Context.—Percutaneous image-guided core biopsy is increasingly becoming the method of choice to evaluate impalpable breast lesions presenting with mammographically detected calcifications or as a mammographically detected mass. Infrequently, a diagnosis of a primary lobular lesion is rendered by needle core biopsy. Although lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) are not themselves detectable by mammography, they can be associated with calcifications. The management of patients with a primary diagnosis of LCIS or ALH on needle core biopsy is uncertain. Recommendations include excisional biopsy, tamoxifen citrate therapy, mammographic surveillance, or a combination of these approaches.

Objective.—The purpose of this study was to report the histologic findings of excisional biopsies performed after ALH or LCIS was found in a needle core biopsy.

Design.—Hematoxylin-eosin–stained slides of 20 needle core biopsy specimens from patients with a primary diagnosis of LCIS or ALH were retrieved from the consultation and surgical pathology files of New York Presbyterian Hospital–Weill Medical College of Cornell University. Histologic diagnoses were confirmed in all cases.

Results.—Fourteen cases of primary LCIS and 6 cases of ALH found on needle core biopsy were identified. Subsequent excisional biopsy of the 14 LCIS cases revealed the following: LCIS, ductal carcinoma in situ, invasive carcinoma (1 patient; 7%); LCIS, infiltrating lobular carcinoma (1 patient; 7%); LCIS, ductal carcinoma in situ (1 patient; 7%); LCIS (8 patients; 57%); and ALH with or without atypical ductal hyperplasia (3 patients; 21%). Among the 6 patients with ALH on needle core biopsy, 1 had infiltrating lobular carcinoma and LCIS and 2 had LCIS in subsequent excision; other excisions for ALH were benign. Overall, 3 (21%) of 14 patients with a primary diagnosis of LCIS on needle core biopsy had a more significant lesion (ductal carcinoma in situ or invasive carcinoma) in a subsequent excisional biopsy.

Conclusions.—Data obtained in this study and in previously published reports lead us to conclude that excisional biopsy may be indicated and should be considered when LCIS is found on needle core biopsy in order to more fully examine the biopsy site for coexistent, clinically inapparent intraductal or invasive carcinoma that may be present in about 25% of these patients. The small number of ALH cases studied produced inconclusive results. We recommend that excisional biopsy be considered if atypical ductal hyperplasia is present with ALH in a needle core biopsy or if the diagnosis of the biopsy specimen is discordant with the mammographic findings.

Percutaneous image-guided core biopsy is an increasingly used method of choice for the evaluation of impalpable breast lesions, such as those presenting with mammographically detected calcifications or as a mammographically detected mass. The limited sampling of lesions when compared to an excisional biopsy specimen adds a new dimension of diagnostic challenge for the pathologist. The samples are often relatively small, sometimes disrupted, and may not be representative of the lesion.1 In addition, issues have surfaced concerning how to treat patients with certain diagnoses rendered on a needle core biopsy (NCB). For instance, the issue of whether a primary diagnosis of atypical ductal hyperplasia (ADH) diagnosed on NCB warrants a subsequent excisional biopsy has been debated and extensively investigated. Several studies have found that ductal carcinoma in situ (DCIS) is often underdiagnosed as ADH by NCB, and presently excisional biopsy is recommended for these patients.2–6 

The clinical management of primary lobular lesions found in NCBs has also recently come to the forefront. Lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) can infrequently be the primary diagnosis rendered in NCB specimens. Although they are known to be virtually undetectable by mammography, occasionally lobular lesions, especially LCIS, can have mammographically detected associated calcifications.7,8 There is controversy about how patients with LCIS or ALH diagnosed by NCB should be managed clinically. Uncertainty about the need for excisional biopsy in these cases stems from conflicting opinions regarding the biologic behavior of lobular lesions. The purpose of our study was to evaluate the histologic findings in excisional biopsies performed on patients with a primary NCB diagnosis of LCIS and/or ALH to determine if the NCB samples provided sufficient information for patient management.

Twenty nonconsecutive patients with a primary diagnosis of LCIS and/or ALH diagnosed by NCB who underwent a subsequent excisional biopsy were obtained from the consultation and surgical pathology files of New York Presbyterian Hospital–Weill Medical College of Cornell University (New York, NY). Hematoxylin-eosin–stained slides from all needle core and excisional biopsy specimens were reviewed, and histologic diagnoses were confirmed. Histologic criteria for LCIS included lobular expansion by a monomorphous population of small cells with scant cytoplasm and round nuclei involving terminal ducts, lobules, or both. Atypical lobular hyperplasia was defined as histologic changes of LCIS to a lesser quantitative or qualitative degree.8 Coexistent benign proliferative lesions were documented. Patients with NCBs containing coexistent lesions, such as DCIS and invasive carcinoma, which would by themselves prompt an excisional biopsy, were excluded.

