Lobular neoplasia in breast core needle biopsy specimens is associated with a low risk of ductal carcinoma in situ or invasive carcinoma on subsequent excision.

Abstract

To address the significance of lobular neoplasia (LN) in breast core needle biopsy specimens, we prospectively obtained LN cases and correlated results of subsequent tissue sampling. LN was diagnosed by core needle biopsy in 467 women; in 101 (21.6%), invasive carcinoma (IC) or ductal carcinoma in situ (DCIS) was diagnosed concurrently. Two patients (0.4%) had previous diagnoses of IC or DCIS, and 17 (3.6%) had a concurrent diagnosis of contralateral IC or DCIS. Of 366 patients without a concurrent diagnosis of IC or DCIS, subsequent tissue diagnoses were available for 156 cases (42.6%). Of 60 cases of LN and atypical ductal hyperplasia on the biopsy, 5 had IC and 10 had DCIS on the excision (total, 25%). Of 4 women with LN and a mucocele-like lesion on the biopsy, none had IC or DCIS on excision. Of 92 with LN alone on the biopsy, 7 had IC (6) or DCIS (1) on excision. Two cases were in sites away from the biopsy site, 3 in subsequent excisions of the biopsy site, and 2 after previous excision of the biopsy site without finding IC or DCIS. Although LN is associated with a high overall rate of IC and DCIS (30%), excision of the biopsy site for women with LN alone on core needle biopsy has a very low rate of IC and DCIS in our center. Women in whom biopsy sites are excised are still at risk for subsequent DCIS and IC.

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Am J Clin Pathol 2006;126:310-313
DOI: 10.1309/GT453DBMLRNPNKL2
© American Society for Clinical Pathology
Anatomic Pathology / LOBULAR NEOPLASIA IN BREAST BIOPSY SPECIMENS
Lobular Neoplasia in Breast Core Needle Biopsy Specimens
Is Associated With a Low Risk of Ductal Carcinoma In Situ
or Invasive Carcinoma on Subsequent Excision
Andrew A. Renshaw, MD,1Robert P. Derhagopian, MD,2Pilar Martinez, MD,3
and Edwin W. Gould, MD1
Key Words: Breast; Carcinoma; Lobular carcinoma in situ; Lobular neoplasia; Core; Biopsy
DOI: 10.1309/GT453DBMLRNPNKL2
A b s t r a c t
To address the significance of lobular neoplasia
(LN) in breast core needle biopsy specimens, we
prospectively obtained LN cases and correlated results
of subsequent tissue sampling. LN was diagnosed by
core needle biopsy in 467 women; in 101 (21.6%),
invasive carcinoma (IC) or ductal carcinoma in situ
(DCIS) was diagnosed concurrently. Two patients
(0.4%) had previous diagnoses of IC or DCIS, and 17
(3.6%) had a concurrent diagnosis of contralateral IC
or DCIS. Of 366 patients without a concurrent
diagnosis of IC or DCIS, subsequent tissue diagnoses
were available for 156 cases (42.6%). Of 60 cases of
LN and atypical ductal hyperplasia on the biopsy, 5 had
IC and 10 had DCIS on the excision (total, 25%). Of 4
women with LN and a mucocele-like lesion on the
biopsy, none had IC or DCIS on excision. Of 92 with
LN alone on the biopsy, 7 had IC (6) or DCIS (1) on
excision. Two cases were in sites away from the biopsy
site, 3 in subsequent excisions of the biopsy site, and 2
after previous excision of the biopsy site without finding
IC or DCIS. Although LN is associated with a high
overall rate of IC and DCIS (30%), excision of the
biopsy site for women with LN alone on core needle
biopsy has a very low rate of IC and DCIS in our
center. Women in whom biopsy sites are excised are still
at risk for subsequent DCIS and IC.
