Should the Extent of Lobular Neoplasia on Core Biopsy
Influence the Decision for Excision?
Lisa E. Esserman, MD,* Ladan Lamea, MD,* Silvio Tanev, MD,†and Robert
*Breast Imaging and†Pathology Department, Mount Sinai Medical Center, Miami Beach, Florida
excisional biopsy is indicated following the diagnosis of lobular neoplasia (LN) on core biopsy. Retrospective review of
patient records with diagnosis of LN as highest risk diagnosis on core biopsy was performed. LN was defined to include
both atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) and was categorized as focal or diffuse. The
pathology was correlated with the mammographic finding to determine whether the diagnosis of LN was incidental or related
to the mammographic finding. For those patients who did not undergo excision, follow-up data are presented along with
treatment information. A total of 4,555 breast core biopsies were performed at our institution from January 1997 through
March 2005. Of these, 35 patients were diagnosed with LN. Twenty six (74%) went on to excision and nine (26%) were fol-
lowed. Biopsy was recommended for mammographically detected calcifications in the majority of cases. Twenty four (92%)
of the 26 excised cases had focal LN and 2 of 26 (8%) had diffuse LN. Infiltrating lobular carcinoma was diagnosed in both
cases of diffuse LN and no infiltrating carcinoma was seen when focal LN was diagnosed on core. Excision may not be
necessary when a diagnosis of only focal LN is made on core biopsy. Diffuse LN may indicate an associated invasive can-
cer and should prompt excision. n
Key Words: atypical lobular neoplasia, diffuse/focal lobular neoplasia, excision, lobular carcinoma in situ
Abstract:The purpose of this study was to determine whether there is a criterion that can be utilized to determine if
cles on this subject, particularly when it is diagnosed
on image-guided core biopsy. It is difficult to make uni-
versal recommendations based on the small numbers in
the individual series and make conclusions when the
study designs vary (variable percentages of patients
upgraded to carcinoma who had LN on core biopsy
ranging from 0% to 50% have been reported) (1).
In 1941, Foote and Stewart (2) described lobular
carcinoma in situ (LCIS) for the first time as ‘‘a non-
invasive lesion arising from lobules and terminal
ducts.’’ They concluded that LCIS is an incidental
microscopic finding, which is multicentric and from
which invasive cancer can arise. Simple mastectomy
was recommended for the treatment of LCIS because
of the possibility of associated invasive cancer.
LN is an uncommon finding (3) with incidence of
0.5% to 3.6% in core biopsies (1,3,4). The true
incidence is not known in the general population, as
he management of lobular neoplasia (LN) remains
controversial, despite a myriad of published arti-
there are no clinical or radiologic signs (4) (2,5,6). The
diagnosis has been increasing in recent years, probably
due to greater recognition of LN as a pathologic entity
other factors include the increased utilization of mam-
mography; and core biopsy (7). A greater frequency of
detection may also be related to larger sampling volumes
with vacuum-assisted biopsy and larger gauge needles.
Reports show that it is more common in younger
white women (3). It is multifocal and in 60–80% of
mastectomy specimens, bilateral (7).
LN is most often discovered incidentally when the
core biopsy is recommended for clustered microcalcifi-
cations. It can occasionally be associated with the cal-
cifications; however, it is usually a histopathologic
diagnosis only, as there are no distinctive mammo-
graphic features (8,9).
Management of LN has been controversial depend-
ing on whether it has been considered to be a precur-
sor of invasive carcinoma or a marker for an
increased risk for breast cancer. Researchers who have
advocated surgical excision have included Arpino
et al. (1), Lee et al. (8), Page et al. (4), Berg et al. (9),
Middleton et al. (10), Dmytrasz et al. (11), O’Driscoll
et al. (12), Bauer et al. (13), Foster et al. (7) among
others. Some of them recommended surgery only if:
Address correspondence and reprint requests to: Lisa E. Esserman,
Mount Sinai Comprehensive Cancer Center, 4306 Alton Road, Miami Beach,
FL 33140, USA, or e-mail: firstname.lastname@example.org.
