Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ as Revealed by Large-Core Needle Breast Biopsy: Results of Surgical Excision

Transcription

1 Marla L. Rosenfield Darling 1 Darrell N. Smith 1 Susan C. Lester 2 Carolyn Kaelin 3 Donna-Lee G. Selland 1 Christine M. Denison 1 Pamela J. DiPiro 1 David I. Rose 1 Esther Rhei 3 Jack E. Meyer 1 Received January 28, 2000; accepted after revision May 2, Department of Radiology, Brigham and Women s Hospital, 75 Francis St., Boston, MA Address correspondence to M. L. Rosenfield Darling. 2 Department of Pathology, Brigham and Women s Hospital, Boston, MA Department of Surgery, Brigham and Women s Hospital, Boston, MA AJR 2000;175: X/00/ American Roentgen Ray Society Atypical Hyperplasia and In Situ as Revealed by Large-Core Needle Breast Biopsy: Results of Surgical Excision OBJECTIVE. This investigation compares the frequency of histologic underestimation of breast carcinoma that occurs when a large-core needle biopsy reveals atypical ductal hyperplasia or ductal carcinoma in situ with the automated 14-gauge needle, the 14-gauge directional vacuum-assisted biopsy device, and the 11-gauge directional vacuum-assisted biopsy device. SUBJECTS AND METHODS. Evaluation of 428 large-core needle biopsies yielding atypical ductal hyperplasia (139 lesions) or ductal carcinoma in situ (289 lesions) was performed. The results of subsequent surgical excision were retrospectively compared with the needle biopsy results. RESULTS. For lesions initially diagnosed as ductal carcinoma in situ, underestimation of invasive ductal carcinoma was significantly less frequent using the 11-gauge directional vacuum-assisted biopsy device when compared with the automated 14-gauge needle (10% versus 21%, p < 0.05) but was not significantly less frequent when compared with the 14-gauge directional vacuum-assisted device (10% versus 17%, p > 0.1). For lesions diagnosed initially as atypical ductal hyperplasia, underestimation of ductal carcinoma in situ and invasive ductal carcinoma was significantly less frequent using the 11-gauge directional vacuum-assisted biopsy device compared with the 14-gauge directional vacuum-assisted device (19% versus 39%, p = 0.025) and with the automated 14-gauge needle (19% versus 44%, p = 0.01). CONCLUSION. The frequency of histologic underestimation of breast carcinoma in lesions initially diagnosed as atypical ductal hyperplasia or ductal carcinoma in situ using large-core needle biopsy is substantially lower with the 11-gauge directional vacuum-assisted device than with the automated 14-gauge needle and with the 14-gauge directional vacuum-assisted device. L arge-core needle biopsy of the breast has become a widely used alternative to open surgical biopsy for the initial diagnosis of suspicious abnormalities visible on mammography or sonography. Early experiences with a 14- gauge automated biopsy needle showed that large-core needle biopsy had a diagnostic accuracy comparable with that of surgical excision after wire localization [1 4]. Technical advances have allowed further improvement in accuracy with the introduction of the directional vacuum-assisted biopsy device, allowing retrieval of larger quantities of tissue with a single insertion of a 14- or 11-gauge needle using stereotactic guidance [5 7]. Despite improvements in technique, histologic underestimation of disease frequently occurs when lesions initially diagnosed using large-core needle biopsy as either atypical ductal hyperplasia or ductal carcinoma in situ are excised surgically. Previous reports have cited underestimation rates ranging from 11% to 75% for atypical ductal hyperplasia (subsequently diagnosed as ductal carcinoma in situ or invasive ductal carcinoma after surgical excision) and from 15% to 35% for ductal carcinoma in situ (subsequently diagnosed as invasive ductal carcinoma) using an automated 14-gauge needle [4, 8 23]. The few groups of researchers evaluating the directional vacuum-assisted device with a 14- gauge needle have shown improvement in underestimation rates ranging from 0% to 38% for atypical ductal hyperplasia and from 0% to 19% for ductal carcinoma in situ [14, 16, 17, 23]. Recent experiences with the 11- gauge directional vacuum-assisted device have been reported that suggest further slight improvement, citing underestimation rates of AJR:175, November