The significance of lobular neoplasia (LN; including atyp-
ical lobular hyperplasia [ALH] and lobular carcinoma in situ
LCIS]) in breast core specimens is not entirely clear. Although
most previous studies have shown a risk of invasive carcinoma
(IC) or ductal carcinoma in situ (DCIS) of approximately 15%
when the biopsy site has been excised ❚Table 1❚,1-11preliminary
studies from this institution have failed to confirm such a find-
ing.12In response to this, we prospectively identified women
with a diagnosis of LN on core needle biopsy at our institution
and correlated the results of additional tissue sampling in
these women for a 4-year period.
Materials and Methods
The results of breast core needle biopsy specimens inter-
preted from September 1, 2001, to January 31, 2006, at
Baptist Hospital of Miami, Miami, FL, were reviewed. Cases
from our previous study12were not included. All biopsy spec-
imens with a diagnosis of LN (ALH or LCIS) were identified.
Additional lesions identified in the biopsy specimen also were
identified. These included the presence of DCIS or IC, muco-
cele-like lesions, and atypical ductal hyperplasia (ADH).
Criteria for ADH were those identified by others.13In brief,
these lesions were restricted to intraductal proliferations with
some, but not sufficient, features of DCIS. The criteria for LN
were those outlined by others.14,15
Cases of LN were divided into ALH and LCIS. In addition,
cases with larger cells than normal, ie, pleomorphic LN, also
were identified. In cases in which tissue was available in the
core needle biopsy specimen for immunohistochemical analy-
sis, E-cadherin testing was performed as detailed elsewhere.16

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DOI: 10.1309/GT453DBMLRNPNKL2
311311
© American Society for Clinical Pathology
Anatomic Pathology / ORIGINAL ARTICLE
All breast core needle biopsy specimens were obtained
by the clinicians. More than 95% were performed by the radi-
ology department and consisted almost exclusively of 11- and
14-gauge core needle biopsy specimens obtained under ultra-
sound or stereotactic guidance.
All specimens were received fixed and routinely
processed. Up to 5 cores were processed in a single block; if
more than 5 cores were present, an additional block was pre-
pared. Each block was sectioned entirely to produce at least 5
slides and 2 levels per slide.17
Additional tissue follow-up was obtained from the
records of the Baptist Hospital pathology department.
Statistical analysis was performed using a 2-tailed Fisher
exact test.
Results
A total of 467 women had LN diagnosed on core needle
biopsy during the study period. The age of the women ranged
from 31 to 96 years (median, 56 years). Of the cases, 116
(24.8%) were confirmed by a lack of E-cadherin staining.
Of the 467 women, 101 (21.6%) had IC (74) or DCIS
(27) diagnosed concurrently. In addition, 2 (0.4%) patients
had previous diagnoses of IC (1) or DCIS (1), and 17 (3.6%)
had a diagnosis of IC (11) or DCIS (6) in the other breast at
the time of the diagnosis of LN.
For 156 (42.6%) of 366 patients without a concurrent
diagnosis of IC or DCIS in the same breast, subsequent tissue
diagnoses were available. The results are summarized in
❚Table 2❚. The ages of the women ranged from 31 to 88 years
(median, 55 years). The lesion was in the right breast in 94, the
left breast in 60, and in both breasts in 2. Biopsies were per-
formed for calcifications in 119 cases and for a mass lesion in
47. Of the LN lesions, 42 were confirmed with E-cadherin
staining. Ten cases represented the pleomorphic variant of
LCIS. The women had 127 excisions, 17 subsequent core nee-
dle biopsies, and 12 mastectomies. The excisions ranged from
2 to 13.5 cm (mean, 5.3 cm).
Of 60 cases of LN and ADH, follow-up revealed IC in
5 women (8%) and DCIS in 10 (17%) for a total of 25%.
