risk of breast cancer in women with benign breast disease. J Natl Cancer Inst 1980; Page
DL,
Williams Relation
8.
10.
Vander
Zwaag
R, Rogers
LW,
WE, Hertmann WH. between component parts of fibrocystic disease complex and breast cancer. J Nail Cancer Inst 1978; 61:1055-1063. Nielsen M, Thomsen JL, Primdahl 5, Dyreborg J, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study of 1 10 medicolegal autopsies. Br J Cancer 1987; 56:614-619. Nielsen M, Jensen J, Andersen J. Precancerous and cancerous breast lesions duri.ng lifetime and at autopsy: a study of 83 women. Cancer 1984; 54:612-615. Rubin E, Visscher DW,.Alexander RW, Urist MM, Maddox WA. Proliferative disease and atypia in biopsies performed for nonpalpable lesions detected mammo-
graphically.
764
HJ.
of long-term
15.
16.
LT, Walker
Cancer
Bright Relationship
65:13-20. 7.
Rados of the
follow-up
Cancer 1985; 55:2698-2708. WD, Page DL. Risk factors
study Cancer
intraductal
ducts.!
9.
References 1.
breast disease. N EngI J Med 1985; 312: 146-151. Cancer Committee of the College of American Pathologists. Is “fibrocystic disease” of the breast precancerous? Arch
than
with ALH, paralleling the mammographic findings of DCIS and LCIS. Mammographic findings that currently lead to recommendations for surgical biopsy, especially clustered calcifications, would be expected to result in the discovery of AR in some women. In other cases, AR is mammographically occult and will be found fortuitously at biopsy performed for other reasons. Since it has been shown that women with AR are at high risk for developing subsequent carcinoma in either breast, frequent clinical breast examination as well as at least yearly mammographic follow-up is recommended if dcfinifive surgical therapy is not undertaken. In this context, the reliability of the follow-up mammographic cxamination, especially in a dense breast, must be carefully weighed. U
17.
RA, Morrison between
AS,
Brisson
J, et al.
mammographic
and
histologic features of breast tissue in women with benign biopsies. Cancer 1988; 61:266-271. Cotran R, Kumar V, Robbins S. The breast. In: Cotran R, Kumar V. Robbins 5, eds. Robbins’ pathologic basis of disease. 4th ed. Philadelphia: Saunders, 1989; 1187-1189. Kopans D. Breast imaging. Philadelphia: Lippincott, 1989; 9-15. Vilde F, Arkwright S. Lesions manmaires associ#{233}esau cancer du sein, etude de deux cents pi#{232}cesd’ex#{233}r#{232}se. Ann Pathol 1987; 7:279-284. Azzopardi JG, Ahmed A, Millis RR. Problems in breast pathology. In: Bennington JL, ed Major problems in pathology. Vol 11. London: Saunders, 1979; 446-459. Dershaw DD, Abramson A, Kinne DW. Ductal carcinoma in situ: mammographic findings and clinical implications. Radiology 1989; 170:411-415. Pope TL, Fechner RE, Wilhelm MC, Wanebott J, Paredes ES. Lobular carcinoma in situ of the breast: mammographic features. Radiology 1988; 168:63-68.
1988; 61:2077-2082.
June
1991
A. Helvie,
MD
#{149} Christian
Hessler,
MD2
#{149} Thomas
S. Frank,
Atypical Hyperplasia of the Mainmographic Appearance Histologic Correlation’
W
The mammograms and histologic slides of 58 cases of atypical hyperplasia (AH) of the breast were retrospectively reviewed to determine the geographic correlation (direct, near, or remote) between mammographic abnormalities (if present) and the histologic findings. A direct mammographic-histologic correlation was found In 24 of the 58 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Clustered microcalcifications were the most common mammographic abnormality that was directly correlated with AH at histologic examination. Atypical ductal hyperplasia was much more frequently associated with a direct mammographichistologic correlation than was atypical lobular hyperplasia (48% vs 9%). The authors conclude that, although no pathognomonic appearance of AH was discovered, mammographic abnormalities similar to those of small cancers could be directly correlated with histologic findings in 41% of cases. Since AH has been shown to be associated with a fiveto tenfold increased risk of subsequent invasive carcinoma, frequent clinical and at least yearly ma.mmographic follow-up is suggested once AH is discovered.