2 Darling et al. from 10% to 27% for atypical ductal hyperplasia and from 4% to 15% for ductal carcinoma in situ [20, 22 26]. This investigation was undertaken to evaluate the results of surgical excision of a large series of atypical ductal hyperplasia and ductal carcinoma in situ lesions diagnosed using large-core needle biopsy. The frequencies of histologic underestimation of lesions diagnosed using the automated 14-gauge needle, the 14-gauge directional vacuum-assisted device, and the 11-gauge directional vacuumassisted device were compared. Subjects and Methods From August 1, 1991, to December 31, 1999, 3873 imaging-guided large-core needle biopsies of the breast were performed at our hospital. Included in this experience were 2364 masses and 1509 clusters of calcifications. A retrospective review of the results of these large-core needle biopsies and subsequent wire localization and surgical excision was performed. There were 292 cases of ductal carcinoma in situ (252 clusters of calcifications and 40 masses) and 148 cases of atypical ductal hyperplasia (122 clusters of calcifications and 26 masses) for a total of 440 lesions in 413 patients. Patients ranged in age from 24 to 89 years, with a mean age of 54 years and a median age of 52 years. Lesion size ranged from 2 to 80 mm (mean, 12.6 mm) for ductal carcinoma in situ lesions and from 2 to 41 mm (mean, 9.7 mm) for atypical ductal hyperplasia lesions. Surgical excision with preoperative wire localization of each of these 440 lesions was recommended and was performed in 428 (97.3%). The final histologic diagnosis was compared with the large-core needle biopsy diagnosis. Among the 12 patients who did not undergo surgery were two with ductal carcinoma in situ and three with atypical ductal hyperplasia who refused surgery and elected for mammographic follow-up at 6-month intervals. The remaining seven were patients with atypical ductal hyperplasia (n = 6) and ductal carcinoma in situ (n = 1) who delayed surgical excision. Of the 428 biopsies yielding ductal carcinoma in situ or atypical ductal hyperplasia for which surgical follow-up was obtained, 403 were performed using stereotactic guidance on a dedicated stereotactic core biopsy unit (Mammotest [August 1991 through August 1994], Fischer Imaging, Denver, CO; and DSM [September 1994 through December 1999], Lorad, Danbury, CT), which was equipped with digital imaging beginning in Sixty-seven biopsies (40 calcifications and 27 masses) were performed with a 14-gauge automated biopsy device using the multiple-pass technique [4]; four to 11 core samples (mean, 7 samples) were obtained from each cluster of calcifications and three to eight core samples (mean, 5 samples) were obtained from each mass. From May 1996 through December 1999, all stereotactic biopsies were performed with a directional vacuum-assisted biopsy device (Mammotome; Ethicon Endo-Surgery, Cincinnati, OH) using a standardized technique that has been previously described [7]. These included 75 lesions (69 clusters of calcifications and 6 masses) biopsied with a 14-gauge needle (4 15 core samples; mean, 8 samples) and 261 lesions (255 clusters of calcifications and 6 masses) biopsied with an 11-gauge needle (5 22 core samples; mean, 9 samples). For calcification sampling, if a specimen radiograph did not show any particles of calcification, additional samples were removed [27]. Samples of targeted calcifications were obtained in all cases. For stereotactic biopsies using the 11-gauge directional vacuum-assisted biopsy device, if complete mammographic removal of the lesion occurred, a 2 2 mm radiopaque localizing clip (MicroMark; Ethicon Endo-Surgery) was inserted into the biopsy site to provide an accurate target for wire localization before excisional biopsy should it be necessary [23, 28, 29]. The remaining 25 lesions yielding ductal carcinoma in situ or atypical ductal hyperplasia on large-core needle biopsy were masses that were biopsied with an automated 14-gauge biopsy needle using sonographic guidance with a 7.5-MHz linear array transducer (AI Performa Plus; Acoustic Imaging, Denver, CO). From four to eight core samples (mean, 5 samples) were obtained from each mass. No calcification clusters were sampled using sonographic guidance. Comparison was made between the histologic diagnosis based on large-core needle biopsy specimens and that based on