Breast Imaging
Radiology
Harmindar K. Gill, MD
Olga B. Ioffe, MD
Wendie A. Berg, MD, PhD
Index terms:
Breast, biopsy, 00.114, 00.1261,
00.1267, 00.12985
Breast, diseases, 00.31, 00.32, 00.72,
00.815
Published online before print
10.1148/radiol.2281020447
Radiology 2003; 228:50 –57
Abbreviations:
ADH ⫽ atypical ductal hyperplasia
DCIS ⫽ ductal carcinoma in situ
1
From the Department of Radiology,
Johns Hopkins University School of
Medicine, Baltimore, Md (H.K.G.), and
Departments of Pathology (O.B.I.) and
Radiology (W.A.B.) and Greenebaum
Cancer Center (W.A.B.), University of
Maryland, 419 W Redwood St, Suite
110, Baltimore, MD 21201. From the
2000 RSNA scientific assembly. Re-
ceived April 18, 2002; revision re-
quested June 19; final revision received
November 6; accepted November 27.
Address correspondence to W.A.B.
(e-mail: waberg@umaryland.edu).
Author contributions:
Guarantor of integrity of entire study,
W.A.B.; study concepts and design,
W.A.B.; literature research, W.A.B.,
H.K.G., O.B.I.; clinical studies, W.A.B.,
H.K.G., O.B.I.; data acquisition, W.A.B.,
H.K.G., O.B.I.; data analysis/interpreta-
tion, W.A.B., H.K.G.; manuscript prepa-
ration and editing, W.A.B.; manuscript
definition of intellectual content, W.A.B.,
O.B.I.; manuscript revision/review and fi-
nal version approval, W.A.B., H.K.G.,
O.B.I.
© RSNA, 2003
50
When Is a Diagnosis of
Sclerosing Adenosis
Acceptable at Core Biopsy?1
PURPOSE: To determine concordance of imaging findings and diagnosis of scle-
rosing adenosis at histopathologic core biopsy and to establish the accuracy of core
biopsy when cancer was coexistent.
MATERIALS AND METHODS: From a database of 1,166 percutaneous biopsies in
which sclerosing adenosis was reported, 88 (7.5%) lesions were identified, and
imaging and histopathologic findings were reviewed for concordance. Sclerosing
adenosis proved to be a minor component at core biopsy for 44 lesions, including
one invasive ductal carcinoma, one ductal carcinoma in situ (DCIS), one focus of
atypical ductal hyperplasia (ADH), and one atypical lobular hyperplasia. Sclerosing
adenosis was a major (ⱖ50%) component for 44 lesions, including four malignan-
cies, all DCIS manifested as clustered calcifications (pleomorphic [n ⫽ 2] or amor-
phous [n ⫽ 2]), and seven foci of ADH manifested as amorphous calcifications. In 30
patients with 33 lesions without atypia or malignancy, sclerosing adenosis was the
major finding at core biopsy (21 lesions at 14-gauge core biopsy and 12 at 11-gauge
vacuum-assisted biopsy); these patients formed the study population. Mammo-
graphic (33 lesions) and sonographic (18 lesions) features were recorded. Twenty-
seven lesions had at least 20-month follow-up (n ⫽ 25) or excision (n ⫽ 2).
RESULTS: One spiculated mass was considered discordant and was excised, show-
ing a prospectively unrecognized radial sclerosing lesion with several 2–5-mm foci of
invasive tubular and lobular carcinoma. Seventeen (53%) of 32 lesions manifested
as masses; 10 (59%) were circumscribed, five (29%) were indistinctly marginated
(one with punctate calcifications), and two (12%) were partially circumscribed and
partially obscured (one with amorphous calcifications). Fifteen (47%) lesions man-
ifested as clustered calcifications; nine (60%) were amorphous and indistinct, four
(27%) were pleomorphic, and two (13%) were punctate. Of 27 lesions with
acceptable follow-up, 26 (96%) were believed to have been accurately sampled at
core biopsy. Of six radial sclerosing lesions associated with the original 88 lesions,
only three (50%) were prospectively recognized.
CONCLUSION: Sclerosing adenosis is an acceptable result at core biopsy of circum-
scribed masses and nonpalpable indistinctly marginated masses and for clustered
amorphous, pleomorphic, and punctate calcifications. Recognition and reporting of
coexistent radial sclerosing lesions is encouraged and may prompt excision. Malig-
nancy can be seen with sclerosing adenosis; core biopsy was accurate in six (86%)
of seven coexistent malignancies in this series.
© RSNA, 2003
Sclerosing adenosis is a type of adenosis, which is a proliferative lesion of the terminal duct
lobular unit characterized by an increased number of acini that may either produce a mass
(florid adenosis, or the extreme, adenosis tumor) (1) or become surrounded by stromal
sclerosis (sclerosing adenosis). Described by Foote and Stewart (2), adenosis represents a
spectrum of benign alterations of breast tissue, the minimal form of which is an incidental
microscopic change considered to be but a variation of normal (3).
Adenosis and sclerosing adenosis retain the lobular architecture, but it becomes exag-
 gerated and distorted. The involved lob-
ules show an increased number of acini,
which become compressed and obliter-
ated by stromal fibrosis in sclerosing ad-
enosis (Fig 1). There is atrophy of the
epithelial cells and increase in the num-
Radiology
ber of myoepithelial cells that become
very prominent. The process is more pro-
nounced in the center of former lobules,
whereas the periphery is characterized by
cystically dilated epithelial profiles. Al-
though usual forms of sclerosing adeno-
sis retain lobular architecture, there are
instances in which sclerosing adenosis
extends into fat or even shows perineural
invasion (4). By definition, individual
lobular units have at least 50% of their
acini involved with the sclerosing pro-
cess.