OMEN
benign
shows
a diagnosis
Radiology
#{149} Breast,
00.31,
data
calcifica-
From
Medical
of Radiology
Center,
From the 1990 RSNA scientific 29; revision received December M.A.H. Current Switzerland. C RSNA, 2
address: 1991
Department
1500
(M.A.H.,
E Medical
performed
METHODS
able
for review.
mammography
C.H.,
D.M.I.)
during
and Pathology
even those
for palpable years.
(T.S.F.),
Since
University
A total
of 58 cases
(55
women) comprised our study population. The women ranged in age from 32 to 77 years (median, 49 years). The age distnibutions were as follows: 32-45 years (16 cases), 46-60 years (27 cases), and 61-77 years (15 cases). A positive family history of carcinoma in mother, sister, or daughten was obtained in 13 of 52 cases (25%) (the medical history for six cases was unknown). Oral contraceptive pills or supplcmcntab estrogen had been used in 19 of 50 cases (38%) (8 unknown). Eight of 55 (15%) women had had contralateral breast carcinoma, including six cases of invasive ductal carcinoma, one of invasive lobular carcinoma, and one of intraductal cardnoma. The histologic subtype of AR (ductal or lobular) was different than the carcinoma subtype (ductal or lobular) in four of those eight women. Thirty-two cases of AR were in the right breast and 26 in the left. Unlike previous pathologic series of AR
cases.
All breast biopsy samples obtained from January 1986 through April 1990 at our institution that contained AH were reviewed. This time period was chosen because most women underwent preoper-
00.32.
00.71,00.72
1991; 179:759-764
the Departments
We
AND
MD
the goal of this study was to correlate the mammographic features of AR with the histologic findings, we excluded all cases in which synchronous breast cancer and AR were contained within the same breast. Also excluded were cases in which a biopsy was performed without preoperative mammography or in which manmogmams were unavailable for review. Other cases were excluded because adequate histologic material was not avail-
(1,2,4),
mammographic-not
ated surgical
ative
I
(1-9).
M. Ikeda,
cal-findings
abnormalities
of Michigan
of
a retrospective study to determine the mammographic features of AR and to correlate those features with the histologic findings. PATIENTS
Index terms: Breast, biopsy tion, 00.81 #{149} Breast neoplasms, Breast, parenchymal pattern,
breast
atypical hyperplasia (AR) have a fivefold increased risk of subsequent invasive breast carcinoma developrnent in either breast (1-3). If theme is a positive family history for breast cancer, this risk doubles and becomes equal to the risk of carcinoma in situ (1). AH can be considered a “borderline” lesion between normal breast tissue and frank carcinoma in both histologic appearance and risk of subsequent invasive carcinoma. However, it is unknown whether AH is a necessary precursor to all carcinorna in situ and invasive breast carcinoma. At the very least, AH is a marker indicating women who arc at significantly higher risk for development of invasive breast carcinoma. If AH is a precursor to carcinoma, even in a minority of cases, its detection and removal become even more important. There is little known about the mammographic features of AH in spite of extensive pathologic and epiderniologic
#{149} Debra
Breast: and
in whom
biopsy
MD
Imaging
clini-
were the trigger that biopsy in the majority
Forty-one
of 58 cases
(71%)
initiof were
biopsy either on the basis of mammographic change (21 cases) or abnormalities on the initial mammogram (20 cases). Eight cases (14%) were sampled for biopsy primarily for a palpabbc finding with or without a mammographic correlate. Five cases (9%) were sampled for blind biopsy and four (7%) were sampled for biopsy for other rcasons. Dedicated screen film mammographic equipment was used, including a 500T or recommended
for
Dr. Rm TC-2910, Ann Arbor, MI 48109-0326. assembly. Received October 4, 1990; revision requested November 13; accepted February 22, 1991. Address reprint requests to of Radiology,
Center
Centre
Hospitalier
Univisitair
Vandois,
Lausanne,
Abbreviations: plasia, kM
ADH
atypical
ductal
hyper-
atypical hyperplasia, ALH atypical lobular hyperplasia, DCIS ductal carcinoma in situ, LCIS lobular carcinoma in situ.