surgically excised specimens for each lesion. A lesion was considered to be an underestimation if the surgical results yielded a discordant, higher grade lesion that is, an underestimation was a lesion diagnosed using large-core needle biopsy results as atypical ductal hyperplasia but found at surgical excision to be ductal carcinoma in situ or invasive ductal carcinoma. Similarly, an underestimation was a lesion diagnosed initially as ductal carcinoma in situ but found at surgery to be invasive ductal carcinoma. If no residual atypical ductal hyperplasia or ductal carcinoma in situ was found in an accurately localized surgical specimen (needle biopsy tract identified), the lesion was considered to have been completely excised at the time of the large-core needle biopsy. The lesions for which the large-core needle biopsy diagnosis was the same as the surgical diagnosis were considered to be concordant. Statistical analysis was performed using either the chi-square test or Fisher s exact test when appropriate. Statistical significance was assigned a p value of less than Results Of the 289 cases of ductal carcinoma in situ diagnosed using large-core needle biopsy, 40 were found at surgical excision to be invasive ductal carcinoma yielding an underestimation rate of 14% for the three devices combined. When evaluated separately, 14 (21%) of 67 underestimations of invasive ductal carcinoma were with the automated 14-gauge needle, eight (17%) of 47 underestimations of invasive ductal carcinoma were with the 14-gauge directional vacuum-assisted biopsy device, and 18 (10%) of 175 underestimations of invasive ductal carcinoma were with the 11-gauge directional vacuum-assisted biopsy device (Table 1). When these results are compared, the number of underestimations with the 11- gauge directional vacuum-assisted biopsy device is significantly lower than that with the automated 14-gauge needle (p < 0.05). Differences between the 11- and 14-gauge directional vacuum-assisted biopsy devices (p > 0.1) and between the 14-gauge directional vacuum-assisted device and the automated 14-gauge needle (p > 0.5) did not reach statistical significance. Of the 139 lesions diagnosed as atypical ductal hyperplasia using large-core needle biopsy, 38 (27%) were found at surgical excision to be either ductal carcinoma in situ (27 lesions) or invasive ductal carcinoma (11 lesions) for the three devices combined. With the automated 14-gauge needle, 11 (44%) of 25 lesions (8 ductal carcinoma in situ and 3 invasive ductal carcinoma) were underestimated. With the 14-gauge directional vacuum-assisted biopsy device, 11 (39%) of 28 lesions (8 ductal carcinoma in situ and 3 invasive ductal carcinoma) were underestimated. With the 11-gauge directional vacuumassisted biopsy device, 16 (19%) of 86 lesions (11 ductal carcinoma in situ and 5 invasive ductal carcinoma) were underestimated (Table 2). When these results are compared, the number of underestimations with the 11-gauge directional vacuum-assisted biopsy device is significantly lower than that with the automated 14-gauge needle (p = 0.01) and that with the 14-gauge directional vacuum-assisted biopsy device (p = 0.025). Differences between the 14- gauge directional vacuum-assisted device and the automated 14-gauge needle did not reach statistical significance (p > 0.5). The initial lesion was completely excised at the time of core biopsy with no residual ductal carcinoma in situ or atypical ductal hyperplasia in the surgical specimen in 12 (13%) of 92 lesions with the automated 14-gauge needle, 10 (13%) of 75 lesions with the 14-gauge directional vacuum-assisted biopsy device, and 56 (30%) of 185 lesions with the 11-gauge directional vacuum-assisted biopsy device. The slight increase in the rate of complete excision with the 11-gauge directional vacuum-assisted 1342 AJR:175, November 2000