Clinical and radiologic information was available for 20 patients with a primary diagnosis of LCIS and/or ALH diagnosed by NCB who underwent subsequent excisional biopsy. All of the patients were women, aged 43 to 70 years. The right breast was involved in 11 patients and the left was involved in 9. Two patients had prior DCIS in the contralateral breast; one of these women was treated with lumpectomy, the other with mastectomy.

The reasons for NCB were mammographically detected calcifications in 18 patients and a mammographically detected mass in the remaining 2 patients. The number of cores obtained in known cases varied from 6 to 25. The type of equipment and needle gauge size used was not known. The specific reason for excisional biopsy in each case was not known.

The histologic findings are summarized in Table 1. Among 14 instances of LCIS in the NCB, 8 had LCIS only and 6 had both LCIS and ADH. Subsequent excisional biopsy in 8 LCIS patients revealed more LCIS in 4 patients (50%), LCIS and DCIS in 1 patient (12.5%), LCIS and infiltrating lobular carcinoma in 1 patient (12.5%), and ADH with ALH in 2 patients (25%). Excisional biopsy in the 6 patients with LCIS and ADH revealed additional LCIS and ADH in 3 patients (50%); LCIS, ADH, and ALH in 1 patient (16.7%); and LCIS, DCIS, infiltrating lobular carcinoma, and invasive ductal carcinoma in 1 patient (16.7%) (Figure 1).

Table 1. 

Diagnosis in Needle Core and Subsequent Excisional Biopsy Specimens in 20 Patients*

Diagnosis in Needle Core and Subsequent Excisional Biopsy Specimens in 20 Patients*
Diagnosis in Needle Core and Subsequent Excisional Biopsy Specimens in 20 Patients*
Figure 1.

Lobular carcinoma in situ (LCIS). A, Needle core biopsy specimen from a patient showing LCIS (hematoxylin-eosin, original magnification ×200). B, Columnar cell ductal hyperplasia with atypia in the same needle core biopsy specimen shown in A (hematoxylin-eosin, original magnification ×200). C, Subsequent excisional biopsy with infiltrating lobular carcinoma (best seen lower left) (hematoxylin-eosin, original magnification ×200). D, Invasive ductal carcinoma, moderately differentiated, was also present. Ductal carcinoma in situ, micropapillary type, was present elsewhere in the excisional biopsy (hematoxylin-eosin, original magnification ×200).Figure 2. Atypical lobular hyperplasia (ALH). A, This excisional biopsy from a 54-year-old patient who had ALH on needle core biopsy had lobular carcinoma in situ in a duct on subsequent excisional biopsy (hematoxylin-eosin, original magnification ×100). B, Atypical ductal hyperplasia was also present (hematoxylin-eosin, original magnification ×100).

Figure 1.

Lobular carcinoma in situ (LCIS). A, Needle core biopsy specimen from a patient showing LCIS (hematoxylin-eosin, original magnification ×200). B, Columnar cell ductal hyperplasia with atypia in the same needle core biopsy specimen shown in A (hematoxylin-eosin, original magnification ×200). C, Subsequent excisional biopsy with infiltrating lobular carcinoma (best seen lower left) (hematoxylin-eosin, original magnification ×200). D, Invasive ductal carcinoma, moderately differentiated, was also present. Ductal carcinoma in situ, micropapillary type, was present elsewhere in the excisional biopsy (hematoxylin-eosin, original magnification ×200).Figure 2. Atypical lobular hyperplasia (ALH). A, This excisional biopsy from a 54-year-old patient who had ALH on needle core biopsy had lobular carcinoma in situ in a duct on subsequent excisional biopsy (hematoxylin-eosin, original magnification ×100). B, Atypical ductal hyperplasia was also present (hematoxylin-eosin, original magnification ×100).

Five of 6 patients with ALH in the NCB had concurrent benign lesions without atypia, and 1 patient had coexisting ADH. Among the 5 patients with ALH and benign lesions without ADH, excisional biopsy yielded LCIS and ADH in 1 (20%) and LCIS alone in 1 (20%) (Figure 2). The remaining 3 patients had benign findings. The single patient with ALH and ADH in an NCB had LCIS and infiltrating lobular carcinoma in the excisional specimen.