759
600T
(General
Mamex
Electric
CGR,
Paris)
DC Mag (Technomed
shore,
NY).
formed known
A few
and
USA,
studies
were
a
Bay-
pen-
Table 1 Mammographlc
were neviewed by two nadiobogists (M.A.H., C.H.). Abnormalities, when present, were classified into the following broad categories: micnocalcifications, nodular masses, spiculated masses, areas of asymmetric opacity, and architectural
tions
distortions.
were
number,
further
Microcalcifications Ngdular opacity Spiculated mass
classified
distortion
and
was graded
as being
normal
while
high-suspicion
low-,
lesions
recommended since only
moderate-,
would
and
usually
classified (10,11).
Corresponding
slides ment
viewed firm
the
diagnosis
(T.S.F.)
of AH,
in cases
of small,
hyperchromatic
on the basis
clinical
findings)
amined moplasty
in
grossly,
and,
that
the
microscopically
than
(whether
760
#{149} Radiology
the
versus
Correlation
ALH
Direct
Near
Remote
Direct
Near
(n20)
(n11)
(n11)
(n=1)
(n=4)
Remote (n=6)
5
0
1
0
0
0
7 8 0
5 6 0
2 1 7
0 1 0
1 3 0
0 1 5
cases
of combined
processed
ALH
and
ADH
per
joint
pathologist
into
three
ities
cifications
man-
ab-
If abnor-
reading
sesthe
the
histo-
direct,
are not included.
corresponded
were
noted
to be
site
ductal
duct
calcifications
the
inti-
AH.
Near
correlations were classified as such when the mammographic abnormality was on the same microscopic slide as the area of
AH and appeared ty, but
not
to be in close
directly
related,
lesions
mammographically
occult
were
either from
the area of AH. Although most lesions could be readily classified with this systern, a few were difficult to classify. For example, an isolated cluster of rnicrocalcifications contained within a small spccimen from a wire localized biopsy would be classified as remote when the calcifications were not on the slide containing AH, even though these calcifications may
been
immediately
adjacent
to the
removal
of the
subjective,
was
a consensus
readily
reached
on all
correlations. classified as direct or had a specimen radio-
gle case of a 4-cm was also palpable
two included a sinasymmetric opacity that and a case in which a
large
also
obtained.
nodule
These
was
these cases, geographic could be established mens and histologic During the study biopsies
were
palpable.
of all
benign
performed
biopsy
In
both
of
relationships from the gross specislides. period, 2,664 breast or
our institution. There were noses of carcinoma. AH was
proximi-
or remote
the
All but two cases near correlations
reviewed
at
1,538 diagpresent in 7%
specimens.
RESULTS
to the actual
area of AH. Remote
have
somewhat
graph of
the microscopic focus in this category, even were not apparent containing
before
mammographic-histologic
AH at histologic examination, this was considered to be a geographic direct conrelation. Usually, the mammographic finding was at the exact site of the AH. A
case in which
of AH
specimen. In this case, we underestimated the correlation as remote rather than near. Hence, although this classification agreement
to the
at the
area
was
correlation abnormal-
of AH. For example, if discovered microcal-
exact
or
categories:
geographically
histologic area mammographically
in the
cx-
time
near, and remote. A direct meant that the mammographic
half
specimen
and
relations
which
mammograms were careWe classified the mamhistologic geographic con-
lu-
and
no visible
during
logic slides and fully reviewed. mographic and
surrounded was included calcifications
re-
examined.
during
at Mammography
Moderate Low
mately of AH though
malities were then discovered, additional sections were processed. After the diagnosis of AH was confirmed, the geographic relationship of the microscopic focus of AH was correlated to the mammographic abnormality. This
was determined
of Suspicion
High
radiologists,
did
acinar
in less
was
sections
at
Note-Five
included
of mammographic
if there
between
Level
.