3 Large-Core Needle Biopsy of Breast TABLE 1 Lesions Results of Surgical Excision of In Situ No In Situ a Two procedures were performed using sonographic guidance. b Eight procedures were performed using sonographic guidance. c Five procedures were performed using sonographic guidance. No. of Cases of In Situ Invasive Underestimation of Invasive (%) Calcifications (n = 34) Masses (n = 29) 2 a 23 b 8 c 28 Total (n = 67) Calcifications (n = 43) Masses (n = 4) Total (n = 47) Calcifications (n = 173) Masses (n = 2) Total (n = 175) TABLE 2 Lesions Results of Surgical Excision of Atypical Hyperplasia No Atypical Hyperplasia No. of Cases of Atypical Hyperplasia In Situ Invasive Underestimation of In Situ and Invasive (%) Calcifications (n = 6) Masses (n = 19) 10 a 3 b 4 a 2 b 31 Total (n = 25) Calcifications (n = 26) Masses (n = 2) Total (n = 28) Calcifications (n = 82) Masses (n = 4) Total (n = 86) a Three procedures were performed using sonographic guidance. b Two procedures were performed using sonographic guidance. biopsy device compared with the 14-gauge needles was not statistically significant (p > 0.1). For all needle types combined, atypical ductal hyperplasia lesions were significantly more frequently completely excised than were ductal carcinoma in situ lesions (42% versus 6%, p < 0.001). For each needle type evaluated separately, complete excision of atypical ductal hyperplasia lesions was significantly more frequent than of ductal carcinoma in situ lesions with the 11-gauge directional vacuum-assisted device (p < 0.001) and with the automated 14-gauge needle (p < 0.001). Differences in complete excision were not statistically significant when the two types of lesion were compared for the 14-gauge directional vacuum-assisted biopsy device (p = 0.08). Discussion Atypical ductal hyperplasia is a histologically borderline lesion that has some but not all the features of ductal carcinoma in situ. These features may include a uniform population of cells, smooth geometric spaces between cells or micropapillary formations with even cellular placement, hyperchromatic nuclei, or any combination of these three features. Atypical ductal hyperplasia also lacks the extent of involvement required to meet the strict criteria for ductal carcinoma in situ. Involvement of a single duct or an aggregate diameter of involvement of less that 2 mm constitutes a diagnosis of atypical ductal hyperplasia, and a more extensive lesion with the same histologic features is labeled ductal carcinoma in situ [30 32]. Given the importance placed on the extent of disease in differentiating between these two similar entities, the underestimation of ductal carcinoma in situ encountered when atypical ductal hyperplasia is retrieved on a large-core needle biopsy is likely explained by sampling error. A similar argument can be made for the phenomenon of underestimation of invasive carcinoma when areas of invasion are missed by large-core needle biopsy sampling and only areas containing ductal carcinoma in situ or atypical ductal hyperplasia are retrieved. The development of the directional vacuum-assisted biopsy device and the introduction of the 11-gauge needle has allowed improved accuracy in sampling clusters of calcifications and masses [7, 16, 17, 20, 22 24, 26]. Although the number of lesions in each of the prior series was relatively small, the collective data provided by these investigators indicate a decrease in the rate of histologic underestimation when comparing the 14-gauge automated needle with either the 14-gauge directional vacuum-assisted biopsy device or the 11-gauge directional vacuumassisted biopsy device. The 11-gauge directional vacuum-assisted biopsy device removes a larger quantity of tissue per sample (96 mg) than the 14-gauge directional vacuum-assisted biopsy device (40 mg) and the automated 14-gauge needle (17 mg) [5, 6]. Calcification retrieval and complete mammographic lesion removal are more likely with the directional vacuum-assisted biopsy device instrument [7, 17, 25]. These improvements in tissue acquisition afforded by the newer device have diminished, but not eliminated, the problem of underestimation. Regarding underestimations of invasive ductal carcinoma that yielded only ductal AJR:175, November