Sclerosing adenosis also can be seen as a
component of other proliferative lesions,
such as intraductal and/or sclerosing pap-
illoma and complex sclerosing lesion, and
can be present within fibroadenomas. Fur-
ther, sclerosing adenosis can coexist with
both invasive and in situ cancers. Scleros-
ing adenosis can manifest as a palpable
mass or as a suspicious finding at mam-
mography that consists of architectural
distortion, indeterminate microcalcifica-
tions, or both (5,6).
We sought to determine concordance of
imaging findings and a diagnosis of scle-
rosing adenosis at histopathologic core bi-
opsy and to establish the accuracy of core
biopsy when cancer was coexistent.
MATERIALS AND METHODS
Patients and Lesions
Imaging findings and details of the
procedures were prospectively recorded
in a database for 1,166 consecutive core
biopsies performed at the University of
Maryland from July 1995 through Octo-
ber 2000. Our institutional review board
did not require its approval or patient
consent for review of the database, as it is
maintained for quality assurance and is
password protected. We identified 88
(7.5%) biopsies, with sclerosing adenosis
listed on the original histopathologic re-
port. The original histopathologic slides
were reviewed again by a breast patholo-
gist (O.B.I.). In 44 (50%) cases, sclerosing
adenosis proved to be a minor compo-
nent of the core biopsy (Fig 2). For these
cases, sclerosing adenosis was seen with
cancer (n ⫽ 2), fibrocystic changes (n ⫽
18), fibroadenoma (n ⫽ 10), papilloma
(n ⫽ 6), radial scar (n ⫽ 2), radial scleros-
ing lesion (n ⫽ 2), and one each of atyp-
ical ductal hyperplasia (ADH), atypical
Volume 228 䡠 Number 1
lobular hyperplasia, duct adenoma, and
granulomatous inflammation. One of
the malignancies was an invasive ductal
carcinoma manifested as a palpable, mam-
mographically occult, sonographically in-
distinct marginated mass that was sampled
with a 14-gauge biopsy, with cancer in-
volving the area of sclerosing adenosis. The
second malignancy, with sclerosing adeno-
sis as a minor component, was ductal car-
cinoma in situ (DCIS) manifested as clus-
tered punctate calcifications, in which
sclerosing adenosis was adjacent and
which also contained calcifications at 11-
gauge biopsy. One focus of ADH mani-
fested as amorphous calcifications, and
one atypical lobular hyperplasia with re-
gional punctate and amorphous calcifica-
tions both within and adjacent to it each
showed adjacent minor sclerosing adeno- Figure 1. Photomicrograph of sclerosing ad-
sis with calcifications at 11-gauge biopsy. enosis at 11-gauge vacuum-assisted biopsy of
clustered amorphous calcifications (arrows).
In 44 lesions, sclerosing adenosis com-
Stromal fibrosis causes compression and oblit-
prised the majority of the lesion sampled eration of the epithelial profiles, which are in-
at core biopsy. Four lesions included foci creased in number. The resulting architectural
of DCIS: two clustered amorphous calci- distortion is evident. (Hematoxylin-eosin
fications and two clustered pleomorphic stain; original magnification, ⫻4.)
calcifications, both with calcifications in
the cancer and adjacent sclerosing ad-
enosis; all were sampled with 11-gauge
directional probe (Mammotome; Biopsys,
biopsy. Seven lesions included foci of
division of Ethicon Endo-Surgery, Cincin-
ADH; six manifested as amorphous calci-
nati, Ohio), with a median of 12 specimens
fications, which were sampled with 11-
(range, 6–18) obtained circumferentially.
gauge biopsy, and one was an indistinctly
Specimen radiography was performed after
marginated mass, which was sampled
all biopsies and specimens containing cal-
sonographically with 14-gauge biopsy. Cal-
cifications were inked according to the
cifications were seen in both ADH and scle-
method of Berg et al (7). For all lesions
rosing adenosis in all six calcified lesions.
manifested as calcifications, calcifications
All atypical and malignant lesions were ex-
were retrieved. Clip placement (Micromark
cised, with no change in diagnoses.
I or II; Biopsys, division of Ethicon Endo-
In 33 of 44 lesions in 30 patients, scle-
Surgery) was performed coaxially with the
rosing adenosis was the major and clini-
probe for all 11-gauge biopsies.
cally most important finding (with no
atypia or malignancy) at core biopsy. These
Imaging and Review
patients formed the study population (Fig
2). Of the 33 lesions, 15 were masses that The age of patients and any risk factors
were sampled with a 14-gauge automated for breast cancer that are routinely asked
biopsy gun (Bard Monopty, Covington, in our screening program (family history
Ga) with sonographic guidance by using a of breast cancer, personal history of
linear-array broadband transducer with breast cancer, or atypia) were reviewed.
