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Breast Imaging |
1 From the Departments of Diagnostic Radiology (W.A.B., H.E.M.) and Pathology (O.B.I.) and the Greenebaum Cancer Center (W.A.B.), University of Maryland School of Medicine, Baltimore; and the Department of Radiology, Mercy Medical Center, Baltimore, Md (H.E.M.). Received April 25, 2000; revision requested June 16; revision received July 10; accepted July 25. Address correspondence to W.A.B., University Imaging Center, 419 W Redwood St, Suite 110, Baltimore, MD 21205-1595 (e-mail: waberg@umaryland.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Results from 1,400 consecutive core-needle breast biopsies were reviewed. Twenty-five (1.8%) biopsy samples with the diagnosis of lobular neoplasia (15 with ALH and 10 with LCIS) adjacent to or in a targeted benign lesion were found. Lesions were excised (n = 15) or followed up (n = 10) at least 22 months.
RESULTS: Of the 15 lesions with ALH, 13 (87%) were adjacent to (n = 12) or associated with (n = 1) microcalcifications, and two (13%) were in masses. Six lesions with residual calcifications were excised. One lesion was diagnosed as ductal carcinoma in situ (DCIS), and five were benign (residual ALH was seen in four). One excised mass showed residual ALH. Six lesions were gone at follow-up, one cluster of microcalcifications was decreased in size, and one fibroadenoma with ALH was stable. Of the 10 lesions with LCIS, seven (70%) were adjacent to (n = 6) or associated with (n = 1) microcalcifications, and three (30%) were in or adjacent to masses. Five lesions with LCIS and residual microcalcifications were excised. Three yielded atypical ductal hyperplasia (ADH); one, residual LCIS; and one, ALH. Three masses with LCIS were excised. One showed residual LCIS; one, a papilloma with adjacent LCIS; and one, a fibroadenoma with LCIS in it. One cluster of microcalcifications was gone at follow-up, and one was stable.
CONCLUSION: After a diagnosis of lobular neoplasia at core biopsy, residual microcalcifications are viewed in the context of a patient at higher risk of cancer. Of 11 lesions with residual microcalcifications, three (27%) were ADH and one (9%) was DCIS.
Index terms: Breast, biopsy, 00.1261, 00.1267, 00.30 • Breast, diseases, 00.71, 00.72 • Breast neoplasms, diagnosis, 00.1261, 00.1267, 00.30
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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The diagnosis of lobular neoplasia at core-needle breast biopsy would not be considered concordant for the targeted abnormality but would usually represent an incidental finding. When cancer is also present with ALH or LCIS, excisional biopsy is performed routinely. When the targeted lesion is sampled with benign concordant results and ALH or LCIS is also present at core biopsy, some authors have performed excision (5,6). The basis for final management of these uncommon entities is not well established; therefore, the purpose of this study was to review our experience with follow-up of lesions diagnosed with ALH or LCIS at core-needle breast biopsy.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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The histopathologic findings were routinely reviewed together with the imaging features to establish concordance. A discordant result or a result of atypical ductal hyperplasia (ADH) or radial scar prompted a recommendation for excisional biopsy. The histopathologist also rarely recommended excisional biopsy because of uncertainty about a possible phyllodes tumor, complex sclerosing lesion, or cellular atypia. A result of malignancy was the basis for definitive treatment. Discrete benign and concordant diagnoses were accepted and followed up for 2 years.
At percutaneous biopsy, lobular neoplasia was found in 42 (3.0%) of the 1,400 lesions. A coexistent diagnosis at that site prompted excisional biopsy of 17 lesions: nine lesions with infiltrating lobular carcinoma and LCIS, one with infiltrating ductal carcinoma and LCIS, one with ductal carcinoma in situ (DCIS) and LCIS, four with ADH and LCIS (diagnosed at core biopsy), and two with ALH and ADH. The diagnosis was confirmed at excisional biopsy in 16 lesions. The remaining lesion was diagnosed with ALH and ADH at core biopsy, but DCIS was found at excisional biopsy.