Percutaneous image-guided NCB of the breast is an increasingly popular modality for evaluating breast lesions.9 This procedure results in less deformity of the breast than does surgical biopsy, which not only is cosmetically more acceptable to the patient, but also leads to minimal scarring seen on subsequent mammograms.10 It has also been shown that NCBs can spare some patients with benign lesions from undergoing surgery and reduce the total number of surgeries in other patients.9,11–14 

The histologic specimens procured by this procedure have created a new dimension of diagnostic challenge for the pathologist. Owing to the limited amount of breast tissue obtained, the pathologist is faced with the expectation to make a specific diagnosis on the basis of less abundant, disaggregated, and sometimes disrupted or distorted samples. This diagnostic difficulty stems from the inherent nature of the NCB specimen, leading to the observation that “What you see is what you have and it may not be all there is,” or “What you have may be all there is.“ 1 

The issue of how to manage LCIS or ALH diagnosed by NCB involves not only the inherent limitations of the procedure, but also the unpredictable clinical course of these patients. Most patients with ALH or LCIS do not progress to invasive carcinoma. The overall cumulative risk of developing invasive carcinoma has been estimated to range from 30% to 35% for LCIS, and it is lower for ALH.15 Some consider LCIS and ALH to be only markers of cancer risk,16 and current treatment usually involves clinical follow-up with or without antiestrogenic drugs. Data on the risk for carcinoma in women with ALH or LCIS have been based on diagnosis made in excisional surgical biopsy specimens, which provide a relatively generous tissue sample. In these reports, patients with coexisting DCIS or invasive carcinoma were excluded from analysis of risk attributable for LCIS alone. If patients with LCIS or ALH diagnosed in an NCB sample are to be clinically managed on the basis of this procedure alone, it is necessary to determine whether pathologic examination of such samples can reliably exclude the presence of coexisting DCIS or invasive carcinoma and therefore provide information tantamount to that provided by the evaluation of an excisional biopsy specimen.

To date, the few reports on the histologic findings of excisional biopsy performed on patients with a diagnosis of LCIS and/or ALH in an NCB have appeared in the radiologic literature (Table 2). The largest series was a retrospective review of 32 424 patients who had percutaneous biopsies at 13 institutions.17 Included were 89 patients with an NCB diagnosis of LCIS and 154 with ALH. Surgical excision was performed in 58 LCIS cases and 84 ALH cases. Among the 58 cases with LCIS in an NCB, 12 (21%) had invasive carcinoma and 8 (14%) had DCIS in the excisional biopsy. A significant limitation of this study was the absence of pathologic consensus review, but the overall results are comparable to our series.

Table 2. 

Reported Histologic Diagnoses of Lobular Lesions in Needle Core and Subsequent Excisional Biopsies

Reported Histologic Diagnoses of Lobular Lesions in Needle Core and Subsequent Excisional Biopsies
Reported Histologic Diagnoses of Lobular Lesions in Needle Core and Subsequent Excisional Biopsies

A smaller group of patients was described by Liberman and colleagues,18 who found that 3 (21%) of 14 patients with LCIS diagnosed by NCB had DCIS (2 cases) or invasive lobular carcinoma (1 case) in the subsequent excisional biopsy specimen. In this study, 4 NCB LCIS specimens were classified as the “florid” type, in which there are morphologic features overlapping with DCIS, and 2 (50%) of these patients had a more significant lesion in the subsequent excisional biopsy specimen. Florid LCIS (a recently described variant of LCIS8 that features marked ductal expansion, comedonecrosis, and calcifications) is not widely appreciated, and some of these cases may have been classified as DCIS in other series. It has been subsequently reported that florid LCIS is more likely to have associated invasive lobular carcinoma than the classical variant. Sapino and coworkers7 found that 4 (40%) of 10 of their cases of florid LCIS had concurrent invasive lobular carcinoma. In our series, 2 of the cases were of the florid type of LCIS. Excisional biopsy revealed residual classic LCIS for both cases. An immunohistochemical stain for E-cadherin performed on the florid LCIS in these 2 cases demonstrated complete absence of staining in lesional tissue, confirming the diagnosis of LCIS. In a current incomplete study, we observed that 13 (62%) of 21 cases of florid LCIS had associated invasive carcinoma, 9 of which were of the lobular type. Furthermore, although formal studies have not been published regarding the frequency of concurrent LCIS and columnar cell hyperplasia, it has been reported that these 2 entities are not uncommonly found together in conjunction with invasive carcinoma, specifically invasive tubular carcinoma and/or invasive lobular carcinoma.19 

The results of the foregoing studies and other reports are summarized in Table 2. The frequency of finding a more significant lesion (ie, DCIS or invasive carcinoma) after NCB ranged from 0% to 35% for LCIS and 17% to 33% for ALH. Overall, DCIS or invasive carcinoma was found in 30.8% of excisions after LCIS was diagnosed in an NCB and in 21.7% after ALH was diagnosed in an NCB.