center frequency of 10 MHz (Acoustic Im- Mammograms were obtained for all 33
aging, Tempe, Ariz). A median of five spec- lesions and were reviewed again by two
imens were obtained (range, 2–7). Five le- authors (H.K.G. and W.A.B.) in consen-
sions that manifested as clustered sus for size and the Breast Imaging Re-
calcifications were subjected to biopsy with porting and Data System, or BI-RADS,
stereotactic guidance (LoRad [now Ho- features of the lesions subjected to bi-
logic]; DSM, Danbury, Conn) by using a opsy. Mammographically circumscribed
14-gauge automated biopsy gun (Manan masses recommended for biopsy were ei-
Medical Products, Northbrook, Ill), with a ther new (n ⫽ 2), enlarging (n ⫽ 3), pal-
median of six passes (range, five to six). pable (n ⫽ 2), or ipsilateral (n ⫽ 1) to
Another 13 lesions (11 clustered calcifica- cancer. Spot magnification views were
tions, one spiculated mass, and one cir- available for all lesions with calcifica-
cumscribed mass with calcifications) were tions. If both pleomorphic and amor-
subjected to biopsy by using stereotactic phous calcifications (8) were present, the
guidance and an 11-gauge vacuum-assisted lesion was classified as pleomorphic. If
Sclerosing Adenosis at Core Biopsy 䡠 51
Radiology
Figure 2. Diagram of the study population. ALH ⫽ atypical lobular hyperplasia, IDC ⫽ invasive ductal carcinoma, ILC ⫽ invasive lobular
carcinoma.
both amorphous and punctate calcifica-
tions were present, the lesion was classi-
fied as amorphous. Sonography was per-
formed for 18 mass lesions, and static
images were reviewed again by the same
two authors in consensus for size, margin
analysis, echogenicity, and posterior fea-
tures according to the draft of the BI-
RADS ultrasonographic lexicon (9).
We routinely recommend excision for
all malignant and atypical results and
when imaging findings are considered
highly suspicious for malignancy. We also
recommend excision after needle biopsy
yields a radial scar or a radial sclerosing
lesion due to a potential risk of associated
malignancy (10,11). Six-, 12-, and 24-
month follow-up is recommended for all
other results. Of the 33 lesions, one was
excised due to a highly suspicious mam-
mographic finding and one was excised as
part of a mastectomy for the ipsilateral in-
vasive ductal cancer with associated scle-
rosing adenosis. After biopsy, imaging fol-
low-up of at least 20 months (mean, 36
months; range, 20 – 66 months) was avail-
able for 25 (81%) of the 31 remaining le-
sions. The six lesions with no follow-up were
four nonpalpable circumscribed masses, one
indistinctly marginated mass, and one clus-
ter of amorphous calcifications believed to
have been removed at initial biopsy.
52 䡠 Radiology 䡠 July 2003
Concordance
A lesion was considered well sampled
at core biopsy and concordant with the
diagnosis of sclerosing adenosis in the
following circumstances: We required
the absence of atypia or malignancy at
histopathologic examination; sclerosing
adenosis was the most important finding.
We deliberately sampled to include the
edge of masses; for masses, the interface
between a lesion and fat had to be seen at
histopathologic examination. The scle-
rosing adenosis had to appear as a dis-
crete process, representing 50% or more
of the material present, with the lesion
diameter at histopathologic examination
within 2 mm of the diameter at mam-
mography and/or sonography (or occu-
pying the entire specimen for masses ⬎2
cm in diameter). For calcifications, sev-
eral situations applied. For foci less than
10 mm in diameter, the entire lesion was
believed to have been removed or nearly
removed; for foci 10 mm or greater, the
equivalent of at least two specimens had
to contain at least five calcifications each
at specimen radiography. In each sce-
nario, equivalent calcifications had to be
identified at histopathologic examina-
tion in areas of sclerosing adenosis. For
all lesions with calcifications, sclerosing
adenosis had to represent at least 50% of
the lesion present at histopathologic exam-
ination. Finally, if the imaging findings
were highly suggestive of malignancy, and
core biopsy findings showed only scleros-
ing adenosis, discordance was suspected
and excision was recommended.
Malignancies
We separately analyzed all final diag-
noses of malignancy with coexisting scle-
rosing adenosis in the context of other
imaging and histopathologic findings at
review of the original 88 lesions. For le-
sions manifested as calcifications, we ex-
amined whether calcifications were in
malignancy, sclerosing adenosis, neither,
or both.
RESULTS
The mean age of the 30 patients with 33
foci of sclerosing adenosis as the major
and most important finding at core bi-
opsy (no malignancy or atypia) was 48
years (age range, 35–72 years), with 23
(70%) of the lesions in women younger
than 50 years and 19 (58%) of the lesions
in women aged 45–54 years. Of the 30
patients, nine (30%) had a personal his-
tory of prior (n ⫽ 4) or concurrent (n ⫽ 5)
Gill et al
 breast cancer (four ipsilateral and five
contralateral). The mean lesion diameter
was 13 mm (range, 2– 41 mm).
Twenty-seven lesions had follow-up af-
ter initial biopsy. Of 14 foci of calcifica-
Radiology

tions with follow-up, 11 (79%) were gone

and three (21%) had stable residual calcifi-
cations. Thirteen masses had follow-up.
One spiculated mass was excised because
of a highly suspicious imaging appearance
and yielded several small foci (ⱕ2 mm in
diameter) of invasive carcinoma with tubu-
lar and lobular features adjacent to and
involving a radial sclerosing lesion (evi-
dent retrospectively at the core biopsy, Fig
3). This represents a false-negative core bi-
opsy finding. Another indistinctly margin-
ated mass ipsilateral to cancer was excised
at mastectomy and was confirmed to be
sclerosing adenosis. Eight masses (four cir-
cumscribed, three indistinctly marginated,
and one partially obscured) were stable,
and two circumscribed masses and one
partially obscured mass had increased in
diameter. The patients chose continued
follow-up despite recommendation for re-
peat biopsy. One mass doubled in largest
diameter in the first 3 years of follow-up
but then remained stable for 2 additional
years. Two masses showed 20% increase in
the largest diameter in the first 2 years of
follow-up and then remained stable for 2
and 3 additional years.

