Multinucleation in Lobular Carcinoma In Situ: A Histologic Feature Specific for the Pleomorphic Variant
Luis Z Blanco, Jr., Aparna Mahajan, Kalliopi P Siziopikou, Barbara Susnik, Megan E Sullivan. Northwestern University Feinberg School of Medicine, Chicago, IL; Abbott-Northwestern Hospital, Minneapolis, MN
Background: Classically, lobular carcinoma in situ (LCIS) is composed of dyshesive cells with intracytoplasmic vacuoles that expand the lobules, with some cells that are small, round and monotonous (type A) and others that are moderately enlarged with more abundant eosinophilc cytoplasm (type B). In contrast, pleomorphic LCIS (PLCIS) cells have marked nuclear enlargement similar to high grade ductal carcinoma in situ. However, determining moderate vs. marked nuclear enlargement is subjective and can make distinguishing true PLCIS from CLCIS with abundant type B cells a challenge. As the frequency of bi- and multinucleated (B/M) cells is generally greater in more proliferative lesions, we evaluated cases of PLCIS and CLCIS for the presence and number of B/M to determine if this more objective morphologic feature helps in the differential diagnosis.
Design: All cases diagnosed as PLCIS from 2001 to 2012 were identified in the pathology database, both with and without associated invasion (IC). The hematoxylin and eosin (H&E) stained slides and the E-cadherin stains were reviewed to confirm the diagnosis (N=20). The number of B/M cells vs. the total cell count per high power field (HPF) was recorded. A group of consecutive CLCIS cases was subjected to the same analysis (N=26).
Results: The number of LCIS cells counted per case ranged from 372 to 3530 (average=1455) with 1-3 HPF examined per case. The average age was 57.8 (range: 43-86 years) for the CLCIS group, and was 58.2 (range: 43-75 years) for the PLCIS group. Overall, binucleated cells were more frequent in PLCIS compared to CLCIS (94% vs. 29%, p=0.0001). Multinucleated cells were present in 18% of PLCIS and were absent in CLCIS (p=0.006). The frequency and quantity of B/M per HPF was considerably less in CLCIS compared with PLCIS (Table 1). 15% of PLCIS cases had >5 B/M in a HPF; this was never seen in CLCIS (p=0.016). There was no significant difference in B/M between PLCIS and PLCIS with IC (p=0.96).