4 Darling et al. carcinoma in situ on large-core needle biopsy, our findings of a 21% underestimation rate for the automated 14-gauge needle, 17% for the 14-gauge directional vacuum-assisted biopsy device, and 10% for the 11-gauge directional vacuum-assisted biopsy device are consistent with the work of other investigators and depict this trend toward increased accuracy. Previously reported underestimations range from 15% to 67% for ductal carcinoma in situ diagnosed using the 14-gauge automated needle [4, 8, 10, 12, 17, 18, 20, 21]. This wide variability is likely caused by the small number of cases in some of these studies (range, 3 55 cases; mean, 26.5 cases). Burbank [17] found an underestimation rate of 0% of 32 ductal carcinoma in situ lesions biopsied with the 14-gauge directional vacuum-assisted biopsy device, although lesion size, biopsy technique, and patient age were comparable with our series; this difference may be caused by the larger average number of specimens per lesion (and therefore the lower chance of sampling error) obtained in his study (mean, 26 specimens) compared with our study (mean, 8 specimens). For the 11-gauge directional vacuumassisted biopsy device, the previous series have shown underestimation rates of from 4% to 15% [20, 23, 24], similar to our findings. One additional series of 12 cases of ductal carcinoma in situ lesions reported by Liberman et al. [25] yielded zero underestimations. In this study, the mean number of specimens was greater than that in our series (15 versus 9 specimens), and this difference combined with the small number of cases may explain the lower underestimation rate compared with our data (Table 3). Evaluation of our data for the automated 14-gauge needle reveals that the overall underestimation rate of ductal carcinoma in situ and invasive ductal carcinoma for lesions yielding only atypical ductal hyperplasia on large-core needle biopsy is 44%. Results of underestimation rates from prior studies [4, 8, 9, 11 19, 21 23] have ranged from 11% to 75%, with sample sizes of from two to 54 cases (mean, 22.4 cases), which is comparable with our series. The largest series was reported by Jackman et al. [16] in which 54 lesions yielding atypical ductal hyperplasia on large-core needle biopsy were surgically excised; 18 ductal carcinoma in situ lesions and eight invasive ductal carcinoma lesions were found for an overall underestimation rate of 48%. The lowest reported rate of underestimation for the automated 14-gauge TABLE 3 Comparison of Investigations of Large-Core Needle Biopsies Yielding In Situ Resulting in Underestimation of Invasive Researchers No. of Cases with Surgical Follow-Up needle is 11% by Lin et al. [19]. In this series, 18 lesions were diagnosed as atypical ductal hyperplasia on large-core needle biopsy; one lesion proved to be ductal carcinoma in situ after immediate excision, and one proved to be ductal carcinoma in situ after excision when the calcifications recurred at an unspecified follow-up interval. These investigators did not specify the mean number of core specimens obtained but state that it was rarely more than six (Table 4). Evaluation of the 14-gauge directional vacuum-assisted biopsy device in our experience shows an underestimation rate of 39% for core biopsies yielding atypical ductal hyperplasia. This finding compares favorably with that of a series [23] that reported a 38% underestimation rate for this device, with 24 atypical ductal hyperplasia lesions yielding seven ductal carcinoma in situ and two invasive ductal carcinoma lesions at excision. Both of these rates are higher than the two rates reported in the other large series for this device: Burbank [17] had a 0% underestimation rate for eight lesions, and Jackman et al. [16] showed an overall underestimation of 18% for 74 atypical ductal hyperplasia lesions yielding 10 ductal carcinoma in situ No. of Cases of Invasive Revealed at Surgery Underestimation of Invasive (%) This study Won et al. [20] Jackman et al. [21] Liberman et al. [18] Burbank [17] Meyer et al. [4] Liberman et al. [10] Jackman et al. [8] This study Burbank [17] This study Won et al. [20] Meyer et al. [23] Liberman et al. [24] Liberman et al. [25] and three invasive ductal carcinoma lesions at surgery. In these latter two reports, the mean number of tissue specimens was greater than that in our series, 27 and 15.8 core specimens, respectively, compared with a mean of eight core specimens. Other factors such as lesion size, biopsy technique, and patient age are comparable; therefore, the lower average number of specimens obtained may again account for the higher rate of underestimation that we report in this group (Table 4). For the 86 biopsies performed with the 11- gauge directional vacuum-assisted biopsy device yielding atypical ductal hyperplasia, the underestimation rate for ductal carcinoma in situ and invasive carcinoma was 19%. Brem et al. [26] and Philpotts et al. [22] have recently reported similar results in their series with underestimation rates of 25% (4 of 16 lesions) and 26.7% (4 of 15 lesions), respectively. In an evaluation of calcium retrieval, Liberman et al. [24] reported a slightly lower underestimation rate, with one (10%) of 10 atypical ductal hyperplasia lesions revealing ductal carcinoma in situ at excision. Compared with the findings of Liberman et al., our mean number of core 1344 AJR:175, November 2000