Concordance
Thus, of the 33 lesions with sclerosing
adenosis as the major finding, one that
manifested as a spiculated mass was ex-
cised and proved to be malignant, and,
therefore, sclerosing adenosis was indeed
a discordant result. The mammographic
and sonographic features of the 33 le-
sions are summarized in the Table. Of 17
masses accepted as sclerosing adenosis, 10
(59%) were circumscribed (eight at mam-
mography and 10 at sonography), five
(29%) were indistinctly marginated, and
two (12%) were partially circumscribed
and partially obscured. One indistinctly Figure 3. Images in a 40-year-old woman with history of prior contralateral cancer, with
marginated mass contained punctate calci- sclerosing adenosis, radial sclerosing lesion, and multiple small foci of invasive ductal (tubular)
fications (Fig 4), and one indistinctly mar- and lobular carcinoma. (a) Craniocaudal spot magnification mammogram shows 15-mm spicu-
lated mass (arrow). (b) Photomicrograph of 11-gauge stereotactic biopsy specimen initially
ginated mass contained amorphous calci-
interpreted as only sclerosing adenosis. Because of the highly suspicious mammographic find-
fications (Fig 5). The latter 17 results were ings, excision was recommended. Second review demonstrated this associated radial sclerosing
considered concordant. lesion at core biopsy as suggested by the central elastosis (arrowheads). (Hematoxylin-eosin stain;
Of the 15 foci of calcifications without original magnification, ⫻20.) (c) Low-power microscopic view of the excisional specimen shows
an associated mass, all were clustered. a portion of the radial sclerosing lesion. A small (2-mm in diameter) focus of invasive ductal
Calcification morphology was amor- (tubular) carcinoma (arrow) is noted adjacent to and involving the sclerosing lesion. Other
scattered foci of tumor manifested as isolated nests of cells and single cells. (Hematoxylin-eosin
phous or indistinct for nine (60%) of 15
stain; original magnification, ⫻15.) (d) High-power microscopic view of invasive ductal (tubular)
calcifications (Fig 6), pleomorphic for carcinoma at excisional histopathologic examination (close-up of area marked in c). Note that
four (27%), and punctate for two (13%). individual duct profiles (arrowheads) lack an outer myoepithelial layer, which is compatible with
Calcifications were seen in areas of scle- tubular carcinoma. (Hematoxylin-eosin stain; original magnification, ⫻40.)
rosing adenosis in all cases, and these
results were considered concordant.

Volume 228 䡠 Number 1 Sclerosing Adenosis at Core Biopsy 䡠 53


Imaging Features of 33 Lesions Yielding Sclerosing Adenosis at Core Biopsy
Lesion No. of Lesions Mammography Sonography
Masses (n ⫽ 18)
Spiculated 1 (6)* 1 ND
Radiology
Circumscribed 10 (56) 8 10
Indistinctly marginated 5 (17) 2† 5 the increased risk of breast cancer with
Obscured and circumscribed 2 (11) 2 2
Not seen NA 5‡ 1†
Clustered calcifications (n ⫽ 15)
Amorphous and indistinct 9 (60) 9 NA
Pleomorphic 4 (27) 4 NA
Punctate 2 (13) 2 NA
Note.—Data in parentheses are percentages. NA ⫽ not applicable, ND ⫽ not done.
* The one 15-mm spiculated mass was excised, yielding tiny foci of invasive carcinoma with
tubular and lobular features adjacent to and involving a radial sclerosing lesion (Fig 3).
† One indistinctly marginated mass had associated amorphous and punctate calcifications at
mammography and was not seen at sonography (Fig 5c).
‡ Of the five masses not seen mammographically, two were sonographically circumscribed and
three were sonographically indistinctly marginated.
Accuracy
Of the 27 lesions with acceptable fol-
low-up, 26 (96%) were believed to
have been adequately sampled at core
biopsy.
Malignancies
Overall, of 88 lesions with sclerosing
adenosis, seven (8%) proved to be malig-
nant. Of seven malignancies, five (71%)
were clustered calcifications in both DCIS
and sclerosing adenosis. Two foci of DCIS
manifested as pleomorphic calcifications;
two, as amorphous; and one, as punctate
calcifications. The two invasive cancers
were masses; one was spiculated (Fig 3),
and one was palpable and indistinctly
marginated and seen only at sonography.
Figure 4. Craniocaudal spot magnification Of seven coexistent malignancies, six
mammogram in a 43-year-old woman with an (86%) were accurately diagnosed at core
indistinctly marginated mass containing clus- biopsy.
tered punctate microcalcifications (arrow).
Of the 88 lesions, six (7%) had an as-
Eleven-gauge vacuum-assisted biopsy yielded
sociated radial sclerosing lesion, and only
sclerosing adenosis.
three (50%) of these six were prospec-
tively recognized. As described, the one
spiculated mass had an associated pro-
spectively unrecognized radial sclerosing
Of the 33 lesions showing sclerosing
lesion at core biopsy and was excised,
adenosis as the major and clinically most
yielding malignancy.
important finding at core biopsy, three
(9%) had incidental small papillomas iden-
tified only at a second review of the his- DISCUSSION
topathologic examination. Two of these
three lesions were found to also have an Sclerosing adenosis is a proliferative le-
associated radial sclerosing lesion that was sion most common in perimenopausal
not reported initially; one was a 10-mm women. An increased risk of breast can-
circumscribed mass that proved to be sta- cer ranging from 1.7- to 3.7-fold has been
ble for 52 months of follow-up, and the reported in most series (12,13). Tavassoli
second was a 3-mm focus of pleomorphic and Norris (14) found that among 82
calcifications believed to have been com- women with ADH and a 12-year follow-
pletely removed at 11-gauge biopsy and up, 17% of those who also had sclerosing
gone at follow-up. adenosis developed invasive carcinoma
54 䡠 Radiology 䡠 July 2003
compared with only 4% of those without
sclerosing adenosis. Interestingly, 30% of
patients in our series had a personal his-
tory of cancer separate from the site of
sclerosing adenosis.
