Demographics and Case Characteristics
There were 10,024 breast core biopsies performed at our institution during this time period. Of these, 117 biopsies had a diagnosis of isolated ALH, without another finding that by itself would be an indication for excisional biopsy (such as ADH), and without discordant radiology/clinical impression. Two additional cases were excluded due to missing slides and/or history. An additional 26 cases showed LCIS (with or without ALH, and without other findings such as ADH); these cases also did not have discordant radiology/clinical impressions at biopsy.
Of the 117 ALH cases, 42 had 3 or fewer foci of ALH and a follow-up excision (35.9%), representing biopsies from 41 patients; and 14 biopsies had more than 3 foci and a corresponding follow-up excision (12.0%), representing biopsies from 13 patients. The group with 3 or fewer foci (minimal ALH) represented 75.0% of the 56 biopsies with a paired excision. These findings are shown in Figure 3. In most cases, a focus was composed of one lobular unit with ALH; in rare cases a focus was composed of up to 3 adjacent lobular units with ALH.
Cases With Minimal ALH
The patients with minimal ALH were all women with an age range of 40.6 to 85.5 years, a mean age of 54.4 years, and a median age of 52.9 years. Thirty-five of 41 patients were White and 6 were African-American. Nine patients had a family history of invasive breast cancer in a first-degree relative. Four patients had a history of prior invasive breast cancer (2 cases in the same breast and 2 in the contralateral breast). One patient had a prior history of LCIS in the same breast. Thirty-five core biopsies (83.3%) were performed for microcalcifications, with the remaining 7 (16.7%) performed for a mass or sonographic abnormality. Sixteen biopsies were obtained using 14-gauge needles, with the remaining 26 obtained with 11-gauge needles. The average number of ALH foci was 1.7, with a median of 1 focus. Twenty-two cases had 1 focus, 10 cases had 2 foci, and 10 cases had 3 foci. Additional findings in the core biopsies included nonproliferative changes (cysts, apocrine metaplasia, fibrosis, and columnar cell change), proliferative changes (sclerosing adenosis, usual ductal hyperplasia, columnar cell hyperplasia, and micropapillomas), and fibroadenomas. The most significant of these findings in each biopsy are included in Table 1.
On follow-up excision, 26 cases (61.9%) showed residual ALH and 13 cases (31.0%) were entirely non-neoplastic. Three cases (7.1%) had atypical lesions other than ALH: 2 cases showed LCIS (1 focally), and 1 case had focal mild ADH away from the biopsy site. The details of these individual cases are listed in Table 1.
Of the 41 patients in the minimal ALH group, there was a mean of 3.2 years of follow-up, with a range of 1 month to 10.6 years (median follow-up 2.8 y). Two patients died during this time period from unrelated causes. One woman developed a focus of ductal carcinoma in situ (DCIS) in the contralateral breast 1.5 years after core biopsy. Another woman had concurrent and subsequent DCIS in the contralateral breast; she was also diagnosed with ALH on core biopsy in the same breast as the original biopsy 2.3 years later, followed by an excision also revealing ALH (this patient had 2 biopsies in our minimal ALH group). None of the other women in this group were subsequently diagnosed with high-risk breast lesions in either breast, as per the records available at our institution.
Cases With More than 3 Foci of ALH on Core Biopsy
In this group, foci of ALH ranged from 4 to 11, with a mean of 7.1 foci and a median of 7 foci. On excision, 9 cases showed residual ALH, 4 cases showed LCIS, and 1 case had focal ADH in addition to ALH. No cases were entirely benign.
Cases With LCIS on Core Biopsy
Of the 26 cases with LCIS on core biopsy, 12 cases had in-house follow-up excision (46.1%). Of these cases, 8 (61.5%) had another type of lesion on excision: infiltrating carcinoma with LCIS (3 cases), DCIS with LCIS (2 cases), LCIS with ADH (1 case), and ADH (2 cases). Two cases showed residual LCIS and 2 showed isolated ALH. No cases were entirely benign. It is noteworthy that in the 3 cases of invasive carcinoma (2 infiltrating carcinomas with ductal and lobular features as well as 1 infiltrating lobular carcinoma), the invasive component was small (0.15, 0.3, and 0.8 cm), and there was a background of extensive LCIS.