ª 2007, Copyright the Authors
Journal compilation ª 2007 Blackwell Publishing, Inc., 1075-122X/07
The Breast Journal, Volume 13 Number 1, 2007 55–61
patient had prior or synchronous breast cancer, LN
associated with another high-risk lesion, or cases with
histologic features of ductal carcinoma in situ (DCIS)
(13), or discordance between imaging and histologic
findings (14). Failure of core needle biopsy (CNB) to
diagnose the underlying pathologic abnormality ranges
from 2% to 17% (12).
Other studies show that conservative therapy, like
enough as Fisher et al. (15), and Liberman et al. (16)
have concluded. Fisher et al. showed that low inci-
dence and delay in development of invasive cancer
(usually more than 15 years) are evidence of the
absence of direct progression of LN to malignancy.
Other researchers who voted in favor of conservative
therapy are Renshaw et al. (14) and Frykberg et al.
(5) (Table 1).
Some studies which are in favor of excisional sur-
gery only in special situations, recommend guidelines
such as histologic feature of the specimen, which sug-
gest necessity of excisional surgery if there is pleo-
Cohen (18) showed (in pool study) that 19% of
cases (159) of LN on core biopsies were upgraded to
DCIS or invasive carcinoma at the time of excision.
He believes that there is limited data that show corre-
surgery. Upgraded cases were seen with all needle
gauges and all types of biopsy devices.
Currently at our institution, no further surgical
treatment is recommended if LCIS is found on exci-
sion. The management of patients with LN as the
highest risk lesion diagnosed on core biopsy is not
clear. In this study, we tried to determine if there is a
or tamoxifen,can be
pathologic criterion that can help determine the need
for excision following diagnosis of LN or CNB.
MATERIALS AND METHODS
Retrospective review of all patient records from
January 1997 through March 2005 was performed.
The protocol was reviewed by our hospital institu-
tional review board and waiver of authorization was
issued for this retrospective study.
Patients with a diagnosis of LN, including the diag-
noses of atypical lobular hyperplasia (ALH), and LCIS
were identifiedfrom computerized
pathology tracking of consecutive biopsies from Mam-
mography Reporting Systems, Seattle, Washington, and
handwritten biopsy logs as well as pathology reports.
All patients who had associated invasive carcinoma,
intraductal carcinoma or DCIS, atypical ductal hyper-
plasia (ADH) and other high-risk lesions such as
radial scar and atypical papilloma, were excluded.
Cases with a diagnosis of LCIS and/or ALH with or
without other non–atypical breast lesions were inclu-
ded; as in the study by Foster et al. (7). Patients with
no excision or mammographic follow-up were exclu-
ded. The minimum follow-up time was 24 months for
those patients who did not go on to excision.
A 90? lateral view of the targeted breast was
obtained in addition to the mediolateral oblique
(MLO) view and craniocaudal (CC) mammogram in
all cases prior to biopsy. All core biopsies were
vacuum assisted with 11 gauge needles (Mammotone;
Ethicon Endosurgery, Cincinnati, OH). The biopsies
and mammographic interpretations were performed
by three radiologists, all with a subspecialty in Breast
Imaging and certified according to the Mammography
Quality Standards Act.
The range of experience of the radiologists was
10–20 years in practice in 2005 and 2–12 years
experience in 1997.
A mean of 13 core samples were obtained per
biopsy site (range 7–34). Specimen radiographs were
obtained for all targeted microcalcifications. A clip
was placed in all cases through the biopsy needle at
the time of the biopsy. Postprocedure 90? lateral and
craniocaudal mammograms were obtained in all cases
and compared to prebiopsy films to document the
relationship of the clip to the targeted lesion. Core
biopsy specimens containing microcalcifications were
Table 1. Literature Review of Recommendations
following Diagnosis of Lobular Neoplasia (LN) on
Page et al. (4)
O’Driscoll et al. (12)
Shin and Rosen (6)
Bauer et al. (13)
Dmytrasz et al. (11)
Foster et al. (7)
Arpino et al. (1)
Middleton et al. (10)
Liberman et al. (16)
Renshaw et al. (14)
56 • esserman et al.
placed in separate formalin vials from those without
microcalcifications, on the basis of the specimen radio-
graph, according to institutional protocol.
