Pleomorphic lobular carcinoma in situ: Upgrade rate to invasive carcinoma, association with other neoplastic processes, and clinical outcomes.

e12565 Background: Pleomorphic lobular carcinoma in situ (pleoLCIS) is a special morphologic subtype of LCIS. Data about its natural history is very limited and its management remains controversial. We performed a retrospective review of this entity to assess frequency of associated lesions on biopsy, upgrade rate on subsequent excision, and clinical outcomes at our institution. Methods: Pathology database search identified breast core and excisional biopsies containing pleoLCIS (2001-2024). Health records were reviewed to record pathologic diagnoses, clinico-radiologic correlates, and interventions employed. Upgrade rate was calculated for cases without coexisting invasive carcinoma, atypical ductal hyperplasia (ADH), and/or ductal carcinoma in situ (DCIS). Results: 120 cases of initial breast biopsy (111 cores, 9 excisions) contained pleoLCIS, supported by e-cadherin immunohistochemistry in 119 (99.2%) cases. Coexisting invasive carcinoma (n=84), DCIS (n=8) and ADH (n=5) were seen on biopsy. Of 23 biopsies without coexisting invasion/ADH/DCIS, 13 also showed classic or florid LCIS. Radiologically, 13/23 had calcifications, 4 had focal lesions, and 6 showed nonmass enhancement. 2/23 patients had palpable mass, including 1 with associated Phyllodes tumor. Subsequent excision of “pure” pleoLCIS on biopsy showed invasive carcinoma in 12 (52.2%), DCIS in 1 (4.3%), and additional LCIS in 10 (43.5%) patients. 3/10 patients with only LCIS after excision received hormonal therapy alone. PleoLCIS was excised to negative margins in 116/120 cases. 56/120 patients received adjuvant radiation, including 1 without DCIS or invasive carcinoma. 7/120 patients had loco-regional recurrence, 3 of whom also had concurrent distant failure. All 13/120 patients with distant failure had invasive disease on initial biopsy. Cohort median follow-up was 6.2 years [interquartile range 3.5-10.6]. Conclusions: Pleomorphic LCIS was associated with invasive carcinoma in 96/120 (80%) cases either on initial biopsy or on subsequent excision. More than half of biopsies containing only pleoLCIS were upgraded to invasive disease on excision. Elevated rate of associated invasive disease may justify treating pleoLCIS similarly to DCIS and invasive carcinoma, as occurred in this study with most excising pleoLCIS to negative margins.