Case 1

Forty-five-year-old female with a screening mammogram showing an area of suspicious microcalcifications measuring 5 mm in diameter reported as BIRADS category 4 – a suspicious abnormality. Stereotactic core-needle biopsy with an 11-gauge needle and a total of ten core samples reveal ALH. On further analysis of the final pathology, there are fibrocystic changes only, with some associated calcium in the benign fibrocystic ducts. There is a single focus of ALH. A clip is in good position and it appears on post-biopsy mammogram that all of the microcalcifications were removed.

Our recommendation for this patient would be for continued observation and a discussion of chemopreventive strategies, such as tamoxifen.

Concordance is achieved when the pathologic findings provide a sufficient explanation for the radiologic appearance. These lesions can generally be observed. It is recommended that the issue of concordance be carefully reviewed and that the surgeon, radiologist, and pathologist are in agreement with these findings. When evaluating the literature carefully, lesions of pure ALH that have demonstrated documented radiologic–pathologic concordance consistently have a low rate of upstaging to a malignancy (Table 10.3).

The data we have collected from the Mayo Clinic addresses the upstage rate of pure LN [28]. We performed a retrospective review evaluating all patients that underwent core-needle biopsy between 1993 and 2010. We excluded any core biopsy that contained an associated high-risk lesion such as PLCIS, ADH, radial scar, papilloma, flat epithelial atypia (FEA), ipsilateral invasive carcinoma, or DCIS. The final analysis included 184 cases, with 74 % of the core biopsies performed for suspicious microcalcifications, 21 % for a solid mass or nodule, and 5 % for an area deemed suspicious by breast MRI. We identified 147 (80 %) patients with ALH and 37 (20 %) with LCIS. Of these, 81 (55 %) of the ALH cases and 20 (54 %) of LCIS cases underwent definitive operative removal of the lesions.

The rate of upstage upon surgical excision for ALH was 1.5 % (1/81) and 5 % (1/20) for LCIS. The single ALH case that was upstaged had a discordant biopsy result and was upgraded to DCIS. Of the ALH lesions that had no other associated high-risk features and pathologic–radiographic concordance on needle biopsy, none were upstaged at the time of excisional biopsy (Table 10.4). These upstage rates are very low and consistent with other studies evaluating the upstage rates of pure LN that have undergone meticulous review of the pathologic–radiographic concordance [19, 42–44]. Similar findings were recently published from a prospective series by Murray et al. [43].

Our series is somewhat unique in that it included the entire cohort of LN lesions, including those that were observed and did not undergo excisional biopsy. Follow-up data was available for 65 cases that were merely observed without surgical excision, with a mean follow-up period of 53 months. In patients with ALH, 1/51 (2 %) developed an ipsilateral cancer and for those with LCIS, 3/14 (21.4 %) developed an ipsilateral cancer. This ipsilateral breast event rate is high; however, it is worth noting that all patients with LCIS that developed a subsequent ipsilateral malignancy did so in a different quadrant than the initial biopsy, suggesting excisional surgical biopsy would not have influenced the future events. This is also a relatively small cohort, as the majority of patients with LCIS in our series did go onto excisional biopsy, thus caution is advised in making conclusions based on this subset of 14 patients. With regard to the contralateral breast, 2.7 % of patients with ALH and 3.8 % with LCIS developed a contralateral malignancy during the follow-up period.

All of the subsequent cancers that developed were invasive ductal carcinoma in origin. Although these rates appear to be much lower than the expected rate of development of malignancy in such patients with LN, the lifetime incidence for the development of ipsilateral or contralateral or malignancy was 21 % (31/145) for those with ALH and 29 % (10/35) for those with LCIS. These lesions are associated with an increased risk of future breast cancer and these patients should be under surveillance and strongly consider chemoprevention. This is discussed in more detail below.

Hwang et al. reported on a series of 48 patients with pure ALH, of which the upstage rate was 2 % [19]. Of note, the upgraded lesion was a biopsy performed for a mass lesion. This report also provided follow-up data for patients that did not undergo excision following a diagnosis of LN. The mean follow-up period was 49 months for 148 cases of LN without subsequent excision and demonstrated a 2 % incidence of subsequent ipsilateral carcinomas, including one case within a different site than the original biopsy identifying LN.

Brem et al. reported on a multi-institution series of LN [39], analyzing 67 LCIS and 97 ALH cases that underwent complete excision. The upgrade rate reported was substantial, 25 % for those with LCIS and 22 % (21/97) for those with ALH. However, of the 164 lesions excised, 74 (45 %) were noted to have radiologic–pathologic discordance. A major limitation of this study lies in the fact that there were several institutions included and no retrospective pathology overview, resulting in potential variability in the interpretation of LN. Rendi et al. reported on 68 patients with pure LN [42]. Two cases (4.1 %) of ALH were upstaged, with one being a mass lesion that was noted to be discordant. Thus, the true upstage rate of pure, concordant ALH in this series is likely closer to 2 %.

Extent of disease is also an important factor to be evaluated. Esserman et al. demonstrated that the extent of lobular neoplasia in a core biopsy specimen may predict whether or not excision is required [45]. They distinguished diffuse lobular neoplasia (>1 lobule per core affected) from focal lobular neoplasia (less than or equal to 1 lobule per core) and found that upgrades to malignancy were more likely to be associated with diffuse LN. Although the number of patients included was small (35 patients), these findings would support that in patients with simply a focus of LN, observation can be considered.

Case 2

A 52-year-old female undergoes a screening mammogram that reveals a 1.5-cm diameter area of suspicious microcalcifications (BIRADS 4). A stereotactic biopsy with a 14-gauge core needle and four core samples reveals ALH and ADH with the microcalcifications associated with the atypical ducts. Post-biopsy mammogram reveals the clip in good position with many microcalcifications remaining.

Our recommendation would be for an excisional biopsy to obtain an adequate sample for final pathologic analysis to rule out an underlying occult malignancy. This is a conservative surgical excision. In general, this is a diagnostic procedure, and we are attempting to obtain an adequate representative sample to assure there is no upstaging. The rationale for excision in this case is twofold; the calcifications in question have not been adequately sampled, and a definitive diagnosis must be obtained due to the presence of a higher-risk lesion. As covered in another chapter, excisional biopsy is standard for ADH and results in approximately a 10–20 % upstage [46]. At the time of this publication, core-needle biopsy alone for ADH has not been able to stratify a low enough risk group that an occult cancer can be excluded. The management of such cases should be directed toward removal of the highest-risk lesion. The higher-risk lesion would trump the ALH and standard of care for the ADH would be followed.

The disadvantage of a more aggressive wire localized lumpectomy stems from the fact that lobular neoplasia is a risk factor for the development of breast cancer. This risk occurs in all quadrants and is bilateral; thus a more aggressive surgery, short of a bilateral mastectomy, does not prevent the potential development of a future malignancy. We are not prepared at the time of excisional biopsy to proceed to definitive mastectomy, reconstruction, or axillary staging if the lesion is upstaged. In the rare case where there is extensive calcifications throughout a large area or scattered throughout the breast and follow-up imaging may be inadequate, deciding what is an adequate sampling and observing can be unsettling and mastectomy may be an option. This should be the exception, not the rule.