Lobular carcinoma in situ (LCIS) is an uncommon noninvasive lesion first documented as an “atypical proliferation of acinar cells” by Ewing [1] in 1919. In 1941, Foote and Stewart [2] first designated the lesion as LCIS and described it as a precancerous lesion of the proliferative mammary epithelium. As previously suggested in a study by Foote and Stewart [2], the presence of LCIS can be a risk stratifier and may represent a precancerous stage in the multistep process of carcinogenesis. Indeed, the following studies have shown that unlike ductal carcinoma in situ (DCIS), LCIS is more likely to be a risk factor rather than a true early cancerous lesion [3-6]. LCIS is often discovered incidentally from biopsies performed on the breast for other reasons. Accordingly, the incidence of LCIS in the general population is difficult to accurately determine. Nonetheless, the incidence of LCIS in otherwise benign breast biopsies is reported to be 0.02% to 3.8% [3,7,8]. The Surveillance, Epidemiology, and End Results data from 1978 to 1998 showed that the highest incidence rate of LCIS was 3.19/100,000 person-years, which is substantially lower than that of DCIS (12.73/100,000 person-years) during the same period [9]. This relatively low incidence of LCIS is a main reason for the prevailing controversy in the diagnosis and treatment of this disease.

Early studies have reported high rates of multifocal and bilateral lesions in patients with LCIS. In a case series of patients who underwent contralateral biopsy procedures during curative surgery for ipsilateral LCIS, more than 50% of the patients had multifocal or multicentric lesions, and one-third had bilateral lesions [10-12]. However, it is widely accepted that LCIS usually does not present characteristic abnormal findings in conventional imaging studies [13,14], impeding the detection of these additional lesions. Pope et al. [13] reviewed the imaging findings of 26 patients with LCIS and reported that most LCIS cases do not show distinctive mammography (MMG) features, with the exception of a small proportion of patients with MMG calcification or asymmetry. Sonnenfeld et al. [14] reviewed 41 consecutive cases of LCIS and also concluded that most of the microcalcifications that resulted in the diagnosis of LCIS were due to the benign pathological process occurring near the LCIS.

The accuracy and sensitivity of breast imaging have improved dramatically during the last few decades. Therefore, the ability of modern breast imaging studies, including MMG, breast ultrasonography (USG), and magnetic resonance imaging (MRI) to detect multifocal or bilateral LCIS should be re-evaluated. The purpose of this study was to evaluate the incidence of multifocal and bilateral LCIS of the breast in Korean women. Additionally, we explored the characteristics and roles of the current breast imaging studies in detecting multifocal and bilateral lesions in LCIS patients.

This retrospective study was approved by the Institutional Review Board of Seoul National University Hospital (IRB number: 1410-028-616) and conducted in accordance with the Helsinki Declaration. The requirement for informed consent was waived.

In this study, we reviewed the clinicopathological characteristics and imaging results for 48 patients who were diagnosed with pure LCIS, and we evaluated the incidence of multifocal/multicentric or bilateral lesions detected by multiple breast imaging modalities. The most commonly observed finding on MMG and USG was microcalcification in 66.7% of patients and an irregularly shaped mass in 64.6% of patients, respectively. Among 19 additional imaging abnormalities in the ipsilateral breast, 10 multifocal/multicentric lesions were diagnosed with LCIS, resulting in a 20.8% rate of multifocal/multicentric LCIS. In the contralateral breast, one LCIS (2.1%) and seven other malignancies (invasive carcinoma and DCIS, 14.6%) were also diagnosed.

LCIS has been previously reported to involve multifocal or multicentric lesions in the ipsilateral breast in more than half the patients and bilateral LCIS in approximately a third of patients [10-12]. In our study, however, additional LCIS lesions were detected at a significantly lower rate in either breast, even with the use of the latest breast imaging technologies, including digital MMG, USG with Doppler and elasticity imaging, and MRI. This difference may be due to the difference in methods used to evaluate additional lesions. In the study by Rosen et al. [10], 108 of 125 evaluated patients underwent mastectomy for the ipsilateral breast, and 24 had bilateral mastectomy. More extensive examination of the excised breast could have resulted in the detection of additional LCIS lesions that otherwise would have not been detected.

Breast MRI performed in 35 of 48 patients in this study provided limited information beyond MMG and USG for detecting additional LCIS lesions. All 16 additional abnormalities in the ipsilateral breast and 11 in the contralateral breast that were detected on MRI were noted on breast USG. These findings are comparable to several studies that evaluated the use of screening MRI during follow-up for LCIS patients. A study by King et al. [17] showed that there was no additional benefit in cancer detection in women receiving MRI compared to those with annual MMG and breast examinations. Another study by Schwartz et al. [18] demonstrated that screening MRI in women with atypical lesions or LCIS resulted in additional tests in one-fifth of the patients, but with a positive predictive value of only 20%. In a study evaluating the usefulness of MRI in addition to MMG and USG in Korean women with invasive breast cancer, the increase in the detection rate of additional malignancy was only 2.0% for the ipsilateral breast and 0.9% for the contralateral breast compared to 4.6% to 16% in the Western population [19]. When taking these results into account, it is suggested that aggressive evaluation for additional lesions using breast MRI is of limited value in Korean women with LCIS.

There are several limitations to this study. One is the retrospective nature of this investigation. This may have affected the selection of patients, which depended on the review of pathologic reports and imaging findings. Furthermore, the interpretation of the preoperative breast MRI and USG were made by the same radiologist, which raises the concern that the MRI and USG imaging findings may have influenced each other. Another limitation is the small number of patients included in the study. While our study involves a relatively large group of Korean LCIS patients, the number is still insufficient to draw definitive conclusions.

In conclusion, in a modern series of Korean LCIS patients, the incidence of the multifocal/multicentric or bilateral LCIS was lower than that in the historic case series. The role of breast MRI in addition to MMG and breast USG in the detection of additional lesions in LCIS patients had limited value. Further large-scale prospective studies are necessary to evaluate the role of various breast imaging studies in patients with LCIS.