Several observations may help explain
sclerosing adenosis. Findings of one
study (15) demonstrated increased estro-
gen receptor expression, as well as Ki-67
in sclerosing adenosis, radial scars, papil-
lomas, fibroadenomas, and phyllodes tu-
mors but not in apocrine cysts. Shoker et
al (15) suggest that the degree of dysregu-
lation of estrogen receptor correlates
with the degree of risk of developing
breast cancer. Increased estrogen recep-
tor expression in proliferative lesions
may also help explain the observation of
Cahn et al (16): Predisposing lesions
(sclerosing adenosis, papilloma, or ADH)
were seen in 36 (63%) of 57 women re-
ceiving hormonal replacement therapy,
whereas only 30 (30%) of 99 women with
nonproliferative lesions were treated
with hormonal replacement therapy
(odds ratio, 3.9).
Sclerosing adenosis can coexist with
cancer, as was seen in 8% of lesions in
this series. For six (86%) of the seven
lesions, the coexistent cancer was suc-
cessfully sampled, and, to our knowl-
edge, for the other 80 benign lesions the
diagnosis was accurate, with an overall
accuracy of 99% (87 of 88 lesions). For
the 27 lesions with sclerosing adenosis as
the major finding at core biopsy and an
acceptable follow-up, 26 (96%) were ac-
curately sampled. One mammographi-
cally spiculated mass had in retrospect a
radial sclerosing lesion at core biopsy
that was associated with sclerosing ad-
enosis and was found to have several
2-mm or smaller foci of infiltrating carci-
noma with tubular and lobular features
in and around the radial sclerosing lesion
at excision (false-negative core biopsy
finding). In the series of Nielsen (1), five
(19%) of 27 adenosis tumors were associ-
ated with DCIS. Carcinoma can be a mi-
nor component of sclerosing lesions, as
was the case in five (71%) of seven can-
cers in this series. Westenend and Liem
(17) recently reported one false-negative
core biopsy diagnosis with missed associ-
ated DCIS and invasive carcinoma in a
6-cm mass, which showed only scleros-
ing adenosis at core biopsy.
Sclerosing adenosis can be difficult to
distinguish from infiltrating carcinoma
both mammographically and microscop-
ically. In the series of Tinnemans et al
(18), two patients underwent unneces-
sary mastectomy on the basis of interpre-
Gill et al
 tation of sclerosing adenosis on a frozen
section as cancer. In the series of 27 ad-
enosis tumors reported by Nielsen (1),
three patients underwent unnecessary
mastectomy. Distinction between adeno-
sis and infiltrating carcinoma is based on
Radiology

the presence (and hyperplasia) of an

outer myoepithelial cell layer in adenosis
and its absence in invasive cancer. A use-
ful adjunct in such a differential diagno-
sis is the use of immunostaining for
smooth muscle actin in myoepithelial
cells and thereby in sclerosing adenosis
but not in invasive cancers (19).
Involvement of sclerosing adenosis by
in situ carcinoma can be extremely diffi-
cult to distinguish from invasive carci-
noma (20,21). This has been reported
with both ductal (22,23) and lobular car-
cinomas in situ (24 –26). Staining for
smooth muscle actin to demonstrate
myoepithelial cells or for collagen type
IV or laminin to demonstrate preserva-
tion of basement membrane can help, as
both are lost in invasive lesions (22,23).
Sclerosing adenosis can be part of a
papilloma, a radial scar, or the larger
complex sclerosing lesion. Indeed, asso-
ciated complex or radial sclerosing le-
sions were seen in six (7%) of 88 lesions
in this series. While radial sclerosing le- Figure 5. Images in a 43-year-old woman with bilateral masses due to sclerosing adenosis.
sions can be incidental findings, when (a, b) Palpable, circumscribed mass (indicated with a radiopaque marker) in the outer left breast
depicted mammographically they are containing a single coarse calcification (arrow) both at (a) mammography and (b) transverse
usually seen as spiculated masses or areas sonography (10-MHz). The mass yielded sclerosing adenosis at 14-gauge sonographically guided
core biopsy. (c) Mediolateral spot magnification mammogram reveals amorphous and punctate
of isolated architectural distortion (27).
calcifications (arrowheads) within an indistinctly marginated mass in the right breast, which
Across several series (10,11,27), small as- developed 5 years later. (d) Photomicrograph reveals focus of sclerosing adenosis with calcifica-
sociated carcinomas (usually DCIS or tu- tions (arrowheads) at stereotactically guided 11-gauge biopsy, with associated fibrocystic changes.
bular cancer) were seen in 48 (22%) of (Hematoxylin-eosin stain; original magnification, ⫻20.)
221 excised radial sclerosing lesions and
another 39 (18%) lesions had associated
ADH or lobular carcinoma in situ.