Stereotactic biopsies were performed on a dedicated
prone table (Fisher, Denver, CO, USA). Only one core
biopsy, for a mass, was performed utilizing ultrasound
guidance (Logic400; GE Medical Systems, Milwaukee,
WI, USA), with a variable transducer 9–13 MHZ, with
the patient in the supine position. All patients who went
on to excision had image guided needle localization.
The term LN is used to describe a spectrum of pro-
liferations in lobules of the breast and encompasses
the diagnoses of ALH and LCIS. Histologically, LCIS
is typically characterized by proliferation of monoton-
ous cells which completely fill and distend the lumens
of the ductules. The cells are evenly spaced and show
lack of cohesion. The nuclei are rounded, minimally
pleomorphic and usually without hyperchromatism.
According to Page and associates (4), more than one
half of the acini in a terminal duct lobular unit
(TDLU) should be involved in order to render a diag-
nosis of LCIS. Microscopically there are other similar
appearing proliferations in the lobules, that fall short
of fulfilling the quantitative criteria for LCIS, which
are categorized as ALH.
Pathology Data Collection
The surgical pathology database of Mount Sinai
Medical Center, Miami Beach, Florida from January
1997 to March 2005 was searched and representative
slides of patients diagnosed with LN on needle biopsy
were obtained. All hematoxylin and eosin (H&E)-
stained file slides of representative blocks of formalin-
fixed/paraffin-embedded tissues were reviewed by two
pathologists to confirm the original diagnosis and to
determine the extent of involvement of diagnostic
cores by LN. The slides were prepared from tissues
fixed in 10% formalin, embedded in paraffin and cut
at 4 micron-microtome sections for routine histologic
examination. For patients who went on to excision,
the biopsy site was noted by identifying fat necrosis,
multinucleated giant cells and foreign body reaction
related to clip and pellet (Fig. 1a,b).
E-cadherin (17) staining was used when there was
any doubt about lobular or ductal origin of the lesion.
The cases were classified as diffuse LN (when greater
than one lobule per core was involved at the time of
biopsy) and focal LN (if less than or equal to one lobule
was involved). LN was only classified as diffuse or focal
if at least two core samples were present (Fig. 2a,b). In
our study at least seven core samples were submitted
(range of 7–34, mean of 13). Two of the cases were out-
side cases with no data available on number of cores).
Patient age, family history, and personal prior his-
tory of breast cancer were recorded. Positive family
history was defined to include one or more relatives
with breast cancer in our study. The size of the lesion
was measured on nonmagnified views as the maxi-
mum diameter before and after core biopsy. Data was
Follow-up data were recorded for those who did not
undergo excision, including administration of tamoxi-
fen or subsequent biopsy.
The age range of patients with LN on CNB was
32–82 years with a mean of 56 years. Initially, 48 of
Figure 1. (a) Pathology slide showing fat necrosis at biopsy site
with different sized fat cells and giant cell, arrow (H&E stain, mag-
nification 10x). (b) Defect from clip pellet at biopsy site (H&E stain,
Should the Extent of Lobular Neoplasia on Core Biopsy Influence the Decision for Excision? • 57
4,555 patients were identified as having LN on CNB
(11 with ALH and 37 with LCIS). Three were reclassi-
fied to other benign lesions after pathologic review
with the aid of E-cadherin, immunoperoxidase stain-
ing. These diagnoses were intraductal hyperplasia,
myopepithelial hyperplasia, and intralobular prolifer-
ation. Another case was eliminated because of con-
comitant ADH found at core biopsy. The remaining
incidence was 44 of 4,555 cases or 0.96% which is in
the range of 0.5–3.6% reported in the literature (4).
Eight additional cases were excluded because of lack
of excision or appropriate follow-up (<24 months),
which left 35 cases in our study (nine patients with
ALH and 26 with LCIS).
Eleven gauge-directed vacuum-assisted core biopsy
(DVAB) were stereotactically guided in 34 of 35
patients, 33 for microcalcification and one for mass.