Study Population
In the 1,400 core needle biopsies, 25 foci of lobular neoplasia (15 with ALH and 10 with LCIS) were identified adjacent to (or in) a targeted benign nonpalpable lesion in 24 patients. The 25 foci represent the study population. Five of the foci were masses; four were sampled at US-guided biopsy with a 14-gauge automated biopsy gun (mean, five specimens; range, four to six), and one was sampled stereotactically with an 11-gauge vacuum-assisted probe (15 samples). Twenty of the foci were manifest as clustered microcalcifications and were sampled at stereotactic biopsy. One was sampled with a 14-gauge automated biopsy gun (six samples), and 19 were sampled with an 11-gauge vacuum-assisted probe (mean, 12 specimens; range, six to 14).
ALH at core biopsy.—The 15 foci of ALH were found in 15 women (age range, 37–68 years; mean age, 52.7 years; median age, 52 years). Follow-up was performed if a satisfactory result was obtained at core biopsy that was concordant with the mammographic or US lesion sampled and if no residual lesion was seen at mammography. Seven of the ALH lesions were excised. Mammographic follow-up was available at 22–36 months for the remaining eight lesions.
Three (20%) of the 15 patients had synchronous cancer diagnosed at core biopsy at a separate site: ipsilateral DCIS 17 cm away in a different quadrant in one patient and contralateral infiltrating ductal carcinoma in two patients. Another of the 15 patients had undergone biopsy of microcalcifications at the same site 3 years earlier; the diagnosis was LCIS adjacent to the targeted microcalcifications in fibrocystic change.
LCIS at core biopsy.—The 10 foci of LCIS were found in nine women (age range, 45–88 years; mean age, 58.2 years; median age, 52 years). Needle localization and excisional biopsy was recommended for all 10 lesions. Surgical risk was considered too high in an 88-year-old patient, and follow-up was available at 27 months. One patient chose only follow-up. Thus, histopathologic results were available for only eight of the 10 lesions with LCIS.
Synchronous cancer was found in two of the nine patients: invasive lobular carcinoma 15 cm from the core biopsy site in one patient and contralateral invasive ductal carcinoma in one. One patient with two foci of LCIS died of heart disease, and autopsy was performed; she had undergone contralateral mastectomy for invasive ductal carcinoma 12 years earlier. One patient had undergone excisional biopsy of microcalcifications at the same site 2 years earlier; the diagnosis was LCIS adjacent to the targeted microcalcifications in fibrocystic change. One patient had undergone contralateral mastectomy for invasive ductal carcinoma 10 years earlier.
Data Analysis
Results were analyzed (W.A.B., O.B.I.) with the 
2 test. Differences with a P value less than .05 were considered significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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After a diagnosis of LCIS at core biopsy, adjacent ADH was seen at excisional biopsy in three (60%) of five lesions with residual microcalcifications. Similarly, adjacent DCIS was seen at excisional biopsy in one (17%) of six lesions with residual microcalcifications and a diagnosis of ALH at core biopsy (P 
.2).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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In one series, histopathologic evidence of residual (and possibly antecedent) LCIS was found in 72 (99%) of 73 breasts with invasive lobular carcinoma (11). LCIS coexists with 21%–22% of DCIS foci (12,13). The presence of LCIS is considered a risk factor that indicates an increased risk of breast cancer in either breast; risk estimates of subsequent invasive cancer average 17% and range from 12% to 33% (1,13–21). In one series, this risk persisted for at least 20 years of follow-up (17). The majority of invasive cancer that develops is invasive ductal carcinoma. From 35% to 50% of the subsequent cancer is invasive lobular carcinoma, whereas only 5%–10% of all breast cancer is invasive lobular carcinoma (reviewed in reference 22).