Normal/Benign
population
cells
were
0 0 0 13
to con-
their entirety. Reduction specimens were examined five
ALH:
and
of
Mammography
the cells
obliterate
moved
0
0 0 0 0
(ADH) and (ALH), with
in which
men or that did so only of the lobular unit. All biopsy specimens
1
1 1 1 0
ADH
of the
which
by a uniform
completely
normality,
of ADH Correlation
Level Suspicion
within the hyperplastic ducts fulfilled some, but not all, of the criteria of intraductal carcinoma, including rounded, uniform cells, regular cell placement of oval cells without streaming or onientation, and a cnibriform architectural arrangement. Cases in which ducts incompletely demonstrated these features or in which these features were limited to a single intraductal space were diagnosed as ADH. None of our cases had frank intraductal necrosis. The diagnosis of ALH was made in cases in which lobular acini
distended
1
Histologic
the criteria established by Page et al (1), Dupont and Page (2), and Cotran et al (12). Specifically, the diagnosis of ADH
were
1)
-
1)
-
Table 2 Comparison Histologic
from the Departfiles and were re-
ductal hyperplasia lobular hyperplasia
was made
(n
Normal(n13)
bemam-
by means
by a pathologist
atypical atypical
opacity
Distortion(n
hematoxylin-eosin
were retrieved of Pathology
4 2 0
be
knowledge has noted an association tween dense breasts and AH, each mogram was Wolfe system
12 2 0
and
for biopsy. Additionally, previous study to our
one
Remote (n19)
or
probably benign or having low suspicion, moderate suspicion, or high suspicion of carcinoma. A probably benign lesion would usually be recommended for inter-
val follow-up,
Near (n15)
11 4 5
2)
(n
nodule(n1) Asymmetric
geographic
27)
8) 5) and
Microcalcifications
by their
Correlation
Direct (n24)
(n (n (n
Microcalcifications
Microcalcifica-
morphology,
mabity
sions
Correlation
Mammographic Finding
distribution. A level of suspicion for hanboring malignancy was assigned to each mammographic abnormality. Each abnor-
were
and Histologic
Histologic
mammograms
not
Findings
at outside institutions with unbut dedicated equipment. All
Mammognaphic abnormalities were present in 45 cases (78%). included 27 cases of clustered
These micro-
calcifications, eight nodules, five spiculated masses, two calcifications with architectural distortion, one calcification with nodule, one asymmetric opacity, and one area of distomtion. 13
Mammograms (22%). The of suspicion
cases
levels
were normal mammognaphic were as follows:
June
in
1991
-
%-
2;-’
-
.
-
,
.
#{149}.
‘#{149}.:..
.1’
-.
-
.
#{149}
0..
.
a.’
_i
.
#{149}...sl:..,#{149}.)
,s...e . p
-
.-
‘:
, P
#{149}.?
#{149}
a..
#{149}
,., ,
#{149}_.,
. -
,
Microcalcifications
directly
.
.
_%._
.-
,
,..
#{149}f? i
,
‘
#{149}#{149}#{149}#{149}
#{248}#{149}
-
.
#{149} - .
-,
‘
:
#{149} s
: ‘
:#{149}Y0.,
#{149}‘;#{149}
.
..
.
#{149} .
‘.
*.-.
c.
b. 1.
.-_ .
./.
#{149}*s.
.a.
-
..
.-..----
Figure
s;
‘:
.4’: ::
#{149}#{149}.
I.,.
#{149} -
.
.
.#{149}#{149}#{149}..
---
#{149}.
.;#{149}f.
. .
:
(
,.
.:.
correlated
with
AH in the left breast
and
intraductal
carcinoma
of the right
breast.
Microcalcifications
both breasts had developed in a 13-month period. (a) Specimen radiograph shows extensive punctate right breast microcalcifications, which were associated with pure intraductal cancer at histologic examination. Black bar indicates 5 mm. (b) Innumerable faint microcalcifications in the left breast were also present on the mammogram. These microcalcifications were directly related to an area of AH at histologic examination. Although fewer in number than those in the opposite breast, their morphology is very similar. Black bar indicates 5 mm. (c) Photomicrograph of left breast biopsy specimen shows microcalcifications (arrows) within an area of focal AH, which shows a direct conrelation (hematoxylin-eosin stain; original magnification, X200). in
ALH; 20)
the
rest
were
on contained
either
ADH
features (n 3).
ADH and ALH The microcalcifications bated directly number from
4
9,.