Only one of eleven gauge DVAB was performed under
ultrasound guidance for a mass, in which nine core
samples were retrieved. The size range of clustered
microcalcification was 2–12 mm with a mean of
5.5 mm. In all cases of targeted microcalcifications,
the calcifications were visualized in the core biopsy
The incidence of diffuse LN on CNB was 2 of 35
(5.7%) and that of focal LN on CNB was 33 of 35
(94.3%). The number of patients who went on to exci-
sion was 26 of 35 (74%). The mean diameter of
excised specimens was 6.27 cm. Excision in all cases
was performed within 4 months of core biopsy. Among
the patients who underwent excision, 24 of 26 (92.3%)
had focal LN on CNB, and 2 of 26 (7.7%) patients had
diffuse LN on CNB. Upon excision, both of the cases
with diffuse LN on CNB were found to have infiltrating
lobular carcinoma (ILC). The ILCs were not associated
with the targeted lesions in either case; microcalcifica-
tions in one, and fibroadenoma in the other (Fig. 3a–d).
In both of these cases, LN was classified as LCIS.
No invasive carcinomas were found on excision in
patients with focal LN. Upon excision of patients with
focal LN on CNB, 15 of 26 (57.7%) had no residual
LN, 11 of 26 (42.3%) had residual LN, among these,
1 of 11 (with residual calcification) had a single focus
of low-grade DCIS. In this case, LCIS was found at
the site of a second remote group of calcifications,
localized at the same time. The patient was then trea-
ted with tamoxifen alone.
In 6 of 33 (18%) of the LN cases, calcifications
were identified within the LN on pathology slides
(Fig. 4a,b). The LN was focal in all of these cases. And
in 27 of 33 (82%) calcifications were incidental to LN.
In both cases of ILC at excision, the LN was inci-
dental to the targeted finding. An example is shown in
Residual calcifications were observed in 10 of 35
patients on mammograms. One of the cases with dif-
fuse LN had residual calcifications that were inciden-
tal to the ILC found on excision. One of the cases
with focal LN had residual calcifications that were
incidental to the LCIS, and DCIS found on excision.
In 8 of 10 patients who had residual calcifications, no
cancer was found on excision.
The duration of follow-up for cases that were not
excised was 24–93 months (mean 51 months) with
Figure 2. (a) Focal lobular neoplasia on pathology slide showing
two cores with one lobule in one core involved with lobular neopla-
sia, arrow (H&E stain, magnification 2·) in a 54-year-old patient
with microcalcification on mammography films as indication for
core biopsy. (b) Pathology slide showing diffuse LN with multiple
lobules involved in multiple cores, arrows (H&E stain, magnification
2·). In a 46-year-old patient with microcalcification on mammogra-
phy films as indication for core biopsy.
58 • esserman et al.
no clinical evidence of disease or subsequent biopsy.
Tamoxifen use was recorded in four of nine (44%)
of the nonexcised cases. Among the patients who
did not have subsequent excision, 67% (6/9) had
family history of breast carcinoma. Of those, three
of nine (33%) were placed on tamoxifen. In patients
who did not undergo excision, three of nine (33%)
had no family history. Only one of nine patients
(11%) without family history was placed on tamoxi-
Twenty three of twenty six (88%) showed no intra-
ductal or invasive carcinoma on excision, and 6 of 23
(26%) of these patients were treated with tamoxifen.
Positive family history was observed in 9 of 23 (39%)
of the nonupgraded excised cases, and four of nine
(44%) of these were treated with tamoxifen. Among
patient who underwent excision with no family his-
tory, 2 of 14 (14%) were treated with tamoxifen.
The incidence of LN in our study was 43 of
4,555 cases or 0.8% which is in the range of 0.5–
3.6% reported in the literature (4). Upon excision,
the diagnosis of LN (ALH or LCIS) was upgraded to
DCIS or invasive carcinoma in 3 of 34 cases (9%).
The only cases found to have infiltrating carcinoma
on excision were the two cases of diffuse LN on
Figure 3. (a) Clustered calcifications on mammogram MLO view, arrow, in a 46-year-old patient with microcalcification on mammography
films as indication for core biopsy. (b) Concordant benign diagnosis for microcalcifications in expanded lobules (H&E stain, magnification
2·) in the same patient. (c) Incidental diffuse lobular neoplasia on core (H&E stain, magnification 10·) in the same patient. (d) Upgrade to
ILC on excision, stromal invasion of noncohesive malignant cells, arranged individually or in narrow trabeculae, indicated by arrow (H&E
stain, magnification 20·) in the same patient.
