Pleomorphic and florid lobular carcinoma in situ of the Breast: A systematic review of current evidence and knowledge gaps

Introduction: Pleomorphic (PLCIS) and florid (FLCIS) lobular carcinoma in situ are uncommon entities, characterized by significant architectural distortion and cellular atypia. Their rarity poses three key clinical challenges: diagnostic variability, histologic upgrade and risk of local recurrence (LR). Currently, no standardized management guidelines exist. This systematic review provides the most comprehensive synthesis to date of the available evidence on clinical, radiologic, pathologic, and molecular characteristics of P/FLCIS, and evaluates outcomes associated with different treatment strategies. Methods: A systematic literature search was conducted across major biomedical databases up to June 2025. Eligible studies were original case series reporting primary data on P/FLCIS. Results: From 5402 screened records, 38 studies were included, comprising 629 total cases: 411 PLCIS, 98 FLCIS, and 120 categorized as LCIS with pleomorphic or non-classic features. The pooled upgrade rate was 35.3% (PLCIS 35.1%, FLCIS 33.3%; p = 0.843), predominantly to invasive carcinoma (28.8%). Among 258 pure P/FLCIS cases with available follow-up (median, 50 months) the overall LR rate was 12.4% (PLCIS 13.1%, FLCIS 9.1%; p = 0.618), with invasive recurrences representing the majority (62.5%; p = 0.04). Margin status was significantly associated with risk of LR (positive margins 38.2%, close margins (<2 mm) 20.0%, negative margins 3.0%; p < 0.001). Data on adjuvant treatments were inconsistent and heterogeneous. Conclusions: Given the high upgrade rate and significant risk of LR for P/FLCIS, complete surgical excision with negative margins is strongly advised to ensure definitive diagnosis and reduce future breast events. The role of adjuvant therapies remains unclear, highlighting the urgent need for standardized, multicenter studies to guide optimal clinical management.