The current study demonstrated that the upgrade rate of preoperative LCIS was 16.4%. A relatively significant proportion of the patients with preoperative LCIS had hidden invasive cancer that might be missed if only core needle biopsy is used as a definitive diagnostic tool. A previous study reported an 8.4–9.3% rate of upgrade for LCIS, which was considerably higher than the acceptable target for surveillance, and the authors suggested excision of preoperative LCIS confirmed by a core needle biopsy [5]. Li et al. suggested that LCIS might be a precursor of invasive carcinoma, and localized treatment for LCIS is warranted [7]. Cheng et al. also suggested that lumpectomy is the most appropriate management for LCIS [8]. In this study, all upgrade groups were diagnosed by core needle or vacuum assisted biopsy, not by excisional biopsy (Fig. 2b). This result suggested that excision could be considered in case of LCIS for reliable tissue confirmation.
Nevertheless, there is controversy about the treatment of LCIS diagnosed on core needle biopsy, because of the varying upgrade rates mentioned in the literature (Table 4). Schmidt et al. reported that the true upgrade rate of LCIS was 4% on excluding pleomorphic LCIS and image-discordant lesions [9]. They suggested that surgery for classic LCIS is unnecessary, and careful radio-pathological correlation during initial biopsy is critical. Wen and Brogi suggested that classic LCIS on core needle biopsy with concordant imaging does not require surgical resection [10]. However, our study showed a relatively high rate of upgrade of LCIS, regardless of the presence of pleomorphism. There was no association between the upgrade rate and presence of pleomorphic LCIS or comedo necrosis in this study. Even though the pathologic slides of all cases of LCIS were reviewed by a specialized pathologist, no pleomorphism or comedo necrosis was detected in the upgrade group. Pleomorphic LCIS is considered to be an aggressive type of LCIS associated with high-grade DCIS and invasive cancer [11, 12]. In the previous studies, the upgrade rates of pleomorphic LCIS were relatively high, at 20–100% [9, 13, 14]. Hence, the NCCN guidelines recommend surgical excision for pleomorphic LCIS [1]. The difference in the upgrade rate of pleomorphic LCIS between the previous and current study might be due to the small sample size of each study and inter-observer variability in the pathological evaluations.
Table 4
Upgrade rates of lobular neoplasia or LCIS during the recent 5 years
Authors | Years | Pathology | N | Upgrade rate | Features |
Benjamin C. Calhoun [12] | 2016 | LN | 76 | 13% | Included pLCIS as an upgraded pathology |
Thaer Khoury [13] | 2016 | LN LCIS | 63 34 | 24% 32% 67% (pLCIS) | MRI-guided core biopsy |
Schmidt H [9] | 2018 | LN | 115 | 11% (all LN) 4% (except pLCIS and discordant lesions) | Observation vs. excision |
Desai AA [14] | 2018 | pLCIS | 15 | 20% | |
Iskender Sinan Genco [18] | 2019 | LN cLCIS | 287 115 | 3.8% 7% | Classic LN diagnosed on breast core needle biopsy |
Holbrook AI [19] | 2019 | LN | 66 | 7.6% | |
Nakhlis F [20] | 2019 | NC-LCIS | 76 | 36% | Supporting routine excision |
LCIS lobular carcinoma in situ, LN lobular neoplasia, NC-LCIS non-classic lobular carcinoma in situ, pLCIS pleomorphic lobular carcinoma in situ |
The definition of concordant images and pathologic results is variable [15]. Youk et al. summarized five categories of radio-pathological correlation in a sonography-guided core needle biopsy of a breast lesion: concordant malignancy, discordant malignancy, concordant benign, discordant benign, and borderline or high-risk [15]. Before the AJCC system 8th edition was published, LCIS was considered a malignant lesion; thus, when core needle biopsy for a BI-RADS category 4a lesion reveals classic LCIS, it could be considered either as discordant benign or borderline. When the radio-pathological correlation is borderline, a multidisciplinary approach or surgical excision to identify the hidden malignancy could be adopted. However, after the AJCC system 8th edition was published, when core needle biopsy for a category 4a lesion revealed classic LCIS, it was considered as concordant benign and not borderline or high-risk. In such cases, surgical excision should not be routinely recommended according to the NCCN guidelines. Since most previous studies used data obtained before the AJCC system 8th edition was published, the definition of the radio-pathological correlation for classic LCIS was considered to be either discordant benign or borderline. When we reviewed a previous study, the exact definition of the radio-pathological correlation was not specified [16, 17]. Since the general recommendation of close follow-up for classic LCIS is based on ambiguous or arbitrary definition of the radio-pathological correlation for classic LCIS, it is difficult to routinely follow the revised guidelines for classic LCIS. A more detailed definition of the radio-pathological correlation for LCIS should be developed to avoid miscommunication among physicians, radiologists, pathologists, and surgeons.
The current study found that microcalcification on mammography and the expression of PR were significant in predicting the likelihood of upgrade of LCIS. A previous study reported a similar association between the upgrade rate of LCIS and mammographic calcification [5]. This result was similar to that observed in our study. Therefore, when cases of LCIS diagnosed on preoperative biopsy involve mammographic microcalcification and PR positivity, hidden invasive cancer or DCIS might be discovered after surgical excision (Fig. 3).
There were some limitations to this study. First, we analyzed a small number of cases. Few cases of preoperative LCIS were evaluated for calculating the upgrade rate. Second, when we reviewed the pathologic data, including data on pleomorphism, there were some missing data that might have affected the accuracy of the analysis. In the future, more large-scale, long-term research on LCIS is necessary. Finally, our research has the limitations of a retrospective study. Nevertheless, the current study has valuable implications for clinical practice. Our study focused only on LCIS and not on lobular neoplasia or atypical lobular hyperplasia. We found that the ambiguity in the definition of radio-pathological correlation in the previous studies might have weakened the evidence of the current guidelines. In the current study, multivariate analysis found two significant predictors of the upgrade of preoperative LCIS.