The management of core biopsies missed cancer in our series. It is not clear distortions, with none of 28 calcifica-
yielding radial sclerosing lesions remains at this time that excision is required tions without atypia proving to be malig-
somewhat controversial. Liberman’s re- when calcifications have been well sam- nant (32). No associated malignancies
view (28) revealed that three (13%) of 23 pled percutaneously with a benign con- were missed when sampling was per-
lesions yielding a radial sclerosing lesion cordant result and an incidental radial formed with a directional vacuum-as-
at core biopsy proved to be malignant at scar is identified at histopathologic ex- sisted device and when at least 12 speci-
excision. Reynolds (29) found that 43% amination. In this series, in the one case mens were obtained (32).
of radial sclerosing lesions that were vis- of pleomorphic calcifications yielding If the central elastosis of a radial scle-
ible mammographically as spiculated le- sclerosing adenosis with a radial scar, in rosing lesion is not adequately demon-
sions or masses with architectural distor- retrospect, the lesion was believed to strated in core specimens, only sclerosing
tion proved to be malignant, compared have been completely removed, with no adenosis may be seen. Indeed, the one
with a 1.2% malignancy rate when a ra- residual lesion at 24-month follow-up. cancer missed at core biopsy in this series
dial sclerosing lesion was an incidental Philpotts et al (31) found no malignan- did have an associated radial sclerosing
adjacent finding at histopathologic ex- cies among eight radial scars diagnosed at lesion evident at second review (Fig 3).
amination when core biopsy was per- stereotactic biopsy of calcifications. Bren- Recognition of the radial sclerosing le-
formed for another lesion. While scleros- ner et al (32) reviewed findings of 157 sion at core biopsy can be problematic
ing adenosis can cause a spiculated mass core biopsies yielding a radial scar with because the overall architecture is not al-
both in this setting and without an asso- 24 months of follow-up. Of 29 lesions ways evident. Indeed, in our study, three
ciated radial sclerosing lesion (30), the with associated ADH, eight (28%) proved (9%) of 33 core biopsies with sclerosing
risk of missing an associated carcinoma to be malignant (32). Of 128 lesions with- adenosis as the major finding proved to
would seem to justify excision when a out associated atypia, five proved to be have an unreported radial sclerosing le-
spiculated mass yields only sclerosing ad- malignant, including two (3%) of 60 sion in retrospect, and only three (50%)
enosis at core biopsy, as in the one masses and three (8%) of 40 architectural of six associated radial sclerosing lesions

Volume 228 䡠 Number 1 Sclerosing Adenosis at Core Biopsy 䡠 55


Radiology
Figure 6. Mediolateral spot magnification
mammogram in a 54-year-old woman with
clustered amorphous calcifications (arrow) due
to sclerosing adenosis, which was proven at
11-gauge vacuum-assisted stereotactic biopsy.
were prospectively recognized. When
present at core biopsy, it appears impor-
tant that the pathologist attempt to rec-
ognize and report a radial sclerosing le-
sion, as it may affect the decision to
excise the lesion.
Fibroadenomas can show a spectrum
of associated fibrocystic lesions, includ-
ing sclerosing adenosis. These fibroade-
nomas are often referred to as complex
and carry an increased risk of malig-
nancy, as much as threefold in either
breast (33). Indeed, when we reviewed
lesions initially interpreted as sclerosing
adenosis, we found 10 (11%) of 88 were
seen within fibroadenomas and six (7%)
had small adjacent papillomas not re-
ported initially. Shabtai et al (34) found
23% of fibroadenomas with associated
sclerosing adenosis. We are unable to
specifically address the frequency of scle-
rosing adenosis in all fibroadenomas in
our database.
Isolated sclerosing adenosis and simple
adenosis have been reported in associa-
tion with amorphous indistinct calcifica-
tions (35,36), ADH (35,36), and typically
low-grade DCIS (36,37). Further, all of
these entities can coexist. In one large
series (12), atypical lobular hyperplasia
was found to be 2.7 times more common
in sclerosing adenosis lesions than in
other biopsy findings. Clustered amor-
phous calcifications were the most com-
mon type associated with sclerosing ad-
enosis in this series, though pleomorphic
and punctate calcifications were also
seen. Provided the calcifications have
been well sampled at core biopsy, scleros-
ing adenosis is an acceptable result for
such lesions. As described by Preece (38),
56 䡠 Radiology 䡠 July 2003
sclerosing adenosis can also be evident
mammographically as scattered bilateral
punctate and amorphous calcifications,
though such findings are usually consid-
ered benign or probably benign and do
not generally result in biopsy (39,40). We
do not accept a diagnosis of sclerosing
adenosis for core biopsy of calcifications
of any morphology in a segmental or lin-
ear distribution nor for individually lin-
ear or fine-branching calcifications typi-
cal of high-grade DCIS (37,41– 43).
Both in the series of Liberman et al (44)
and that of Philpotts et al (45), no under-
estimation of disease occurred when all
calcifications were believed to have been
removed at 11-gauge biopsy. In the series
of Berg et al (36), three of 113 stereotactic
biopsies yielding amorphous calcifica-
tions were underestimates (97% accura-
cy). Since completion of this analysis, we
found one 4-mm focus of amorphous cal-
cifications in a linear distribution, which
had been only minimally sampled at ste-
reotactic vacuum-assisted biopsy (with
two calcifications in one core specimen)
that yielded sclerosing adenosis; this
proved to be DCIS at excision.
Masses caused by nodular sclerosing
adenosis have been previously reported
(1,6,46,47). In the series of DiPiro et al
(6), seven (70%) of 10 such masses were
circumscribed at mammography and five
(71%) of seven were oval at sonography.