.‘
0.
r1
_.4L__
forms
j
V
‘
cluster
b.
2. Microcalcifications directly correlated with AH on screening mammograms. Specimen radiograph shows clustered innumerable minute punctate microcalcifications adjacent to the localization wire. Black bar indicates 5 mm. (b) Photomicrograph of biopsy specimen shows microcalcifications (arrows) within ducts involved with AH with focal cribriforming (hematoxylin-eosin stain; original magnification, X200).
(a)
normal on benign, 16 cases (28%); bow suspicion, 21 cases (36%); moderate suspicion, 15 cases (26%); and high suspicion, six cases (10%). A direct mammogmaphic-histologic comnclation was found in 24 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Table 1 companes the mammographic findings and the histologic correlation.
ADH
accounted
cases (72%) in 11 (19%), both trasts logic Note ADH only
Volume
for 42 of the
58
of AH. ALH was present and five (9%) cases had
ADH and ALH. Table 2 conthe mammognaphic and histocorrelation of ADH and ALH. that 20 of the 42 cases (48%) of had direct correlation, while one of the 1 1 cases (9%) of ALH
179
#{149} Number
3
were
median .
a. Figure
had
direct
seven
correlation.
of the
had normal mammography, cases (46%)
Conversely,
42 cases
(16%)
of ADH
on benign findings at while five of the 11 of ALH had normal or be-
nign findings. These differences flect, in large part, the absence case of calcification on spiculated mass
having
ALH. The
a direct
comein
meof any
correlation
with
mammographic-hisincluded
cases
of
(n 1 1), spicubated masses (n 5), nodular opacities (n 4), asymmetric opacities (n 1), distortion (n = 1), micmocalcifications and distortion (n = 1), and microcalcifications and nodule (n 1). Only of the
24 direct
correlates
was
noted
in three
diameter was
of the
5 mm
(range,
cases.
The
calcification 3-13
mm).
At histologic examination, the cabcifications were found to be located in mammary ducts within areas of AM in all
cases
earlier.
but
No cell
the
one
necrosis
mentioned
was
present
in any case with microcalcifications. Three of the five spiculated masses that were direct correlates had radial scbenosing lesions associated with AH (Fig 3). In the two remaining cases, the AM was surrounded by irregular fibrosis mimicking the appearance of
a small of the (mange, The
size 24 direct
tobogic correlates microcalcifications
one
that 1, 2) ranged to innumerable,
with a median of eight. In all but two cases, the individual cabcifications appeared irregular in form. The calcifications were variable in size and shape in all but one case. Linear
Si\
#{149}1
,
(Figs four
(n
of both
mm). duced
carcinoma.
The
median
size
spiculated masses was 10 mm 7-20 mm). four nodular masses ranged in
from
5 to 11 mm
Fibrosis surrounding the mammographic
(median,
10 AM profinding in
two of those cases. In the third case, the AH was associated with a papilboma that produced the mammogmaphic nodule, and in the fourth case, ductal hypcnplasia, AM, and fibrosis constituted the “nodule.” The single case of asymmetric
Radiology
#{149} 761
,
.
#{163}
a. 3. Spiculated sion shows an 8-mm power photomicrograph original
C.
mass directly correlated with AH and a radial sclerosing lesion. spiculated mass. Note calcifications associated with a degenerating shows focal AH X50). (c) High-power
magnification,
opacities produced taming
that directly by palpable AM. The single
(arrow) within a radial photomicrograph
21 as P2, Although
correlated was fibrosis condistortion
was also associated fibrosis. The single
with case
zero
extenof mi-
was
an unusual
case
ing this
fibroadenoma case, although
22 and agnosis
ADH
of a degencrat-
containing AH. the correlation
In
was geographically “direct,” the mammographic findings probably bated entirely to the fibroadenoma. The 15 cases of near correlation consisted
of 1 2 micnocalcifications,
two nodular calcification
masses, and one microwith distortion. Calcifi-
cations associated with sclcrosing adenosis near the area of AH were present in three of the 12 cases of micnocalcifications. In most cases, how-
the
calcifications
were
One of the two nodular caused by focal fibrosis The second nodule was immediately adjacent to nounced focus of AM case, it is possible that
the
duct,
producing
masses was near the AM. a small cyst a pro-
(Fig AH
the
5). In this obstructed
small
cyst.