Inherent limitations in the current study include variables beyond our control, such as the number of cores obtained and type of equipment and needle gauge size used. Furthermore, the cases were not from a consecutive or randomized series of patients, and therefore we do not know what proportion of LCIS cases are represented in this series. The seemingly limited number of cases studied is a reflection of the rarity of cases of LCIS found on needle core biopsy that are ultimately excised by surgical biopsy. The reasons for performing excisional biopsy in the cases studied are unknown. In some cases, surgery may have been due to the coexistence of ADH or mammographic abnormalities that might have led to surgical biopsy even in the absence of LCIS. We feel that when our findings are considered together with other reports, there is considerable evidence for excisional biopsy for most patients who have LCIS found in an NCB sample, because approximately 25% of these patients have coexistent DCIS or invasive carcinoma at or near the NCB site. The latter lesions would result in a major change in clinical management.

Factors that stratify patients with LCIS in an NCB with respect to the likelihood of finding DCIS or invasive carcinoma in the excisional biopsy have not been defined to date. Discordance between pathologic findings and the radiologic impression is considered to be an indication for surgical biopsy, and this strategy would be reinforced by finding LCIS in the NCB. The presence of florid LCIS or ADH, particularly of the columnar cell type, are also relatively strong indications for surgery. The E-cadherin immunostain is very useful for distinguishing between some variants of DCIS and florid LCIS, which may have classic or pleomorphic cytology.

The indications are less clear for surgical biopsy after ALH is found in an NCB. The diagnostic criteria that have been described by various investigators for LCIS and ALH overlap to some degree. Nonetheless, the likelihood of finding DCIS or invasive carcinoma in an excisional biopsy after the NCB diagnosis of ALH is lower than for LCIS both in this study and in prior reports. In the present series, concurrent ADH and ALH in the NCB was associated with the subsequent detection of carcinoma, but no firm conclusion can be drawn from this small series. It is likely that most patients who have ADH and ALH in an NCB will undergo surgical excision, because ADH is already an indication for this procedure. Surgical excision of the NCB site should be performed if the pathologic diagnosis of an NCB with ALH is not concordant with the radiologic abnormality that was the initial impetus for biopsy. Other indications for considering surgical biopsy include a strong family history of breast carcinoma, prior or concurrent contralateral carcinoma, previous breast conservation treatment of ipsilateral carcinoma, and risk assessment, since chemoprevention (ie, tamoxifen citrate) may be an option for LCIS but not necessarily for ALH. Future follow-up studies of patients with ALH in an NCB may provide useful data to help in the treatment of these women at the time of initial diagnosis.