5 Large-Core Needle Biopsy of Breast TABLE 4 Researchers Comparison of Investigations of Large-Core Needle Biopsies Yielding Atypical Hyperplasia Resulting in Underestimation of In Situ and Invasive with Surgical Follow-Up specimens was lower, with nine specimens versus 14 specimens. Because other factors were comparable, a smaller number of specimens combined with a larger number of cases may also account for the difference in this group (Table 4). We have shown that in our series of largecore biopsies, use of the 11-gauge directional vacuum-assisted biopsy device results in the lowest rate of underestimation of disease for lesions initially diagnosed as atypical ductal hyperplasia or ductal carcinoma in situ when compared with other widely used needle types. On the basis of our experience, our current practice is to sample all suspicious No. of Cases of at Surgery of Invasive at Surgery Underestimation of In Situ and Invasive (%) This study Meyer et al. [23] Philpotts et al. [22] 30 6 a 20 Jackman et al. [21] Lin et al. [19] Stolier [14] Jackman et al. [16] Moore et al. [15] Gadzala et al. [13] Liberman et al. [18] Burbank [17] 18 8 a 44 Tocino et al. [12] Dershaw et al. [11] Meyer et al. [4] Liberman et al. [9] Jackman et al. [8] This study Meyer et al. [23] Stolier [14] Jackman et al. [16] Burbank [17] 8 0 a 0 This study Brem et al. [26] Meyer et al. [23] Philpotts et al. [22] 15 4 a 26.7 Liberman et al. [24] calcifications judged to be amenable to stereotactic biopsy using the 11-gauge directional vacuum-assisted biopsy device. If atypical ductal hyperplasia or ductal carcinoma in situ is diagnosed on the basis of the large-core needle biopsy, surgical excision is recommended. Although our average number of core specimens obtained with the 11- gauge needle was less than that of those few studies showing lower underestimation rates, the sample sizes of the other studies were small. Evaluation of a larger number of cases would be needed to determine the optimal number of core specimens required to significantly lower the underestimation rate while at the same time to minimize the risk of complications such as bleeding or infection. At this point, our practice is to obtain an average of nine core specimens and to confirm radiographically that the targeted calcifications are in the specimens. The 14-gauge directional vacuum-assisted device and the automated 14-gauge needle are not currently used for stereotactic biopsy of calcifications at our institution. If a suspicious mass is visible sonographically, large-core needle biopsy is performed at our institution with an automated 14-gauge needle; direct sonographic visualization of the needle within the mass at the time of the biopsy is used to confirm targeting accuracy. For masses that are also visible mammographically, an 11-gauge stereotactic biopsy is performed only if the operator deems the mass too small or indistinct to target accurately under sonographic guidance. Although the data presented in this study show that the 11-gauge directional vacuum-assisted device has a lower underestimation rate than the automated 14-gauge needle for all lesions combined, the number of masses was small and therefore no statistically meaningful information can be obtained regarding masses alone. Our current practice regarding biopsy of masses has not changed on the basis of the results of this study. When no residual atypical ductal hyperplasia or ductal carcinoma in situ was identified histologically after a large-core needle biopsy in an adequately localized surgical specimen, the lesion was considered to have been completely excised at the time of core biopsy. Complete excision occurred in 13% of our cases when the automated 14-gauge needle was used, in 13% of cases when the 14-gauge directional vacuum-assisted biopsy device was used, and in 20% of cases when the 11-gauge directional vacuum-assisted biopsy device was used. The larger volume of tissue per specimen obtained by the 11-gauge needle likely accounts for the higher incidence of complete lesion removal in this group, although the difference was not statistically significant (p > 0.1) [6]. For all needles combined, atypical ductal hyperplasia lesions (42%) were statistically more likely to have been completely removed than were ductal carcinoma in situ lesions (6%) (p < 0.001). The smaller size of atypical ductal hyperplasia lesions in this series (range, 2 41 mm; mean, 9.7 mm) compared with that of the ductal carcinoma in situ lesions (range, 2 80 mm; mean, 12.6 mm) may account for this difference. AJR:175, November