The only case of distortion and calcification was related to a radial sclcnosing lesion adjacent to a focus of
ALH. Overall by means
breast of the
demonstrated
density Wolfe
rather
as measured classification
equal
distnibu-
tion except for the breast density pattern Ni, which was undemnepresented. Actual distribution was as fobbows:
762
15 cases #{149} Radiology
were
classified
and
as DY,
ALH
patient
study, was only patients
12 have
carcinoma
after receiving One patient with
with
the
at a di-
a subsequent
initially
with
ADH
in
the lower inner quadrant of the breast developed a nonpalpable inregular 7-mm invasive ductab cancinoma in the upper outer quadrant. An additional patient had a concurrent diagnosis of intnaductal cancer in the might breast and ADH in the left (Fig 1). Both lesions were nonpalpable micnocabcifications.
in adja-
cent ducts on lobules often associated with areas of hypemplasia. One case of microcalcification was associated with sclerosis of a fibroadenoma.
in the period two
an ipsibatenal 9 months of AM.
five as Ni. ranged from
DISCUSSION The goal of screening mammography is the detection of small cancinomas before metastatic dissemination, resulting in improved survival mates in
women
mammography
who
undergo (13).
screening However,
in
with
use of coned
compres(b)
Lowstain;
X200).
diagnosed as AM are extremely close to frank carcinoma in situ, both momphobogically and biologically. Additionalby, it is known that once AM is diagnosed, the risk of subsequent invasive carcinoma occurring in either breast is approximately five times that of the general population, and the relative risk increases to approximately 10 times that of the general population if a positive family histo-
ry is present
(1,2,4,5,12)
and
equals
that of carcinoma in situ of the breast (3). Although it is established that AM is a high-risk lesion, a more uncertain issue is the relationship of AH to the pathogenesis of breast cancinoma. Whether AH is a necessary precursor for all carcinoma in situ and the frequency of eventual development of a frank carcinoma from a focus of AM are unknown (12). In one study (14), 51% of breast carcinomas had adjacent AM, which implies a close relationship between AH and carcinoma in at least some lesions. Therefore, although prognostic information can be obtained when AM is found,
it is not
necessarily
connect
that a premalignant condition has been surgically eradicated from the breast. With this information as background, we were interested to learn to
other organ systems at risk for cancem, intervention is directed at the histologic precursors of carcinoma as well as early carcinoma. For example, cervical dysplasia is often treated before the advent of frank carcinoma in situ. Can such logic be applied to treatment of the breast, and, in panticuban, to that of AM? Histologically, by definition, AM has some but not all of the momphologic features of carcinoma in situ. As such, the distinction between AH and carcinoma in situ is admittedly somewhat subjective, and some cases
obtained
in the upper right corner. adipose tissue (hematoxylin-eosin stain; original magnification,
by
negative mammognam had a lobular carcinoma in situ sampled for biopsy from a new palpable thickening. The
other mc-
years
follow-up Presently,
developed
(a) Mammogram fibroadenoma
sclerosing lesion surrounded of area of AH (hematoxylin-eosin
17 as P1, and follow-up
to four
mean months.
cmocalcification and distortion consisted of severe AH with microcalcifications and adjacent fibrosis (Fig 4). The case of calcification and nodule
even,
5-
b.
Figure
case sive
-
assume
whether
AM
had
a characteristic
appearance.
mammogmaphic some
pathologists
reaching
define
a maximum
(5), AM would visualized mammogram,
be expected
arc
they
histologic
to be
studies
histobogic-mammognaphic
Hence,
present
must findings
crocalcifications largest
as
of 2 mm
at mammography.
if abnormalities jacent
size
not
Since AM
on of
AM
fibrosis. do
on
relate
a
to ad-
such as miThe two not
include comrela-
June
1991
direct .
:
.
,
1’
.
I
: ,.
c
.
,
,
.
.
.
e-
.
9
b. AH.