Rosen
,
P. P.
Preface.
In: Breast Pathology: Diagnosis by Needle Core Biopsy. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:xii
.
Tocino
,
I.
,
B. M.
Garcia
, and
D.
Carter
.
Surgical biopsy findings in patients with atypical hyperplasia diagnosed by stereotaxic core needle biopsy.
Ann Surg Oncol
1996
.
3
:
483
488
.
Jackman
,
R. J.
,
F.
Burbank
, and
S. H.
Parker
.
et al
.
Atypical ductal hyperplasia diagnosed at stereotactic breast biopsy: improved reliability with 14-gauge, directional, vacuum-assisted biopsy.
Radiology
1997
.
204
:
485
488
.
Brem
,
R. F.
,
V. S.
Behrndt
, and
L.
Sanow
.
et al
.
Atypical ductal hyperplasia: histologic underestimation of carcinoma in tissue harvested from impalpable breast lesions using 11-gauge stereotactically guided directional vacuum-assisted biopsy.
AJR Am J Roentgenol
1999
.
172
:
1405
1407
.
Jackman
,
R. J.
,
K. W.
Nowels
, and
J.
Rodriguez-Soto
.
et al
.
Stereotactic, automated, large-core needle biopsy of nonpalpable breast lesions: false-negative and histologic underestimation rates after long-term follow-up.
Radiology
1999
.
210
:
799
805
.
Jackman
,
R. J.
,
K. W.
Nowels
, and
M. J.
Shepard
.
et al
.
Stereotaxic large-core needle biopsy of 450 nonpalpable breast lesions with surgical correlation in lesions with cancer or atypical hyperplasia.
Radiology
1994
.
193
:
91
95
.
Sapino
,
A.
,
A.
Frigerio
, and
J. L.
Peterse
.
et al
.
Mammographically detected in situ lobular carcinomas of the breast.
Virchows Arch
2000
.
436
:
421
430
.
Rosen
,
P. P.
Lobular carcinoma in situ.
In: Rosen's Breast Pathology. 2nd ed. Philadelphia, Pa: Lippincott, Williams & Wilkens; 2001:581–626
.
Lee
,
C. H.
,
T. I. K.
Egglin
, and
L. E.
Philpotts
.
et al
.
Cost-effectiveness of stereotactic core needle biopsy: analysis by means of mammographic findings.
Radiology
1997
.
202
:
849
854
.
Kaye
,
M. D.
,
C. A.
Vicinanza-Adami
, and
M. L.
Sullivan
.
Mammographic findings after stereotactic biopsy of the breast performed with large-core needles.
Radiology
1994
.
192
:
149
151
.
Liberman
,
L.
,
M. C.
Fahs
, and
D. D.
Dershaw
.
et al
.
Impact of stereotactic core biopsy on cost of diagnosis.
Radiology
1995
.
195
:
633
637
.
Rubin
,
E.
,
P. J.
Dempsey
, and
N. S.
Pile
.
et al
.
Needle localization biopsy of the breast: impact of a selective core needle biopsy program on yield.
Radiology
1995
.
195
:
627
631
.
Liberman
,
L.
,
L. R.
LaTrenta
, and
D. D.
Dershaw
.
et al
.
Impact of core biopsy on the surgical management of impalpable breast cancer.
AJR Am J Roentgenol
1997
.
168
:
495
499
.
Smith
,
D. N.
,
R.
Christian
, and
J. E.
Meyer
.
Large-core needle biopsy of nonpalpable breast cancers: the impact on subsequent surgical excision.
Arch Surg
1997
.
132
:
256
259
.
Bodian
,
C. A.
,
K. H.
Perzin
, and
R.
Lattes
.
Lobular neoplasia: long term risk of breast cancer and relation to other factors.
Cancer
1996
.
78
:
1024
1034
.
Haagenson
,
C. D.
,
N.
Lane
, and
R.
Lattes
.
et al
.
Lobular neoplasia (so-called lobular carcinoma in situ) of the breast.
Cancer
1978
.
42
:
737
769
.
Lechner
,
M. C.
,
R. J.
Jackman
, and
R. F.
Brem
.
et al
.
Lobular carcinoma in situ and atypical lobular hyperplasia at percutaneous biopsy with surgical correlation: a multi-institutional study [abstract].
Radiology
1999
.
213
:
106
.
Liberman
,
L.
,
M.
Sama
, and
B.
Susnik
.
et al
.
Lobular carcinoma in situ at percutaneous breast biopsy: surgical biopsy findings.
AJR Am J Roentgenol
1999
.
173
:
291
299
.
Rosen
,
P. P.
Columnar cell hyperplasia is associated with lobular carcinoma in situ and tubular carcinoma.
Am J Surg Pathol
1999
.
23
:
1561
.
Burak
,
W. E.
,
K. E.
Owens
, and
M. B.
Tighe
.
et al
.
Vacuum-assisted stereotactic breast biopsy: histologic underestimation of malignant lesions.
Arch Surg
2000
.
135
:
700
703
.
Liberman
,
L.
,
D. D.
Dershaw
, and
J. R.
Glassman
.
et al
.
Analysis of cancers not diagnosed at stereotactic core breast biopsy.
Radiology
1997
.
203
:
151
157
.
Cangiarella
,
J.
,
J.
Waisman
, and
W. F.
Symmans
.
et al
.
Mammotome core biopsy for mammary microcalcification: analysis of 160 biopsies from 142 women with surgical and radiologic followup.
Cancer
2001
.
91
:
173
177
.
Philpotts
,
L. E.
,
N. A.
Shaheen
, and
K. S.
Jain
.
et al
.
Uncommon high-risk lesions of the breast diagnosed at stereotactic core-needle biopsy: clinical importance.
Radiology
2000
.
216
:
8
.
Berg
,
W. W.
,
O.
Ioffe
, and
S.
Ratakonda
.
et al
.
What is the significance of incidental lobular neoplasia (ALH or LCIS) on core needle breast biopsy? [abstract].
AJR Am J Roentgenol
1999
.
172
:
9
10
.

Presented in part at the 90th meeting of the United States and Canadian Academy of Pathology, Atlanta, Ga, March 6, 2001.

Author notes

Reprints: Sandra J. Shin, MD, Department of Pathology, Starr 1028, New York Presbyterian Hospital–Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021 (sjshin@mail.med.cornell.edu)