6 Darling et al. Complete histologic removal at diagnostic stereotactic biopsy has been described previously. For atypical ductal hyperplasia and ductal carcinoma in situ lesions, Burbank [17] found higher rates of complete histologic removal using the 14-gauge directional vacuum-assisted biopsy device (18%) than using the automated 14-gauge needle (4%). Another study reported that in five (18%) of 28 lesions diagnosed as ductal carcinoma in situ using the 11-gauge directional vacuum-assisted biopsy device, no residual ductal carcinoma in situ was found at surgical excision [23]. Liberman et al. [25] examined 12 lesions diagnosed as ductal carcinoma in situ using 11-gauge directional vacuum-assisted needle biopsy in which the mammographic lesion was completely removed at the time of the biopsy that is, no residual abnormality was visible. Histologically, only 25% of these lesions had no residual ductal carcinoma in situ at the site at surgical excision. Of three invasive cancers in this series that were also mammographically completely removed at the time of biopsy, all had residual invasive carcinoma at surgery. Importantly, Liberman et al. caution that on the basis of their data, complete mammographic removal of a lesion at the time of percutaneous large-core needle biopsy does not ensure complete histologic removal and cannot be used as a measure of the adequacy of lesion removal. Although our study and the work of others have shown that complete histologic removal of atypical ductal hyperplasia and ductal carcinoma in situ lesions can occur using the currently available large-core needle biopsy techniques, further investigation is warranted before attempting to use the percutaneous vacuum-assisted technique as a therapeutic tool. In our current practice, no attempt is made to completely mammographically remove a lesion at the time of large-core needle biopsy. In summary, the data presented here confirm that histologic underestimation of disease may occur with imaging-guided large-core needle biopsy when the core specimens yield atypical ductal hyperplasia or ductal carcinoma in situ. The introduction of the directional vacuum-assisted biopsy instrument and the use of the 11-gauge needle have substantially diminished the likelihood of underestimation. It is imperative that breast lesions diagnosed as yielding either atypical ductal hyperplasia or ductal carcinoma in situ using large-core needle biopsy results still undergo surgical excision to exclude the presence of a higher grade lesion that may have been missed because of sampling error. Acknowledgment We thank Lisa Loftus-Smith for her help in preparation of this manuscript. References 1. Parker SH, Lovin JD, Jobe WE, Burke BJ, Hopper KD, Yakes WF. Nonpalpable breast lesions: stereotactic automated large-core biopsies. Radiology 1991; 180: Elvecrog EL, Lechner MC, Nelson MT. Nonpalpable breast lesions: correlation of stereotaxic large-core needle biopsy and surgical biopsy results. Radiology 1993;188: Parker SH, Burbank F, Jackman RJ, et al. Percutaneous large-core breast biopsy: a multi-institutional study. Radiology 1994;193: Meyer JE, Christian RL, Lester SC, et al. Evaluation of nonpalpable solid breast masses with stereotaxic large-needle core biopsy using a dedicated unit. AJR 1996;167: Burbank F, Parker SH, Fogarty TJ. Stereotactic breast biopsy: improved tissue harvesting with the Mammotome. Am Surg 1996;62: Burbank F. Stereotactic breast biopsy: comparison of 14- and 11-gauge Mammotome probe performance and complication rates. Am Surg 1997;63: Meyer JE, Smith DN, DiPiro PJ, et al. Stereotactic breast biopsy of clustered microcalcifications with a directional, vacuum-assisted device. Radiology 