4. Irregular distorted opacity This patient had had a contralateral
with
rare microcalcifications
directly
breast carcinoma. (a) Specimen strates an irregular opacity (arrows) at tip of localization needle associated crocalcifications. Note fatty tissue surrounding mass. (b) Photomicrograph men shows AH (arrows) with surrounding fibrosis and central calcifications eosin stain; original magnification, X50).
correlated
with
radiograph demonwith two tiny miof biopsy speci(hematoxylin-
t . .
1:.. -
C
..
/
j,
/.
,
.
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..
. .
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,
.
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.
mass
‘i;.. 8-
In our study of 58 cases, mammographic abnormalities, often similar to those of small carcinomas, were geographically directly correlated with the histologic findings of AM in 41% of cases. All but one of the cases with direct correlates were ADH. If
mabity
one postulates that theme some type of local effect
examination.
Calci-
Volume
179
#{149} Number
3
area
of AM that
is associated
cification deposition tion, an even higher our mammognaphic
related (66%)
Of
considerable
difference
noted
inbe-
of microcalcifications
in
DCIS,
but not in lobular carcinoma in situ (LCIS). Microcalcifications are frequently seen in association with DCIS at the site of the carcinoma and,
to the
mammographic
ap-
with AM, were either
rebates. Microcalcifications common indication opsy and had the
may be around an
with
not
could dealing
all
the
cal-
on fibrotic neacpercentage of findings arc con-
as 39 of the 58 cases near on direct cor-
of DCIS).
It
is gen-
mect or near correlation was found and the marked differences in mammographic correlations between ADH and ALH, we do not believe this to be true. Fibrosis associated with AM produced mammognaphic nodular opacities, spiculations, and asymmetric opacities. Whether AM caused the fibrosis in these cases on was merely coincidental is speculative. Altemnativeby, an outside stimulus may induce both the AH and fibrosis.
We conclude
were the most a surgical binumber of
that
pathognomonic
was
discovered,
cancers with the of cases.
although
appearance
normabities for highest
features
be argued that, since one with a histologic entity
crabby under 2 mm without a macroscopic correlate, the discovery of AM is always fortuitous. Because of the high percentage of cases in which di-
tion (1,2). Mammograms were obtamed in about half of the women with AH in the study by Ashikami et al from 1960 to 1972 (4). Thirty-one percent of those mammograms were “suspicious,” although nearly all patients had a coexistent breast abnomfications were the most frequent mammognaphic abnormality, although mammographic-histobogic correlation was not discussed. In the study by Rubin et al, among 10 patients with lesions of AM, eight had microcalcifications at wire-localized biopsy and two had steblate masses; no correlation between the mammographic and histologic findings was offered (10).
presence
but
with
near correlation to AH. (a) Mammogram shows an isolated mm benign-appearing nodule that developed over a 24-month period (arrow). This nodule did not meet all sonographic criteria for a simple cyst. (b) Photomicrograph of the biopsy specimen demonstrates the nodule to be a simple cyst (c). AH (arrows) is located immediately adjacent to the cyst, a near correlation (hematoxylin-eosin stain; original magnification, X50).
at physical
lesion.
pearances of DCIS and LCIS. This mcbationship would not be unexpected if the mammographic features parabbel the histologic features (ic, if ADH contains most but not all features of DCIS at histologic examination, then the mammognaphic features of ADH might be expected to contain some
b. Nodular
(15).
is the
is parallel
t,
.1
.
5.
in with-
itous finding (15,17). The overall difference in direct correlation between ADH and ALH was striking (48% vs 9%) and, again,
./. .
Figure
masses of direct
in fact, may be the sole mammographic abnormality (16). In contrast, microcalcifications in LCIS arc often in adjacent tissue and may be a fontu-
...,d
.
at histo-
tween directly correlating cases of ADM and ALH in regard to microcalcifications. In our study, micmocabcifications were frequently directly associated with ADH, but never with ALH. This finding is parallel to the
;.
: Figure
sclemosing
(DCIS)
tenest -
AH
Spicubated percentage
The pathogenesis of micmocalcification in association with ADM is unknown, but it does not appear to melate to cell necrosis, as is believed to occur in some ductal carcinoma in situ
.
with
correlations with AM, although three of these cases the AM was in a radial
.,
amu#{216}
:‘
correlations
logic examination. had the highest
#{149}1.