Should the Extent of Lobular Neoplasia on Core Biopsy Influence the Decision for Excision? • 59
CNB. There were no infiltrating carcinomas found
upon excisional biopsy for focal LN. Only one of
thirty-two patients with focal LN showed a single
focus of low-grade DCIS. In this case, another
remote site of LCIS was found at excision. In our
study, ALH and LCIS were combined under the
heading of LN because of the difficulty in daily prac-
tice of accurately separating these lesions. When the
data were broken down into ALH and LCIS, there
was no difference in our findings. The majority of
our cases (26/35 or 74%) were LCIS. If LCIS
is indeed multifocaland
(4), chemopreventive measures may be more effective
than local excision, as risk reduction of developing
a subsequent breast cancer of up to 56% can be
achieved with tamoxifen (7). In our study, the use of
tamoxifen was similar in the nonexcised group and
the nonupgraded excised group; 44% versus 33%. A
greater percentage of patients with family history
were placed on tamoxifen in both groups. Patients
history, versus no family history was 33% versus
11%, and 44% versus 14% in nonupgraded excised
Excision of LN diagnosed on CNB was recommen-
ded by our radiologists after April 2000. Samples of
current literature are shown in Table 1. The more
recent studies support excision but conclusions are
based on small numbers of cases in many instances.
To our knowledge, there is no other study in which
the amount of LN has been evaluated as a criterion
for excision, following core biopsy.
Figure 4. (a) Clustered microcalcifications on stereo scout. Stereo
scout in a 70-year-old patient with microcalcification on mammo-
graphy films as indication for core bx. (b) Calcifications in LN (H&E
stain, magnification 2·) in the same patient.
Figure 5. (a) Focal lobular neoplasia incidental to microcalcifications targeted on mammogram (H&E stain, magnification 40·). In a
46-year-old patient with microcalcification on mammography films as indication for core bx. (b) Mammogram showing clustered microcalcifi-
cations, MLO view in the same patient. (c) Calcification in expanded lobular unit with columnar alteration (ELUCA) on pathology, (H&E
stain, magnification 20·) in the same patient.
60 • esserman et al.
In all three upgraded cases, the LN was incidental to
the targeted finding, either mass or microcalcifications.
In 27 of 33 (82%) patients, the LN was not associated
with the calcifications. Therefore if there is a concor-
dant diagnosis for the mammographic lesion and there
is residual lesion on mammogram, LN may not be a
helpful indicator of the need for excision. Excision may
be warranted if the area has been inadequately sam-
pled. The most objective criterion for inadequate samp-
ling is lack of retrieval of calcifications. Lomoschitz
et al. (19) states that 12 or more cores are needed.
However, number of cores may not necessarily be a
proper indication of adequate sampling particularly if
cores are small and the targeting is inadequate.
Nonconcordance is the primary reason to recom-
mend excision after a benign diagnosis on CNB and
that certainly would hold true if LN is found. For
example, if the targeted lesion is a mass and the only
diagnosis is LN, then excision should be performed.
Another reason to excise LN would be if the distinc-
tion between LCIS from DCIS with cancerization of
lobules is unclear. E-cadherin stain may be helpful in
this situation (20).
The major limitation of this study is the small num-
ber of cases and the limited follow-up in some of the
patients who did not undergo excision. Our numbers
are too small to generate statistical significance and
there are not enough data points to perform a chi-
In conclusion, diffuse LN on core biopsy shows a
strong association with invasive carcinoma and should
prompt excision. The need for excision is questioned
for concordant biopsy findings when only focal LN is
diagnosed on core biopsy as we found no cases of
infiltrating carcinoma and only 1 of 32 cases or 3%
upgrade to a single focus of low-grade DCIS. Further
studies with greater number of patients are needed to
corroborate our findings. A prospective multicenter
trial could help address this question. In addition the
use of other modalities such as MRI may further help
identify those patients with associated or synchronous
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