Although general guidelines for the management of ADH and DCIS diagnosed on core biopsy have been established,32 there is persistent controversy regarding management of noninvasive lobular neoplasia, and especially ALH, in the literature. Part of this disagreement stems from the issue of whether lobular neoplasia is a true precursor to invasive carcinoma, or rather a predictor of increased risk. Although it does seem to share some of the molecular alterations of invasive lobular carcinoma,2,6,18 lobular neoplasia still does not confer the same degree of risk to patients as a diagnosis of DCIS.10,32
Studies have shown a significant incidence (up to 52% of cases) of upstaging ADH to DCIS or invasive carcinoma on follow-up excision.1,4,22,23,25 However, the literature is conflicting on the likelihood of finding a higher grade lesion than ALH after core biopsy. Rates of upstaging as high as 19% to 20% have recently been reported,12,20 with many authors recommending excision for any diagnosis of atypia, including ALH.1,5,12,15,24 However, other studies assert the opposite, citing very low rates of DCIS or invasive cancer on immediate surgical excision of ALH.14,19,21,26,27,31,34 Differences may be attributable to technical aspects of imaging and/or performing the biopsy, histologic interpretation,9,19 or patients at higher risk for disease because of other factors.
We note in our study that the group of 14 cases with 4 or more foci of ALH showed ALH, LCIS, or ADH on follow-up excision; these findings are similar to that of our minimal ALH group, (although there were no entirely benign cases). However, we justify the focus of our study population on minimal incidental ALH (with 3 or fewer foci) for several reasons. First, this minimal ALH group represents a tightly clustered majority of the biopsies we reviewed (75.0%), whereas the biopsies with more than 3 foci were varied and dissimilar; some of those cases had extensive ALH that could be interpreted as LCIS by some pathologists. Second, the group with more than 3 foci only had 14 biopsies from 13 patients, likely too small to draw conclusions about the risks of upgrade in these cases. Therefore, we believe that limiting our recommendations to cases with 3 or fewer foci will lead to more reproducible findings, and will hopefully allow us to avoid some of the disparities that have been seen between some other studies.
We chose to evaluate “pure” cases that were not associated with more aggressive lesions or suspicious radiologic findings to get a better estimate of the true risk of isolated ALH. Unlike the upgrade rate with LCIS in our study (with at least 41.7% showing infiltrating carcinoma or DCIS—this rate may even be artificially low because 14 women did not have follow-up excision in-house), our cases of minimal ALH did not show lesions on excision that would have required further surgery. Although the need for excision of more extensive ALH or LCIS may remain a topic of debate, we propose that follow-up surgery should not be necessary for minimal ALH, if strict criteria are used to separate out these lesions. Along these lines, Ely et al13 have shown that examples of minimal ADH diagnosed on core biopsy may not require follow-up surgery.
Our findings are in keeping with those of Nagi et al27 and Hwang et al,19 who similarly suggest that of utmost importance is the radiographic and clinical impression of the lesion. If there is discordance with the biopsy findings, an excision is still warranted. Furthermore, these patients will continue to require close follow-up, as ALH carries a bilateral increased risk of invasive disease (4 to 5 times the general population),11,17,28 approximately 3 times more likely to arise in the ipsilateral than contralateral breast.30
It should be noted that all of our cases had biopsies with either 11 or 14-gauge needles under stereotactic or ultrasound guidance, and our findings may not be able to be extrapolated to populations of patients who have core needle biopsies using other devices or needle sizes. Additional limitations include the relatively small number of biopsies with minimal ALH and paired excisions as well as short-term follow-up in some cases; with a larger sample size, it is possible that rare higher risk lesions might be detected. The retrospective nature of the review also introduced an inherent bias due to our knowledge of patients' clinical courses over the decade; this may have influenced our exclusion of some cases in which the initial biopsy clearly missed the lesion. However, the uniformity of our study population, gained by the opportunity to evaluate both the biopsies and the excisions in the proper clinical and radiographic context, strengthens our findings. Indeed, the available follow-up on these patients validates our risk stratification by biopsy when minimal ALH is present; in fact only 3 woman were diagnosed with lesions more significant than ALH at the immediate excision (none of which would require more surgery), with only one additional patient diagnosed with subsequent disease in the same breast during our study period. This might be another indication that a more serious lesion was not missed in these cases.
In conclusion, none of our minimal ALH cases had a lesion on excision that would have required further treatment, suggesting that these patients could have been managed more conservatively. We propose that minimal incidental ALH (limited to 3 or fewer foci) on core biopsy, with close radiologic correlation, clinical observation, and follow-up, does not require excision.
The authors thank Dr Pedram Argani and Dr Ralph Hruban for critically reviewing this manuscript.
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Keywords:© 2010 Lippincott Williams & Wilkins, Inc.
atypical lobular hyperplasia; core biopsy; excision