1997; 204: Jackman RJ, Nowels KW, Shepard MJ, Finkelstein SI, Marzoni FA. Stereotaxic large-core needle biopsy of 450 nonpalpable breast lesions with surgical correlation in lesions with cancer or atypical hyperplasia. Radiology 1994;193: Liberman L, Cohen MA, Dershaw DD, Abramson AF, Hann LE, Rosen PP. Atypical ductal hyperplasia diagnosed at stereotactic core biopsy of breast lesions: an indication for surgical biopsy. AJR 1995; 164: Liberman L, Dershaw DD, Rosen PP, et al. Stereotaxic core biopsy of breast carcinoma: accuracy at predicting invasion. Radiology 1995;194: Dershaw DD, Morris EA, Liberman L, Abramson AF. Nondiagnostic stereotaxic core breast biopsy: results of rebiopsy. Radiology 1996;198: Tocino I, Garcia BM, Carter D. Surgical biopsy findings in patients with atypical hyperplasia diagnosed by stereotaxic core needle biopsy. Ann Surg Oncol 1996;3: Gadzala DE, Cederbom GJ, Bolton JS, et al. Appropriate management of atypical ductal hyperplasia diagnosed by stereotactic core needle breast biopsy. Ann Surg Oncol 1997;4: Stolier AJ. Stereotactic breast biopsy: a surgical series. J Am Coll Surg 1997;185: Moore MM, Hargett CW, Hanks JB, et al. Association of breast cancer with the finding of atypical ductal hyperplasia at core breast biopsy. Ann Surg 1997;225: Jackman RJ, Burbank F, Parker SH, et al. Atypical ductal hyperplasia diagnosed at stereotactic breast biopsy: improved reliability with a 14-gauge, directional, vacuum-assisted biopsy. Radiology 1997; 204: Burbank F. Stereotactic breast biopsy of atypical ductal hyperplasia and ductal carcinoma in situ lesions: improved accuracy with directional, vacuumassisted biopsy. Radiology 1997;202: Liberman L, LaTrenta LR, Van Zee KJ, Morris EA, Abramson AF, Dershaw DD. Stereotactic core biopsy of calcifications highly suggestive of malignancy. Radiology 1997;203: Lin PH, Clyde C, Bates DM, Garcia JM, Matsumoto GH, Girvin GW. Accuracy of stereotactic core-needle breast biopsy in atypical ductal hyperplasia. Am J Surg 1998;175: Won B, Reynolds HE, Lazaridis CL, Jackson VP. Stereotactic biopsy of ductal carcinoma in situ of the breast using an 11-gauge vacuum-assisted device: persistent underestimation of disease. AJR 1999; 173: Jackman RJ, Nowels KW, Rodriguez-Soto J, Marzoni FA, Finkelstein SI, Shepard MJ. Stereotactic, automated, large-core needle biopsy of nonpalpable breast lesions: false-negative and histologic underestimation rates after long-term follow-up. Radiology 1999;210: Philpotts LE, Shaheen NA, Carter D, Lange RC, Lee CH. Comparison of rebiopsy rates after stereotactic core needle biopsy of the breast with 11-gauge vacuum suction probe versus 14-gauge needle and automatic gun. AJR 1999;172: Meyer JE, Smith DN, Lester SC, et al. Large-core needle biopsy of nonpalpable breast lesions. JAMA 1999;281: Liberman L, Smolkin JH, Dershaw DD, Morris EA, Abramson AF, Rosen PP. Calcification retrieval at stereotactic, 11-gauge, directional, vacuum-assisted breast biopsy. Radiology 1998;208: Liberman L, Dershaw DD, Rosen PP, Morris EA, Abramson AF, Borgen PI. Percutaneous removal of malignant mammographic lesions at stereotactic vacuum-assisted biopsy. Radiology 1998;206: Brem RF, Behrndt VS, Sanow L, Gatewood OMB. Atypical ductal hyperplasia: histologic underestimation of carcinoma in tissue harvested from impalpable breast lesions using 11-gauge stereotactically guided directional vacuum-assisted biopsy. AJR 1999;172: Meyer JE, Lester SC, Frenna TH, White FV. Occult breast calcifications sampled with large-core biopsy: confirmation with radiography of the specimen. Radiology 1993;188: Liberman L, Dershaw DD, Morris EA, Abramson AF, Thornton CM, Rosen PP. Clip placement after stereotactic vacuum-assisted breast biopsy. Radiology 1997;205: Burbank F, Forcier N. Tissue marking clip for stereotactic breast biopsy: initial placement accuracy, long-term stability, and usefulness as a guide for wire localization. Radiology 1997;205: Page DL, Rogers LW. Combined histologic and cytologic criteria for the diagnosis of mammary atypical ductal hyperplasia. Hum Pathol 1992; 23: Page DL, Jensen RA. Evaluation and management of high risk and premalignant lesions of the breast. World J Surg 1994;18: Tavassoli FA. Intraductal hyperplasia, ordinary and atypical. In: Tavassoli FA, ed. Pathology of the breast. Norwalk, CT: Appleton & Lange, 1992: AJR:175, November 2000