The possibility that LCIS is directly premalignant is not excluded, but subsequent invasive cancer is seen only rarely at that site (23). After a diagnosis of LCIS at excisional biopsy in several series, the risk of residual infiltrating carcinoma in the same breast is 1%–6%, and at least half of such cancers are found in a different quadrant from the site of the original biopsy (24–26). At follow-up in one series, three (38%) of eight invasive cancers were seen at the site of prior LCIS (27).
There is a spectrum of change from ALH to LCIS. ALH represents a proliferation of monomorphic cells in a nondistended lobule or small lobular duct, whereas LCIS is characterized by distention. To reflect this spectrum of change and to avoid the connotation of malignancy per se, use of the term "lobular neoplasia" has been advocated (1). Compared with the general population, the risk of subsequent breast cancer is four- to fivefold after a diagnosis of ALH and approximately 11-fold after a diagnosis of LCIS (20,21,28). The presence of ALH in combination with a family history of breast cancer increases the risk of subsequent invasive cancer eightfold; the magnitude of risk is similar with ALH and ADH (20).
In the multicenter study by Lechner et al (29), 25% of cases of LCIS at core biopsy were malignant at excision, and 21% of cases of ALH diagnosed at core biopsy proved malignant at excision. The rate of subsequent malignancy found at excision was highly variable across institutions, suggesting variations in the histopathologic criteria for the initial diagnosis of LCIS or ALH. In this series, only one (8%) of 13 foci with lobular neoplasia at core biopsy proved malignant at excision. Any recommendation for final management after a diagnosis of ALH or LCIS at core biopsy must be based on a consideration of the outcomes at one’s own institution.
If a conservative course of follow-up is considered, several histopathologic variables should be evaluated. The severity of LCIS discovered at core biopsy may correlate with the risk of subsequent breast cancer and may also be relevant in the decision about management. Ottesen et al (27) report that the risk of subsequent invasive breast cancer is higher when at least 10 lobules are involved with LCIS.
DCIS and LCIS can have similar appearances at histopathologic examination, which further confounds management recommendations (30). Cells of DCIS can extend not only along the duct but also into the terminal duct lobular unit. When monomorphic cells distend the lobule, it can reflect cancerization of the lobules from DCIS, and it can be difficult to distinguish from LCIS. Similarly, cells of ALH or LCIS can involve the ducts, so-called pagetoid spread; both entities arise in the terminal duct lobular unit (31). When ductal involvement is present, the risk of subsequent invasive cancer increases. In the long-term follow-up study of Page et al (32), the relative risk in patients with ALH and ductal involvement was 6.8 compared with a relative risk of 2.7 in patients with ALH without ductal involvement; the mean relative risk with or without ductal involvement was 4.3.
Findings in a study (5) to evaluate results at excisional biopsy after a diagnosis of LCIS at core biopsy suggest that excisional biopsy is warranted if histopathologic features overlap with those of DCIS. Two (50%) of four such lesions were proved malignant. One (20%) of five lesions with LCIS or ALH in combination with a high-risk lesion such as radial scar or ADH proved malignant. This risk of malignancy is similar to that with ADH alone at core biopsy in other series (33,34). In five core biopsy specimens with a result of only LCIS, no malignancies were found at excision (5).
Thus it appears that if more severe findings are present at histopathologic examination of core specimens, including involvement of multiple lobules or ducts, excision is appropriate. Methods to help differentiate DCIS from ductal involvement with ALH or LCIS are being developed. Immunohistochemical staining for E-cadherin expression can help differentiate these entities, because E-cadherin expression is lost in lobular lesions (35–37).
Lobular neoplasia is itself a high-risk finding; therefore, any residual lesion must be viewed with greater suspicion. On the basis of findings in our study, this concept is particularly true for residual microcalcifications. When residual microcalcifications were present, we found a substantial risk of ADH or DCIS at the site of lobular neoplasia at core biopsy. Even when microcalcifications are retrieved at core biopsy, an adjacent breast cancer can be missed. At detailed histopathologic review, microcalcifications are found both in and adjacent to 35% of cancers and only adjacent to 16% (38,39). Failure to diagnose breast cancer is far more likely when microcalcifications are sampled at stereotactic core biopsy than when masses are sampled (40,41).