Of 4 women with LN and a mucocele-like lesion, none had
IC or DCIS on follow-up. Of 92 women with LN alone, 7
(8%) had a subsequent diagnosis of IC (6) or DCIS (1) on
follow-up. However, 2 cases (2%) were found in sites
away from the biopsy site, 3 (3%) in subsequent excision
specimens of the biopsy site, and 2 in women who had
❚Table 1❚
Results of Excision for Lobular Neoplasia Alone on Core Needle Biopsy
Cases With
ALH
Cases With
LCIS
Cases With
LN
Cases With
Follow-up
With DCIS
Without IC StudyWith IC
O’Driscoll et al2
Berg et al3
Shin and Rosen4
Irfan and Brem5
Crisi et al6
Renshaw et al12
Middleton et al7
Dmytrasz et al8
Bauer et al9
Foster et al10
Arpino et al11
Elsheikh and Silverman1
Total
070
0
0
0
72
1
1
1
0
0
0
2
0
4
1
4
1
0
3
0
2
0
6
1
1
2
2
5
15
6
7
13
6
17
13
0
20
0
13
97
10
14
0
12
9
14
0
0
15
0
20
101
15
20
7
10
0
4
0
13
0
45
0
72
16
15
17
6
7
26
21
33
19016 (8.4%) 23 (12.1%)
ALH, atypical lobular hyperplasia; DCIS, ductal carcinoma in situ; IC, invasive carcinoma; LCIS, lobular carcinoma in situ; LN, lobular neoplasia.
❚Table 2❚
Cases of Lobular Neoplasia on Core Needle Biopsy
DCIS on Excision
of Biopsy Site
IC on Excision
of Biopsy SiteNo. of Cases No. With Follow-up
ALH
ALH + mucocele
ALH + ADH
LCIS
LCIS + mucocele
LCIS + ADH
158 400
0
8
1
0
2
1
0
3
1
0
2
33
39
115
27
52
1
33
1
48
ADH, atypical ductal hyperplasia; ALH, atypical lobular hyperplasia; DCIS, ductal carcinoma in situ; IC, invasive carcinoma; LCIS, lobular carcinoma in situ.

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DOI: 10.1309/GT453DBMLRNPNKL2
© American Society for Clinical Pathology
Renshaw et al / LOBULAR NEOPLASIA IN BREAST BIOPSY SPECIMENS
undergone previous excision of the biopsy site without
finding IC or DCIS.
The needle biopsy and subsequent excisional biopsy
specimens of the 3 women with DCIS and IC in the biopsy
site were reviewed. In 1 case with DCIS alone in the excision,
review of the initial core needle biopsy specimen revealed a
small focus of larger atypical cells that were positive for E-
cadherin. On review, this focus was interpreted alternatively as
pleomorphic LCIS or ADH by different observers in the
pathology department. The cells in this focus strongly resem-
bled the cells in the DCIS in the subsequent excision. In the
second case, the excision of the biopsy site was performed 8
months after the biopsy, consisted of a specimen 10 cm in
diameter, and contained a 4-mm well-differentiated invasive
ductal carcinoma. This focus was not seen in continuity with
the scar of the biopsy site. In the final case, in the 6-cm sub-
sequent excision, the biopsy site could be seen traversing right
through the area of DCIS, but no DCIS could be found in the
needle biopsy specimen itself. A separate 5-mm focus of well-
differentiated invasive ductal carcinoma also was found in the
excision. Again, this focus could not be seen in continuity with
the biopsy site.
The rate of DCIS or IC in the excision of the biopsy site
was significantly lower for LN alone (3%) than for LN with
ADH (25%; P < .0001).
Discussion
The goal of this study was to determine the true rate of
DCIS and IC in subsequent excisions for LN alone on core
needle biopsy. We were puzzled that our experience with this
situation was so different from that reported by other centers.
To help resolve the issue, we set out to prospectively obtain a
very large number of patients from our center with LN on core
needle biopsy and thoroughly correlate the previous and sub-
sequent tissue diagnoses in these women. Our results show
that many of these women (30%) will have DCIS or IC in the
same or opposite breast before or after the biopsy of LN.