.
mammographic similar
could
no of AM
to those
be directly
abof small
correlated
histologic findings in 41% This correlation with ADH
Radiology
#{149} 763
occurred
much
more
frequently
Page
DL,
MS.
Atypical
female
study. 2.
Dupont breast
11.
Pathol Lab Med 1986; 110:171-173. Ashikari R, Huvos AG, Snyder RE, et al.
12.
4.
5.
A clinicopathologic sions of the breast. 317. Tavassoli FA, Norris
3.
the results atypical
6.
Dupont
breast:
WD, Rogers LW, hyperplastic lesions a long-term
cancer
in women
with
for proliferative
#{149} Radiology
of atypical le1974; 33:310A comparison
follow-up
hyperplasia
hyperplasia
of the
breast.
of
13.
for and
intra-
14.
Cancer
1990; 65:518-529. Hutchinson WB, Thomas DB, Hamlin WB, Roth GJ, Peterson AV, Williams B. Risk of breast cancer in women with benign breast disease. J Natl Cancer Inst 1980; Page
DL,
Williams Relation
8.
10.
Vander
Zwaag
R, Rogers
LW,
WE, Hertmann WH. between component parts of fibrocystic disease complex and breast cancer. J Nail Cancer Inst 1978; 61:1055-1063. Nielsen M, Thomsen JL, Primdahl 5, Dyreborg J, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study of 1 10 medicolegal autopsies. Br J Cancer 1987; 56:614-619. Nielsen M, Jensen J, Andersen J. Precancerous and cancerous breast lesions duri.ng lifetime and at autopsy: a study of 83 women. Cancer 1984; 54:612-615. Rubin E, Visscher DW,.Alexander RW, Urist MM, Maddox WA. Proliferative disease and atypia in biopsies performed for nonpalpable lesions detected mammo-
graphically.
764
HJ.
of long-term
15.
16.
LT, Walker
Cancer
Bright Relationship
65:13-20. 7.
Rados of the
follow-up
Cancer 1985; 55:2698-2708. WD, Page DL. Risk factors
study Cancer
intraductal
ducts.!
9.
References 1.
breast disease. N EngI J Med 1985; 312: 146-151. Cancer Committee of the College of American Pathologists. Is “fibrocystic disease” of the breast precancerous? Arch
than
with ALH, paralleling the mammographic findings of DCIS and LCIS. Mammographic findings that currently lead to recommendations for surgical biopsy, especially clustered calcifications, would be expected to result in the discovery of AR in some women. In other cases, AR is mammographically occult and will be found fortuitously at biopsy performed for other reasons. Since it has been shown that women with AR are at high risk for developing subsequent carcinoma in either breast, frequent clinical breast examination as well as at least yearly mammographic follow-up is recommended if dcfinifive surgical therapy is not undertaken. In this context, the reliability of the follow-up mammographic cxamination, especially in a dense breast, must be carefully weighed. U
17.
RA, Morrison between
AS,
Brisson
J, et al.
mammographic
and
histologic features of breast tissue in women with benign biopsies. Cancer 1988; 61:266-271. Cotran R, Kumar V, Robbins S. The breast. In: Cotran R, Kumar V. Robbins 5, eds. Robbins’ pathologic basis of disease. 4th ed. Philadelphia: Saunders, 1989; 1187-1189. Kopans D. Breast imaging. Philadelphia: Lippincott, 1989; 9-15. Vilde F, Arkwright S. Lesions manmaires associ#{233}esau cancer du sein, etude de deux cents pi#{232}cesd’ex#{233}r#{232}se. Ann Pathol 1987; 7:279-284. Azzopardi JG, Ahmed A, Millis RR. Problems in breast pathology. In: Bennington JL, ed Major problems in pathology. Vol 11. London: Saunders, 1979; 446-459. Dershaw DD, Abramson A, Kinne DW. Ductal carcinoma in situ: mammographic findings and clinical implications. Radiology 1989; 170:411-415. Pope TL, Fechner RE, Wilhelm MC, Wanebott J, Paredes ES. Lobular carcinoma in situ of the breast: mammographic features. Radiology 1988; 168:63-68.
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June
1991
