A systematic review and meta-analysis of imaging characteristics and upgrade rates in noninvasive lobular neoplasia of the breast

Abstract

Background: Non-invasive lobular neoplasia (NLN) encompasses a range of lobular breast lesions that may precede invasive breast cancer. Microcalcifications detected through mammography play a crucial role in evaluating breast lesions and are often associated with NLN. This study focuses on the prevalence and significance of microcalcifications in NLN, noting that they can be the sole radiographic finding in many cases. While mammography is highly sensitive for detecting microcalcifications, it has limitations in diagnosing NLN, as some lesions may not show up on scans. Advanced imaging techniques like magnetic resonance imaging (MRI) offer improved diagnostic accuracy, particularly in dense breast tissue, but more research is needed for their routine use. Additionally, the risk of NLN progressing to malignant lesions highlights the importance of vigilant monitoring and management. This study aims to analyze the relationship between microcalcifications and NLN, addressing progression risks and implications for clinical practice. Method: This systematic review and meta-analysis (CRD42022346891) involved a comprehensive search of databases such as PubMed and Scopus from 2000 to 2023, using keywords related to lobular carcinoma and mammography. Eligible English-language studies included those reporting mammographic findings of pure NLN lesions confirmed by histopathologic evaluation and surgical excision. Exclusion criteria involved studies without surgical results or definitive imaging findings. Two independent reviewers assessed titles and abstracts, resolving discrepancies as needed. Data were systematically extracted using a standardized form, with the selection process depicted in a PRISMA flow diagram. Result: Meta-analysis of included studies revealed that the pooled proportion of any mammographic micro-calcification among all NLN lesions was 0.70 (95 CI: 0.63-0.76). Pure microcalcification (without an associated mass or distortion) was the most common presentation, with a pooled proportion of 0.67 (95 CI: 0.60-0.74) among all lesions and 0.99 (95 CI: 0.96-1.00) among lesions presenting with any micro-calcification. The overall pooled upgrade rate to malignancy was 0.18 (95 CI: 0.11-0.25), with a significantly higher rate for lobular carcinoma in situ (LCIS) at 0.22 (95 CI: 0.15-0.30) compared to atypical lobular hyperplasia (ALH) at 0.06 (95 CI: 0.01-0.14). Microcalcifications were present in the majority of upgraded lesions (pooled proportion: 0.78, 95 CI: 0.69-0.87). A small but significant proportion of lesions (0.08, 95 CI: 0.03-0.17) had no mammographic findings. All pooled estimates showed high heterogeneity. Sensitivity analysis confirmed the robustness of the results, while Egger's test indicated potential publication bias. Conclusion: In conclusion this study highlights the significant prevalence of microcalcifications in NLN cases and their critical role as a diagnostic feature. Despite their association with disease progression, microcalcifications are not reliable predictors of malignancy upgrade. Further evaluation is necessary to understand their clinical implications and improve management strategies for patients with NLN.