None were spiculated. Nielsen and
Nielsen (46) reported that sclerosing ad-
enosis could present as a circumscribed
or stellate mass or irregular density with
or without calcifications. As mentioned,
Franquet et al (30) also describe scleros-
ing adenosis as a potential cause of a spic-
ulated mass. Again, we would suggest
that the risk of an associated and un-
sampled cancer at core biopsy in the set-
ting of a spiculated mass justifies exci-
sion. We do accept sclerosing adenosis as
concordant for circumscribed or indis-
tinctly marginated masses. Given the po-
tential risk of associated DCIS and even
invasive cancer, it would also seem pru-
dent to recommend excision or at least
rebiopsy of subsequently enlarging masses
that yield only sclerosing adenosis at core
biopsy, though this requires further study.
The three patients in this series with an
enlarging mass that was previously sam-
pled, yielding sclerosing adenosis, have de-
clined surgical intervention or rebiopsy,
and the masses did subsequently stabilize
at longer term follow-up.
In summary, careful review of the im-
aging and histopathologic findings is re-
quired after a core biopsy diagnosis of
sclerosing adenosis. Such a result is not
acceptable for lesions with high suspi-
cion of malignancy, including spiculated
masses, branching or fine linear calcifica-
tions, or calcifications in a segmental or
linear distribution. Recognition of associ-
ated radial sclerosing lesions may be
problematic; if present, these should be
reported, and excision may be appropri-
ate for masses or architectural distortion
in association with radial sclerosing le-
sions. Excision or rebiopsy may also be
appropriate for subsequently enlarging
masses or increasing calcifications that
yield only sclerosing adenosis at core bi-
opsy because of the potential association
with high-risk lesions, DCIS, and inva-
sive cancer. Sclerosing adenosis is an ac-
ceptable, concordant result at core biopsy
of circumscribed masses and nonpal-
pable indistinctly marginated masses and
at vacuum-assisted biopsy of well-sam-
pled clustered punctate, amorphous,
and/or pleomorphic calcifications.
References
1. Nielsen BB. Adenosis tumour of the
breast: a clinicopathological investigation
of 27 cases. Histopathology 1987; 11:1259 –
1275.
2. Foote F Jr, Stewart F. Comparative studies
of cancerous vs non-cancerous breasts.
Ann Surg 1945; 12:6 –53.
3. Hughes LE, Mansel RE, Webster DJ. Aber-
rations of normal development and invo-
lution (ANDI): a new perspective on patho-
genesis and nomenclature of benign breast
disorders. Lancet 1987; 2:1316 –1319.
4. Taylor HB, Norris HJ. Epithelial invasion
of nerves in benign diseases of the breast.
Cancer 1967; 20:2245–2249.
5. MacErlean DP, Nathan BE. Calcification
in sclerosing adenosis simulating malig-
nant breast calcification. Br J Radiol 1972;
45:944 –945.
6. DiPiro PJ, Gulizia JA, Lester SC, Meyer JE.
Mammographic and sonographic appear-
ances of nodular adenosis. AJR Am J
Roentgenol 2000; 175:31–34.
7. Berg WA, Jaeger B, Campassi C, Kumar D.
Predictive value of specimen radiography
for core needle biopsy of noncalcified
breast masses. AJR Am J Roentgenol 1998;
171:1671–1678.
8. American College of Radiology. Illus-
trated Breast Imaging Reporting and Data
System (BI-RADS). 3rd ed. Reston, Va:
American College of Radiology, 1998.
9. Mendelson EB, Berg WA, Merritt CR. To-
ward a standardized breast ultrasound lex-
icon, BI-RADS: ultrasound. Semin Roentge-
nol 2001; 36:217–225.
10. Sloane JP, Mayers MM. Carcinoma and
atypical hyperplasia in radial scars and
complex sclerosing lesions: importance
of lesion size and patient age. Histopa-
thology 1993; 23:225–231.
11. Frouge C, Tristant H, Guinebretiere JM, et
al. Mammographic lesions suggestive of
radial scars: microscopic findings in 40
cases. Radiology 1995; 195:623– 625.
12. Jensen RA, Page DL, Dupont WD, Rogers
LW. Invasive breast cancer risk in women
Gill et al
 with sclerosing adenosis. Cancer 1989;
64:1977–1983.
13. Bodian CA, Perzin KH, Lattes R, Hoff-
mann P, Abernathy TG. Prognostic signif-
icance of benign proliferative breast dis-
ease. Cancer 1993; 71:3896 –3907.
14. Tavassoli FA, Norris HJ. A comparison of
Radiology
the results of long-term follow-up for
atypical intraductal hyperplasia and in-
traductal hyperplasia of the breast. Can-
cer 1990; 65:518 –529.
15. Shoker BS, Jarvis C, Clarke RB, et al. Ab-
normal regulation of the oestrogen recep-
tor in benign breast lesions. J Clin Pathol
2000; 53:778 –783.
16. Cahn MD, Tran T, Theur CP, Butler JA.
Hormone replacement therapy and the
risk of breast lesions that predispose to
cancer. Am Surg 1997; 63:858 – 860.
17. Westenend PJ, Liem SJ. Adenosis tumor
of the breast containing ductal carcinoma
in situ, a pitfall in core needle biopsy.
Breast J 2001; 7:200 –201.
18. Tinnemans JG, Wobbes T, Holland R, et
al. Mammographic and histopathologic
correlation of nonpalpable lesions of the
breast and the reliability of frozen section
diagnosis. Surg Gynecol Obstet 1987;
165:523–529.
19. Bussolati G, Alfani V, Weber K, Osborn
M. Immunocytochemical detection of ac-
tin on fixed and embedded tissues: its
potential use in routine pathology. J His-
tochem Cytochem 1980; 28:169 –173.
20. Eusebi V, Collina G, Bussolati G. Carci-
noma in situ in sclerosing adenosis of the
breast: an immunocytochemical study.