Although philosophies differ about the need to excise a lesion that is likely to be ADH, it is considered a premalignant lesion. To reflect this potential progression and the spectrum of changes from usual hyperplasia to ADH to DCIS, use of the term "ductal intraepithelial neoplasia" has recently been advocated (42). Pathologists do not always concur on the differentiation of ADH from DCIS. Furthermore, recent data suggest that ADH should be considered part of a DCIS lesion and excised to decrease the rate of local recurrence (43). Given the likelihood of coexistent ADH, our results suggest that excisional biopsy of residual microcalcifications at that site should be considered after a result of ALH or LCIS at core needle breast biopsy.
Remote lesions in the same and contralateral breast also need to be viewed with higher suspicion after lobular neoplasia is found. With a diagnosis of LCIS, the risk of contralateral synchronous cancer exceeds the risk of unsuspected ipsilateral cancer (range, 12%–21%) (16).
Mammographic-histopathologic concordance must be clearly established in every case after core needle biopsy, especially in cases of lobular neoplasia. In one series (3), microcalcifications depicted at mammography were the indication for biopsy in 49% of breast lesions with LCIS, although the microcalcifications were adjacent to the LCIS in the "vast majority" of cases. There was no mammographic abnormality in 44% of lesions (3). In one (8%) of 13 ALH lesions and one (14%) of seven LCIS lesions, microcalcifications were found in both fibrocystic changes and ALH or LCIS. It should be noted that 19 (95%) of 20 targeted microcalcifications with a diagnosis of lobular neoplasia were sampled with an 11-gauge vacuum-assisted probe. The volume of tissue acquired with an 11-gauge probe is more than five times greater than that acquired with a 14-gauge automated biopsy gun (44). Increasing the volume of tissue sampled increases the likelihood of retrieving adjacent entities such as lobular neoplasia.
In our study, one focus of LCIS was manifest as a mass at mammography (Fig 3). Microcalcifications were seen both in and adjacent to one lesion with LCIS and one focus with ALH. The remaining 88% (22 of 25) of foci of lobular neoplasia were mammographically occult. In general, if a mass is sampled and the most discrete finding at histopathologic examination is LCIS or ALH, repeat biopsy is appropriate (45).
Lobular neoplasia is a relatively uncommon entity, and results such as ours are limited by the small number of patients. Data from larger multicenter series are needed to allow more definitive management recommendations. In addition, longer term follow-up of patients who do not undergo excisional biopsy may be beneficial.
Women with a biopsy result of lobular neoplasia are at increased risk for breast cancer. After a result of lobular neoplasia at core biopsy, management of the site itself is likely to remain controversial. On the basis of findings in this study, we make the following recommendations for management after a diagnosis of lobular neoplasia at core biopsy. If no residual lesion is depicted at mammography, close mammographic surveillance (for 2 years at 6-month intervals followed by annual examinations) may be reasonable. Fibroadenomas with internal or adjacent lobular neoplasia may be reasonably treated with follow-up. In the presence of residual microcalcifications, excisional biopsy may be appropriate.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, W.A.B.; study concepts, W.A.B., H.E.M.; study design, W.A.B.; definition of intellectual content, W.A.B., H.E.M., O.B.I.; literature research, W.A.B.; clinical studies, W.A.B., H.E.M., O.B.I.; data acquisition, W.A.B., H.E.M.; data analysis, W.A.B., O.B.I.; manuscript preparation, W.A.B.; manuscript editing, W.A.B.; manuscript review, W.A.B., H.E.M., O.B.I.; manuscript final version approval, W.A.B., H.E.M., O.B.I.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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