However, few of them will have DCIS or IC in the subsequent
excision. The rate of this finding is much less than that seen in
other centers and much less than that seen for ADH and LN at
our center. Indeed, the rate of DCIS and IC found in this study
is well within the reported false-negative rate for core needle
biopsy reported in the literature (1.2%-9.1%).18-20
In addition, the specific pathologic features of the needle
biopsy and excision specimens suggest that these cases may
represent false-negative interpretations of the needle biopsy
(case 1), an incidental finding not associated with the biopsy
site itself (case 2), and false-negative sampling in the biopsy
(case 3). Our results strongly suggest that although women
with LN clearly have a high risk of IC and DCIS in the same
and the opposite breasts, previously and subsequently, subse-
quent excision of cases with LN alone on core needle biopsy
identifies extremely few of these cases and is not necessarily
warranted in all cases. In addition, women who undergo exci-
sion of the biopsy site are still at risk for development of
DCIS or IC.
There are several possible explanations for the differ-
ences we report. First, the current series is by far the largest
series of cases reported to date. It is possible that the rate of
DCIS and IC in previous reports may be less if more cases had
been followed up.
Second, this is only the second report1to identify cases
prospectively. It is possible that cases identified retrospective-
ly may be biased toward patients who had other reasons to
obtain a subsequent excision.
Third, few of the previous studies distinguished clearly
between tumors found in the biopsy site itself and tumors
found in subsequent excisions of other sites in the same
breast.6It is possible that some of the subsequent cases of
DCIS and IC reported by others may not necessarily have
been associated with the biopsy site.
Fourth, our pathology department exhaustively samples
all core needle biopsy specimens, thus reducing the chance
that a lesion that was sampled by the radiologist is not seen by
the pathologist.17The amount of processing in previous stud-
ies has been variably reported. However, we still believe, as
suggested in our earlier report,12that the primary reason we do
not find DCIS and IC in subsequent excision specimens
relates to our radiologists. Although we have been unable to
determine a satisfactory way to assess the amount of tissue
removed at the time of biopsy, it is clear in comparison with
core biopsy specimens received in consultation from other
centers that our radiologists obtain more tissue. We believe
that the large amount of tissue obtained at the time of the biop-
sy significantly reduces the chance of missing a significant
lesion and most likely accounts for the very low incidence of
DCIS and IC in the subsequent excisions.
This scenario is similar to that described for high-grade
prostatic intraepithelial neoplasia in prostate biopsy speci-
mens.21When only 6 biopsy specimens were obtained rou-
tinely, high-grade prostatic intraepithelial neoplasia was asso-
ciated strongly with carcinoma on repeated biopsy. However,
when more tissue was obtained, the risk of carcinoma in sub-
sequent biopsies is no more than that seen in men with a
benign initial diagnosis. In contrast, atypical foci “suspicious”
for carcinoma in prostate biopsy specimens remain strongly
associated with a risk of carcinoma in subsequent biopsies,
regardless of the amount of tissue obtained in the initial biop-
sy. This would be analogous to ADH, which has been shown
to be a risk factor in breast cores in virtually all studies to date.
If sampling should prove to be the reason for the differences
in the preceding results, then following the rate of IC and

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© American Society for Clinical Pathology
Anatomic Pathology / ORIGINAL ARTICLE
DCIS after a diagnosis of LCIS may be a useful quality con-
trol method for breast core biopsies.
Regardless of the reasons, our results show that the sig-
nificance of LN on core needle biopsy specimens does seem
to differ at different centers. In centers with appropriate fol-
low-up information, routine excision of all biopsy sites for LN
may not always be necessary.
Although LN is associated strongly with IC and DCIS
overall (30%), excision of the biopsy site for women with LN
alone on core needle biopsy has a very low rate of IC and
DCIS (3%). Women who undergo excision of biopsy sites are
still at risk for subsequently developing IC.
From the Departments of 1Pathology, 2Surgery, and 3Radiology,
Baptist Hospital of Miami, Miami, FL.
Address reprint requests to Dr Renshaw: Dept of Pathology,
Baptist Hospital of Miami, 8900 N Kendall Dr, Miami, FL 33176.
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