Semin Diagn Pathol 1989; 6:146 –152.
21. Fechner RE. Carcinoma in situ involving
sclerosing adenosis (letter). Histopathol-
ogy 1996; 28:570.
22. Rasbridge SA, Millis RR. Carcinoma in
situ involving sclerosing adenosis: a
mimic of invasive breast carcinoma. His-
topathology 1995; 27:269 –273.
23. Prasad ML, Osborne MP, Hoda SA. Obser-
vations on the histopathologic diagnosis
of microinvasive carcinoma of the breast.
Anat Pathol 1998; 3:209 –232.
24. Fechner RE. Lobular carcinoma in situ in
sclerosing adenosis: a potential source of
Volume 228 䡠 Number 1
confusion with invasive carcinoma. Am J
Surg Pathol 1981; 5:233–239.
25. Oberman HA, Markey BA. Noninvasive
carcinoma of the breast presenting in ad-
enosis. Mod Pathol 1991; 4:31–35.
26. Jung WH, Noh TW, Kim HJ, Kim DY, Lee
HD, Oh KK. Lobular carcinoma in situ in
sclerosing adenosis. Yonsei Med J 2000;
41:293–297.
27. Hassell P, Klein-Parker H, Worth A, Poon
P. Radial sclerosing lesions of the breast:
mammographic and pathologic correla-
tion. Can Assoc Radiol J 1999; 50:370–375.
28. Liberman L. Clinical management issues
in percutaneous core breast biopsy. Ra-
diol Clin North Am 2000; 38:791– 807.
29. Reynolds HE. Core needle biopsy of chal-
lenging benign breast conditions: a com-
prehensive literature review. AJR Am J
Roentgenol 2000; 174:1245–1250.
30. Franquet T, De Miguel C, Cozcolluela R,
Donoso L. Spiculated lesions of the
breast: mammographic-pathologic corre-
lation. RadioGraphics 1993; 13:841– 852.
31. Philpotts LE, Shaheen NA, Jain KS, Carter
D, Lee CH. Uncommon high-risk lesions
of the breast diagnosed at stereotactic
core-needle biopsy: clinical importance.
Radiology 2000; 216:831– 837.
32. Brenner R, Jackman R, Parker S, et al. Per-
cutaneous core needle biopsy of radial
scars: when is excision necessary? AJR
Am J Roentgenol 2002; 179:1179 –1184.
33. Dupont WD, Page DL, Parl FF, et al. Long-
term risk of breast cancer in women with
fibroadenoma. N Engl J Med 1994; 331:
10 –15.
34. Shabtai M, Saavedra-Malinger P, Shabtai
EL, et al. Fibroadenoma of the breast:
analysis of associated pathological enti-
ties—a different risk marker in different
age groups for concurrent breast cancer.
Isr Med Assoc J 2001; 3:813– 817.
35. Stomper PC, Cholewinski SP, Penetrante
RB, Harlos JP, Tsangaris TN. Atypical hy-
perplasia: frequency and mammographic
and pathologic relationships in exci-
sional biopsies guided with mammogra-
phy and clinical examination. Radiology
1993; 189:667– 671.
36. Berg WA, Arnoldus CL, Teferra E, Bharga-
van M. Biopsy of amorphous breast calci-
fications: pathologic outcome and yield
at stereotactic biopsy. Radiology 2001;
221:495–503.
37. Bassett LW. Mammographic analysis of
calcifications. Radiol Clin North Am
1992; 30:93–105.
38. Preece PE. Sclerosing adenosis. World
J Surg 1989; 13:721–725.
39. Sickles E. Breast calcifications: mammo-
graphic evaluation. Radiology 1986; 160:
289 –293.
40. Sickles EA. Periodic mammographic fol-
low-up of probably benign lesions: results
in 3,184 consecutive cases. Radiology
1991; 179:463– 468.
41. Stomper PC, Connolly JL. Ductal carci-
noma in situ of the breast: correlation
between mammographic calcification
and tumor subtype. AJR Am J Roentgenol
1992; 159:483– 485.
42. Hermann G, Keller RJ, Drossman S, et al.
Mammographic pattern of microcalcifi-
cations in the preoperative diagnosis of
comedo ductal carcinoma in situ: his-
topathologic correlation. Can Assoc Ra-
diol J 1999; 50:235–240.
43. Parker J, Dance DR, Davies DH, Yeoman
LJ, Michell MJ, Humphreys S. Classifica-
tion of ductal carcinoma in situ by image
analysis of calcifications from digital
mammograms. Br J Radiol 1995; 68:150 –
159.
44. Liberman L, Smolkin JH, Dershaw DD,
Morris EA, Abramson AF, Rosen PP. Calci-
fication retrieval at stereotactic, 11-gauge,
directional, vacuum-assisted breast biopsy.
Radiology 1998; 208:251–260.
45. Philpotts LE, Lee CH, Horvath LJ, Lange
RC, Carter D, Tocino I. Underestimation
of breast cancer with 11-gauge vacuum
suction biopsy. AJR Am J Roentgenol
2000; 175:1047–1050.
46. Nielsen NS, Nielsen BB. Mammographic
features of sclerosing adenosis presenting
as a tumour. Clin Radiol 1986; 37:371–
373.
47. Berg WA, Hruban RH, Kumar D, Singh
HR, Brem RF, Gatewood OM. Lessons
from mammographic-histopathologic cor-
relation of large-core needle breast biopsy.
RadioGraphics 1996; 16:1111–1130.
Sclerosing Adenosis at Core Biopsy 䡠 57